Chronic kidney disease

Background

Definition

• Structural or functional kidney disorder lasting at least [3 months]

KDIGO Classification

• Defined as 3 or more months of either GFR < 60 or 1 or more marker of kidney damage:
  • Proteinuria
  • Urine sediments
  • Tubular electrolyte disorder
  • Kidney transplant
  • Structural disease
• Categories & grades:
  • Grade 1: GFR ≥90 (normal) with a marker of kidney disease
  • Grade 2: GFR 60-89 with a marker of kidney disease
  • Grade 3a: GFR 45-59
  • Grade 3b: GFR 30-44
  • Grade 4: GFR 15-29
  • Grade 5: GFR <15, ESRD

Epidemiology

• 8% of population have GFR < 60
• 4% of population have proteinuria despite normal GFR

Differential Diagnosis

• Diabetes
• Cardiovascular disease/HTN
  • Ischemic nephropathy
  • Nephrosclerosis
• Glomerulonephritis
• PCKD
• Drugs, especially lithium, cyclosporine, tacrolimus, tenofivir
• Other disease associations
  • Inflammatory bowel disease: oxalate nephropathy
  • Rheumatoid arthritis: amyloidosis
  • Cirrhosis: Type 2 hepatorenal syndrome
  • Solid tumours: membranous nephropathy
  • Severe CHF: cardiorenal syndrome
  • Post-AKI: incomplete recovery of ATN in hospital

Investigations

Laboratory

• GFR
  • MDRD underestimates the GFR in healthy patients
  • CKD-Epi is the newer equation and possibly more accurate
  • Radioisotopic GFR is the gold standard, inulin clearance is the gold standard for research
  • Cystatin C may complement or replace creatinine in the future
• Urinalysis, though "protein" only picks up albumin
• Urine ACR and PCR

Imaging

• Abdominal ultrasound

Management

• Education re: dialysis and transplant
• Refer to nephrology when:
  • GFR drops by 5+ per year
  • Acute on chronic kidney injury
  • eGFR < 30 (Stage 4)
  • Proteinuria >1g/day
  • Difficulty controlling BP
• BP control
  • ACEi + CCB + diuretic
  • If albuminuria, target <130/80, else <140/90
• Proteinuria
  • If proteinuria >500mg/d or ACR>30mg/mmol, start ACEi/ARB regardless of BP
  • If diabetes and microalbuminuria, start ACEi/ARB
• Metabolic acidosis (normal anion gap)
  • Oral sodium bicarbonate 0.5-1 mEq/kg/d to maintain bicarb between 23-29 mmol/L
• Avoid nephrotoxic mediation like NSAIDs

Initial Investigations

• Urinalysis to help diagnose glomerulonephritis or AIN
• ACR, a component of the KFRE score
• Urea, to help rule out volume depletion
• Urine electrolytes, with low urine Na (FENA<1%) suggesting volume depletion
• Ultrasound of the kidneys to assess for structural kidney disease and renal stones, plus or minus arterial Dopplers if suspecting renovascular disease
• Serum protein electrophoresis
• 24-hour urine protein and urine electrophoresis, if urine ACR >300 mg/mmol (<3 g/d)
• CK, to rule out rhabdomyolysis
• ANCAs, if UA shows blood and protein and there's a rapid decline in kidney function
• CBC with blood film, looking for evidence of a TMA

Routine Investigations

• Annually for patients with stage 2 or higher: creatinine, Na/K/Cl/CO2, ACR
• Every 3-6 months for patients with stage 4 or higher:
  • Na/K/Cl/CO2, creatinine, urea
  • Ca/Mg/PO4/albumin/PTH
  • ACR
  • CBC, ferritin, transferrin saturation

Sick Day Medications

• Some medications should be held during an acute illness, before surgery, or with IV contrast
• Includes ACEi, ARB, aldosterone antagonists, SGLT-2 inhibitors, diuretics, NSAIDs, metformin, sulfonylureas, and direct renin inhibitors
• Hold ACEi/ARB when planning pregnancy

Complications

• Anemia: treat iron deficiency before adding Epo, targetting 105-115
• Hypocalcemia: give calcium between meals or rocaltrol (if the hyperphosphatemia is treated)
• Hyperphosphatemia: give a phosphate binder like calcium or Renagel with meals
• Metabolic bone disease: maintain normal phosphate with diet, binders, and vitamin D
• Acidosis: supplement bicarb when < 22
• Hyperkalemia from poor GFR, ACEi, DM
• Pruritis: moisturizers, steroids, antihistamines

Prognosis

• GFR declines linearly over time
• Progression predicted by
  • Previous rate of progression
  • Hypertension **
  • Proteinuria **
  • Metabolic acidosis
• High risk of cardiovascular mortality compared to general population
  • 30 year olds on dialysis have same risk as 80 year olds in the general population
  • Risk increases with a decreasing GFR

Further Reading

• An approach to treating older adults with chronic kidney disease. CMAJ. 2023;195(17):E612-E618. doi: 10.1503/cmaj.221427