Nephrology lectures

Chronic Kidney Disease

(CKD)
Soha Nageb
Lecturer of Internal Medicine
Internal Medicine Department
Faculty of Medicine
MUE
Scope of this lecture:
A.Identification of definition and diagnosis of
CKD
B.identification of reversible causes of CKD.
C. provision of treatment to slow progression
,
of CKD.
D.Diagnosis, and management of the
metabolic complications of CKD G4–G5.
E.preparation for dialysis and/ or
transplantation
DEFINITION:
Epidemiology of chronic kidney disease: an update 2022
ISN
 Kidney Damage
Evidence of kidney
eGFR damage
.
• Albuminuria
• Urinary sediments
• Tubular damage
• Renal pathology
• Abnormal imaging:
PCKD, small contracted
kidney
Measurement of GFR (using Inulin Clearance)
GFR can be directly measured by measuring the renal clearance of
inulin. Inulin is a plant carbohydrate, Inulin is used to measure
clearance because of two key properties:
1- inulin doesn't bind to blood proteins, meaning it is freely filtered
2- inulin is neither reabsorbed nor secreted
Estimation of GFR (eGFR)
1- Creatinine clearance can be used as a rough estimate
of GFR: Because only a small amount of creatinine is
secreted by renal tubules. Many eGFR formulas are
present, with the adjustment for race, sex, and gender
results in an increased value for eGFR.
2- (3) formulas are Cockcroft-Gault, MDRD, and EPI.
3- Novel biomarkers, like Cystatin-c are already in use,
others are under trials for more accurate eGFR formulas.
4- Easily use MD-CALC application for eGFR.
Definition and staging of CKD according
to KDOQI guidelines
Causes of CKD
• Diabetes mellitus
70% of causes
• Hypertension
• vascular disease (renal a. stenosis)
• Glomerulonephritis.
• Chronic tubulointerstitial nephritis.
• Cystic diseases: Polycystic kidney disease
• Urologic diseases: (Obstructive nephropathy)
Prostatic disease
Nephrolithiasis
Retroperitoneal fibrosis/tumor
Congenital/reflux
Screening for CKD:

Unexplained
edema:

Chronic
nephrotoxic drugs:
Clinical picture of CKD
A- Asymptomatic: Stages 1–4 CKD • H o r m o n a l i m b a l a n c e : decreased
B- Uremic syndrome. with the progressive libido and menstrual irregularities.
decline in GFR, accumulation of metabolic • P e r i c a r d i t i s : (complication of CKD,
waste products, uremic toxins, result in the present with pleuritic chest pain.

GFR (<5–10 mL/min/1.73 m2)

• G e n e ra l s y m p t o m s : fatigue, • generally ill appearance
anorexia, nausea,
• halitosis (uremic fetor)
• N e u ro l o g i c s y m p t o m s : memory
• Flapping tremors
impairment, insomnia, restless legs, and
twitching • Myoclonus, seizures.

• G e n e ra l i ze d p r u r i t u s (without rash) • uremic encephalopathy

C- volume overload: lower limb edema, pleural effusion, pulmonary edenma,
ascites, pericardial effusion.

D- Hypertension: due to impairad sodium excretion, and volume overload.

E- Drug metabolism (increase toxicity) important example is: insulin and an
increasing risk of significant hypoglycemia if doses are not appropriately
reduced.
F- Picture of complications:
I. Hemaological: anemia, thrombathenia,
impaired immunity
I. CKD-MBD (metabolic bone disease)
 INVESYTIGATIONS
1. Diagnoses of CKD:
• A. Abnormal GFR persisting for at last 3 months (creatinine, cystatin C, eGFR).
• B. Persistent proteinuria (urine dipstick, quatitative methods)
• C. Renal imaging e.g.,
(even GFR is normal).
echogenic kidneys bilaterally (less than 9–10 cm) suggests
the chronic scarring of advanced CKD.

• Adult polycystic kidney disease.

• Diabetic nephropathy.
• Amyloidosis.
• Obstructive uropathy.
• 2. Diagnosis of aetiology and/ or reversible insult:
• 3. Assess comorbidities:
A. Cardiovascular Complications

B. Hematologic Complications

C. Electrolytes and acid-base

D. Metabolic Bone Disease

E. Neurologic Complications

F. Endocrine Disorders
 Cardiovascular Complications
• 80% of patients with CKD die from CVD morbidities, before reaching ESKD.
• Dialysis patients, 45% will die of a cardiovascular cause.
1- Hypertension is the most common complication of CKD;
• Pathogenesis: Hyper-reninemic states, exogenous erythropoietin
administration, and sodium homeostasis
• Control:
non-pharmacologic therapy (diet, exercise, weight loss).
Pharmacological: Diuretics (thiazides work well in early CKD, but loop
diuretics with a GFR <30, ACEI, ARBs (have antiproteinuric effect but watch
for potassium level)
2. Coronary artery disease:
• Traditional modifiable risk factors for CVD, such as hypertension, tobacco, and
hyperlipidemia, should be aggressively treated.

• Uremic vascular calcification involving disordered phosphorus homeostasis

3. Heart failure
• hypertension
• volume overload
• anemia.
• atherosclerosis and vascular calcification
4. Atrial fibrillation: approach 20% in patients receiving dialysis. anticoagulation for
prevention of thromboembolic events becomes challenging due to risks of bleeding

5. Pericarditis: include pleuritic chest pain and a friction rub. Cardiac tamponade can
occur. uremic pericarditis is a mandatory indication for hemodialysis.
Metabolic Bone Disease
• Declining GFR leads to phosphorus
retention. This results in hypocalcemia as
phosphorus complex with calcium, deposits
in soft tissues, and stimulates PTH.
• Loss of renal mass result in low 1,25(OH)
vitamin D production. hypovitaminosis D
leads to secondary hyperparathyroidism.
• A typical pattern as early as CKD stage 3 is
1. Hyperphosphatemia, hypocalcemia,
2. Hypovitaminosis D,
3. Elevated PTH
• Renal osteodystrophy: increase the risk of
fractures.
1- osteitis fibrosa cystica:
• Result of secondary hyperparathyroidism and
the osteoclast-stimulating effects of PTH.
• This is a high-turnover disease with bone
resorption and subperiosteal lesions.
• Result in bone pain and proximal muscle
weakness.
2- Adynamic bone disease:
• low-bone turnover
• it may result iatrogenically from suppression of
PTH or via spontaneously low PTH production.
3- Osteomalacia: lack of bone
mineralization result from hypovitaminosis D
Treatment:
1- Control of hyperphosphatemia (dietary phosphorus
restriction)- oral phosphorus binders (block absorption of
dietary phosphorus with meals) e.g., Calcium containing
binders- non-calcium containing binders (sevelamer
carbonat and lanthanum carbonate
2- Active vitamin D supplements
3- Serum 25-OH vitamin D levels should be monitored
regularly and brought to normal
3- elevated serum phosphorus or calcium levels Cinacalcet
targets the calcium-sensing receptors of the parathyroid
gland and suppresses PTH production.
Hematologic Complications
1. Anemia:
• Pathogenesis: decreased erythropoietin production (stage 3 CKD).
• “anemia of chronic disease.” high levels of hepcidin, blocks GI iron absorption
and mobilization of iron from body stores
• Treatment:
with is the initial therapy in pre-ESKD CKD.
For those who do not respond due to poor GI absorption.
(ESAs e.g., recombinant erythropoietin
[epotin alfa and darbepotin) starting an ESA less than 9 g/dL.
• intravenous, or subcutaneous.
• ESAs should be titrated to an Hgb of 10–11 g/dL
• higher Hgb increases the risk of stroke
• Hypertension is a common complication of treatment with ESAs.
• 2. Coagulopathy: in stage 4–5 CKD is mainly due to
• platelet dysfunction (uremic toxins)
• Desmopressin
• Dialysis improves the bleeding time
Hyperkalemia Acid Base Disorders:
Risk factors: • metabolic acidosis is due to decreased
• Stage 4-5 CKD GFR; proximal or distal tubular defects
• high potassium diets • Chronic acidosis sequel:
• Medications that decrease renal • Excess hydrogen ions are buffered by
potassium secretion (spironolactone, bone; contributes to the metabolic
NSAIDs, ACE inhibitors, ARBs) or block bone disease
cellular potassium uptake (beta- • Muscle protein catabolism (growth
blockers). retardation in children with CKD)
• cellular destruction causing release of • Treatment:
intracellular contents, such as hemolysis
• Reduction of dietary animal protein and
and rhabdomyolysis.
increased fruit and vegetable intake
• administration of oral sodium
bicarbonate
Neurologic
Complications Endocrine Disorders
Uremic encephalopathy: • Decreased libido and erectile
dysfunction are common in advanced
• Symptoms begin with difficulty in CKD.
• Men have decreased testosterone
concentrating and can progress to levels.
lethargy, confusion, seizure, and coma. • Women are often anovulatory

• Physical findings may include altered

mental status, and astrixis.

• This findings improves with dialysis.

 Management of CKD
• The medical care of patients with CKD should focus on the following:
• Diagnosing and treating the cause of CKD.
• Delaying or halting the progression of CKD.
• Management of complications of CKD.
• Planning for long-term renal replacement therapy.
• Diet in CKD patients.
Stages of CKD

At all stages, persistent albuminuria confers added risk for chronic kidney disease
progression and cardiovascular disease
1- Treating the cause: In any patient with kidney disease, it is
important to identify and correct all possibly reversible insults or
exacerbating factors
Reversible causes of kidney Management
injury.

• Obstruction Reveal the obstruction (surgical or

nephrostomy tube)

• Extracellular fluid volume Replenish fluids

depletion or significant
hypotension
• Nephrotoxic agents Alternative drugs
NSAIDs, aminoglycosides Adjust the doses

• Severe/urgent hypertension Urgent blood pressure control

Blood pressure

• Heart failure exacerbation Control cardiac status

 2-Delay the progression
• Aggressive blood pressure control to target values per current guidelines
• Treatment of hyperlipidemia to target levels per current guidelines
• Aggressive glycemic control per the American Diabetes Association (ADA)
recommendations (target hemoglobin A1c [HbA1C] < 7%), Use of sodium–
glucose cotransporter 2 (SGLT2) inhibitors
• Avoidance of nephrotoxins, including intravenous (IV) radiocontrast media,
nonsteroidal anti-inflammatory drugs (NSAIDs), and aminoglycosides
• Use of renin-angiotensin system (RAS) blockers (ACEs, ARBs) in patients with
diabetic kidney disease (DKD) and proteinuria
• Use of nonsteroidal mineralocorticoid receptor (MR) antagonists
Blood pressure control
• Level <140/90 in non diabetic non proteinuric CKD

• Level <130/80 in diabetic or proteinuric patients

• ACEIs. ARBs are preferred first line drugs as they

have beneficial role in improving glomerular
hypertension and proteinuria
 Management of complications
• Anemia: When the hemoglobin level is below 10 g/dl, treat with an
erythropoiesis-stimulating agent (ESA) such as Epoetin Alfa or Darbepoetin Alfa;
caution should be exercised in patients with malignancy.
• CKD-MBD: Hyperphosphatemia: Treat with dietary phosphate binders and dietary
phosphate restriction. Hypocalcemia: Treat with calcium supplements with or
without calcitriol. Hyperparathyroidism: Treat with calcitriol, vitamin D analogues, or
calcimimetics.
• Volume overload: Treat with loop diuretics or ultrafiltration.
• Metabolic acidosis: Treat with oral alkali supplementation.
• Uremic manifestations: Treat with long-term renal replacement therapy
(hemodialysis, peritoneal dialysis, or kidney transplantation)
• Cardiovascular complications: Treat as appropriate
• Growth failure in children: Treat with growth hormone
 Diet in CKD
• 1. Protein. Reduced intake of animal protein may slow CKD
progression. However, significant protein restriction is not advisable
in those with cachexia or low serum albumin.
• 2. Salt and water restriction: to avoid hypertension, nd volume
overload
• 3. Potassium restriction:
• 4. Phosphorus restriction:
• Processed foods and cola beverages should be avoided. Foods rich in
phosphorus such as eggs, dairy products, nuts, beans, and meat, but
avoid protein malnutrition