Diagnostic Approach to Chronic Kidney Disease
Test all patients suspected of having CKD with both serum creatinine to calculate eGFR and a random spot urine albumin-to-creatinine ratio (UACR), as both provide independent prognostic information and are required for proper diagnosis and staging. 1
Initial Diagnostic Tests
Essential Laboratory Measurements
Measure serum creatinine and calculate eGFR using the CKD-EPI 2021 equation (creatinine-based eGFRcr), or preferably the combination of creatinine and cystatin C (eGFRcr-cys) if available, as this provides more accurate GFR estimation 1, 2
Obtain urine albumin-to-creatinine ratio (UACR) on a random spot urine sample rather than dipstick testing, as UACR provides quantitative assessment and superior sensitivity for detecting early kidney damage 1, 3
CKD is diagnosed when either eGFR <60 mL/min/1.73 m² OR UACR ≥30 mg/g persists for at least 3 months, as a single abnormal measurement may reflect acute kidney injury rather than chronic disease 1, 2
Confirming Chronicity
Repeat testing within 2-4 weeks to 3 months is mandatory to distinguish CKD from acute kidney injury or acute kidney disease, as chronicity requires persistence of abnormalities for at least 3 months 1
Review historical eGFR and UACR measurements if available to establish duration of kidney dysfunction 1
Look for imaging findings such as reduced kidney size (<9 cm length) or reduced cortical thickness (<0.5 cm), which indicate chronicity 1
Examine medical history for conditions known to cause CKD, particularly diabetes duration ≥10 years in type 1 diabetes or presence at diagnosis in type 2 diabetes 1
Risk-Based Screening Strategy
Mandatory Screening Populations
Screen immediately in all patients with diabetes, hypertension, age >60 years, family history of kidney disease, cardiovascular disease, or obesity, as these groups account for the vast majority of CKD cases 1, 2, 3
Diabetes patients: 20-40% will develop CKD, with diabetic kidney disease being the leading cause of end-stage kidney disease in the United States 1, 2
Hypertension patients: 91% of CKD patients have hypertension, creating a dangerous cycle that accelerates kidney function decline 1, 4
Age >60 years: CKD prevalence increases substantially with advancing age 1, 4
Cardiovascular disease: 46% of CKD patients have atherosclerotic heart disease, and CKD markedly increases cardiovascular mortality risk 1, 4
When NOT to Screen
Do not perform routine screening in asymptomatic adults without risk factors, as the absolute risk of CKD and adverse outcomes is small in this population, and potential harms from false positives and unnecessary interventions outweigh benefits 1, 4
Determining the Underlying Cause
Systematic Etiologic Evaluation
Establish the cause of CKD through clinical context, personal and family history, medications, physical examination, and laboratory measures, as identifying the etiology guides treatment decisions 1
Diabetes and hypertension together account for the majority of CKD cases in developed countries, with diabetes being present in 48% and hypertension in 91% of CKD patients 1, 2
Identify nephrotoxic exposures including NSAIDs, lithium, calcineurin inhibitors, aminoglycosides, heavy metals, and agrochemicals 4, 2
Look for hematuria, pyuria, or casts on urinalysis that suggest glomerulonephritis or other primary kidney diseases requiring different management 1
Consider kidney biopsy when etiology is uncertain, particularly when kidneys appear normal-sized on imaging, as up to 30% of presumed diabetic kidney disease patients have alternative diagnoses on biopsy 4
Comprehensive Baseline Assessment
Additional Laboratory Testing
Obtain a complete metabolic panel, CBC, lipid panel, HbA1c (if diabetic), urinalysis, and PTH when eGFR <60 mL/min/1.73 m² to screen for CKD complications and cardiovascular risk factors 5, 2
Measure sodium, potassium, chloride, bicarbonate to detect metabolic acidosis and hyperkalemia 5
Check hemoglobin to screen for anemia, which commonly develops when eGFR falls below 60 mL/min/1.73 m² 5, 2
Measure calcium, phosphate, and intact PTH when eGFR <60 mL/min/1.73 m², as PTH begins rising at this threshold and bone disease may be present 5
Obtain 25-hydroxyvitamin D level to assess for vitamin D deficiency 5
Cardiovascular Assessment
Obtain a 12-lead ECG to assess for left ventricular hypertrophy and arrhythmias, as cardiovascular disease is the leading cause of death in CKD patients 5
- Consider echocardiography if ECG is abnormal or cardiac symptoms are present 5
Staging and Risk Stratification
Combined GFR and Albuminuria Classification
Stage CKD using both eGFR category (G1-G5) and albuminuria category (A1-A3), as the combination determines progression risk and monitoring intensity more accurately than either alone 1, 5
eGFR categories: G1 (≥90), G2 (60-89), G3a (45-59), G3b (30-44), G4 (15-29), G5 (<15 mL/min/1.73 m²) 1
Albuminuria categories: A1 (<30 mg/g), A2 (30-300 mg/g), A3 (>300 mg/g) 1
Higher albuminuria and lower eGFR independently predict cardiovascular events, CKD progression, and mortality 1
Monitoring Frequency Based on Risk
Tailored Surveillance Strategy
Adjust monitoring frequency based on combined GFR-albuminuria risk stratification, with higher-risk patients requiring more intensive follow-up 1, 5
Low risk (eGFR ≥60 with UACR <30 mg/g): Monitor annually 5
Moderate risk (eGFR 45-59 or UACR 30-300 mg/g): Monitor every 6 months 5
High risk (eGFR 30-44 or UACR >300 mg/g): Monitor every 3-4 months 5
Very high risk (eGFR <30 mL/min/1.73 m²): Refer to nephrology and monitor monthly 1, 5
Nephrology Referral Criteria
Mandatory Referral Indications
**Refer to nephrology when eGFR <30 mL/min/1.73 m² (Stage 4), or earlier if uncertainty about etiology, difficult management issues, or rapid progression** (>30% decline in eGFR within 4 weeks or continuously declining eGFR despite optimal management) 1, 5, 2
Albuminuria ≥300 mg/g despite optimal treatment with ACE inhibitor or ARB 5
Continuously increasing albuminuria levels despite maximal therapy 1, 5
Resistant hypertension requiring ≥3 antihypertensive agents including a diuretic 5
Difficulty managing CKD complications such as anemia, secondary hyperparathyroidism, metabolic acidosis, or hyperkalemia 1, 5
Significant hematuria in diabetic patients suggesting non-diabetic kidney disease 4
Common Diagnostic Pitfalls to Avoid
Critical Errors in CKD Diagnosis
Never rely on serum creatinine alone without calculating eGFR, as creatinine is an unreliable marker of kidney function that varies with muscle mass, age, and sex 1, 6
Never skip albuminuria testing even when eGFR is normal or mildly reduced, as albuminuria can be the sole manifestation of early CKD and provides independent prognostic information 1
Do not assume chronicity based on a single abnormal eGFR or UACR, as acute kidney injury or acute kidney disease can present identically and requires different management 1
Do not use age-adjusted definitions of CKD, as there are no age-adjusted definitions for diabetes or hypertension, though individual implications differ by age group 1
Avoid discontinuing ACE inhibitors or ARBs for minor creatinine increases ≤30% in the absence of volume depletion, as this removes critical nephroprotection 1, 5