What is the approach to evaluating and managing a patient with chronic kidney disease (CKD), particularly those with underlying conditions such as diabetes or hypertension?

Evaluation of Chronic Kidney Disease

Begin CKD evaluation by confirming chronicity through repeat testing of both eGFR and urine albumin-to-creatinine ratio (ACR) over at least 3 months, then classify disease using the three-dimensional KDIGO framework: cause, GFR category (G1-G5), and albuminuria category (A1-A3). 1

Initial Detection and Confirmation

• Test all at-risk patients (those with diabetes, hypertension, cardiovascular disease, or family history of kidney failure) using both serum creatinine for eGFR calculation and spot urine ACR 1, 2
• Use creatinine-based eGFR (eGFRcr) as the initial assessment; if cystatin C is available, combine both markers (eGFRcr-cys) for more accurate GFR estimation in adults at risk 1
• Confirm chronicity by repeating abnormal tests after 3 months to distinguish CKD from acute kidney injury or acute kidney disease 1
• Proof of chronicity can also be established through review of past measurements, imaging showing reduced kidney size or cortical thinning, kidney biopsy findings of fibrosis, or medical history of conditions causing CKD 1

Three-Dimensional Classification System

The KDIGO 2024 guidelines mandate classifying CKD using all three dimensions simultaneously 1:

1. Cause of CKD

• Establish etiology through clinical context, personal and family history, social and environmental factors, medications, physical examination, laboratory measures, imaging, and when indicated, genetic testing or kidney biopsy 1
• Common causes include diabetic kidney disease, hypertensive nephrosclerosis, glomerulonephritis, polycystic kidney disease, and obstructive uropathy 2

2. GFR Category

• G1: eGFR ≥90 mL/min/1.73 m² (normal or high, with other evidence of kidney damage)
• G2: eGFR 60-89 mL/min/1.73 m² (mildly decreased)
• G3a: eGFR 45-59 mL/min/1.73 m² (mildly to moderately decreased)
• G3b: eGFR 30-44 mL/min/1.73 m² (moderately to severely decreased)
• G4: eGFR 15-29 mL/min/1.73 m² (severely decreased)
• G5: eGFR <15 mL/min/1.73 m² (kidney failure) 1

3. Albuminuria Category

• A1: ACR <30 mg/g (normal to mildly increased)
• A2: ACR 30-300 mg/g (moderately increased)
• A3: ACR >300 mg/g (severely increased) 1

Risk Stratification and Prognosis

• Use externally validated risk equations to estimate absolute risk of kidney failure in patients with CKD G3-G5, rather than relying solely on GFR and albuminuria categories 1
• A 5-year kidney failure risk of 3-5% triggers nephrology referral consideration; 2-year risk >10% indicates need for multidisciplinary care; 2-year risk >40% mandates preparation for kidney replacement therapy 1
• For cardiovascular risk prediction, use externally validated models developed within CKD populations or that incorporate both eGFR and albuminuria 1
• Disease-specific prediction equations should be used for IgA nephropathy and autosomal dominant polycystic kidney disease 1

Comprehensive Laboratory Evaluation

Beyond eGFR and ACR, assess the following 1, 2, 3:

• Complete metabolic panel: Serum creatinine, electrolytes (sodium, potassium, chloride, bicarbonate), calcium, phosphorus
• Complete blood count: To detect anemia (hemoglobin target monitoring)
• Lipid panel: For cardiovascular risk assessment
• Hemoglobin A1c: In diabetic patients
• Parathyroid hormone (PTH) and 25-hydroxyvitamin D: When eGFR <45 mL/min/1.73 m²
• Iron studies: Serum ferritin and transferrin saturation before initiating erythropoiesis-stimulating agents 4

Monitoring Schedule

• CKD G1-G2: Monitor eGFR and ACR annually 3
• CKD G3a: Monitor every 6 months 5, 3
• CKD G3b-G4: Monitor every 3 months 1, 3
• CKD G5: Monitor monthly or as clinically indicated 1
• Check serum creatinine, potassium, and bicarbonate 2-4 weeks after any medication changes, particularly when initiating or adjusting ACE inhibitors, ARBs, or diuretics 5

Imaging and Additional Testing

• Renal ultrasound: Assess kidney size, cortical thickness, and rule out obstruction or structural abnormalities 1
• Kidney biopsy: Consider when diagnosis is uncertain, when specific treatment would change management, or when rapid progression occurs without clear cause 1
• Avoid gadolinium-based contrast agents in patients with eGFR <30 mL/min/1.73 m² due to risk of nephrogenic systemic fibrosis 2

Nephrology Referral Criteria

Immediate referral is mandatory when 6, 3, 7:

• eGFR <30 mL/min/1.73 m² (CKD G4-G5)
• ACR ≥300 mg/g (severe albuminuria, A3 category)
• Rapid decline in eGFR (>5 mL/min/1.73 m² per year or >25% decline within 3 months)
• Persistent electrolyte abnormalities (hyperkalemia, metabolic acidosis) despite treatment
• Uncontrolled hypertension despite multiple agents
• Suspected glomerulonephritis or systemic disease affecting kidneys
• Hereditary kidney disease
• Recurrent or extensive nephrolithiasis

Critical Management Principles During Evaluation

• Avoid nephrotoxins: NSAIDs, aminoglycosides, contrast agents, and proton pump inhibitors when possible 6, 2
• Adjust medication dosing based on eGFR for renally cleared drugs (many antibiotics, oral hypoglycemics, anticoagulants) 2, 3
• Evaluate iron status before treating anemia: supplemental iron is required when ferritin <100 mcg/L or transferrin saturation <20% 4
• Do not target hemoglobin >11 g/dL with erythropoiesis-stimulating agents due to increased risks of death, cardiovascular events, and stroke 4

Common Pitfalls to Avoid

• Do not assume single abnormal eGFR or ACR represents CKD—acute kidney injury or transient proteinuria from infection, exercise, or fever can cause temporary abnormalities 1
• Do not delay treatment initiation while waiting to confirm chronicity if CKD is highly likely based on clinical context (e.g., long-standing diabetes with retinopathy) 1
• Do not use age-adjusted definitions of CKD—while older patients have higher prevalence, reduced eGFR and albuminuria carry prognostic significance at all ages 1
• Do not combine ACE inhibitors with ARBs or direct renin inhibitors—this increases risks of hyperkalemia, hypotension, and acute kidney injury without additional benefit 5
• Do not withhold ACE inhibitor/ARB therapy if serum creatinine increases up to 30% within 4 weeks of initiation—this is expected and acceptable 5