What is the diagnostic approach for a patient with suspected chronic kidney disease, considering their age, medical history, and symptoms such as fatigue, swelling, or changes in urination?

Diagnosis of Chronic Kidney Disease

Diagnose CKD by measuring both serum creatinine to calculate eGFR and urine albumin-to-creatinine ratio (ACR), with CKD confirmed when either eGFR <60 mL/min/1.73 m² or ACR ≥30 mg/g persists for at least 3 months. 1, 2

Core Diagnostic Criteria

CKD requires both an abnormality AND persistence for >3 months to distinguish it from acute kidney injury: 1, 2

• eGFR <60 mL/min/1.73 m² (representing loss of ≥50% of normal kidney function) 1, 2
• OR albuminuria ≥30 mg/g on urine ACR 2
• Duration requirement: ≥3 months of either abnormality 1, 2

Essential Diagnostic Tests

Both tests are mandatory for comprehensive CKD evaluation—do not rely on eGFR alone: 1, 2

Kidney Function Assessment

• Serum creatinine to calculate eGFR using the 2021 CKD-EPI equation (most accurate for routine practice) 2, 3, 4
• For adults at risk, use creatinine-based eGFR (eGFRcr) initially 1
• If cystatin C is available, use combined creatinine-cystatin C eGFR (eGFRcr-cys) for more accurate staging 1, 2
• Consider cystatin C when creatinine-based equations may be inaccurate (extremes of muscle mass, malnutrition, amputation) 3

Kidney Damage Assessment

• Urine albumin-to-creatinine ratio (ACR) on random spot urine specimen 1, 2, 5
• ACR ≥30 mg/g indicates kidney damage (sex-specific cutpoints: >17 mg/g in men, >25 mg/g in women) 1
• Confirm with 2 of 3 positive specimens over 3 months 2

Confirming Chronicity (≥3 Months Duration)

Do not assume chronicity from a single abnormal test—this could represent acute kidney injury: 1

Establish chronicity through: 1, 2

• Review past eGFR measurements from medical records 1, 2
• Review past albuminuria/proteinuria results 1, 2
• Imaging findings: reduced kidney size (<9 cm longitudinal diameter), cortical thinning, increased echogenicity 1, 2, 6
• Kidney biopsy showing fibrosis and atrophy 1
• Medical history: diabetes >10 years, long-standing hypertension, family history of kidney disease 1, 2
• Repeat measurements within and beyond 3 months 1, 2

Clinical caveat: If CKD is highly likely based on clinical context (e.g., diabetic with retinopathy), initiate CKD-specific treatments at first presentation without waiting 3 months for confirmation 1

Staging CKD

Stage by both GFR category (G1-G5) and albuminuria category (A1-A3) for complete risk stratification: 2, 7

GFR Categories

• G1: ≥90 mL/min/1.73 m² (normal/high, but kidney damage present) 2, 7
• G2: 60-89 mL/min/1.73 m² (mildly decreased) 2, 7
• G3a: 45-59 mL/min/1.73 m² (mildly-moderately decreased) 2, 7
• G3b: 30-44 mL/min/1.73 m² (moderately-severely decreased) 2, 7
• G4: 15-29 mL/min/1.73 m² (severely decreased) 2, 7
• G5: <15 mL/min/1.73 m² (kidney failure) 2, 7

Albuminuria Categories

• A1: <30 mg/g (normal to mildly increased) 2
• A2: 30-300 mg/g (moderately increased) 2
• A3: >300 mg/g (severely increased) 2

Determining the Underlying Cause

Establish etiology systematically as this guides treatment: 1, 2

History Elements

• Diabetes duration and control (type 1: screen after 5 years; type 2: screen at diagnosis) 2
• Hypertension duration and control 2
• Nephrotoxic exposures: NSAIDs, lithium, calcineurin inhibitors, aminoglycosides, contrast agents 2, 5
• Family history of kidney disease or genetic disorders 2
• Systemic diseases: lupus, vasculitis, multiple myeloma 2

Laboratory Evaluation

• Complete blood count (anemia, eosinophilia) 2
• Comprehensive metabolic panel (electrolytes, calcium, phosphate, bicarbonate) 2
• Urinalysis with microscopy: hematuria, pyuria, casts (suggests glomerulonephritis) 2
• Additional tests based on suspicion: complement levels (C3, C4), ANA, ANCA, hepatitis B/C, HIV, serum/urine protein electrophoresis 2

Imaging

• Renal ultrasound to assess kidney size, echogenicity, cortical thickness, and exclude obstruction 2, 6
• Small kidneys (<9 cm) suggest chronicity, but normal-sized kidneys do not exclude CKD (diabetic nephropathy, infiltrative disorders, early FSGS maintain normal size) 2, 6

Kidney Biopsy Indications

• Unclear etiology when results would change management 1, 2
• Rapidly progressive disease (eGFR decline >5 mL/min/year) 2
• Nephrotic syndrome (proteinuria >3.5 g/day with edema, hypoalbuminemia) 2
• Suspected glomerular disease with active urinary sediment 2

Screening High-Risk Populations

Screen annually with both eGFR and ACR in: 2, 5, 8

• Diabetes (type 1: start 5 years after diagnosis; type 2: start at diagnosis) 2
• Hypertension 2, 5, 8
• Age >60 years 5, 8
• Family history of kidney disease 5, 8
• Cardiovascular disease 3, 8
• Obesity 2

Nephrology Referral Criteria

Refer promptly when: 2, 5

• eGFR <30 mL/min/1.73 m² (stage G4-G5) 2, 5
• ACR >300 mg/g (severely increased albuminuria) 5
• Rapid eGFR decline (>5 mL/min/year or >10 mL/min over 5 years) 2
• Uncertain etiology or atypical features 2
• Difficult-to-manage complications: resistant hypertension, hyperkalemia, metabolic acidosis, anemia 2
• Continuously increasing albuminuria despite optimal treatment 2

Critical Pitfalls to Avoid

• Never rely on serum creatinine alone—always calculate eGFR using validated equations 2, 4
• Never skip albuminuria testing—eGFR and ACR provide independent prognostic information for cardiovascular events and mortality 2
• Do not assume a single abnormal test confirms CKD—repeat testing is essential to distinguish from AKI 1
• Do not assume normal-sized kidneys exclude CKD—diabetic nephropathy and infiltrative disorders maintain kidney size 2, 6
• Do not wait for symptoms—CKD is typically asymptomatic until advanced stages 3, 8