What are the diagnostic evaluation and management strategies for chronic kidney disease (CKD)?

Diagnostic Evaluation and Management of Chronic Kidney Disease

Definition and Diagnostic Criteria

CKD is diagnosed when kidney abnormalities persist for more than 3 months, defined by either eGFR <60 mL/min/1.73 m² OR evidence of kidney damage (primarily albuminuria ≥30 mg/g). 1

Essential Diagnostic Tests

• Test ALL at-risk patients using BOTH urine albumin measurement (albumin-to-creatinine ratio, ACR) AND eGFR assessment—neither test alone is sufficient 1, 2
• Use creatinine-based eGFR (eGFRcr) as the primary method; if available, combine with cystatin C (eGFRcr-cys) for more accurate GFR estimation, particularly when eGFRcr is 45-59 mL/min/1.73 m² without other markers of kidney damage 1
• Repeat abnormal tests to confirm CKD—a single abnormal value may represent acute kidney injury rather than chronic disease 1

Establishing Chronicity (≥3 months duration)

Prove chronicity through any of the following 1:

• Review of past GFR measurements
• Review of past albuminuria/proteinuria measurements
• Imaging showing reduced kidney size or cortical thinning
• Kidney biopsy showing fibrosis/atrophy
• Medical history of conditions causing CKD (diabetes, hypertension)
• Repeat measurements within and beyond 3 months

Do not assume chronicity from a single abnormal test—it could be acute kidney injury or acute kidney disease 1

CKD Staging System

GFR Categories 2

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

Albuminuria Categories 2

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

Stage CKD using BOTH GFR and albuminuria categories together—this combined staging guides prognosis and treatment intensity 2

Differential Diagnosis: Establishing the Cause

Determine the underlying cause using clinical context, personal/family history, medications, physical examination, laboratory tests, imaging, and when appropriate, kidney biopsy. 1

Common Causes to Evaluate 3, 4

• Diabetic kidney disease (most common in developed countries)
• Hypertensive nephrosclerosis (second most common)
• Glomerulonephritis (primary or secondary)
• Polycystic kidney disease (family history critical)
• Obstructive uropathy (imaging essential)
• Drug-induced nephropathy (NSAIDs, lithium, calcineurin inhibitors)
• Renovascular disease

Diagnostic Workup for Cause 1

Basic evaluation for all patients:

• Complete metabolic panel with electrolytes
• Urinalysis with microscopy (look for casts, cells, crystals)
• Renal ultrasound (kidney size, cortical thickness, obstruction, cysts)
• Medication review for nephrotoxins

Additional tests based on clinical suspicion:

• Serum and urine protein electrophoresis (if proteinuria without diabetes)
• Complement levels (C3, C4) and autoantibodies (ANA, ANCA) if glomerulonephritis suspected
• Hepatitis B, C, HIV serologies if indicated
• Kidney biopsy when cause unclear and results would change management 1

Comprehensive Management Strategy

Blood Pressure Management

Target BP <130/80 mmHg for all CKD patients. 5

• Use ACE inhibitor or ARB as first-line therapy when albuminuria ≥30 mg/g is present 1, 5
• If no albuminuria, dihydropyridine calcium channel blocker or thiazide diuretic are acceptable alternatives 1
• Often require all three drug classes to achieve BP targets 1
• Temporarily discontinue ACE inhibitor/ARB 48-72 hours before elective surgery or during acute illness with volume depletion 2

Diabetes Management (if applicable)

Target HbA1c ≤7% for most diabetic CKD patients (individualize based on comorbidities). 5

Medication hierarchy for diabetic CKD 1:

1. SGLT2 inhibitor (first-line for kidney and cardiovascular protection)
2. GLP-1 receptor agonist (long-acting formulation with documented cardiovascular benefits) if glycemic targets not met with metformin and SGLT2i 1
3. Nonsteroidal MRA (finerenone) may be added to RASi + SGLT2i for additional kidney protection 1

For nonsteroidal MRA initiation 1:

• Only start if baseline potassium ≤4.8 mmol/L
• Dose: 10 mg daily if eGFR 25-59; 20 mg daily if eGFR ≥60
• Check potassium at 1 month, then every 4 months
• Hold if potassium >5.5 mmol/L; adjust diet/medications and restart when ≤5.0 mmol/L

Cardiovascular Risk Reduction

Prescribe statin therapy for 2:

• All adults ≥50 years with CKD G1-G2
• All adults with CKD G3a-G5 (consider statin/ezetimibe combination)
• Adults 18-49 years with coronary disease, diabetes, prior stroke, or elevated CV risk

Low-dose aspirin for secondary prevention in those with established ischemic cardiovascular disease 2

Lifestyle Modifications

Physical activity: Moderate-intensity exercise for cumulative 150 minutes per week (or as tolerated based on cardiovascular capacity and frailty risk) 1

Dietary recommendations 1, 2:

• Sodium restriction (individualized based on BP and volume status)
• Protein intake 0.8 g/kg/day for CKD G3-G5; avoid high protein intake >1.3 g/kg/day 1
• Plant-based "Mediterranean-style" diet preferred over animal-based foods 2
• Limit ultraprocessed foods 1
• Potassium restriction for those with history of hyperkalemia (limit high-bioavailable potassium foods like processed foods) 1

Weight management: Advise weight loss for obese patients with CKD 1

Tobacco cessation: Strongly encourage discontinuation of all tobacco products 1

Medication Safety

Review ALL medications at each visit 2:

• Adjust doses based on current eGFR for renally cleared drugs 2
• Avoid nephrotoxins, particularly NSAIDs 3, 6
• Monitor drug levels for medications with narrow therapeutic windows 2
• Review and limit over-the-counter medicines and herbal supplements 2

Monitoring for CKD Complications

Monitor regularly for 3, 6:

• Hyperkalemia (especially with RASi, MRA use)
• Metabolic acidosis (consider treatment if bicarbonate <18 mmol/L) 1
• Anemia (evaluate and treat per guidelines)
• Mineral bone disorder (calcium, phosphorus, PTH, vitamin D)
• Volume overload

Monitoring Frequency

Frequency of eGFR and ACR monitoring depends on CKD stage and albuminuria category 1:

• Higher risk (lower GFR, higher albuminuria) = more frequent monitoring (up to 4 times yearly)
• Lower risk stages = annual monitoring may suffice
• Monitor at least annually for all CKD patients 1

Nephrology Referral Criteria

Refer to nephrology when 2, 3, 6:

• eGFR <30 mL/min/1.73 m² (all patients with CKD G4-G5)
• Severe albuminuria (ACR ≥300 mg/g or A3 category)
• Rapid decline in kidney function (>5 mL/min/1.73 m² per year)
• Acute kidney injury superimposed on CKD
• Difficulty determining cause of CKD
• Complex management issues (refractory hypertension, electrolyte abnormalities, anemia management)

Critical Pitfalls to Avoid

• Do not rely on eGFR alone—always assess albuminuria, as patients with normal eGFR but elevated albuminuria have CKD and increased cardiovascular risk 1, 2
• Do not diagnose CKD from single abnormal test—confirm with repeat testing over 3 months unless clinical context strongly suggests chronicity 1
• Do not continue ACE inhibitor/ARB during acute illness with volume depletion—temporary discontinuation prevents acute kidney injury 2
• Do not prescribe NSAIDs in CKD patients—these are nephrotoxic and accelerate progression 3, 6
• Do not delay nephrology referral for eGFR <30—early specialist involvement improves outcomes and reduces costs 6