Chronic Kidney disease - Internal medicine

Question 1

CKD Classification according to GFR

Answer 1

Stage 1:
GFR: ≥ 90 mL/min/1.73 m²
Description: Only CKD if other evidence of kidney damage: protein/hematuria.

Stage 2:
GFR: 60-89 mL/min/1.73 m²
Description: Pathology on biopsy/imaging, tubule disorder, transplant

Stage 3a:
GFR: 45-59 mL/min/1.73 m²
Description: Mild–moderate ↓GFR
Stage 3b:
GFR: 30-44 mL/min/1.73 m²
Description: Moderate–severe ↓GFR

Stage 4:
GFR: 15-29 mL/min/1.73 m²
Description: Severely decreased GFR.

Stage 5:
GFR: < 15 mL/min/1.73 m² or on dialysis
Description: Kidney failure.

Question 2

Definition of Chronic kidney disease

Answer 2

Progressive abnormalities of kidney function for >3 months, with either:
- GFR <60 mL/min/1.73 m2; or
- Markers of kidney damage, including: hematuria, proteinuria, or anatomic abnormalities.

Question 3

The most common causes of CKD

Answer 3

1. DM
2. Hypertension
3. Glomerular diseases
4. Idiopathic
5. Congenital
6. Pyelonephritis

Question 4

Clinical Features and complications of CKD (1. Fluid, electrolyte and acid base disturbance)

Answer 4

• Volume expansion and contraction (edema, dehydration)
• As long as water intake does not exceed the capacity for free water clearance, the extra cellular fluid volume expansion will be isotonic and the patient will remain normonatremic. On the other hand, hyponatremia will be the consequence of excessive water ingestion.
• Patients with CRF also have impaired renal mechanisms for conserving Na+ AND H2O. When an extra renal cause for fluid loss is present (e.g., vomiting, diarrhea, sweating, fever), these patients are prone to volume depletion and dehydration.
• In the face of Sodium intake patients may retain Na+ and water which may lead to congestive heart failure, peripheral edema and ascites.

Question 5

Clinical Features and complications of CKD (2. Potassium Homeostasis )

Answer 5

• Most commonly, clinically significant hyperkalemia does not occur until the GFR falls to below 10 mL/min.
• Factors that contribute to increased serum K+ level are:
  o Endogenous a K+
  load (e.g., hemolysis, trauma, infection) or
  o Exogenous K+
  (e.g. administration of stored blood, K+
• containing medications, K+ -containing dietary salt substitute).
  o Acidosis: facilitates influx of K+ form intracellular fluid (ICF)to ECF
  o Drugs: potassium sparing diuretics, ACE inhibitors.

Question 6

Clinical Features and complications of CKD (3. Metabolic Acidosis)

Answer 6

Acidosis is a common disturbance during the advanced stages of CKD. With advancing renal failure, total urinary net daily acid excretion is usually reduced markedly

Question 7

Clinical Features and complications of CKD (4. Renal osteodystrophy and Metabolic bone disease)

Answer 7

– Is due to disturbance in bone phosphate and calcium metabolism.
- Hyperphosphatemia is a feature of advanced renal failure. The serum phosphate concentration rises in patients with a GFR < 20 mL/min.
- Calcium: - The total plasma Ca2+ concentration in patients with CRF is often significantly lower than normal. Patients with CKD tolerate the hypocalcemia quite well; rarely is a patient symptomatic from the decreased Ca2+ concentration. Note that the low serum level of Ca++ is attributed to secondary hyperparathyroidism.
- Reduced synthesis of 1,25 (OH)2D3 during CKD plays a key role in the pathogenesis of hyperparathyroidism, both directly and through hypocalcemia. The abnormal vitamin D metabolism may be related to the renal disease itself (since the active vitamin D metabolite is normally produced in the proximal tubule) and to the hyperphosphatemia, which has a suppressive effect on the renal 1α-hydroxylase enzyme.

Some of the resulting bony abnormalities are:
1. Osteitis fibrosa cystica: is due to osteoclastic bone resorption of especially terminal phalanges, long bones and distal end of clavicle
2. Renal rickets (Osteomalacia)
3. Osteosclerosis: enhanced bone density in the upper and lower margins of vertebrae

Question 8

Clinical Features and complications of CKD (5. Cardiovascular complications)

Answer 8

• Congestive heart failure and/or pulmonary edema: it may be due to:
• Volume over load
• Increase pulmonary capillary permeability
  – Hypertension:
  The most common complication of end stage renal disease. It results from fluid overload. Sometimes sever form of hypertension may occur.
  – Pericarditis: metabolic toxins are responsible for pericarditis.
  – The pericardial effusion is often hemorrhagic

Question 9

Clinical Features and complications of CKD (6. Hematologic abnormalities)

Answer 9

1. Normocytic normochromic anemia: which may be severe (Hemoglobin 4-6 gm/dl) The cause of anemia is multifactorial:
   - Decreased synthesis of erythropoietin (the most important factor)
   - Toxins suppressing bone marrow function
   - Blood loss (mainly GI blood loss)
   - Decreased life span of RBC
2. Bleeding tendency: attributed to platelet dysfunction
   - Patients may manifest with bleeding and easily bruiseability
   - GI bleeding or intracranial hemorrhage
3. Susceptibility to infection: is due to
   - Change in leukocyte formation and function
   - Lymphocytopeneia and atrophy of lymphoid tissue

Question 10

Clinical Features and complications of CKD (7. Neuromuscular abnormalities)

Answer 10

– Early stage: irritability, inability to concentrate drowsiness, insomnia
– Intermediate stage:
- Mild behavioral change, poor judgment
- Neuromuscular irritability: hiccup, cramps, fasciculation, twitching of muscles
– Terminal stage:
- Asterixis, myoclonus, chorea, seizure
- Stupor which may even lead to coma
- Peripheral neuropathy: distal sensory polyneuropathy
– Restless leg syndrome: ill-defined sensation or discomfort on the legs

Question 11

Clinical Features and complications of CKD (8. Gastro intestinal abnormalities
)

Answer 11

– Early symptoms: anorexia, hiccup, nausea and vomiting
– Uremic fetor: the patient’s breathe smells like urine.
– Mucosal ulceration leads to GI bleeding and peptic ulcer diseases.

Question 12

Clinical Features and complications of CKD (9. Endocrine and Metabolic abnormalities)

Answer 12

– Hypogonadism is common
– In men: decreased plasma testosterone level, impotence, oligospermia
– In women: amenorrhea, inability to carry pregnancy to term.

Question 13

Clinical Features and complications of CKD (10. Dermatologic abnormalities)

Answer 13

– Pallor due to anemia
– Ecchymosis, hematoma
– Pruritis, and excoriation (Ca++ deposits and 2ry hyperparathyroidism)
– Uremic frost: is seen in advanced uremia. It is due to high concentration of urea in the sweat, and after evaporation of the sweat, a fine white powder can be found on the skin surface.
- Muddy brown or grey skin coloration (earthy look)
- Half and half nails (the distal part of nail plate is reddish brown while the proximal part is white)
- Perforating dermatoses.

Question 14

Investigations used in CKD

Answer 14

1. Laboratory investigations:
   - Urea and electrolytes (U&E) (compare with previous).
   - Hb (normochromic, normocytic anemia).
   - Glucose (DM).
   - ↓Ca2+, ↑PO43- ↑parathyroid hormone (PTH) (renal osteodystrophy).
   - Directed investigation of intrinsic renal disease: ANA, ANCA, antiphospholipid antibodies, paraprotein, complement, cryoglobulin, antiGBM, hepatitis serology, anti-phospholipase A2 receptor (PLA2R)(membranous nephropathy). Note: ESR is not helpful as ↑ in CKD and proteinuric states.
   - Urine: Dipstick, microscopy, culture and sensitivity (MC&S), A:CR or P:CR, Bence Jones.
2. Imaging:
   - US for size, symmetry, anatomy, corticomedullary differentiation, and to
   exclude obstruction.
   - In CKD kidneys may be small (<9cm) except in infiltrative disorders (amyloid, myeloma), APKD, and DM. If asymmetrical consider renovascular disease.
   - Scarring may be seen on US but isotope scans are more sensitive.
3. Histology:
   - Consider renal biopsy in progressive disease, nephrotic syndrome, systemic disease, AKI without recovery.
   - Biopsy is unlikely to change treatment if GFR stable and P:CR <150. DM with neuropathy/retinopathy may not need biopsy unless atypical, i.e. nephrotic, haematuria, other systemic symptoms.

Question 15

Management of CKD

Answer 15

I. Diet:
- Low-protein diet
- Na+ restriction; target of <2 g/d (5 g/d of salt)
– preventing HTN and volume overload
– preventing electrolyte imbalances
- K+ restriction (40-60 mmol/d)
- PO43– restriction (1 g/d)
- Avoid extra-dietary Mg2+ (e.g. antacids): preventing uremia and potentially delaying decline in GFR
- Protein restriction with adequate caloric intake in order to limit endogenous protein catabolism

II. Medical:
- HTN: loop diuretics when GFR <25 mL/min
- Dyslipidemia: statins (target LDL <2 mmol/L)
- Calcium and phosphate disorders:
– Consider vitamin D and calcitriol (1,25-dihydroxy-vitamin D) if hypocalcemic, but hold if hyperphosphatemic (reduces PTH)
– Sevelamer (phosphate binder) if both hypercalcemic and hyperphosphatemic
- Cinacalcet for hyperparathyroidism (sensitizes parathyroid to Ca2+, decreasing PTH)
- Metabolic acidosis: sodium bicarbonate
- Anemia: Erythropoietin injections for Hb <90 g/L (9 g/dL) and target Hb between 90-115g/L (9-10.5 g/dL). IV iron administration often required for iron deficiency
- Clotting abnormalities: desmopressin (DDAVP) if patient has clinical bleeding or invasive procedures (acts to reverse platelet dysfunction).

III. Dialysis or Renal transplantation for end stage kidney disease.