Guidelines for Clinical Care

Quality Department Ambulatory

Chronic Kidney
Disease Guideline Management of Chronic Kidney Disease
Team
Team Leader Patient population: Adults with chronic kidney disease (CKD).
Jennifer Reilly Lukela, MD Objectives: (1) Identify populations that may benefit from more systematic screening for CKD and
General Medicine provide an overview of methods for screening and diagnosis. (2) Outline treatment options for patients
Team Members with CKD to decrease progression of renal deterioration and potentially decrease morbidity and
R. Van Harrison, PhD mortality. (3) Highlight common co-morbid conditions such as cardiovascular disease and diabetes,
Medical Education emphasizing the importance of aggressive management of these conditions to potentially decrease
Masahito Jimbo, MD morbidity and mortality among patients with CKD.
Family Medicine
Key points
Ahmad Mahallati, MD
Nephrology Background
Rajiv Saran, MBBS • Despite increasing prevalence of CKD, it is often under-recognized and under-treated. [A]*
Nephrology • Evidence for screening and management of early stage CKD is limited due to absence of large
Annie Z. Sy, PharmD randomized controlled trials.
Quality Management
Program Definition and Staging (Tables 1 and 2)
• Kidney damage for ≥ 3 months, defined by structural or functional abnormalities of the kidney, with
or without decreased glomerular filtration rate (GFR).
Initial Release:
November, 2013 Diagnosis
Interim/Minor Revision: • For patients with diabetes, screen annually for microalbuminuria if not on an ACE inhibitor or ARB
March 2014 and for creatinine and estimated GFR [IA]. Consider screening for CKD among patients at increased
June 2016 risk, especially those with hypertension [IA] or age ≥ 55 years. [IID]
July 2019
• Laboratory studies needed to diagnose and stage CKD include eGFR (usually calculated using the
CKD-EPI equation) and urine studies for the presence or absence of albuminuria. [IC]
Ambulatory Clinical • Ultrasound imaging for structural kidney disease may be helpful in certain populations. [IID]
Guidelines Oversight Treatment
Karl T. Rew, MD
R. Van Harrison, PhD • Lifestyle modifications (dietary management, weight management, physical activity) are the initial
components of treatment and secondary prevention. [IA]
• Blockade of the renin angiotensin aldosterone system with either an angiotensin converting enzyme
Literature search service inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is the cornerstone of treatment to prevent
Taubman Health Sciences or decrease the rate of progression to end-stage renal disease. [IA]
Library • Blood pressure control reduces renal disease progression and cardiovascular morbidity/ mortality.
- Target BP <130/80 mm Hg if without hypotension risk (eg, without: orthostatic hypotension, heart
failure, older age). (SBP of < 130 mm Hg ([IA] for ASCVD); DBP < 80 mm Hg [IA].)
For more information:
- Consider a target BP of <140/90 mm Hg if risk for hypotension.
734-936-9771 • Optimally manage comorbid diabetes and address cardiovascular risk factors to decrease risk for
cardiovascular disease, which is the leading cause of mortality for patients with CKD. [IA] Statin or
statin/ezetimibe therapy is recommended in all CKD patients age ≥ 50 years to decrease the risk of
© Regents of the cardiovascular or atherosclerotic events. [IA]
University of Michigan • Monitor for other common complications of CKD including: anemia, electrolyte abnormalities,
abnormal fluid balance, mineral bone disease, and malnutrition. [ID]
• Avoid nephrotoxic medications to prevent worsening renal function. [ID]
These guidelines should not
Monitoring and Follow Up
be construed as including all • The timing and frequency of CKD monitoring and follow up depends on disease severity and risk for
proper methods of care or
excluding other acceptable
progression; assess GFR and albuminuria a minimum of once per year. [ID] (table 16)
methods of care reasonably • For CKD stages G3b-G5, monitor labs more frequently due to increased risk for hyperkalemia.
directed to obtaining the same
results. The ultimate judgment • Refer CKD stage G4 or G5 (see Table 2) to nephrology for co-management and preparation for renal
regarding any specific clinical replacement therapy. Consider referral at earlier stage to assist with diagnosis of underlying cause
procedure or treatment must
be made by the physician in and/or treatment of common complications of CKD. [IC]
light of the circumstances
presented by the patient. * Strength of recommendation:
I= generally should be performed; II = may be reasonable to perform; III = generally should not be performed.
Levels of evidence for the most significant recommendations
A = randomized controlled trials; B=controlled trials, no randomization; C=observational studies; D=opinion of expert panel

1 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 1. Definition of CKD Table 2. Staging of CKD
CKD is classified by the CGA system:
Cause, GFR category, Albuminuria category
Abnormalities of kidney structure or function (defined
by markers of kidney injury or decreased GFR) present GFR GFR Terms
for > 3 months with implications for health. (Either Category (mL/min/
criterion is sufficient for diagnosis.) 1.73 m2)
1. Markers of kidney damage (one or more): G1 > 90 Normal or high
• Albuminuria (AER ≥ 30 mg/24 hrs; ACR ≥ 30 G2 60-89 Mildly decreased
mg/g) G3a 45-59 Mildly to moderately
• Urine sediment abnormalities decreased
• Electrolyte and other abnormalities due to G3b 30-44 Moderately to severely
tubular disorders decreased
• Abnormalities detected by histology G4 15-29 Severely decreased
• Structural abnormalities detected by imaging G5 < 15 Kidney failure
• History of prior kidney transplantation
Albuminuria AER ACR Terms
2. GFR < 60 mL/min/1.73 m2 Category (mg/24hrs) (mg/g)
A1 < 30 < 30 Normal to
* GFR = glomerular filtration rate; AER = albumin excretion
rate; ACR = albumin-to-creatinine ratio
mildly increased
A2 30-300 30-300 Moderately
Modified from KDOQI Clinical Practice Guidelines for the increased
Evaluation and Management of Chronic Kidney Disease: A3 > 300 > 300 Severely
(2013) increased
AER = albumin excretion rate
ACR = albumin-to-creatinine ratio

Table 3. Common Risk Factors for the Table 4. Common Causes of Acute or Acute
Development of CKD on Chronic Kidney Injury
Diabetes Volume depletion
Hypertension Acute urinary obstruction
Age ≥ 55 years Use of diuretics, ACE or ARB
Family history of kidney disease Use of NSAIDs, iodinated contrast agents, or other
Obesity or metabolic syndrome nephrotoxic agents
Heart failure
Acute glomerulonephritis or acute intestinal nephritis
Liver failure
Malignancy (eg, myeloma)

Table 5. Key Aspects of the Medical History Table 6. Commonly Used Equations
in Evaluating Patients with CKD to Estimate Glomerular Filtration Rate (eGFR)
Prior kidney disease or dialysis MDRD (Modification in Diet and Renal Disease Study) 4-
Incidental albuminuria or hematuria (microscopic or variable equation
gross) in the past GFR (mL/min/1.73 m2) = 186 x (SCr) -1.154 x (Age) -0.203 x (0.742 if
Urinary symptoms such as nocturia, frequency, polyuria, female) x (1.210 if African-American)
urgency, hesitancy; a history of foamy or frothy urine CKD-EPI (Epidemiology Collaboration) equation
may indicate prior heavy proteinuria
History of nephrolithiasis GFR = 141 x min(SCr/κ,1)α x max(SCr/κ,1)-1.209 x 0.993Age x 1.018
Family history of kidney disease [if female] x 1.159 [if black]
Diseases that share risk factors with CKD: DM, HTN, Patient weight is not required for eGFR using either equation. Results are
CAD, PAD, heart failure normalized to 1.73 m2 body surface area - BSA (accepted average adult
surface area). Equations tend to underestimate GFR if large body surface
Systemic diseases that might affect kidney (eg,
area (eg, obese or large, muscular) patients and overestimate GFR in small
rheumatologic diseases, especially SLE; Sjogren’s; body surface area patients. Both equations should be used with caution
Progressive Systemic Sclerosis) when assessing GFR in those with extremes of body habitus or muscle
History of use of medications that might affect renal mass, during pregnancy, and in the elderly.
function: OTC (especially NSAIDs and herbal Online CKD EPI & MDRD GFR Calculator (with SI Units):
medications) or prescription (eg, lithium, calcineurin http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm
inhibitors)

2 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 7. Common Agents for Renin Angiotensin Aldosterone Blockade

Dosage Range Dose Adjustments Based on

Generic for Normal GFR (mL/min/1.73 m2) Cost 30 days
Comments
(Brand) Name Kidney (Percentage of Usual Dosage) Generic
Function 30-59 10-29 < 10 Brand
Angiotensin Converting Enzyme Inhibitors (ACE-I)
Benazepril 10 - 40 mg/day 75% 50% 25% $5-7 Can cause acute increase in SCr
(Lotensin) (divided q12-24h) $28 all and/or potassium; continue
Enalapril 5 - 40 mg/day 50-100% 50% 25% $14 all medication if increase is < 30%;
(Vasotec) (divided q12-24h) $50-150 monitor renal function and
Captopril 25 - 50 mg q8-12h 75% 50-75% 50% $73-109 potassium levels with initiation
(Capoten) $150-235 and with each dosage change,
Ramipril 2.5 - 20 mg/day 50% 25-50% 25% $7-10 every 1-2 weeks until values
(Altace) (divided q12-24h) $193-475 return to baseline (usually within
Fosinopril 10 - 40 mg/day - - 75-100% $9 all 4-6 weeks)
(Monopril) (divided q12-24h) $33 all
Lisinopril 10 - 40 mg q24h 50-75% 50% 25-50% $6 all
(Prinivil, Zestril) $48-430
Quinapril 10 - 80 mg/day 50% 25-50% 25% $9-13
(Accupril) (divided q12-24h) $156-314
Trandolapril 1 - 4 mg/day - 50% 50% $11-15
(Mavik) (divided q12-24h) $33 all
Moexipril 7.5 - 30 mg/day 50% 50% 50% $28-58
(Univasc) (divided q12-24h) $38-79
Perindopril 4 - 16 mg q24h 50% Max dose of Max dose of $20-73
(Aceon) 2 mg q48h 2 mg q48h $62-151
Angiotensin Receptor Blockers (ARBs)
Losartan 50 - 100 mg q24h - - - $6 all Can cause acute increase in SCr and/or
(Cozaar) $120-164 potassium; continue medication if
Irbesartan 150 - 300 mg q24h - - - $10-13 increase is < 30%; monitor renal
(Avapro) $194-234 function and potassium levels with
Candesartan 16 - 32 mg/day - - - $60 all initiation and with each dosage
(Atacand) (divided q12-24h) $224-294 change, every 1-2 weeks until
Olmesartan 20 - 40 mg q24h - - n/a values return to baseline (usually
50% within 4-6 weeks)
(Benicar) $238-330
Valsartan 80 - 320 mg q24h - - - $13-19
(Diovan) $254-330
Telmisartan 40 - 80 mg q24h - - - $18-21
(Micardis) $233 all
Aldosterone Antagonists
Eplerenone 25 – 100 mg/day 50% Avoid Avoid $60-107 Contraindicated in patients with SCr ≥
(Inspira) (divided 12-24h) $369-738 2 mg/dL (males) or ≥ 1.8 (females)
due to increased risk of
hyperkalemia; monitor potassium
levels with initiation and with each
dosage change; extend dosing
interval or decrease dose by 50% if
necessary
Spironolactone 25 - 200 mg/day - 50% Avoid $6-23 Monitor potassium levels with
(Aldactone) (divided q12-24h) $82-484 initiation and with each dosage
change; extend dosing interval or
decrease dose by 50% if necessary
Cost = Average Wholesale Price minus 10%. AWP from Lexicomp Online 7/19. For generic drugs, Maximum Allowable Cost plus $3 from BCBS of
Michigan MAC List, 7/19.

3 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 8. Other Drugs Commonly Used to Treat Hypertension
Dosage Range Dose Adjustments Based on GFR
(mL/min/1.73 m2) Cost 30 days
Generic (Brand) for Normal
(Percentage of Usual Dosage) Generic Comments
Name Kidney
Brand
Function 30-59 10-29 < 10
Thiazide Diuretics
Hydrochlorothiazide 12.5 - 50 mg q24h - - Avoid $6 Consider avoiding
n/a thiazide diuretics
Metolazone 2.5 - 20 mg q24h - - - $35-44 if GFR < 30 mL/
(Zaroxolyn) $98-101 min/1.73 m2;
Chlorothiazide 0.5 - 1 g - - Avoid $35-67 potassium-sparing
(Diuril) (divided q12-24h) n/a diuretics and
aldosterone
Chlorthalidone 15 - 50 mg q24h - - Avoid $28 blockers can
increase risk of
hyperkalemia in
CKD patients
Potassium-sparing Diuretics
Amiloride 5 mg q24h 50-100% 50% Avoid $22
(Midamor) $35
Other Diuretics
Furosemide 20 - 600 mg q24h - - - $5
(Lasix) $25-36
Torsemide 5 - 200 mg q24h - - - $10-26
(Demadex) $17-164
Calcium Channel Blockers
Amlodipine 5 – 10 mg q24h - - - $5
(Norvasc) $50-65
Verapamil (Calan, 80 – 120 mg q8h - - - $12-37
Covera-HS, Isoptin $443
SR, Verelan)
Felodipine 5 – 10 mg q24h - - - $10
(Plendil) $43-100
Diltiazem IR: 30 – 90 mg q6h - - - $92
(Cardizem) IR: $78-155
CD: 180 – 360 mg CD: $1000
q24h LA: $130-344
LA: 180 – 540 mg
q24h
Nifedipine IR: 10 mg q8h - - - $12-18
(Procardia, Adalat) IR: $267
XL: 30-120 mg q6h XL: $500-1300
CC: $61-102
CC: 30-60 mg
q24h
Beta Blockers
Atenolol 50 - 100 mg q24h 50-100% 50% Max dose 25mg $7 Atenolol is generally
(Tenormin) q24h $412 not recommended
Carvedilol 3.125 - 25 mg q12h - - - $6 for BP control in
(Coreg) $160 CKD patients
Metoprolol tartrate 100 - 450 mg/day - - - $5-20 Atenolol, and
nadolol are elim-
(Lopressor) (divided q12-24h) $81-149
inated renally;
Propranolol 80 - 160 mg q24h - - - $35-44 others are
(Inderal LA) $2000 metabolized
Labetalol (Trandate) 100 - 400 mg q12h - - - $11-20 hepatically and do
$62-188 not need any dose
Bisoprolol (Zebeta) 5 - 20 mg q24h 75% 50-75% 50% $20-36 adjustments due to
$61-122 CKD (eg,
Metoprolol succinate 25 - 400 mg q24h - - - $11-44 metoprolol , pro-
(Toprol XL) $43-204 pranolol, labeta-
Nadolol (Corgard) 40 - 80 mg q24h Extended dosing Extended dosing Extended dosing $43 lol)
interval to q36h interval to q48h interval to q48-60h $164-225
Cost = Average Wholesale Price minus 10%. AWP from Lexicomp Online 7/19. For generic drugs, Maximum Allowable Cost plus $3 from BCBS of
Michigan MAC List, 7/19.

4 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 9. Drugs Commonly Used to Treat Diabetes

Dosage Range Dose Adjustments Based on GFR

(mL/min/1.73 m2) Cost 30 days
Generic for Normal
(Percentage of Usual Dosage) Generic Comments
(Brand) Name Kidney
Brand
Function 30-59 10-29 < 10
Biguanide
Metformin 500-1000 mg bid 50% Avoid Avoid $5-7 Contraindicated in
(Glucophage) $40-80 patients with
eGFR < 30
mL/min/1.73 m2
due to increased
risk of lactic
acidosis. Starting
metformin in
patients with
eGFR between
30-45
mL/min/1.73 m2
is not
recommended.
Assess risk vs.
benefit of
continuing
metformin if
eGFR drops
below 45
mL/min/1.73 m2
Sulfonylureas (Second Generation)
Glipizide
2.5-15 mg q24h 50-100% 50% 50%
$11-13 Active metabolite
(Glucotrol) $27-150 can accumulate
and cause
Glimepiride $7
(Amaryl) 1-2 mg q24h - - - prolonged
$43-70 hypoglycemia in
Glyburide $6-26 patients with
1.25-20 mg q24h 0-50% Avoid Avoid CKD
(Micronase) n/a
Thiazolidinediones
Pioglitazone Can cause dose-
(Actos) related edema.
Contraindicated
15-45 mg q24h - - - in patients with
NYHA Class III
and IV heart
failure.
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Sitagliptin 50 mg q24h
n/a
(Januvia) 100 mg q24h (CrCl ≥ 30 to < 25 mg q24h 25 mg q24h
50) $487
Saxagliptin 2.5-5 mg q24h 2.5mg q24h 2.5mg q24h 2.5mg q24h n/a May increase risk
(Onglyza) (GFR ≤ 50) $454 all for heart failure.
Use with caution
in patients with
known risk factors
for heart failure,
including renal
impairment.
Linagliptin n/a
(Tradjenta) 5 mg q24h - - -
$471
Alogliptin $180 May increase risk
(Nesina) $211 for heart failure.
Use with caution in
patients with
25 mg q24h 12.5 mg q24h 6.25 mg q24h 6.25 mg q24h
known risk factors
for heart failure,
including renal
impairment.

5 UMHS Chronic Kidney Disease Guideline, July 2019

 Dosage Range Dose Adjustments Based on GFR
(mL/min/1.73 m2) Cost 30 days
Generic for Normal
(Percentage of Usual Dosage) Generic Comments
(Brand) Name Kidney
Brand
Function 30-59 10-29 < 10
Incretin mimetics, injectable
Exenatide 5 - 10 mcg bid - Avoid Avoid n/a Post-marketing
(Byetta) $330-660 reports of acute
Exenatide 2 mcg once weekly - Avoid Avoid n/a renal failure and
Extended Release worsening of
$25
(Bydureon) chronic renal
Liraglutide 0.6-1.8 mg q24h - - - n/a failure. Use
(Victoza) caution when
$110 initiating or
Dulaglutide 0.75-1.5 mg once - - - n/a escalating doses
(Trulicity) weekly $27 in patients with
Albiglutide 30-50 mg once - - - n/a renal impairment.
(Tanzeum) weekly $20 Monitor renal
function closely in
patients reporting
adverse GI
effects.
Cost = Average Wholesale Price minus 10%. AWP from Lexicomp Online 6/19. For generic drugs, Maximum Allowable Cost plus $3 from BCBS of
Michigan MAC List, 6/19.

Table 10. Statin/Lipid Treatment in Patients with CKD

CKD Patient Population Treatment

Age ≥ 50 years with eGFR < 60 mL/min/1.73 m2 and no previous kidney transplant (G3a-G5) Statin or statin + ezetimibe 1
Age ≥ 50 years with eGFR ≥ 60 mL/min/1.73 m2 (G1-G2) Statin
Age 18-49 with eGFR ≥ 60 mL/min/1.73 m (G1-G2) and either: known coronary disease
2
Statin
(myocardial infarction or coronary revascularization), diabetes mellitus, prior ischemic
stroke, or estimated 10-year incidence of coronary death or non-fatal myocardial infarction
> 10% 2
Transplant recipient (adult any age) Statin
Hypertriglyceridemia Therapeutic lifestyle changes
Note: Adapted from the KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease, 2013.
1
Option to add ezetemibe is based on the SHARP (Study of Heart and Renal Protection) trial.
2
Calculators to estimate 10-year incidence of coronary death or non-fatal myocardial infarction include: Framingham risk score,
Reynold’s, SCORE, PROCAM, ASSIGN, or QRISK2.

6 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 11. Drugs Commonly Used to Treat Dyslipidemia
Dose Adjustments Based on GFR Cost a 30
Dosage Range (mL/min/1.73 m2)
Generic days
for Normal (Percentage of Usual Dosage) Comments
(Brand) Name Generic
Kidney Function
30-59 10-29 < 10 Brand
Statins b
Atorvastatin 10 - 80 mg q 24h $6-8
- - -
(Lipitor) $340-484
Rosuvastatin 5 - 40 mg q24h Start at 5mg $10-11 Use with caution in Asian
(Crestor) q24h; $282 patients as drug levels
-
Max dose of can be two fold higher
10mg q24h than usual.
Simvastatin 5 - 80 mg q24h c - - Start at 5mg $6 Myopathy risk highest
(Zocor) q24h $112-261 with simvastatin 80mg.
If need more than
simvastatin 40 mg daily,
switch to atorvastatin or
rosuvastatin.
Pitavastatin 2 mg q24h Start at 1mg Start at 1mg Start at 1mg n/a Contraindicated with
(Livalo) (1 – 4 mg q24h) q24h q24h q24h $251 cyclosporine.
Max dose of Max dose of Max dose of
2mg q24h 2mg q24h 2mg q24h
Lovastatin 20 - 80 mg q24h - 50% 50% $5-8 Use doses over 20 mg
(Mevacor) $36-219 with caution in CKD
stages G4 and G5.
Pravastatin 10 - 80 mg q 24h Start at 10mg $11
-
(Pravachol) q24h $71-129
Fluvastatin 20 - 80 mg q24h - 50% 50% $122 Use doses over 40 mg
(Lescol) $135-270 with caution in CKD
stages G4 and G5.
Nicotinic Acid $20-73
500 - 2000 mg daily - 50% 25-50%
(Niaspan) $167-592
Absorption Inhibitors
Bile Acid Resins
Ezetimibe 10 mg daily - - - $14 May be used with other
(Zetia) $373 antihyperlipidemic drugs
Fibrates
Gemfibrozil 600 mg bid - 75-100% 50-100% $11 May increase SCr;
(Lopid) $436 consider alternate
therapy if SCr > 2
mg/dL; more likely to
cause rhabdomyolysis
when used in
conjunction with statins
Fenofibrates
Fenofibrate 40 - 160 q24h 25% 25% Avoid $11-53 Avoid use with statins
(Various) $64-282 due to increased risk of
myopathy
a
Cost = Average Wholesale Price minus 10%. AWP from Lexicomp Online 7/19. For generic drugs, Maximum Allowable Cost plus $3 from BCBS of
Michigan MAC List, 7/19.
b
The risk of myopathy is increased when statins are coadministered with medications that inhibit their metabolism (eg, cytochrome P450
enzyme inhibitors) or with other medications that have been associated with myopathy (eg, cyclosporine, danazol, niacin, fibrates).
Adjust doses as needed, use statins cautiously with fibrates, and avoid coadministration with gemfibrozil if possible.
c
Only patients who have been on simvastatin 80 mg for at least 12 months without evidence of myopathy should continue to be treated at
this dosage.

7 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 12. KDIGO Recommended Statin Dosing in Adults with CKD

Dose (mg/d) for eGFR Category

G3a-G5 (including patients
Statin Dose (mg/d) for eGFR Category G1-G2
receiving dialysis or who have had
a kidney transplant)
Atorvastatin Any dose approved for general population 20 a
Fluvastatin Any dose approved for general population 80 b
Lovastatin Any dose approved for general population not done
Pitavastatin Any dose approved for general population 2
Pravastatin Any dose approved for general population 40
Rosuvastatin Any dose approved for general population c 10 d
Simvastatin Any dose approved for general population 40
Simvastatin/ezetimibe Any dose approved for general population 10/10 e
Adapted from the KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease (2013).
All doses are mg/d. All statins may not be available in all countries. Lower doses than those used in major trials of statins in
chronic kidney disease populations may be appropriate in Asian countries. Cyclosporine inhibits the metabolism of certain
statins, resulting in higher blood levels.
a
Data based on Die Deutsche Diabetes Dialyse Studie
b Data based on Assessment of Lescol in Renal Transplantation trial
c
40 mg of rosuvastatin daily is not recommended for use in patients with CKD G1-G2 who did not have transplants because
it may increase the risk for adverse renal events.
d
Data based on A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of
Survival and Cardiovascular Events
e
Data based on the Study of Heart and Renal Protection trial.

Table 13. Select Drugs That Can Affect Serum Potassium Levels

Increase Potassium Decrease Potassium

Aldosterone receptor antagonists Acetazolamide
Angiotensin II receptor blockers Antacids
Angiotensin-converting enzyme inhibitors Corticosteroids
Beta-blockers Fluconazole
Cyclosporine Insulin
Heparin Loop diuretics
Nonsteroidal anti-inflammatory drugs Salicylates
Potassium-sparing diuretics (amiloride, Stimulant laxatives (senna)
eplenerone, spironolactone, triamterene) Sodium polystyrene sulfonate
Sulfonamide antibiotics Theophylline
Thiazide diuretics

8 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 14. Key Elements of Patient Education for CKD

Elements
• Ensure patient awareness of CKD diagnosis
• “Know your numbers”- make patients aware of their kidney function (eGFR and creatinine) and blood pressure goals
• Discuss the need for screening and treatment of comorbid conditions (eg, diabetes, hypertension, CAD)
• Instruct patients to avoid potentially nephrotoxic OTC medications, especially NSAIDS, herbal medications,
unsupervised use of vitamin and minerals or nutritional protein supplements
• Encourage patients to talk with their primary care physician, nephrologist, or pharmacist before starting new
medications to ensure safety and appropriate renal dosing
• Promote lifestyle modifications
o Diet, with special attention to sodium, potassium and phosphorus intake
o Regular exercise
o A healthy body weight
o Immunizations
o Tobacco cessation
Resources
Patient education resources are available at the National Kidney Foundation Website (kidney.org/)
For links to recommended patient education materials, visit the University of Michigan Clinical Care Guidelines website

Table 15. Drug-Induced Nephrotoxicity: Prevention Strategies, Patient Risk Factors, and Associated Drugs

General Strategies to Prevent Drug-Induced Nephrotoxicity

Assess baseline renal function prior to initiating potentially nephrotoxic drugs
Adjust medication dosages based on renal function as needed
Avoid nephrotoxic drug combinations
Use non-nephrotoxic alternatives whenever possible
Correct risk factors for nephrotoxicity before initiating drug therapy whenever possible
Ensure adequate hydration before and during therapy with potential nephrotoxic drugs
Limit dose and duration of therapy when possible
Key Risk Factors Predisposing Patients to Drug-Induced Nephrotoxicity
Age greater than 60 years Multiple myeloma
Diabetes mellitus Sepsis
Drug-drug interactions resulting in synergistic Underlying kidney dysfunction (eGFR < 60 mL/min/1.73
nephrotoxic effects m2; renal artery stenosis)
Exposure to multiple or high doses of nephrotoxins Vascular disease
Heart failure Volume depletion
History of kidney transplant
Select Drugs Associated with Nephrotoxicity
Allopurinol Lithium
Aldosterone inhibitors Loop diuretics
Angiotensin-converting enzyme inhibitors Methamphetamines
Angiotensin II receptor blockers Methotrexate
Calcium channel blockers Nonsteroidal anti-inflammatory drugs
Cephalosporins Oral sodium phosphate solution
Combined phenacetin, aspirin, and caffeine analgesics Pamidronate
Cyclooxygenase-2 inhibitors Penicillamine
Cyclosporine Penicillins
Digoxin Propylthiouracil
Direct renin inhibitors Proton pump inhibitors
Fluoroquinolones Iodinated contrast agents
Foscarnet Rifampin
Gold Sulfonamides
Hydralazine Tacrolimus
Note: See Tables 18 and 19 for drugs, natural products, and herbs that may affect CKD patients.

9 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 16. Frequency of Monitoring CKD Patients Based on GFR and Albuminuria

Albuminuria Category
A1 A2 A3
Normal to mildly Moderately Severely
increased increased increased
< 30 mg/g 30-300 mg/g > 300 mg/g
< 3 mg/mmol 3-30 mg/mmol > 30 mg/mmol
GFR eGFR
Category (mL/min/1.73
m2)
G1 Normal or high ≥ 90 1/yr if CKD 1/yr q 6 mo
G2 Mildly decreased 60-89 1/yr if CKD 1/yr q 6 mo
G3a Mild to moderately decreased 45-69 1/yr q 6 mo q 4 mo
G3b Moderately to severely decreased 30-44 q 6 mo q 4 mo q 4 mo
G4 Severely decreased 15-29 q 3 mo q 4 mo q 3 mo or less
G5 Kidney failure < 15 q 3 mo or less q 3 mo or less q 3 mo or less
Adapted from KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease, 2013.

Table 17. Risk factors for CKD Progression

Advanced level of GFR decline

Advanced degree of albuminuria
Advanced age
Male gender
Race and ethnicity (ie, higher rates of progression in
African Americans, Hispanics, Pacific Islanders and
Native Americans versus non-Hispanic whites)
Poorly controlled hypertension
Hyperglycemia
Dyslipidemia
Smoking/tobacco use
History of cardiovascular disease
Ongoing exposure to nephrotoxic agents

Table 18. Indications for Referral of Patients with CKD to a Nephrologist

Refer for:
CKD of uncertain cause/etiology (eg, need for renal biopsy)
Persistent or severe albuminuria (eg, albuminuria category A3)
Persistent hematuria (RBC > 20 per HPF or urinary red cell casts)
Rapid decline in GFR or new AKI
All patients with stage G4 or G5 CKD to initiate discussion of potential renal
replacement therapy
Consider referral at earlier stages to assist with management of CKD
complications:
- Refractory hypertension (eg, 4 or more antihypertensive medications)
- Persistent hyperkalemia
- Anemia
- Mineral bone disease
- Fluid overload and/or malnutrition.

10 UMHS Chronic Kidney Disease Guideline, July 2019

 Table 19. Select Drugs and Natural Products That Can Increase or Decrease the Effect
of Immunosuppression Medications (eg, cyclosporine, tacrolimus, sirolimus)
Prescribed for Kidney Transplant Patients*

Prescription Medications: Natural Products:

Amiodarone ↑ Nifedipine ↑ Grapefruit juice ↑
Azole antifungals ↑ Orlistat ↓ St. John’s wort ↓
Carbamazepine ↓ Probucol ↓ Red wine ↑
Carvedilol ↑ Protease inhibitors ↑ Berberine ↑
Colchicine ↑ Quinolones ↑ Chaparral ↑
Diltiazem ↑ Rifamycins ↓ European Barberry ↑
Hydantoins ↓ Serotonin reuptake inhibitors ↑ Tree Turmeric ↑
Lovastatin ↑ Sulfonamides ↓ Echinacea ↑↓
Macrolide antibiotics ↑ Terbinafine ↓
Metoclopramide ↑ Verapamil ↑
Nefazodone ↑
*
↑ indicates that the agent generally increases the effect of immunosuppression medications; ↓ indicates a decreased effect

Table 20. Select Herbs That May Be Harmful to CKD Patients

Alfalfa Coltsfoot Noni juice

Aloe Comfrey Panax
Aristolochic acid Dandelion Pennyroyal
Artemisia absinthium (wormwood plant) Ephedra (Ma Huang) Periwinkle
Autumn crocus Ginger Pokeroot
Bayberry Gingko Rhubarb
Blue cohosh Ginseng Sassafras
Broom Horse chestnut Senna
Buckthorn Horsetail St. John’s wort
Capsicum Licorice Tung shueh
Cascara Lobelia Vandelia cordifolia
Chaparral Mandrake Vervain
Chuifong tuokuwan (Black Pearl) Mate Yohimbe
Nettle

11 UMHS Chronic Kidney Disease Guideline, July 2019

 Clinical Problem and Management Issues abnormalities on imaging studies), or serum electrolyte
abnormalities (eg, renal tubular syndromes).
Chronic kidney disease (CKD) is an increasingly common
clinical problem that raises a patient’s risk for developing In 2002, the Kidney Disease Outcomes Quality Improvement
several life-threatening medical conditions, including end- Initiative (KDIGO) Work Group on CKD provided a
stage renal disease (ESRD) and cardiovascular disease comprehensive definition and staging system of CKD in an
(CVD). Appropriate treatment can delay or prevent these effort to provide a common language among health care
adverse outcomes. However, CKD is often not recognized by providers, patients and researchers, and hopefully improve
clinicians or patients and as a result is often not optimally communication and care for this diagnosis. This staging
treated. system was recently revised and updated in 2013 and
includes increased focus on the cause of kidney dysfunction
Prevalence. The National Health and Nutrition Examination and the presence of albuminuria (Table 2).
Survey (NHANES) study estimated that in 2013-2016,
14.8% of the adult population of the United States had CKD. Etiology. CKD can result from a wide array of distinct
CKD stage G3 (6.4%) was the most prevalent. The estimated pathophysiologic processes associated with abnormal kidney
30 million adults with CKD is an appreciable increase over function and a progressive decline in GFR. The most
the 1994 estimate of 20 million adults. common causes in the U.S. are diabetic and hypertensive
nephropathy. Other causes include glomerulonephritis,
Problems with care for CKD. Despite the increased polycystic kidney disease, malignancy, or obstruction as
prevalence of CKD, it remains under-recognized by both seen in nephrolithiasis or prostate disease.
health care providers and patients, especially in its early
stages when patients are largely asymptomatic. While ethnicity or race was previously thought to be a risk
factor for CKD, based on data from the most recent
A 2007 study assessing the prevalence of CKD found only NHANES study, racial and ethnic minorities do not appear
11.6% of men and 5.5% of women with moderate kidney to have an increased prevalence of CKD in the United States
disease were aware of their diagnosis. Even among patients compared with non-Hispanic whites. However, the risk of
with more severe kidney disease less than half (42%) of progression from CKD to ESRD is higher in African
affected patients were aware of their disease. For Americans, Hispanics, Pacific Islanders and Native
comparison, similar studies have estimated that for other Americans. The reasons for this disparity are unclear.
chronic illness, such as hypertension and diabetes, greater
than 70% of affected patients are aware of their disease Screening
diagnosis.
Despite the increasing incidence and prevalence of CKD, no
This under-recognition of CKD likely results from several organization currently advocates screening the general
factors, including clinicians being uncertain of whom to population for CKD. While the National Kidney Foundation
screen and of how to screen for CKD. Clinician (NKF) does not advocate general screening, it recommends
communication with patients regarding this diagnosis may that all persons should be assessed for the presence of CKD
be problematic and likely fails to convey implications for risk factors (Table 3) to determine whether they are at
future health, morbidity and mortality. increased risk for developing CKD as part of routine health
maintenance.
The consequence of under-recognition of CKD by both
clinicians and patients is that it is also under-treated. This is A recent cost-effectiveness analysis concluded that annual
worrisome as the adverse outcomes of CKD, including urine dipstick testing for albuminuria in patients with
kidney failure and cardiovascular diseases, can be prevented diabetes or hypertension, as well as those aged 55 years and
or delayed with treatment and risk factor modification in the older without concurrent diabetes or hypertension, was cost-
earlier stages of disease. effective. In diabetics, screening for microalbuminuria has
been shown to be more sensitive, and thus is recommended
Clinicians need to identify patients with CKD and manage annually by many professional organizations and guidelines.
them appropriately in order to alter disease progression. (See the UMHS clinical guideline “Management of Type 2
Diabetes Mellitus”.)
Definition and Etiology
Definition. CKD is defined as abnormal kidney structure or Initial Workup and Evaluation
function persisting greater than 3 months. This can be
determined either by evidence of kidney damage (typically Establishing CKD
detected by presence of persistent albuminuria) or by
decreased glomerular filtration rate (GFR). Other markers Review of available medical records indicating presence of
may include evidence of pathologic abnormality (eg, abnormal kidney structure or function for 3 or more months
detected by renal biopsy), structural abnormalities (eg, can establish the diagnosis of CKD (Table 1). Ruling out
acute (or acute on chronic) kidney injury involves clinical
12 UMHS Chronic Kidney Disease Guideline, July 2019
judgment in the clinical context of either estimated GFR Currently, the abbreviated Modification of Diet in Renal
(eGFR) < 60, a drop of > 20% in eGFR, or an increase in Disease equation (MDRD) is used more frequently to
serum creatinine ≥ 0.3. calculate eGFR by laboratories in the United States.
Typically values for both African Americans and non-
During the initial evaluation of CKD, common causes and African Americans are reported, as race is typically unknown
predisposing conditions for acutely decreased eGFR, to the laboratory. Some laboratories only report a value for
including pre-renal and post-renal causes, should be eGFR if it less than 60.
considered based on appropriate clinical history, physical
exam and laboratory studies (Table 4). In general, both the MDRD and CKD EPI (Epidemiology
Collaborative) Equation tend to underestimate GFR in
History. A thorough history is a key component of the overweight or muscular patients and overestimate GFR in
assessment of CKD and often provides clues to the underweight patients. The CKD EPI Equation is somewhat
underlying etiology of renal dysfunction (see Table 5). more accurate than the MDRD equation at GFR > 60. Below
a GFR of 60 the two equations are generally equivalent for
Symptoms of kidney disease often develop only in advanced clinical practice. Both equations should be used with caution
stages, and therefore are less relevant to primary screening when assessing GFR in those with extremes of body habitus
and evaluation of CKD. Of particular interest, however, are or muscle mass, during pregnancy, and in the elderly.
symptoms related to obstructive urologic disease (nocturia,
dribbling, unable to empty bladder, frequency without Urinalysis. Urinalysis is performed to screen for hematuria
dysuria), a history of nephrolithiasis, recurrent urinary tract and albuminuria, both of which are markers of kidney
infections, or hematuria. damage. Urine dipstick is usually adequate for routine
screening. If this reveals any abnormalities or if the index of
Physical exam. No classic or diagnostic physical exam suspicion for presence of microalbuminuria is high (eg,
findings are present in early to moderate stage CKD. screening for nephropathy in a diabetic patient), follow-up
However, certain elements of the exam require special with more specific urine tests (eg, urine microalbumin with
mention and attention. albumin-to-creatinine ratio, and urine microscopy) is
recommended.
A key aspect of the exam is a general assessment of a
patient’s fluid status, assessing for both signs of dehydration Spot urine microalbumin with albumin-to-creatinine ratio.
and fluid overload. Also important is an accurate assessment The preferred urine specimen to assess for microalbumin is
of BP (see UMHS Clinical Care Guideline on Hypertension). the first voided urine in the morning. If an albumin-to-
creatinine ratio of 30-300 mg/g is obtained, consider repeat
A thorough abdominal exam is also required, specifically for testing once in 2 weeks to establish persistence. Potential
renal enlargement, CVA tenderness, or the presence of renal transient or benign etiologies of albuminuria to consider are
bruits. The exam should also include a focused assessment functional albuminuria of exercise, fever, or severe
to rule out signs of or risk for urinary obstruction, including emotional stress.
assessment for bladder distention, a prostate exam in men,
and assessment for pelvic mass or uterine enlargement in Ultrasound. While no formal studies have assessed the risk
women. If there is concern for bladder distention or versus benefit of ultrasound of the kidneys in CKD
obstruction, office evaluation could also include assessment evaluation, the size and echogenicity of kidneys can have
of a post-void residual using either a catheter or a bladder important prognostic value. Findings such as stones, masses,
ultrasound. or hydronephrosis should prompt urologic evaluation.
Patients with significant renovascular abnormalities should
Finally, the physical exam should include assessment for be referred to nephrologist.
clues to common underlying causes of renal disease and for
signs of common co-morbid conditions. Findings include Renal ultrasound may be considered in all patients with
those suggesting underlying connective tissue disorders or eGFR < 60 both for evaluation and establishing a baseline.
evidence of microvascular complications of diabetes (such as Ultrasound is strongly recommended in a patient with any of
retinopathy), as well as a complete cardiovascular the following:
examination to assess for signs of peripheral arterial disease
and/or heart failure. • Symptoms or signs consistent with obstruction
• Family history of cystic kidney disease, especially if age
Laboratory tests. Relevant laboratory tests for CKD > 20 years
include: GFR, urinalysis, and spot urine protein-to-creatinine • Rapid progression of CKD or significant change in the
ratio. rate of progression of CKD

Glomerular Filtration Rate. Persistently reduced GFR is used Renal ultrasound with Doppler should be considered for
in establishing a diagnosis of CKD. The two equations used patients with resistant hypertension, bruit on physical exam,
to estimate GFR are shown in Table 6. or finding of asymmetric kidney sizes on initial ultrasound
or other imaging study.

13 UMHS Chronic Kidney Disease Guideline, July 2019

Staging. The 2013 KDIGO staging criteria for CKD are Initial selection of a specific drug should be based on cost,
outlined in Table 2. The current GFR categories are similar potential side effects, and patient preference (Table 7). Both
to the prior CKD staging system proposed by KDIGO in classes of medications have been studied extensively.
2002 (stages 1-5) with subdivision of stage 3 into G3a and However, a higher volume of evidence and more landmark
G3b due to the difference in the prognostic significance of a studies have been done with ACEIs than with ARBs.
GFR greater than or less than 45. The new system also has Therefore, experts generally recommend starting with an
increased emphasis on the presence and degree of ACEI. However, ACEIs have a higher rate of cough and may
albuminuria. This change reflects the findings from several cause a slightly greater increase of potassium and serum
large meta-analyses (both from pooled general population creatinine levels compared with ARBs.
and CKD cohorts) showing that albuminuria significantly
impacts prognosis and the likelihood of progression in CKD. With decreasing kidney function, starting doses for both
ACEIs and ARBs are lower (see Table 7). Dose titration
should occur slowly as needed for control of blood pressure
Management of CKD or albuminuria.

The direct management of CKD focuses on renin angiotensin Starting ACEI or ARB. As discussed above, when starting
aldosterone blockade (RAAS) and blood pressure control. an ACEI or an ARB, monitoring blood pressure, potassium,
Management also includes optimal management of common and serum creatinine levels is important. Potassium and/or
comorbid conditions such as diabetes and addressing serum creatinine are expected to increase when starting or
cardiovascular risk factors to decrease risk for CVD. Also changing the dose of an ACEI or an ARB. Assess potassium
essential are patient education and a multidisciplinary and serum creatinine levels before starting or changing the
approach to disease management that include dieticians and dose. (If already measured within the previous two weeks,
social workers in addition to other health care providers. that measurement can be used.) One to two weeks after
initiation or dose change, check potassium and serum
Renin Angiotensin Aldosterone Blockade creatinine levels.

Single RAAS agent therapy. RAAS therapy with either an For most patients, a potassium level of up to 5.5 mEq/L and
angiotensin converting enzyme inhibitor (ACEI) or an a serum creatinine increase of up to 30% from baseline are
angiotensin receptor blocker (ARB) is recommended for acceptable within the first three months with close
patients with CKD to prevent or decrease the rate of monitoring. However, the ACEI or ARB may need to be
progression to ESRD. An ACEI or ARB should be the first- reduced or discontinued if the potassium level remains
line agent for antihypertensive therapy for CKD patients and elevated at > 5.5 mEq/L, or if the serum creatinine continues
is recommended for patients with albuminuria regardless of to rise or does not improve. For further discussion of
need for blood pressure control. management of potassium, see the section below on
potassium, phosphorus, and sodium balance.
Angiotensin causes greater vasoconstriction of efferent
arterioles than afferent arterioles, leading to glomerular Dual RAAS therapy. In general, dual therapy with ACEI
hypertension. This leads to hyperfiltration, and prolonged and ARB is not recommended. Studies to date have not
hyperfiltration leads to glomerular structural and functional shown any clinically significant benefits on overall mortality
deterioration. Both ACEI and ARB can reverse this process for dual therapy over monotherapy. Although some additive
and delay renal disease progression. anti-proteinuric effect occurs when two RAAS agents are
used, the ONTARGET study showed that dual therapy
While the reduction of intraglomerular pressure has long- increased the risk of worsening of kidney function and
term benefit, it may cause a small rise in serum creatinine in hyperkalemia. Several large RCTs are currently ongoing to
the short term, since GFR is directly correlated to assess the role of dual therapy for CKD patients specifically.
intraglomerular pressure. A rise of up to 20-30% above the
baseline is acceptable and not a reason to withhold Dual therapy with an ACEI and an ARB should be
treatment unless hyperkalemia develops. considered only for patients with severe albuminuria (> 1
g/day). A nephrology consult should be obtained at this point
In conditions such as bilateral renal artery stenosis, where to help initiate and monitor dual RAAS therapy.
angiotensin serves the critical role of preserving the
intraglomerular pressure and GFR, its blockade could lead to Spironolactone. Increasing evidence indicates that the
acute renal failure. Thus, checking serum creatinine and aldosterone receptor antagonist spironolactone can decrease
potassium about 1-2 weeks after initiating or changing the albuminuria and several small studies have evaluated its
dose of ACEI or ARB is recommended. combination with an ACEI or an ARB. One theory for this
combination regimen is the “aldosterone escape”
Selecting ACEI or ARB. ACEIs and ARBs do not differ phenomenon, which refers to the fact that ACEIs and ARBs
significantly in terms of overall mortality, progression to do not provide sustained decreases in aldosterone levels. The
ESRD, or their anti-proteinuric effects. combination of ACEI and spironolactone is commonly seen
in patients with concomitant heart failure, but may also be
14 UMHS Chronic Kidney Disease Guideline, July 2019
considered for those with severe albuminuria with effective on its own to control BP, then a thiazide or
nephrology input. Patients on combined spironolactone and dihydropyridine calcium channel blocker (eg, amlodipine)
ACEI or ARB therapy should be monitored carefully for may be added. It should be noted that dihydropyridine
hyperkalemia. calcium channel blockers should not be prescribed without
the concomitant usage of ACEI or ARB, since their sole use
Blood Pressure Control may lead to greater hyperfiltration and albuminuria.

Optimum blood pressure control reduces renal disease Once GFR declines to stage G4 or worse, thiazides are
progression and cardiovascular morbidity and mortality. For generally ineffective, and loop diuretics (eg, furosemide) are
patients with CKD, BP targets are: usually needed to control volume-dependent hypertension. It
• < 130/80 mm Hg if without risk for hypotension (eg, should also be noted that patients with more advanced CKD
without: orthostatic hypotension, heart failure, older often have resistant hypertension requiring multiple
age). (SBP of < 130 mm Hg ([IA] for ASCVD); DBP < medications. These patients can be prone to orthostatic
80 mm Hg [IA].) hypotension, and aggressive blood pressure control (<
120/80) should be avoided.
• Consider < 140/90 mm Hg if risk for hypotension. The
BP target is higher to avoid hypotension, which may Combined use of ACEI and ARB for blood pressure control
result in insufficient blood flow to the kidneys, is controversial, with no clear evidence of its benefit and
dizziness, and fainting. (The prevalence of hypotension possibly an increase in adverse events, including
increases with age, from 4% for individuals age 50-59 hyperkalemia and worsening of renal function. (See earlier
years to 19% for individuals over 80 years.) discussion of dual RAAS therapies.)

Recommendations for BP targets in patients with CKD have See Table 8 for an overview of medications commonly used
changed as more evidence becomes available. The 2017 to address hypertension and necessary renal dose
ACC/AHA guidelines recommended reducing SBP to < 130 adjustments.
mm Hg and DBP to < 80 mm Hg, based on new data from
SPRINT. Systolic blood pressure had not been evaluated as For more information on blood pressure control, see the
rigorously as diastolic blood pressure until SPRINT looked UMHS clinical guideline “Essential Hypertension.”
at SBP control and clinical outcomes. For patients with
elevated blood pressure and elevated ASCVD risk,
Management of Comorbid Conditions
aggressive treatment of hypertension provides significant
improvements in clinical outcomes. Current available data
Common comorbid conditions among patients with CKD
suggest that a SBP target of < 130 mm Hg is reasonable.
include diabetes, cardiovascular disease, and
hyperlipidemia. Managing these comorbid conditions
For CKD, the “Kidney Disease: Improving Global
aggressively is important. Suboptimal control of these
Outcomes” (KDIGO) group in 2012 recommended BP
secondary conditions increases the risk for progression of
targets for patients with CKD of < 140/90 mm Hg if urine
CKD. Additionally, the presence of CKD increases the
albumin excretion is < 30 mg per 24 hours and of < 130/80
morbidity and mortality associated with the comorbid
mm Hg if urine albumin excretion is ≥ 30 mg per 24 hours.
conditions themselves.
KDIGO is reviewing its recommendations based on the
results of SPRINT, which included CKD patients. Based on
Diabetes mellitus. Relatively strict control of blood glucose
the results of SPRINT, our recommendation is also to apply
(hemoglobin A1c ≤ 7%) in both type 1 and type 2 diabetes
the target of 130/80 mm Hg to CKD patients with urine
reduces the development of diabetic nephropathy and its
albumin excretion < 30 mg per 24 hours. We add practical
progression. Diligent BP control reduces renal disease
cautions to avoid hypotension and to monitor for
progression and cardiovascular morbidity and mortality
hyperkalemia.
among patients with diabetes.
In certain CKD populations, including the elderly and those
Drugs commonly used for glucose control in patients with
with diabetes mellitus, aggressive BP control could lead to
diabetes are listed in Table 9. Dose adjustments based on
negative outcomes such as acute deterioration in kidney
renal function are noted. Renal deterioration leads to
function, increased risk for cardiovascular events and
decreased renal metabolism of hypoglycemic drugs and/or
orthostatic hypotension. In general, systolic blood pressure
insulin. As a result, dose adjustment of these medications
should remain > 110 mm Hg and even higher if orthostatic
may be required as CKD progresses to prevent
symptoms occur. For diastolic blood pressure, caution is
hypoglycemia.
suggested when diastolic BP falls below 60 mm Hg or less.
Mortality increased when patients with diabetes had diastolic
Preferred antihypertensive therapy among diabetics with
BP below 70.
hypertension is with an ACEI or an ARB. ACEI or ARB
therapy is also recommended for normotensive diabetics
Of the antihypertensive agents, ACEIs and ARBs are
with microalbuminuria. No evidence supports use of RAAS
particularly effective in slowing disease progression in both
diabetic and non-diabetic CKD. If ACEI or ARB is not
15 UMHS Chronic Kidney Disease Guideline, July 2019
therapy for normotensive normoalbuminuric patients with have the highest CVD risk.
diabetes.
Similar to the recent AHA/ACC guideline for lipid
Due to the high incidence of CKD among patients with management in the general population, the recent KDIGO
diabetes, annual surveillance for CKD using serum clinical practice guideline recommends statin therapy in all
creatinine and urine microalbumin to creatinine ratio is CKD patients with > 10% 10-year predicted risk of coronary
recommended for this patient population. disease. Given that all patients ≥ 50 years of age who have
CKD meet this criterion, statin use is recommended for all
For more detailed information regarding diabetes care, see non-dialysis patients with CKD age ≥ 50 years.
the UMHS clinical guideline “Management of Type 2
Diabetes Mellitus”. For patients with CKD ages 18-49 years who are not treated
with chronic dialysis or kidney transplantation, the most
Cardiovascular disease (CVD). Cardiovascular disease is recent guideline recommends suggests statin treatment for:
the leading cause of morbidity and mortality among patients
• Known coronary disease (myocardial infarction or
with CKD.
coronary revascularization)
Recent studies have demonstrated that even early stage CKD • Diabetes mellitus
constitutes a significant risk factor for cardiovascular events • Prior ischemic stroke
and death. Similarly, CVD is a risk factor for progression of • Estimated 10-year incidence of coronary death or non-
CKD. The frequency of cardiovascular complications in fatal myocardial infarction.
patients with CKD can be reduced with appropriate treatment To estimate risk of 10-year incidence of coronary death or
of other CVD risk factors. non-fatal myocardial infarction, any of the validated risk
prediction models may be used (Framingham risk score,
Statins to reduce cardiovascular risk. Statins reduce the SCORE, PROCAM, ASSIGN, Reynolds or QRISK2). For
relative risk of cardiovascular events to a similar extent example, the Framingham risk score is calculated using the
among patients with and without CKD. However, the benefit individual’s age, gender, total cholesterol, HDL cholesterol,
is greater in patients with CKD because of the greater smoking status, and systolic blood pressure.
baseline risk for patients with CKD. In addition to reducing
cardiovascular risk, statins may also have a role in preventing The risk of coronary disease for all kidney transplant patients
progression of kidney disease and reducing albuminuria, is also elevated, therefore statins are recommended for this
though evidence for these outcomes is less robust. population as well.

Based on the most recent KDIGO guideline, statin use is: Recent studies have provided conflicting evidence regarding
• Recommended for all non-dialysis CKD patients ≥ 50 the benefit of statins among patients with ESRD receiving
years of age regardless of stage of disease or the presence renal replacement therapy. Some of the studies have
or absence of albuminuria. demonstrated an increased risk of cerebrovascular events
among dialysis patients taking statins. As a result, current
• Suggested for non-dialysis or non-kidney transplant CKD
guidelines do not recommend the initiation of statin therapy
patients who are 18-49 years of age and have an estimated
in patients on dialysis. CKD patients already taking statins at
risk of > 10% for 10-year incidence of coronary death or
the time of dialysis initiation may continue them.
non-fatal myocardial infarction (includes any with
coronary disease, diabetes mellitus, or ischemic stroke).
Statin drugs and dosing. The use of standard doses of
• Suggested for all kidney transplant patients, regardless of
statins appears safe among most patients with CKD and does
age.
not require special monitoring beyond that for non-CKD
• Suggested to continue in patients already receiving statins patients. More intensive statin regimens have not been well
at the time of dialysis initiation. studied in patients with CKD, and there is concern that this
• Suggested not to be initiated in patients with dialysis- population is at higher risk for adverse events related to the
dependent CKD. medication. This increased risk is thought to be due in part
to decreased renal excretion, likely polypharmacy, and the
Table 10 summarizes the groups for which statin therapy is
high rate of comorbid illness. As a result, cardiovascular
indicated.
benefit of high dose statins needs to be weighed against this
increased risk in this population.
The recent KDIGO clinical practice guideline on lipid
management in patients with CKD recommends against
CKD patients with good renal function may be treated with
using LDL cholesterol as a main target or determinant for
any statin regimen that is approved for use in the general
initiation of statin therapy. This recommendation is based on
population. Good renal function is defined as eGFR ≥
a possible misleading association between LDL cholesterol
60/mL/min/1.73 m2 (G1 and G2) and no history of kidney
level and coronary artery disease risk, especially among
transplantation. Recommendations for statin drugs and
patients with more advanced CKD. In advanced CKD,
dosing in the general population are presented in the UM
confounders such as inflammation and malnutrition may be
Lipid Management guideline. For patients with eGFR
associated with lower LDL cholesterol levels, but in fact
16 UMHS Chronic Kidney Disease Guideline, July 2019
categories G1-G2, the only exception to drugs used in the further research is necessary to clarify their role in the
general population is that 40 mg of rosuvastatin daily is not prevention and treatment of CHD in this population.
recommended because of a potential increased risk for
adverse renal events. For more information on prevention of vascular disease, see
the UMHS clinical guideline “Secondary Prevention of
CKD patients with limited renal function require reductions Coronary Artery Disease.”
from usual statin dosing due to decreased renal excretion.
Limited renal functioning is defined as eGFR < 60 Smoking. Smoking cessation should be strongly
mL/min/1.73 m2 (G3a-G5), including patients on dialysis or recommended among patients with CKD as a means to
with kidney transplant. Tables 11 and 12 outline reducing cardiovascular risk.
recommended dose adjustments and limitations for specific
statins based on renal function. Some studies have also suggested that smoking leads to a
more rapid progression of CKD especially among patients
A large randomized controlled trial (SHARP) compared with diabetes and hypertension. Data are limited on the
combination therapy with statin plus ezetimibe versus impact of tobacco cessation on progression of CKD.
placebo in patients with CKD. A significantly lower
incidence of cardiovascular events occurred in the treatment For more information on smoking cessation, see the UMHS
arm. As a result, the most recent KDIGO guideline suggests clinical guideline “Tobacco Treatment”.
statin + ezetimibe as an alternative to statin monotherapy,
especially in patients with an eGFR ≤ 60 mL/min/1.73 m2 Dyslipidemia. Dyslipidemia is common among patients
(eg, G3a-G5). In clinical practice, this approach may be with CKD. Statin use is now recommended for many CKD
limited by the higher cost of ezetimibe compared with statin patients independent of lipid levels, based on overall
monotherapy. cardiovascular risk. However, baseline assessment of lipid
levels is still recommended in patients with CKD.
Antiplatelet agents. Evidence is limited regarding the use of
aspirin or other antiplatelet agents for both primary and Baseline lipid profile and follow up. All adults with
secondary prevention of CHD among patients with CKD. CKD should have a baseline assessment of their lipid profile
at the time of their diagnosis of CKD. Ideally, the baseline
Due to strong evidence of its benefit among non-CKD lipid profile should be obtained when the patient is fasting
patients and insufficient evidence to recommend a different for a more accurate evaluation of potential dyslipidemias
approach among CKD patients, aspirin has been (including hypertriglyceridemia), which are common in the
recommended for CKD patients with known CHD for setting of CKD. However, if patient convenience or
secondary prevention of future cardiovascular events. compliance is an issue, a non-fasting lipid profile (when the
Aspirin is also often recommended for patients with diabetes. LDL is calculated directly if triglycerides > 400 mg/dL) may
be adequate if the primary goal is to assess cardiovascular
Previously, a post-hoc subgroup analysis of a large primary risk, especially in patients age < 50 years of age. Only total
prevention trial among patients with hypertension cholesterol and HDL-C are needed for most cardiovascular
demonstrated a greater absolute risk reduction in major risk calculators.
cardiovascular events and mortality from the use of aspirin
(75 mg) among patients with CKD compared to patients with The need, indications for and timing of repeat lipid
normal renal function. While there was a trend toward assessment in patients with CKD (with or without statin use)
increased bleeding risk among patients with lower GFR, is unclear. It is likely not required for the majority of patients,
increased risk in this group seemed outweighed by especially those started on statins. The most recent KDIGO
substantial benefits of aspirin use with regard to lipid guidelines advocate a “fire and forget” approach to
cardiovascular disease. statin therapy in patients deemed appropriate for statin use.

More recently, a meta-analysis was completed to address the Repeat assessment of lipids may be necessary or considered
use of antiplatelet agents among persons with CKD both with to assess medication compliance (eg, 6-12 weeks after
known stable or unstable CHD and those “at risk” for CHD. initiation) or if secondary causes of dyslipidemia are
For CKD patients with known stable CHD or “at risk” for suspected. Additionally, in CKD patients not on statin
CHD, antiplatelet regimens (aspirin, aspirin plus therapy, repeat lipids may be needed to reassess cardiac risk
dipyridamole [Aggrenox] or a thienopyridine [Plavix]) at different intervals. As stated above, a non-fasting lipid
appeared to reduce fatal or nonfatal myocardial infarction by profile is adequate to assess cardiovascular risk and to
approximately 33% but their impact on stroke or all-cause monitor statin compliance.
and cardiovascular mortality was uncertain. Among these
stable patients, antiplatelet agents appeared to increase risk Clinicians should be aware that many pay for performance
for minor bleeding but their use did not clearly increase risk programs (eg, based on current HEDIS measures) still
for major bleeding events. recommend annual monitoring, although the indication for
this is not clear.
Given the limited quality of evidence currently available to
address the role of these agents among patients with CKD, Hypertriglyceridemia. Combined dyslipidemias are
17 UMHS Chronic Kidney Disease Guideline, July 2019
common in patients with CKD. potassium and sodium imbalance, fluid imbalance, and
malnutrition. Patients with CKD need to be monitored for
For treatment of high triglycerides, current guidelines for these conditions and treated once a complication is
patients with CKD recommend therapeutic lifestyle changes. identified.
While evidence for use of therapeutic lifestyle changes for
treatment of hypertriglyceridemia is weak, given the low Anemia. Anemia is a complication of CKD that is
potential for negative side effects, this is currently the proportional to eGFR and is independently associated with
recommended management strategy for CKD patients with morbidity and mortality. A significant drop in hemoglobin
serum triglycerides > 500 mg/dL. Therapeutic lifestyle (Hgb) is typically seen among patients with CKD G3b or
changes include dietary modification, increased exercise, worse.
reduced alcohol intake and treatment of hyperglycemia
(especially in patients with concurrent diabetes mellitus). Based on 2013 KDIGO guidelines, anemia in CKD is
Specific dietary changes include following a low fat diet (< defined as Hgb < 13 in men and Hgb < 12 in women.
15% of total calories), reducing intake of mono- and Evaluation should include CBC, reticulocyte count, serum
disaccharides, reducing total carbohydrate intake, and adding ferritin, and transferrin saturation (TSAT) to assess for iron
fish oils in place of long-chain triglycerides. Given the risk deficiency.
of malnutrition in patients with advanced stages of CKD, a
referral to a nutritionist to guide patients in this type of diet If iron deficiency is diagnosed, an age-appropriate evaluation
modification is recommended. Therapeutic lifestyle changes and treatment independent of CKD should be followed. The
are discussed in more detail in the UM Lipid Management target Hgb for all stages of CKD is 10-12 although this is a
guideline. controversial area. Primary care clinicians should consider
referral to a nephrologist if Hgb < 10 and no obvious non-
Previous guidelines have suggested the use of fibric acid renal cause is identifiable with initial work up.
derivatives (eg, gemfibrozil, fenofibrate) in patients with
elevated triglycerides both to reduce risk of pancreatitis and Consideration of use of an erythropoeisis stimulating agent
decrease cardiovascular risk. Based on their most recent (ESA) and/or parenteral iron should be done in consultation
analysis, however, the KDIGO lipid work group felt that with a nephrologist. In general, clinicians should avoid
evidence is insufficient to support the use of fibric acid transfusion in patients with CKD if possible due to potential
derivatives for either of these indications. While these agents sensitization which might delay or preclude kidney
may still be reasonable to consider in CKD patients with transplant in the future. No specific Hgb threshold for
severe dyslipidemias (fasting serum triglycerides > 1000 transfusion exists. Clinical judgment is key; transfusion may
mg/dL), the work group considered the risk for potential side be indicated for symptomatic anemia, especially among
effects to outweigh the potential benefits in the majority of patients with cardiac failure.
patients. As a result, fibric acid derivatives are no longer
recommended to reduce either risk for pancreatitis or reduce For additional details of anemia management in CKD, please
cardiovascular events in this patient population. If refer to the 2013 KDIGO guidelines on anemia in CKD (see
gemfibrozil or fenofibrate are prescribed to CKD patients, annotated references).
renal dose adjustment is required (see Table 11).
CKD mineral bone disease (CKD-MBD). Abnormalities of
For CKD patients with severe dyslipidemias, a referral to a calcium and phosphate metabolism typically become
lipid specialist for further guidance on management could apparent in late stages of CKD (G3b or worse).
also be considered. Observational studies suggest that addressing CKD-MBD in
earlier stages of CKD may potentially slow or prevent
Other lipid medications. The SHARP trial demonstrated progression of CKD and may prevent vascular calcification.
both safety and efficacy for ezetimibe in CKD patients when
used in combination with statins. Combination Clinicians should consider checking Ca, Phos, iPTH, Alk
statin/ezetimibe therapy is currently recommended as an Phos, and 25-OH vitamin D at least once in patients with
alternative to statin therapy alone in CKD patients ≥ 50 years CKD stages G1-G3a. For G3b or worse, a similar lab
of age with eGFR < 60 mL/min/1.73 m2 (eGFR categories assessment would be recommended every 6 months. In
G3a-G5). general, CKD-MBD should be managed in conjunction with
a nephrologist.
Niacin (nicotinic acid) has not been well studied in patients
with advanced CKD. It also has a high risk of adverse effects Vitamin D supplementation is recommended for those with
(flushing, hyperglycemia). As a result, it is not recommended evidence of vitamin D deficiency. Renal hydroxylation is
for treatment of dyslipidemia in the CKD population. generally adequate in CKD stage G1-G3, and any form of
vitamin D would be useful in treating a deficiency. The
Complications of CKD threshold for vitamin D supplementation should be
especially low in geographic areas where patients are at high
CKD can result in several important complications risk for deficiency due to low sun exposure (eg, New
including: anemia, mineral bone disease, metabolic acidosis, England, Midwest).

18 UMHS Chronic Kidney Disease Guideline, July 2019

We recommend referral to nephrologist for the use of active • Dietary sodium restriction should, in general, be
forms of vitamin D or management of vitamin D deficiency emphasized, unless one suspects salt-wasting
or CKD-MBD in CKD stage G4 or G5. nephropathy, which is relatively rare.
• Loop diuretics are preferred when GFR is < 40
Diagnosis and treatment of osteoporosis (including use of mL/min/1.73 m2.
bisphosphonates) should be approached as in the general • Addition of spironolactone or eplerenone might be
population in CKD stages G1-G3. We recommend co- beneficial, especially in proteinuric patients already on
management of osteoporosis with a nephrologist at later maximized RAAS-blocker therapy.
stages of CKD, as dose adjustments will be necessary. • Larger dose loop diuretics (2 to 3 times the usual dose)
are often needed in nephrotic syndrome, due to binding
Metabolic acidosis. A small number of trials have of drugs to albumin.
demonstrated the potential benefit of sodium bicarbonate in • Addition of metolazone to be taken 15-20 minutes
patents at all stages of CKD to prevent kidney disease. before a loop diuretic may increase the response. This
However, given the limited data available and the potential can be done for 3-5 days until approaching euvolemia,
adverse effect on blood pressure, we recommend that the use then reassessed.
of sodium bicarbonate be deferred to a nephrologist. • Adjusting diuretic dose and frequency based on patient’s
accurate weight is preferred.
Potassium, phosphorous and sodium balance. • High dose or combination diuretic therapy should
Hyperkalemia is a frequent problem in CKD, especially in preferably be initiated in consultation with a
patients who might benefit from ACEI or ARB. High (> 5.5
nephrologist.
mEq/L), as well as low (< 4 mEq/L) potassium has been
associated with a shorter time to ESRD and higher mortality Fluid intake. High fluid intake is recommended for three
in patients with CKD stages G3-G5. conditions commonly seen in patients with CKD:
A low-potassium diet is recommended for patients with CKD
• Nephrolithiasis: recommended fluid intake of at least 2-3
for patients with K > 5.5 mEq/L. If the patient’s potassium is
L daily.
normal and stable, fruits and vegetables should not be
• Salt-wasting nephropathies (eg, chronic interstitial kidney
curtailed. However, a close review of medications and diet is
diseases, medullary cystic disease), are rare conditions in
necessary when hyperkalemia of any degree is encountered
which the renal concentrating ability is diminished: these
(see Table 13).
require a daily intake of > 4 L of fluid and a high salt diet.
Target phosphorous levels are 3-5 mg/dL. Phosphate • Central and nephrogenic diabetes insipidus: fluid intake of
restriction or phosphate binders should be prescribed in > 5 L daily may be needed.
consultation with the nephrologist.
Secondary Preventive Care
Modest sodium restriction of approximately 2 g of sodium
per day is recommended in most CKD patients as an adjunct The risk of complications in patients with CKD can be
to pharmacotherapy for better control of blood pressure. reduced by preventive care that includes maintaining a
healthy lifestyle, avoiding nephrotoxic medications,
The National Kidney Foundation provides helpful web- administering appropriate immunizations, and monitoring
based links for clinicians and patients on the topics on for common secondary diagnoses. Emerging evidence
potassium and phosphorus management (Table 14). identifies obesity as a potential modifiable risk factor for
both development and prevention of CKD, so overweight
Fluid balance. Monitoring fluid balance includes addressing and obesity should be aggressively addressed.
hypervolemia, diuretic use, and also salt and water intake.
Patients with CKD are susceptible to both hyper- and Dietary recommendations. Assessment of dietary intake of
hypovolemia. At advanced stages of CKD, the ability to patients with CKD is important. Inadequate caloric intake
compensate for electrolyte and volume changes is and malnutrition are common problem among patients with
progressively compromised. advanced CKD (especially eGFR < 25).

Hypervolemia and diuretics. Subclinical volume expansion Protein. In general, an adequate protein intake of 0.8
may be present even at CKD stage G3a. Overt hypervolemia g/kg/day is recommended for patients with CKD.
may be seen when a patient becomes oliguric or has
nephrotic syndrome, liver disease, or accompanying heart High protein intake (> 1.3 g/kg/day) has been linked with
failure. Regardless of the etiology of hypervolemia, some CKD progression and should be avoided.
practical issues occur for diuretic management in patients
with CKD: The potential risks versus benefits of moderate dietary
protein restriction (0.6 to 0.8 g/kg/day) on the progression of
CKD are unclear. However, any benefit of moderate-to-
intense protein restriction is likely to be small compared with
the benefits of RAAS blockade. Any consideration of protein
19 UMHS Chronic Kidney Disease Guideline, July 2019
restriction below 0.8 g/kg per day should be accompanied by Data from the National Health and Nutrition Examination
regular and close dietary supervision to avoid the real risk of Survey III (NHANES III) have shown that physical activity
malnutrition in CKD patients. was associated with lower mortality in patients with CKD of
stage G3 or worse. Additionally, increased physical activity
Potassium, phosphorous, and sodium. Patients with CKD may lead to better control of hypertension, diabetes, and
should be educated to be aware the intake of foods high in depression. Both aerobic and resistance exercises are
potassium (most important in the patients with beneficial.
hyperkalemia), phosphorous, and sodium. While the DASH
diet has been proven efficacious for treatment of For further information on physical activity
hypertension, hypertensive patients with CKD should follow recommendations and targets, see the UMHS clinical
caution when using the DASH diet due to its high intake of guideline “Obesity Prevention and Management.”
potassium and phosphate. At all stages, CKD patients with
hyperkalemia (K > 5.5) should be advised to follow a low- Avoidance of nephrotoxic medications. Medications can
potassium diet. Several web-based resources exist for cause or worsen kidney dysfunction and these effects are
patients regarding foods high in potassium and phosphorus exacerbated in patients with underlying CKD. Many
(Table 14). commonly used drugs, including over-the-counter
medications, can cause nephrotoxicity. Some of these drugs
The effect of sodium intake on the progression of CKD is are listed in Table 15.
controversial, and multiple inconclusive studies exist. No
specific recommendation is advisable at this time beyond Drug-induced kidney damage can be acute or chronic,
general recommendations to limit sodium in patients with variable in severity, and can affect any part of the kidneys.
hypertension and/or fluid overload, both of which are However, most drug-induced damage is reversible if
common among those with CKD stages G3-G5. detected and treated early. Signs of early kidney damage may
include acid-base abnormalities, electrolyte imbalances, and
Nutritional counseling. Periodic visits with trained renal mild urinary sediment abnormalities.
nutritionists are encouraged to assist patients with moderate
to severe CKD in making appropriate dietary choices. Most Factors predisposing patients to drug-induced nephrotoxicity
insurers cover dietary consultations for patients with a are listed in Table 15. Drugs that have been associated with
diagnosis of CKD. Visits can begin as early as eGFR < 60. nephrotoxicity should be used cautiously in these patient
The American Dietetic Association recommends that populations and concurrent use of multiple nephrotoxic
advanced stage CKD patients be referred to a dietician at agents should be avoided. Table 15 also outlines some
least 12 months before expected initiation of renal general strategies to prevent drug-induced nephrotoxicity.
replacement therapy. Evidence showing impact of this These strategies should be employed in all patients with
intervention on progression of renal disease and mortality is CKD.
limited, so these recommendations are based on expert
opinion. Three commonly used agents deserve additional comment:

Obesity. While no data are available from large scale NSAIDs. Ibuprofen, indomethacin, naproxen, and other
randomized controlled trials, smaller case-control, cohort NSAIDs are associated with a 3-fold increase in risk for
studies and epidemiologic data suggest that obesity may be acute kidney failure, which can occur within days and can be
an independent and potentially modifiable risk factor for reversed if the medication is promptly discontinued. Allergic
CKD. interstitial nephritis may occur around 6 months of therapy
and may need a steroid course to resolve. Of the NSAIDs,
One systematic review suggested that weight loss may be indomethacin is most likely to cause acute kidney failure,
associated with improvement in albuminuria, although and aspirin is least likely to result in damage. NSAID
evidence regarding the durability of this change was limited, treatment also increases the risk of GI bleeding. NSAID use
and no impact on GFR occurred. in patients with heart disease or its risk factors increases
overall risk of heart attack or stroke.
Obesity is a known risk factor for progression of
comorbidities such as type 2 diabetes, hypertension, Oral sodium phosphate products. Oral sodium phosphate
dyslipidemia and CVD. Therefore, counseling overweight (NaP) products (such as Visicol, OsmoPrep) products have
and obese patients with CKD regarding strategies for weight been associated with acute phosphate nephropathy when
loss is appropriate and recommended. used for bowel cleansing prior to colonoscopy or other
procedures. This form of kidney injury is associated with
For further information on treatment of obesity, see the deposits of calcium-phosphate crystals in the renal tubules
UMHS clinical guideline “Obesity Prevention and and may result in permanent kidney damage. Symptoms can
Management”. occur within hours or weeks (up to 21 days reported), and
can include malaise, lethargy, decreased urine output, and
Physical activity. The NKF/KDOQI Guidelines recommend edema. CKD patients, especially those on an ACEI or ARB,
engaging in exercise for 30 minutes most days of the week. are at increased risk of developing acute phosphate

20 UMHS Chronic Kidney Disease Guideline, July 2019

nephropathy. Consider using a polyethylene glycol solution • Obtain an eGFR at least annually in all patients taking
for these patients instead (such as GoLytely). NaP (Fleet) metformin. In patients at increased risk for the
enemas can be used for bowel cleansing before development of renal impairment such as the elderly,
sigmoidoscopy, but should be avoided in elderly patients or renal function should be assessed more frequently.
in those with severely decreased GFR (stage G5) due to the • In patients taking metformin whose eGFR later falls
risk of hyperphosphatemia and subsequent hypocalcemia. below 45 mL/min/1.73 m2, assess the benefits and risks
of continuing treatment. Discontinue metformin if the
Contrast media. Both iodinated and gadolinium-based patient’s eGFR later falls below 30 mL/min/1.73 m2.
contrast media are associated with potential for • Discontinue metformin at the time of or before an
complications among those with CKD. iodinated contrast imaging procedure in patients with an
eGFR between 30 and 60 mL/min/1.73 m2; in patients
Recent studies have cast doubt on the nephrotoxicity of with a history of liver disease, alcoholism, or heart
intravascular administration of iodinated contrast. However, failure; or in patients who will be administered intra-
it remains prudent to be concerned about possible arterial iodinated contrast. Re-evaluate eGFR 48 hours
nephrotoxic effects of intravascular iodinated contrast media after the imaging procedure; restart metformin if renal
in patients with low eGFR (various risk thresholds at eGFR function is stable.
of 30 to 45 mL/min/1.73 m2 have been suggested by specialty
societies). The nephrotoxicity of iodinated contrast agents, Administration of gadolinium-based contrast media used for
when it occurs, likely occurs promptly after administration, magnetic resonance imaging (MRI) is associated with the
although detection typically requires 12-24 hours because development of nephrogenic systemic fibrosis (NSF) in a
time is required for creatinine to be produced and serum small percentage of at-risk patients; all reported cases
creatinine to rise. Should renal functional damage occur, occurred in patients with CKD stages G4-G5. Therefore,
management consists of adequately hydrating the patient; these agents are not recommended for use as contrast agents
recovery usually occurs within 4-10 days after exposure. To for radiography, computed tomography, or angiography, and
minimize the nephrotoxicity risk from these agents, should be used with caution for MRI in patients who have an
clinicians should ensure adequate hydration and may want to eGFR less than 30 mL/min/1.73 m2. If necessary, use of the
consider intravenous administration of normal saline or smallest dose possible and not more than 0.3 mmol/kg of any
sodium bicarbonate infusion. Prophylaxis with drugs such as formulation is recommended. The FDA contraindicates
antioxidants (including N-acetylcysteine or ascorbic acid) Magnevist, Omniscan, and Optimark in patients with AKI or
has no proven reliability. There is some (albeit poorly with chronic, severe kidney disease. Agents considered to be
understood) relationship between the dose of the iodinated at the lowest risk of NSF are Dotarem, Gadavist, MultiHance
agent and nephrotoxicity risk, so that reducing dose (if that and ProHance.
will not interfere with the quality of the study) may be
helpful. Immunizations. The Centers for Disease Control and
Prevention recommend the following for patients with CKD:
Consider holding nephrotoxic drugs, such as NSAIDs, for 24
hours prior to and after exposure to contrast media in patients • Influenza vaccine annually for all CKD patients.
with CKD. The FDA states that metformin should be stopped • Pneumococcal vaccines for patients with end-stage renal
at or before the administration of intravascular iodinated disease or CKD likely to progress to end-stage renal
contrast media, and held for at least 48 hours after contrast disease:
media is administered, due to the risk of lactic acid - Vaccination with both conjugate vaccine
accumulation and toxicity if acute kidney injury from the (PCV13/Prevnar) and polysaccharide vaccine
iodinated contrast agent should occur. (Metformin is not (PPSV23/Pneumovax). If giving the initial
itself nephrotoxic nor does it increase the nephrotoxicity of vaccination, give PCV13 followed by PPSV23 ≥ 8
iodinated contrast agents.) The decision to resume metformin weeks later. If the patient was previously vaccinated
should be based on the follow-up serum creatinine level. with PPSV23, give PCV13 ≥ 1 year after last PPSV23
Some specialty societies suggest that this warning about dose. If the patient was previously vaccinated with
metformin is unnecessary in patients with normal or near- PCV13, give PPSV23 ≥ 8 weeks after PCV13.
normal renal function, given the lack of demonstrable - Give a PPSV23 booster in 5 years.
clinical nephrotoxicity from iodinated contrast agents in this - Give another PPSV23 booster if the patient is age ≥
patient subset. 65 years and if most recent PPSV23 vaccination was
done at age < 65 years and ≥ 5 years ago.
The FDA has updated labeling recommendations on how and • Hepatitis B vaccine for CKD patients nearing ESRD and
when kidney function is measured in patients receiving preparing to go on renal replacement therapy, especially
metformin, including the following information: hemodialysis.
• Before starting metformin, obtain the patient’s eGFR.
• Metformin is contraindicated in patients with an eGFR Renal transplant recipients on chronic immunosuppressive
below 30 mL/min/1.73 m2. therapy should NOT be given live vaccines such as MMR,
• Starting metformin in patients with an eGFR between varicella and herpes zoster vaccines.
30-45 mL/min/1.73 m2 is not recommended.

21 UMHS Chronic Kidney Disease Guideline, July 2019

Monitor for secondary diagnoses. Compared to the general In addition to monitoring for disease progression, labs for
population, CKD patients have a higher prevalence of those with CKD stages G3b-G5 should be monitored
several common diagnoses: frequently (as indicated in Table 16) due to increased risk for
hyperkalemia. Commonly prescribed hypertension
• Depression (found in 20-30% of patients with CKD vs medications (eg, angiotensin converting enzyme inhibitors,
10% of the general population) angiotensin receptor blockers, and potassium-sparing
• Sexual dysfunction diuretics) may result in hyperkalemia in patients with
- In men with CKD, 70% had self-reported erectile decreased renal function.
dysfunction.
- In women with CKD, 40%–80% report sexual While small fluctuations in GFR are common in CKD
dysfunction. patients, a significant decline (20% or more) is concerning
- For comparison, in the general population, only 13%– for CKD progression. Rapid progression is defined as a
33% of men and women report sexual dysfunction. persistent decline in GFR by greater than 4-5 mL/min/1.73
• Obstructive sleep apnea (found in 30% of patients with m2/year. A mild to moderate decline in GFR should prompt
CKD vs 2-4% of the general population). primary care clinicians to review current CKD management
and assess for potential reversible causes of acute kidney
Clinicians should remain alert for the possible presence of injury (AKI) or progression of CKD. A rapid decline in
these conditions in CKD patients. function is an indication for referral to a nephrologist.

Patient Education The progression of CKD, including the time course of and
whether progression leads to ESRD or nephritic syndrome,
Among patients with mild-moderate stage CKD (G1-G4), is highly dependent on the underlying cause of kidney
patient awareness of their diagnosis is poor. This is dysfunction. It can be influenced by adequacy of blood
problematic for many reasons. CKD progression and pressure control and the presence or absence of proteinuria.
complications are clearly impacted by use of common over Depending on the primary care clinician’s comfort level with
the counter medications (including NSAIDs, vitamins and the disease responsible for the patient’s CKD, earlier referral
herbal preparations), dietary and lifestyle choices, and to a nephrologist may be considered.
management of co-morbid conditions like hypertension,
diabetes and dyslipidemia. Improving patient awareness and CKD patients are at increased risk for AKI. Physicians
providing patient education and associated informational involved in their care should actively try to avoid situations
materials may help patients manage their chronic disease and that increase risk for AKI. If high-risk situations are
may lead to improved outcomes (see Table 14). unavoidable (Table 4), monitor closely for acute decline.

Successful chronic disease management involves physician When to refer to a specialist. Indications for referral to a
partnering with nurses, nutritionists, and pharmacists to nephrologist are presented in Table 18. Many patients reach
assist with and improve patient education and behaviors end-stage renal disease (ESRD) without adequate
including lifestyle, diet and medication compliance. preparation for transition to renal replacement therapy
(RRT). Nearly 50% of all patients reaching ESRD in the
Many on-line resources are also available to help patients United States either do not see a nephrologist at all or see one
better manage their disease. only within 6 months prior to requiring RRT. Delayed
referral is associated with higher mortality among patients on
dialysis.
Monitoring and Follow Up
Timely referral in Stage G4 (or earlier if CKD is progressing
Monitoring for progression. The diverse population of
rapidly) allows for adequate physical and psychological
patients with CKD makes the appropriate interval for patient
preparation, including optimization of vascular access and
follow up and laboratory assessment highly variable and
work-up for potential kidney transplantation.
patient specific.
Comprehensive multi-disciplinary care by a nephrology
team that includes nurses, social workers and dieticians is
General guidelines for follow up are provided in the most
recommended. Such care can help slow renal disease
recent KDIGO CKD Guidelines. They suggest the following:
progression, optimize management of CKD complications
prior to initiation of dialysis and provide a higher likelihood
• All patients with CKD should have an assessment of their
of permanent vascular access placement (preferably an AV
GFR and be checked for the presence or absence of
fistula) prior to beginning dialysis. Early referral to
albuminuria at least annually.
nephrology and involvement of a multidisciplinary team also
• Patients at higher risk for progression, such as those in a
increases the likelihood of CKD patients choosing peritoneal
more advanced GFR category or with more advanced
dialysis or other home-based dialysis therapies.
albuminuria, should be screened more frequently (see
Tables 16 and 17).
Other potential indications for nephrology referral outlined
in Table 18 include rapid decline in GFR and the potential

22 UMHS Chronic Kidney Disease Guideline, July 2019

need for renal biopsy to identify the cause of kidney higher risk of developing CKD compared to non-Hispanic
dysfunction. whites, more recent data have raised doubts about this racial
and ethnic variance in prevalence of the condition. Current
data continues to indicate that Hispanics, Native Americans,
Special Populations Pacific Islanders and, in particular, African Americans suffer
from a disproportionately higher incidence of ESRD. For
African Americans, kidney failure also occurs at an earlier
Pregnancy age compared to non-Hispanic whites.
Patients with CKD stage G3 or worse may have an
Transplant Patients
accelerated decline in their renal function during pregnancy.
A multidisciplinary approach is necessary, with involvement
All kidney transplant recipients are considered to have CKD.
of nephrologists and high-risk obstetricians skilled in
While transplant patients will almost always be co-managed
pregnancy management for patients with CKD.
by a nephrologist, the role for primary care clinicians in the
management of transplant patients includes:
Ideally, a patient’s renal function and albuminuria should be
stable and blood pressure should be well controlled prior to
• Early detection of decreased renal function as a possible
attempting pregnancy. Patients who have had a transplant
warning sign of allograft dysfunction
should be encouraged to wait 1 year after a living relative–
donor transplant and 2 years after a cadaveric renal transplant • Prevention, assessment and management of common co-
before attempting pregnancy. morbid conditions after transplant (including new onset
diabetes related to immunosuppressant medications,
Clinicians should also be aware that ACEIs and ARBs are cardiovascular disease, infection, cancer)
contraindicated in pregnancy (they are known to cause birth • Patient education and medication monitoring to reduce
defects). Common agents used for blood pressure control in risk for acute kidney injury.
pregnancy include methyldopa or labetolol, but other
common medications such as hydrochlorothiazide, Common signs of acute rejection or allograft dysfunction can
amlodipine, some beta blockers, and hydralazine are also felt include hypertension, increased creatinine, decreased GFR,
to be safe for use in most pregnant patients. or increased albuminuria. Many of these same signs can also
be associated with immunosuppressant drug toxicity. In
Older Patients general, the threshold for ultrasound imaging among patients
with kidney transplants is much lower as this is relatively
Age is one of the most important underlying risk factors for inexpensive and reasonably accurate to diagnose treatable
CKD, often compounded by the presence of other causes of allograft dysfunction.
comorbidities such as diabetes, hypertension and vascular
disease. With increasing life expectancy, the prevalence of Primary care clinicians should be aware that medications
both CKD and ESRD is rising. The prevalence of CKD commonly used for immunosuppression following kidney
among those over 65 years of age may range between 25%- transplant (such as cyclosporine, tacrolimus, and sirolimus)
35%. Among healthy individuals, creatinine clearance peaks can interact with many medications and with some juices and
at approximately 120-130 mL/min/1.73 m2 around age 30 herbs. Table 19 provides an abbreviated list of these drugs
years and then declines by roughly 8 mL/min/1.73 m2 per and natural products that can interact with
decade. immunosuppressants. Since this is not a comprehensive list,
an assessment for drug interactions should be performed
The equations used to estimate renal function have not been prior to starting any new drug or natural product in patients
validated in large numbers of elderly patients and tend to on immunosuppressant medications.
underestimate GFR.
Complementary and Alternative Medicines
Currently, no age-specific definitions exist for CKD. In
general, older individuals with reduced kidney function are Few studies have been performed regarding complementary
at higher risk for acute kidney injury from pre-renal, renal and alternative medicines in CKD. While small studies have
and post-renal causes. Nephrotoxic drugs have greater shown potential benefits of low dose vitamin C and omega-
impact on the elderly and should be used with particular 3 polyunsaturated fatty acids on kidney function, more
caution. Blood pressure control may need to be customized rigorous clinical trials are needed to confirm this, especially
for elderly patients with CKD including more gradual since high doses of vitamin C (> 500 mg daily) may be
escalation of treatment and careful monitoring for adverse associated with nephrotoxicity due to calcium oxalate crystal
effects. deposition.

Minorities Patients should be advised to avoid herbs if possible,

especially if they are on immunosuppressive therapy. Many
Although African Americans, Native Americans, Hispanics, herbs can potentially interact with prescription medications
Asians and Pacific Islanders were previously felt to have or cause additional kidney damage in patients with
23 UMHS Chronic Kidney Disease Guideline, July 2019
underlying CKD. Table 20 lists herbs that may be especially (depression); sleep quality and sleep disorders; sexual
harmful to CKD patients, such as St. John’s wort and ginkgo. dysfunction, monitoring and follow-up; pregnancy,
Some products (including alfalfa, dandelion, and noni juice) geriatrics, minorities, and other results for the major search
contain potassium, which can cause or exacerbate terms not included in the above specific searches. The
hyperkalemia. Others may contain heavy metals that are specific search strategy is available upon request.
nephrotoxic or ephedra-like compounds that are
vasoconstrictive and can cause or worsen hypertension. The search was conducted in components each keyed to a
Chinese herbal medicines that contain aristolochic acid can specific causal link in a formal problem structure, which is
cause severe and permanent kidney damage. available upon request. The search was supplemented with
very recent clinical trials known to expert members of the
panel. Negative trials were specifically sought. The search
Strategy for Literature Search was a single cycle. Conclusions were based on prospective
randomized clinical trials if available, to the exclusion of
The team began the search of literature by accepting the other data; if randomized controlled trials were not available,
results of the literature searches performed for fairly recent observational studies were admitted to consideration. If no
systematic reviews (see “annotated references” for full such data were available for a given link in the problem
citation): formulation, expert opinion was used to estimate effect size.
Black C, Sharma P, Scotland G, McCullough K, McGurn D, The “strength of recommendation” for key aspects of care
Robertson L, et al. Early referral strategies for was determined by expert opinion.
management of people with markers of renal disease: a
systematic review of the evidence of clinical
effectiveness, cost-effectiveness and economic analysis. Related National Guidelines
[Medline search through Jan 2009.]
Kidney Disease: Improving Global Outcomes (KDIGO) The UMHS Clinical Guideline on Chronic Kidney Disease
CKD–MBD Work Group. KDIGO clinical practice is consistent with:
guideline for the diagnosis, evaluation, prevention, and
ACP. Screening, Monitoring, and Treatment of Stage 1 to 3
treatment of chronic kidney disease–mineral and bone
Chronic Kidney Disease: A clinical Practice Guideline
disorder (CKD–MBD). [full search through Dec 2007,
from the Clinical Guidelines Committee of the American
RTCs through Nov 2008]
College of Physicians
VA/DoD Clinical Practice Guideline for Management of
Chronic Kidney Disease in Primary Care [search through ACIP/CDC. Guidelines for Vaccinating Kidney Dialysis
Dec. 2006] Patients and Patients with Chronic Kidney Disease
K/DOQI clinical practice guidelines for chronic kidney (2012)
disease: evaluation, classification, and stratification. ACC/AHA. Guideline on the Treatment of Blood
Kidney Disease Outcome Quality Initiative. [search Cholesterol to Reduce Atherosclerotic Cardiovascular
through June 2000] Risk in Adults (2013)
To update those searches with more recent literature and to
examine literature on other topics, a systematic search of Kidney Disease: Improving Global Outcomes (KDIGO)
literature on Medline was performed. clinical guidelines for:
• Anemia in Chronic Kidney Disease (2012)
The major search terms were: “chronic kidney disease • CKD Classification and Management. (2013)
excluding end-stage renal disease”; time frame started with • Clinical Practice Guideline for the Evaluation and
1/1/07 unless a more recent review (above) addressed the Management of Chronic Kidney Disease (2013)
topic; type of publication was guidelines, controlled trials • Clinical Practice Guideline for Lipid Management in
(including meta-analyses), and cohort studies; population Chronic Kidney Disease (2013)
was human/adult; and language was English. • Diagnosis, Evaluation, Prevention, and Treatment of
Chronic Kidney Disease–Mineral and Bone Disorder
Within these parameters individual searches were performed (CKD–MBD) (2009)
for the following topics: screening; assessment of renal • Management of Blood Pressure in Chronic Kidney
function/staging; history and symptoms; physical exam; Disease (2012)
laboratory tests; imaging; renin-angiotensin system blockade
National Kidney Foundation. Update of the KDOQI
(ACEI, ARB, optimizing blood pressure, reducing
Clinical Practice Guideline for Diabetes and Chronic
albuminuria, inhibition of renal fibrosis); treatment of
Kidney Disease (2012)
diabetes mellitus and of hypertension; management of
dyslipidemia, smoking, and aspirin therapy; management of USPSTF. Screening for Chronic Kidney Disease (2012)
anemia, mineral bone disease, metabolic acidosis, potassium VA/DoD Clinical Practice Guideline for Management of
and sodium balance, fluid balance/volume management, and Chronic Kidney Disease in Primary Care (2007)
malnutrition; dietary recommendations (sodium, protein,
malnutrition), medication dose adjustment/medications to
avoid/nephrotoxic medications; psychiatric disorders

24 UMHS Chronic Kidney Disease Guideline, July 2019

 Measures of Clinical Performance Annotated References
At this time no major national programs have clinical Baigent C, Landray MJ, Reith C, et al; SHARP Investigators.
performance measures specifically for CKD diagnosis and The effects of lowering LDL cholesterol with simvastatin
treatment. However, all national programs have performance plus ezetimibe in patients with chronic kidney disease (Study
measures for medical conditions often seen in patients with of Heart and Renal Protection): a randomised placebo-
CKD, including hypertension, diabetes, cardiovascular controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92.
disease, dyslipidemia, immunizations, tobacco use, Epub 2011 Jun 12.
dehydration, depression, patient education, and shared This study showed that this drug combination lowered
decision making. These programs include: Centers for cardiovascular events in patients with CKD.
Medicare & Medicaid Services (Physician Quality Reporting
Measures for Group Practice Reporting option, Clinical Beddhu S, Baird BC, Zitterkoph J, Neilson J, Greene T.
Quality Measures for financial incentive for Meaningful Use Physical activity and mortality in chronic kidney disease
of certified Electronic Health Record technology, Quality (NHANES III). Clin J Am Soc Nephrol 2009;4(12):1901-
measures for Accountable Care Organizations), National 1906
Committee for Quality assurance: Healthcare Effectiveness This survey provides incidence and other descriptive
Data and Information Set, and programs in our region (Blue information regarding CKD patients.
Cross Blue Shield of Michigan: Physician Group Incentive
Program clinical performance measures, Blue Care Network: Black C, Sharma P, Scotland G, McCullough K, McGurn
clinical performance measures). D, Robertson L, et al. Early referral strategies for
management of people with markers of renal disease: a
systematic review of the evidence of clinical effectiveness,
Disclosures cost-effectiveness and economic analysis. Health Technol
Assess 2010;14(21).
The University of Michigan Health System endorses the This summary assembles ACIP recommendations for
Guidelines of the Association of American Medical Colleges all vaccines relevant to patients with CKD.
and the Standards of the Accreditation Council for
Continuing Medical Education that the individuals who Chi C, Patel P, Pilishvili T, et al. Guidelines for Vaccinating
present educational activities disclose significant Kidney Dialysis Patients and Patients with Chronic Kidney
relationships with commercial companies whose products or Disease – summarized from recommendations of the
services are discussed. Disclosure of a relationship is not Advisory Committee on Immunization Practices. Atlanta,
intended to suggest bias in the information presented, but is GA: Centers for Disease Control, 2012. Available at
made to provide readers with information that might be of http://www.cdc.gov/vaccines/pubs/downloads/dialysis-
potential importance to their evaluation of the information. guide-2012.pdf (accessed 3/15/13).
This review summarizes available evidence, with
Team Member Company Relationship limited evidence concerning the role of CKD screening
R Van Harrison, PhD (none) or monitoring in improving clinical outcomes, but
Jennifer R Lukela, MD (none) evidence for CKD treatment benefit.
Masahito Jimbo, MD (none)
Ahmad Mahallati, MD (none) Fink HA, Ishani A, Taylor BC, et al. Screening for,
Forest, Renal monitoring, and treatment of chronic kidney disease stages
Research 1 to 3: A systematic review for the U.S. Preventive Services
Rajiv Saran, MBBS Research
funding Task Force and for an American College of Physicians
Institute
Annie Z. Sy, PharmD (none) clinical practice guideline. Annals of Internal Medicine
2012, 156 (8): 570-581.
This review summarizes available evidence, with
limited evidence concerning the role of CKD screening
Review and Endorsement or monitoring in improving clinical outcomes, but
evidence for CKD treatment benefit.
Drafts of this guideline were reviewed in clinical conferences
and by distribution for comment within departments and Fouque D, Laville M. Low protein diets for chronic kidney
divisions of the University of Michigan Medical School to disease in non diabetic adults. Cochrane Database of
which the content is most relevant: Family Medicine, Systematic Reviews 2009, Issue 3. Art. No.: CD001892.
General Medicine, and Nephrology. The final version was DOI: 10.1002/14651858.CD001892.pub3.
endorsed by the Clinical Practice Committee of the Review of the effects of protein restriction in CKD
University of Michigan Faculty Group Practice and the patients.
Executive Committee for Clinical Affairs of the University
of Michigan Hospitals and Health Centers. Kidney Disease: Improving Global Outcomes (KDIGO),
clinical guidelines produced by this organization:
25 UMHS Chronic Kidney Disease Guideline, July 2019
 Kidney Disease: Improving Global Outcomes (KDIGO) The SPRINT Research Group. A randomized trial of
CKD Work Group. KDIGO Clinical Practice Guideline intensive versus standard blood-pressure control. N Engl J
for the Evaluation and Management of Chronic Kidney Med. 2015; 373:2103–2116.
Disease. Kidney International, Supplement, 2013; 3: 1- This major study demonstrated benefits of blood pressure
150. control in patients with and at risk for atherosclerotic
Kidney Disease: Improving Global Outcomes (KDIGO) cardiovascular disease, including patients with CKD.
Blood Pressure Work Group. KDIGO Clinical Practice
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013
Guideline for the Management of Blood Pressure in
ACC/AHA guideline on the treatment of blood cholesterol
Chronic Kidney Disease. Kidney International,
to reduce atherosclerotic cardiovascular risk in adults.
Supplement. 2012; 2: 337–414.
Journal of the American College of Cardiology, 2013, doi:
Kidney Disease Improving Global Outcomes (KDIGO) 10.1016/j.jacc.2013.11.002. Available at
Lipid Work Group. KDIGO Clinical Practice Guideline http://content.onlinejacc.org/article.aspx?articleid=1770217
for Lipid Management in Chronic Kidney Disease. Kidney The guideline shifts from recommending lipid targets to
International, Supplement, 2013; 3:259-305. recommending statin treatment by types of patient groups.
Kidney Disease: Improving Global Outcomes (KDIGO)
CKD–MBD Work Group. KDIGO clinical practice Tobe SW, Dlase CM, GAo P, McQueen M, Grosshenning A,
guideline for the diagnosis, evaluation, prevention, and Wang X, Teo KK, Yusuf S, Mann JF; ONTARGET and
treatment of chronic kidney disease–mineral and bone TRANSCEND investigators. Cardiovascular and renal
disorder (CKD–MBD). Kidney International 2009; 76 outcomes with telmisartan, ramipril, or both in people at high
(Suppl 113): S1–S130. renal risk: results from the ONTARGET and TRANSCENT
studies. 2011; 123(10):1098-1107.
Kidney Disease: Improving Global Outcomes (KDIGO) The studies showed that dual therapy with ACEI and ARB
Anemia Work Group. KDIGO Clinical Practice Guideline had no effect beyond either drug alone.
for Anemia in Chronic Kidney Disease. Kidney
International, Supplement 2012; 2: 279–335. U.S. Preventive Services Task Force. Screening for Chronic
KDIGO developed the above evidence-based and Kidney Disease: U.S. Preventive Services Task Force
evidence-graded clinical guidelines based on systematic Recommendation Statement. AHRQ Publication No. 12-
reviews of relevant literature. Accompanying them are 05166-EF-2, 2012.
details concerning the evidence and references to it. All http://www.uspreventiveservicestaskforce.org/uspstf12/kidn
KDIGO guidelines are available at ey/ckdfinalrs.htm Also published in Annals of Internal
http://www.kdigo.org (accessed 11/17/12). Medicine 16 October 2012;157(8):567-570
This review concludes that evidence is insufficient to
National Kidney Foundation. KDOQI Clinical Practice assess the benefits and harms of routine screening for
Guideline for Diabetes and CKD: 2012 update. Am J CKD. In asymptomatic adults.
Kidney Dis. 2012;60(5):850-886.
The National Kidney Foundation’s Kidney Disease University of Michigan Health System (UMHS) clinical
Outcomes Quality Initiative (KDOQI) updated guidelines:
recommendations for treating patients with diabetes and Toma G, Adelman EE, Harrison RV, Hogikyan RV,
CKD because of recent evidence changing previous O’Connor TP, Thomas MP. Secondary Prevention of
recommendations. Ischemic Heart Disease and Stroke in Adults [update],
2014.
Navaneethan SD, Pansini F, Perkovic V, Manno C,
Engert SF, Laughlin CB, Andreae MA, Bary-Bodine MK,
Pellegrini F, Johnson DW, Craig JC, Strippoli GFM. HMG
Blitz SG, Barwig K, DeLoach SL, Elby S, Rockwell PG,
CoA reductase inhibitors (statins) for people with chronic
McGrath LM. Adult Immunizations [update], 2013.
kidney disease not requiring dialysis. Cochrane Database of
Systematic Reviews 2009, Issue 2. Art. No.: CD007784. Fan AL, Fenske JN, Harrison RV, Jackson EA, Marcelino
DOI: 10.1002/14651858.CD007784. MA. Screening and Management of Lipids [update], 2014.
Review of lipid management in patients with CKD. Jimbo M, Dorsch MP, Ealovega MW, Harrison RV,
Jamerson KA. Essential Hypertention [update], 2014.
Qassem A, Hopkins RH, Sweet DE, et al. Screening,
monitoring, and treatment of stage 1 to 3 chronic kidney Orringer KA, Harrison RV, Nichani SS, Riley MA,
disease: A clinical practice guideline from the Clinical Rothberg AE, Trudeau LE, White Y. Obesity Prevention
Guidelines Committee of the American College of and Management, 2013.
Physicians. Annals of Internal Medicine, 2013; 159: online- Schwenk TL, Terrell LB, Harrison RV, Tremper AL,
first version. Available at Valenstein MA. Depression [update], 2011.
http://annals.org/article.aspx?articleid=1757302
Overview of care in early stages, which is most likely to Serlin DC, Clay MA, Harrison RV, Thomas LA. Tobacco
be performed by primary care clinicians. Treatment [update], 2012.

26 UMHS Chronic Kidney Disease Guideline, July 2019

 Standiford CJ, Vijan S, Cho HM, Harrison RV,
Richardson CR, Wycoff JA. Management of Type 2
Diabetes Mellitus [update], 2012.
UMHS publishes these guidelines in Ann Arbor, MI.
Current versions of all UMHS clinical guidelines are
available through the University of Michigan Health
System
(https://www.uofmhealth.org/provider/clinical-care-
guidelines).

VA/DoD Clinical Practice Guideline for Management of

Chronic Kidney Disease in Primary Care: 2007.
www.healthquality.va.gov/ckd/ckd_v478.pdf
This review provides detailed information regarding
CKD management in primary care practice.

Whelton PK, Carey RM, Aronow WS, et al. 2017

ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/N
MA/PCNA Guideline for the Prevention, Detection,
Evaluation, and Management of High Blood Pressure in
Adults: Executive Summary: A Report of the American
College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. Hypertension. 2018
Jun;71(6):1269-1324. doi:
10.1161/HYP.0000000000000066. Epub 2017 Nov 13.
Review. No abstract available. Erratum in: Hypertension.
2018 Jun;71(6):e136-e139. Hypertension. 2018
Sep;72(3):e33. PMID: 29133354
This guideline includes a review of data concerning the
effect of blood pressure control on health outcomes and
related recommendations for targets for blood pressure
control.

27 UMHS Chronic Kidney Disease Guideline, July 2019