Chronic Kidney Disease

Chronic kidney disease (CKD) is defined as abnormalities in kidney structure or

function, present for 3 months or longer, with implications for health.
CKD is classified by cause of kidney disease, glomerular filtration rate (GFR)
category, and albuminuria level based on new recommendations from the Kidney
Disease: Improving Global Outcomes (KDIGO) guidelines, referred to as CGA
staging (cause, GFR, albuminuria) (Table 74–1).

TABLE 74–1 Glomerular Filtration Rate Categories Based on KDIGO

Classification
GFR Categorya GFR (mL/min/1.73 m2 [mL/s/m2]) Terms
1 >90 (>0.87) Normal or high
2 60–89 (0.58–0.86) Mildly decreased
3a 45–59 (0.43–0.57) Mildly to moderately decreased
3b 30–44 (0.29–0.42) Moderately to severely decreased
4 15–29 (0.14–0.28) Severely decreased
5 <15 (<0.14) Kidney failure
(CKD, chronic kidney disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease: Improving
Global Outcomes.)
a
To meet criteria for CKD there must be a significant reduction in GFR (categories 3a-5) or there
must also be evidence of kidney damage (categories 1 and 2) for 3 months or greater.

A patient is classified with end-stage renal disease (ESRD) when their GFR is below
15 mL/min/1.73 m2 (<0.14 mL/s/m2) and either chronic dialysis or kidney
transplantation is needed to sustain life. KDIGO classification will be used in this
chapter; the term CKD 5D indicates a patient with ESRD requiring dialysis as either
hemodialysis (CKD 5HD) or peritoneal dialysis (CKD 5PD).
Prognosis of CKD depends on cause of kidney disease, GFR at time of diagnosis,
degree of albuminuria, and presence of other comorbid conditions.

PATHOPHYSIOLOGY
Susceptibility factors increase the risk for kidney disease but do not directly cause
kidney damage. They include advanced age, racial or ethnic minority, low income or
education, and exposure to certain chemical and environmental conditions.
Initiation factors directly result in kidney damage and include diabetes mellitus,
hypertension, obesity, autoimmune diseases, systemic infections, family history of
CKD, reduction in kidney mass, and low birth weight.
Progression factors are associated with further decline in kidney function after
initiation of kidney damage. They include diabetes mellitus, hypertension,
proteinuria, obesity, and smoking.
Most progressive nephropathies share a final common pathway to irreversible renal

1
parenchymal damage and ESRD (Fig. 74–1). Key elements of the pathway to ESRD
include loss of nephron mass, glomerular capillary hypertension, and proteinuria.
 FIGURE 74–1. Proposed mechanisms for progression of renal disease.

CLINICAL PRESENTATION
Progression of CKD from category 1 to 5 occurs over decades in the majority of
people who are asymptomatic until they reach CKD 4 or 5. Signs and symptoms seen
with stages 4 to 5 include fatigue, weakness, shortness of breath, mental confusion,
nausea, vomiting, bleeding, anorexia, edema, weight gain, cold intolerance,
peripheral neuropathies, changes in urine output, and abdominal distension.

TREATMENT OF CKD
GENERAL APPROACH
Goal of Treatment: The goal is to delay or prevent the progression of CKD while
minimizing the development or severity of complications.
Use the most current consensus guidelines and the best clinical practices for
management of CKD, such as those developed by KDIGO.

NONPHARMACOLOGIC THERAPY
Restrict protein to 0.8 g/kg/day if GFR is less than 30 mL/min/1.73 m 2.
Encourage smoking cessation to slow progression of CKD and reduce the risk of
CVD.
Encourage exercise at least 30 minutes five times per week and achievement of a
body mass index (BMI) of 20 to 25 kg/m2.

PHARMACOLOGIC THERAPY
Proteinuria and Hypertension
Achieving the target blood pressure is the primary goal for CKD patients with
hypertension and a secondary goal is to control proteinuria. First-line therapy for
patients with diabetic CKD (DCKD) should include an angiotensin-converting
enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) if the patient’s
urine albumin excretion is in category A2 or greater (albumin-to-creatinine ratio
(ACR) between 30 and 300 mg/g (3–30 mg/mmol)). Initiate therapy with the lowest
recommended dose and increase dose until albuminuria is reduced by 30% to 50% or
side effects such as a greater than 30% decrease in estimated GFR or elevation in
serum potassium occur (Fig. 74–2).

(ACEI, angiotensin-converting enzyme inhibitor; ACR, albumin-to-creatinine ratio; AKI, acute

kidney injury; ARB, angiotensin receptor blocker; BP, blood pressure; CCB, calcium channel
blocker; eGFR, estimated glomerular filtration rate.)

FIGURE 74–2. Treatment of hypertension in chronic kidney disease.

(Data from KDIGO Blood Pressure Work Group. KDIGO Clinical Practice
Guideline for the Management of Blood Pressure in Chronic Kidney Disease.
Kidney Int Suppl 2012;2:337–414.)

Nondihydropyridine calcium channel blockers are second-line antiproteinuric drugs

when an ACEI or ARB is contraindicated or not tolerated.
KDIGO guidelines recommend a target blood pressure of 140/90 mm Hg or less if
urine albumin excretion or equivalent is less than 30 mg/24 h (<3 mg/mmol)
(category A1 albuminuria). The target blood pressure for patients with category A2
and higher albuminuria is less than or equal to 130/80 mm Hg and first-line therapy
with an ACEI or ARB is recommended. Addition of a thiazide diuretic may be
 warranted if use of an ACEI or ARB fails to achieve the target blood pressure.
For more information on hypertension, see Chapter 10.

Diabetes
Screen patients with diabetes annually for CKD starting at the time of diagnosis of
type 2 diabetes and 5 years after diagnosis of type 1diabetes by ordering serum
creatinine, estimated GFR, and ACR.
Management of diabetes in patients with CKD includes reduction of proteinuria and
achievement of target blood pressure and HbA1c.
For more information on diabetes, see Chap. 19.

TREATMENT OF SECONDARY COMPLICATIONS

Anemia of CKD
Desired outcomes of anemia management are to increase oxygen-carrying capacity,
decrease signs, and symptoms of anemia, and decrease the need for blood
transfusions.
Guide initiation of iron or erythropoiesis-stimulating agent (ESA) therapy by the
patient’s hemoglobin (Hb), transferrin saturation (TSat), and ferritin (Table 74–2).
The risk of mortality and cardiovascular events is higher in CKD patients treated to
higher Hb target values with an ESA. The target range for Hb in the CKD population
is a topic of much debate.

TABLE 74–2 KDIGO Recommendations for Initiation of Erythropoiesis

Stimulating Agents and Iron in Anemia of Chronic Kidney Diseasea

ND-CKD CKD 5HD and CKD 5PD Pediatric CKD

ESA If Hb <10 g/dL (<100 g/L; Use ESAs to avoid drop Selection of Hb
initiation <6.21 mmol/L). Consider in Hb to <9 g/dL (<90 concentration at which to
rate of fall of Hb, prior g/L; initiate ESA therapy
response to iron, risk of <5.59 mmol/L) by should include
needing a transfusion, starting an ESA when consideration of potential
risk of ESA therapy, and Hb is between 9 and 10 benefits (eg, improvement
presence of anemia g/dL in QOL, school
symptoms before (90 and 100 g/L; 5.59 and attendance, avoidance of
initiating an ESA. [2C] 6.21 mmol/L). [2B] blood transfusions) and
potential harms. [2D]
Do not initiate if Hb
≥10 g/dL (≥100 g/L;
≥6.21 mmol/L). [2D]
Hb level Do not use ESAs to Do not use ESAs to Suggest Hb range of 11–12
intentionally increase Hb intentionally increase Hb g/dL (110–120 g/L, 6.83–
above 13 g/dL (130 g/L, above 13 g/dL (130 g/L, 7.45 mmol/L). [2D]
8.07 mmol/L). [1A] 8.07 mmol/L). [1A]
Do not use ESAs to Do not use ESAs to
maintain Hb above 11.5 maintain Hb above 11.5
g/dL (115 g/L; 7.14 g/dL (115 g/L; 7.14
mmol/L). [2C] mmol/L). [2C]
Iron If TSat is ≤30% (≤0.30) and If TSat is ≤30% (≤0.30) and If TSat is ≤20% (≤0.20) and
initiationb ferritin is ≤500 ng/mL ferritin is ≤500 ng/mL ferritin is ≤100 ng/mL
 (mcg/L; ≤1120 pmol/L). (mcg/L; ≤1120 pmol/L). (mcg/L; ≤225
pmol/L). [2C] [2C] [1D]
(CKD, chronic kidney disease; ESA, erythropoiesis stimulating agent; Hb, hemoglobin; ND-CKD,
nondialysis CKD patients; QOL, quality of life; TSat, transferrin saturation.)
a
The Kidney Disease Outcome Quality Initiative (KDOQI) Anemia Guidelines are discussed in the
text.
b
If TSat and serum ferritin are below suggested levels, consider iron supplementation if goal is to
increase Hb and/or decrease ESA dose. Note: Serum ferritin is an acute-phase reactant-use
clinical judgment when above 500 ng/mL (mcg/L; 1120 pmol/L).

Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines suggest a Hb range

of 11 to 12 g/DL (110–120 g/L; 6.83–7.45 mmol/L) for all CKD patients, a target
TSat of greater than 20% (>0.20), and a serum ferritin of greater than 100 ng/mL
(mcg/L; >225pmol/L) for CKD patients not requiring HD and greater than 200
ng/mL (mcg/L; >450 pmol/L) for CKD 5HD patients.
Oral or IV administration of iron supplementation is recommended in non-HD
patients (eg, CKD category 3 or higher and PD patients). Supplementation with oral
products (see Table 33–2) is more convenient but patients are likely to require IV
iron supplementation, especially if they are receiving an ESA. Adverse effects of oral
iron are primarily GI in nature and include constipation, nausea, and abdominal
cramping which may negatively influence adherence.
IV iron preparations have different pharmacokinetic profiles determined by the size
of the iron-containing core and the composition of the surrounding carbohydrate
(Table 74–3).

TABLE 74–3 IV Iron Preparations

Half- Molecular Dose

Brand Life Weight FDA-Approved FDA-Approved Ranges
Iron Compounds Names (Hours) (Daltons) Indications Dosinga (mg)b
Ferric Injectafer 7–12 150,000 Adult patients Give 2 doses 750
carboxymaltose with separated by at
intolerance to least 7 days of
oral iron or 750 mg per
who have had dose (if body
an weight is
unsatisfactory ≥50 kg) or 15
response to mg/kg per dose
oral iron and (if body weight
in adult is
patients with <50 kg) not to
CKD not on exceed 1500 mg
dialysis per course. Give
either IV push
(100 mg per min)
or diluted in not
more than 250
mL of 0.9 NaCl
as an infusion
over at least 15
minutes
Ferumoxytol Feraheme 15 750,000 Adult patients 510 mg (17 mL) as 510
with iron- a single dose,
deficiency followed by a
anemia second 510 mg
associated dose 3–8 days
 with chronic after the
kidney initial dose.
disease Dilute in 50–
200 mL of
0.9% NaCl or 5%
dextrose and
administer as an
IV infusion over
15 minutes
Iron dextran INFeD 40–60 96,000 Patients with 100 mg over 2 25–
Dexferrum 265,000 iron minutes (25-mg 1000
deficiency in test dose
whom oral required)
iron is Note: Equation
unsatisfactory provided by
or impossible manufacturer to
calculate dose
based on desired
Hb
Iron sucrose Venofer 6 43,000 Adult and Adult: 100 mg over 25–
pediatric CKD 2–5 minutes or 1000
5HD patients 100 mg in
aged 2 years maximum of 100
and older mL of 0.9% NaCl
over 15 minutes
per consecutive
HD session
Pediatric: 0.5 mg/kg
not to exceed
100 mg per dose
over 5 minutes or
diluted in 25 mL
of 0.9% NaCl
administered
over 5–60
minutes (give
dose every 2
weeks for 12
weeks)
Adult and Adult: 200 mg over
pediatric ND- 2–5 minutes on
CKD patients five different
aged 2 years occasions within
and older 14-day period.
There is limited
experience with
administration of
500 mg diluted in
a maximum of
250 mL of 0.9%
NaCl over 3.5 to
4 hours on day 1
and day 14
Pediatric: see
pediatric dosing
for CKD 5HD
(give dose every
4 weeks for 12
weeks)
Adult and Adult: Give 3
 pediatric CKD divided doses
5PD patients within 28 days as
aged 2 years 2 infusions of 300
and older mg over 1.5
hours 14 days
apart followed by
one 400 mg
infusion over 2.5
hours 14 days
later. Dilute in a
maximum of 250
mL of 0.9% NaCl
Pediatric: see
pediatric dosing
for CKD 5HD
(give dose every
4 weeks for 12
weeks)
Sodium ferric Ferrlecit 1 350,000 Adult and Adult: 125 mg over 62.5–
gluconate pediatric CKD 10 minutes or 1000
5HD patients 125 mg in 100
aged 6 years mL of 0.9% NaCl
and older over 60 minutes
receiving ESA Pediatric: 1.5 mg/kg
therapy in 25 mL of 0.9%
NaCl over 60
minutes;
maximum dose
125 mg per
dose
(CKD, chronic kidney disease; ESA, erythropoiesis stimulating agent; ND-CKD, non-dialysis CKD
patients.)
a
Monitor for 30 minutes following an infusion; KDIGO guidelines recommend monitoring for 60
minutes (1B recommendation for iron dextran, 2C recommendation for non-dextran products).
b
With the exception of ferric carboxymaltose and ferumoxytol, small doses (eg, 25–150 mg/wk) are
generally used for maintenance regimens. Larger doses (eg, 1 g) should be administered in
divided doses.

Adverse effects of IV iron include allergic reactions, hypotension, dizziness,

dyspnea, headaches, lower back pain, arthralgia, syncope, and arthritis. Some of
these reactions can be minimized by decreasing the dose or rate of infusion. Sodium
ferric gluconate, iron sucrose, and ferumoxytol have a better safety record than iron
dextran products.
All available ESAs may be administered either IV or subcutaneously (SC) (Table 74–
4). SQ administration of epoetin results in a prolonged absorption phase leading to an
extended half-life allowing target Hb to be maintained at doses 15% to 30% lower than
IV doses.

TABLE 74–4 Erythropoiesis-Stimulating Agents in Chronic Kidney Disease

Brand Route of Half-Life

Drug Name Name(s) Starting Dose Administration (Hours)
Epoetin alfa Epogen, Adults: 50–100 units/kg three times IV or SubQ 8.5 (IV)
Procrit per week 24
Pediatrics: 50 units/kg three times per (SubQ)
week
Darbepoetin Aranesp Adults: IV or SubQ 25 (IV)
 alfa ND-CKD: 0.45 mcg/kg once every 4 weeks 48
CKD 5HD or CKD 5PD: 0.45 mcg/kg once (SubQ)
per week or 0.75 mcg/kg every 2 weeks
Pediatrics:
0.45 mcg/kg once weekly; may give 0.75
mcg/kg once every 2 weeks in ND-
CKD patients
Methoxy PEG- Mircera All adult CKD patients: 0.6 mcg/kg every 2 IV or SubQ 134 (IV)
epoetin beta weeks; Once Hb stabilizes, double the 139
dose and administer monthly (eg, if (SubQ)
administering 0.6 mcg/kg every 2 weeks,
give 1.2 mcg/kg every month)
(CKD, chronic kidney disease; ND-CKD, nondialysis CKD patients; PEG, polyethylene glycol;
SubQ, subcutaneous.)

The prolonged half-lives of darbepoetin alfa and methoxy PEG-epoetin beta allow
for less frequent dosing.
Causes of ESA resistance include iron deficiency, acute illness, inflammation,
infection, chronic bleeding, aluminum toxicity, malnutrition, hyperparathyroidism,
cancer, and chemotherapy.
ESAs are well tolerated. Hypertension is the most common adverse event.

Evaluation of Anemia Therapeutic Outcomes

Evaluate iron indices (TSat; ferritin) before initiating an ESA. Iron status should be
reassessed every month during initial ESA treatment and every 3 months for those on
a stable ESA regimen.
Monitor Hb at least monthly after initiation of an ESA or after a dose change until
hemoglobin is stable. FDA labeling for ESAs recommends weekly monitoring of Hb
until Hb is stable.
For more information on anemia, see Chap. 33.

CKD-Related Mineral and Bone Disorder

Disorders of mineral and bone metabolism (CKD-MBD) are common in the CKD
population and include abnormalities in parathyroid hormone (PTH), calcium,
phosphorus, vitamin D, fibroblast growth factor-23, and bone turnover, as well as
soft tissue calcifications.
Calcium-phosphorus homeostasis is mediated through a complex interplay of
hormones and their effects on bone, the gastrointestinal (GI) tract, kidneys, and the
parathyroid gland. As kidney function declines, phosphate elimination decreases
resulting in hyperphosphatemia and a decrease in serum calcium concentration.
Hypocalcemia stimulates secretion of PTH. As renal function declines, serum
calcium balance can be maintained only at the expense of increased bone resorption,
leading to alterations in structural integrity of bone and other consequences.
The KDIGO guidelines provide desired ranges of calcium, phosphorus, and intact
PTH based on the CKD category (Table 74–5).

TABLE 74–5 KDIGO Monitoring and Goals for Calcium, Phosphorus, and Parathyroid Hormone
 Chronic Kidney Disease Categorya
Parameter 3 4 5 ESRD
Corrected calciumb
Monitoring Every 6–12 Every 3–6 months Every 1–3 months Every 1–3 months
frequencyc months
Goal Maintain normal Maintain normal Maintain Maintain normal
normal range [2D] range [2D] range [2D]
range [2D]
Phosphorus
Monitoring Every 6–12 Every 3–6 months Every 1–3 months Every 1–3 months
frequencyc months
Goal Maintain normal Maintain normal Maintain “Towards normal”
normal range [2C] range [2C] [2C]
range [2C]
Intact PTH
Monitoring Based on baseline Every 6–12 Every 3–6 Every 3–6 months
frequencyc months level and CKD months
progression
Goal Normal rangec Normal rangec Normal rangec 2–9 times the
upper normal
limit [2C]
a
Differences with Kidney Disease Outcome Quality Initiative (KDOQI) guidelines described in text.
b
Corrected for albumin. Note: CMS finalized a rule that will use an uncorrected calcium level >10.2
mg/dL (>2.55 mmol/L) as a quality measure for the QIP starting in 2016.
c
Not graded.

Treatment
Dietary phosphorus restriction, dialysis, and parathyroidectomy are
nonpharmacologic approaches to management of hyperphosphatemia and CKD-
MBD.
PHOSPHATE-BINDING AGENTS
Phosphate-binding agents decrease phosphorus absorption from the gut and are first-
line agents for controlling both serum phosphorus and calcium concentrations (Table
74–6).

TABLE 74–6 Phosphate-Binding Agents for Treatment of Hyperphosphatemia in

Chronic Kidney Disease Patients

Brand Compound Starting Dose

Category Drug Name Content Doses Titrationa Commentsb
Calcium- Calcium PhosLo 25% 1334 mg Increase or Comparable
based acetate (25% elemental three decrease effi to
binders elemental calcium times a by 667 calcium
calcium) (169 mg day with mg per carbonate wit
elemental meals meal (169 lower dose of
calcium per mg elemental cal
667 mg elemental Approximately
capsule) calcium) 4 phosphorus
b per 1 g
calciu
acetate
 Evaluate for
dru
interactions
w calcium
Phoslyra 667 mg
calcium
acetate
per 5 mL
Calcium Tums, Os- 40% 0.5–1 g Increase or Dissolution
carbonatec Cal, elemental (elemental decrease characteristic
Caltrate calcium calcium) by 500 phosphate
bin
three mg per may vary
from
times a meal (200 product to
pro
day with mg Approximately
3
meals elemental phosphorus
b
calcium) per 1 g calciu
carbonate
Evaluate for
dru
interactions
w
calcium
Iron-based Ferric Auryxia 210 mg 420 mg Increase or May increase se
citrate binders tablets (= 1 ferric decrease iron, ferritin, a
iron g ferric three dose by 1 TSat
citrate) times or 2 May cause disc
daily with tablets (dark) stools
meals per meal Evaluate for
dru
interactions
w iron
Sucroferric Velphoro 500 mg 500 mg Increase or May cause disc
oxyhydroxide chewable three decrease (dark) stools
tablets times by 500 Evaluate for
daily with dru mg per interactions
meals w
day iron
Resin Sevelamer Renvela 800 mg tablet 800–1600 Increase or Also lowers low-
binders carbonate 0.8 and 2.4 g mg three decrease density lipopr
powder for times a by 800 cholesterol
oral day with mg per Consider in pati
suspension meals meal at risk for
(once- extraskeletal
daily calcification
dosing Risk of
metaboli
also acidosis with
effective) sevelamer
hydrochloride
risk with carb
formulation)
May interact wit
cipro and
mycophenola
mofetil
Sevelamer Renagel 400 & 800 800–1600 Increase or
 hydrochloride mg caplets mg three decrease
times a by 800
day with mg per
meals meal
Other Lanthanum Fosrenol 500, 750, and 1500 mg Increase or Potential for
elemental carbonate 1000 mg daily in decrease accumulation
 binders chewable divided by 750 lanthanum du
tablets doses with mg/day GI absorption
750 and 1000 meals term consequ
mg oral unknown)
powder Evaluate for dru
interactions (e
cationic antac
quinolone
antibiotics)
Aluminum AlternaGel Content 300–600 mg Not for Not a first-line a
hydroxide varies three long-term risk of alumin
(range times a use toxicity; do no
100–600 day with requiring concurrently
mg/unit) meals titration citrate-contain
products
Reserve for sho
term use (4 w
in patients wit
hyperphospha
not respondin
other binders
Evaluate for dru
interactions
(TSat, transferrin saturation.)
a
Based on phosphorus levels, titrate every 2 to 3 weeks until phosphorus goal reached.
b
GI side effects are possible with all agents (eg, nausea, vomiting, abdominal pain, diarrhea, or
constipation).
c
Multiple preparations available that are not listed.

KDOQI guidelines recommend that elemental calcium from calcium-containing

binders should not exceed 1500 mg/day, and the total daily intake from all sources
should not exceed 2000 mg. This may necessitate a combination of calcium- and non–
calcium-containing products (eg, sevelamer HCL and lanthanum carbonate).
Adverse effects of all phosphate binders are generally limited to GI effects, including
constipation, diarrhea, nausea, vomiting, and abdominal pain. Risk of hypercalcemia
may necessitate restriction of calcium-containing binder use and/or reduction in
dietary intake. Aluminum and magnesium binders are not recommended for regular
use in CKD because aluminum binders have been associated with CNS toxicity and
the worsening of anemia, whereas magnesium binders may lead to hypermagnesemia
and hyperkalemia.
VITAMIN D THERAPY
Serum calcium and phosphorus should be within the normal range before initiation
and during continued vitamin D therapy.
Calcitriol, 1,25-dihydroxyvitamin D3, directly suppresses PTH synthesis and
secretion and upregulates vitamin D receptors. The dose depends on the stage of
CKD (Table 74–7).
TABLE 74–7 Vitamin D Agents

Form of
 Brand Vitamin Dosage Dosage Frequency of
Generic Name Name D Forms Initial Dosea Range Dosing
Nutritional vitamin D
Ergocalciferol Drisdol D2 po Varies based on 400–50,000 Daily (doses of
25(OH) D international 400–2000
levels units international
units)

Cholecalciferolb Generic D3 po Weekly or

monthly for
higher doses
(50,000
international
units)
Vitamin D and Analogs
Form
of
Brand Vitamin Dosage Dosage
Generic Name Name D Forms Initial Dosea,c Range Dose Titrationd
Calcitriol Rocaltrol D3 po 0.25 mcg daily 0.25–5 mcg Increase by 0.25
mcg/day at 4–
8 week
intervals
Calcijex IV 1–2 mcg 0.5–5 mcg Increase by 0.5–1
three times mcg at 2 to 4
per week week
intervals
Doxercalciferole Hectorol D2 po ND-CKD: 1 mcg 5–20 mcg Increase by 0.5
daily mcg at 2-week
ESRD: 10 mcg intervals for daily
three times dosing or by 2.5
per week mcg at 8-week
intervals for three
times per week
dosing
IV ESRD: 4 mcg 2–8 mcg Increase by 1–2
three times mcg at 8-week
per week intervals
Paricalcitol Zemplar D2 po ND-CKD: 1 mcg 1–4 mcg Increase by 1 mcg
daily or 2 mcg (for daily dosing)
three or 2 mcg (for
times per three times per
week if week dosing) at
PTH ≤500 2–4 week
pg/mL (ng/L; intervals
≤54 pmol/L);
2 mcg daily or
4 mcg three
times per
week if PTH
>500 pg/mL
(ng/L; >54
pmol/L)
IV ESRD: 0.04–1 2.5–15 mcg Increase by 2–4
mcg three mcg at 2–4 week
times per intervals
week
(ESRD, end-stage renal disease; ND-CKD, non-dialysis chronic kidney disease; PTH, parathyroid
hormone.)
 a
Dose ratios are as follows: 1:1 for IV paricalcitol to oral doxercalciferol, 1.5:1 for IV paricalcitol to
IV doxercalciferol, and 1:1 for IV to oral calcitriol.
b
Multiple preparations are available that are not listed.
c
Daily orally dosing most common for non-hemodialysis CKD patients, IV dosing three times per
week more often used in the hemodialysis population.
d
Based on PTH, calcium and phosphorus levels. Decreases in dose are necessary if PTH is
oversuppressed and/or if calcium and phosphorus are elevated.
e
Prodrug that requires activation by the liver.

The newer vitamin D analogues paricalcitol and doxercalciferol may be associated

with less hypercalcemia and hyperphosphatemia. Observational studies show all-
cause and cardiovascular survival benefit with these agents.
CALCIMIMETICS
Cinacalcet reduces PTH secretion by increasing the sensitivity of the calcium-
sensing receptor. The most common adverse events include nausea and vomiting.
Cinacalcet lowers serum calcium and should not be started if the serum calcium is
less than the lower limit of normal. The starting dose is 30 mg daily, which can be
titrated to the desired PTH and calcium concentrations every 2 to 4 weeks to a
maximum of 180 mg daily.

HYPERLIPIDEMIA
CKD with or without nephrotic syndrome is frequently accompanied by
abnormalities in lipoprotein metabolism. The KDIGO Lipid Guidelines recommend
that a complete fasting lipid profile be performed in all adults with newly identified
CKD.
KDIGO Lipid Guidelines recommend:
1. Statin treatment in adults age 18 to 49 years with CKD but not treated with
chronic dialysis or kidney transplantation, who have one or more of the following:
known coronary disease; diabetes mellitus; prior ischemic stroke; estimated 10-
year incidence of coronary death or nonfatal MI greater than 10%.
2. Statin or statin/ezetimibe combination in adults > 50 years with estimated GFR <
60 ml/min/1.73m2 but not treated with chronic dialysis or kidney transplantation.
3. Do not initiate statins or statin/ezetimibe combination therapy in adults with
dialysis-dependent CKD. Continue these agents if patient is already taking them at
the time of dialysis initiation.
For more information on dyslipidemias, see Chap. 8.

See Chapter 44, Chronic Kidney Disease, authored by Joanna Q. Hudson and Lori D.
Wazny, for a more detailed discussion of this topic.