by Dr. Marita du Plessis
PATHCHAT Edition No. 18
Please contact your local Ampath pathologist for more information.
Introduction
🔹 Definition of Chronic Kidney Disease (CKD):
- CKD is defined as abnormalities of kidney structure or function lasting longer than three months, with implications for health.
🔹 Updated Classification System (KDIGO 2012):
- CKD is now classified using the CGA system, which includes:
- Cause of CKD.
- Glomerular Filtration Rate (GFR) category.
- Albuminuria category (marker of kidney damage).
- The combination of GFR and albuminuria correlates with adverse outcomes.
Criteria for Diagnosing CKD
🔹 One of the following must be present for more than three months:
✅ 1. Decreased GFR:
- A GFR of less than 60 ml/min/1.73m² (Stages G3a–G5) confirms CKD.
✅ 2. Markers of Kidney Damage (One or More):
- Albuminuria:
- Albumin excretion rate (AER) of 30 mg/day or more.
- Albumin-to-creatinine ratio (ACR) of 3 mg/mmol or more.
- Urine sediment abnormalities: Presence of haematuria, red cell casts, white cell casts, or granular casts.
- Electrolyte and tubular function abnormalities: Indicators of tubular disorders.
- Histological abnormalities: Detected via kidney biopsy.
- Structural abnormalities: Found through renal imaging.
- History of kidney transplantation.
Classification of CKD Using the CGA System
📌 CKD classification now includes cause & albuminuria levels in addition to GFR to improve prognosis accuracy & guide treatment.
1. Assigning the Cause of CKD
✅ CKD causes are classified into two main groups:
- Systemic diseases affecting the kidneys (e.g., diabetes, lupus).
- Primary kidney diseases without systemic involvement (e.g., glomerulonephritis, polycystic kidney disease).
🔹 Examples of CKD Causes:
✔ Glomerular diseases:
- Systemic causes: Diabetes, lupus, infections, drugs, amyloidosis.
- Primary kidney diseases: Glomerulonephritis, focal segmental glomerulosclerosis, membranous nephropathy, minimal change disease.
✔ Tubulointerstitial diseases:
- Systemic causes: Infections, autoimmune diseases, sarcoidosis, nephrotoxic drugs, urate nephropathy, heavy metal exposure (e.g., lead poisoning).
- Primary kidney diseases: Chronic pyelonephritis, kidney stone disease, urinary obstruction.
✔ Vascular diseases:
- Systemic causes: Hypertension, atherosclerosis, cholesterol emboli, vasculitis, thrombotic microangiopathy, systemic sclerosis.
- Primary kidney diseases: Renal-limited vasculitis, fibromuscular dysplasia.
✔ Cystic and congenital diseases:
- Systemic causes: Polycystic kidney disease, Alport syndrome, Fabry disease.
- Primary kidney diseases: Renal dysplasia, medullary cystic disease, podocytopathies.
2. Estimating GFR: Updated Recommendations
✅ Why GFR Calculation Matters:
- GFR below 60 ml/min/1.73m² is diagnostic for CKD.
- Estimated GFR (eGFR) should always be reported alongside serum creatinine levels.
✅ Ampath’s GFR Calculation Method:
- Previously used MDRD equation for GFR estimation.
- Now transitioning to CKD-EPI equation for better accuracy.
🔹 Advantages of CKD-EPI Equation Over MDRD:
- More accurate at GFR values above 60 ml/min/1.73m².
- Less influenced by ethnicity (no race-based correction needed).
- Improves classification accuracy for younger individuals & women.
- Better correlation with actual GFR measurements in clinical practice.
✅ Additional GFR Testing Considerations:
- Cystatin C-based eGFR testing (to be introduced soon at Ampath).
- Exogenous filtration marker clearance tests (not widely available in South Africa).
3. GFR Categories in CKD
🔹 Stages of CKD Based on GFR:
✔ Stage G1: GFR ≥90 ml/min/1.73m² → Normal or high kidney function.
✔ Stage G2: GFR 60–89 ml/min/1.73m² → Mildly decreased kidney function.
✔ Stage G3a: GFR 45–59 ml/min/1.73m² → Mild to moderate CKD.
✔ Stage G3b: GFR 30–44 ml/min/1.73m² → Moderate to severe CKD.
✔ Stage G4: GFR 15–29 ml/min/1.73m² → Severe CKD.
✔ Stage G5: GFR <15 ml/min/1.73m² → Kidney failure.
📌 Stages G1 & G2 are NOT classified as CKD unless markers of kidney damage are present.
4. Albuminuria as a Marker of Kidney Damage
✅ Why Albuminuria Matters:
- Best indicator of glomerular disease progression.
- Higher albumin levels correlate with increased CKD & cardiovascular risks.
✅ Preferred Screening Method:
- Early morning urine albumin-to-creatinine ratio (ACR) is recommended.
- Reagent test strips are discouraged due to low sensitivity.
🔹 Albuminuria Categories:
✔ A1 (Normal to Mildly Increased): ACR <3 mg/mmol (AER <30 mg/day).
✔ A2 (Moderately Increased): ACR 3–30 mg/mmol (AER 30–300 mg/day).
✔ A3 (Severely Increased): ACR >30 mg/mmol (AER >300 mg/day).
📌 The term "microalbuminuria" has been replaced with "moderately increased albuminuria" (A2).
5. CKD Prognosis Based on GFR & Albuminuria
📌 The risk of CKD complications increases with lower GFR and higher albuminuria levels.
✅ Risk Factors for Poor Prognosis:
- GFR decline (especially <30 ml/min/1.73m²).
- Persistent albuminuria (A2 or A3 category).
- Diabetes, hypertension, cardiovascular disease.
✔ Low Risk: GFR ≥60 ml/min/1.73m² + normal albumin levels.
✔ Moderate Risk: GFR 45–59 ml/min/1.73m² + moderately increased albuminuria.
✔ High Risk: GFR 30–44 ml/min/1.73m² + severely increased albuminuria.
✔ Very High Risk: GFR <30 ml/min/1.73m² + severe albuminuria → Kidney failure risk.