Chronic Kidney Disease Diagnosis
Initial Screening and Detection
Test all at-risk patients immediately with both serum creatinine-based estimated GFR (eGFRcr) and urine albumin-to-creatinine ratio (UACR) on a random spot urine sample. 1 This dual testing approach is essential because CKD can present with either reduced kidney function or kidney damage markers, and both provide independent prognostic information. 2
Who to Screen
Target the following high-risk populations for CKD screening: 1, 3, 4
- Diabetes mellitus (any type) - screen immediately at diagnosis for type 2 diabetes 2
- Hypertension - present in approximately 70% of individuals with elevated creatinine 2
- Age >60 years - prevalence increases substantially with advancing age 2
- Family history of chronic kidney disease - significantly increases risk 2, 3
- Cardiovascular disease - strong association with CKD 5
- Obesity - independent risk factor 2
- Racial/ethnic minorities (African American, Hispanic, Asian/Pacific Islander, American Indian) 1
Diagnostic Criteria
CKD is diagnosed when either eGFR <60 mL/min/1.73 m² OR UACR ≥30 mg/g persists for at least 3 months. 1, 2 Do not rely on a single abnormal measurement, as this could represent acute kidney injury rather than chronic disease. 1
Confirming Chronicity (≥3 months duration)
Establish chronicity through any of the following: 1
- Review of past eGFR measurements showing persistent reduction
- Review of past albuminuria or proteinuria measurements
- Imaging findings: reduced kidney size, decreased cortical thickness, or loss of corticomedullary differentiation
- Kidney biopsy showing fibrosis and atrophy
- Medical history of conditions known to cause CKD (diabetes, hypertension, glomerulonephritis)
- Repeat measurements within and beyond the 3-month timepoint
Critical pitfall: Never assume chronicity from a single abnormal eGFR or UACR value - always repeat testing to exclude acute kidney injury or acute kidney disease. 1
Laboratory Assessment Methods
GFR Estimation
Use serum creatinine with the CKD-EPI equation for initial eGFR calculation - never rely on serum creatinine concentration alone. 1 The creatinine assay must be traceable to isotope dilution mass spectrometry (IDMS) methodology. 6
When eGFRcr is less accurate or when GFR critically affects clinical decisions, measure cystatin C and calculate eGFRcr-cys (combined creatinine-cystatin C equation). 1 This is particularly important in: 1, 7
- Extremes of muscle mass (very high or very low)
- Extremes of body size
- Severe malnutrition or obesity
- Diseases of skeletal muscle
- Paraplegia or quadriplegia
- Vegetarian diet
- Rapidly changing kidney function
For the highest accuracy when treatment decisions depend on precise GFR measurement, use measured GFR (mGFR) with exogenous filtration markers such as iohexol or iothalamate clearance. 1, 7
Albuminuria Assessment
Measure UACR on a random spot urine sample - this has replaced 24-hour urine collections for routine screening. 1, 3 UACR has greater sensitivity for detecting low levels of proteinuria compared to protein-to-creatinine ratio (PCR). 8
UACR categories: 1
- A1: <30 mg/g (normal to mildly increased)
- A2: 30-300 mg/g (moderately increased)
- A3: >300 mg/g (severely increased)
Following initial detection of elevated UACR, repeat testing to confirm persistence before diagnosing CKD. 1
Staging CKD
Stage CKD using both GFR categories (G1-G5) and albuminuria categories (A1-A3) to determine prognosis and guide management intensity. 1, 8
GFR categories: 1
- G1: ≥90 mL/min/1.73 m² (with kidney damage markers)
- G2: 60-89 mL/min/1.73 m² (with kidney damage markers)
- G3a: 45-59 mL/min/1.73 m²
- G3b: 30-44 mL/min/1.73 m²
- G4: 15-29 mL/min/1.73 m²
- G5: <15 mL/min/1.73 m² (kidney failure)
The combination of GFR and albuminuria categories determines risk stratification: higher albuminuria and lower GFR indicate progressively higher risk for CKD progression, cardiovascular events, and mortality. 1, 2
Determining the Cause
Systematically evaluate the underlying etiology using clinical context, personal and family history, social and environmental factors, medications, physical examination, laboratory measures, imaging, and when appropriate, kidney biopsy. 1
Key Etiologic Considerations
Diabetes - the leading cause of CKD and end-stage kidney disease in the United States, accounting for 30-40% of cases. 2 Diabetic kidney disease typically presents with normal-sized kidneys despite progressive dysfunction. 2
Hypertension - both a cause and consequence of CKD, present in approximately 70% of patients with elevated creatinine. 2 Uncontrolled hypertension accelerates GFR decline at rates of 4-8 mL/min/year. 2
Glomerulonephritis - consider when hematuria, active urine sediment, or rapidly progressive kidney dysfunction is present. 1
Nephrotoxin exposure - review medications (NSAIDs, lithium, calcineurin inhibitors, aminoglycosides) and environmental exposures (heavy metals, agrochemicals). 2
Additional Diagnostic Testing
Obtain the following baseline tests for all newly diagnosed CKD patients: 1, 8
- Complete metabolic panel (electrolytes, bicarbonate, calcium, phosphate)
- Complete blood count (screen for anemia)
- Lipid panel
- Hemoglobin A1c (if diabetes suspected or present)
- Urinalysis with microscopy
- Renal ultrasound (for patients at increased risk or with unclear etiology)
For CKD stage G3b or higher (eGFR <45 mL/min/1.73 m²), add: 2
- Intact parathyroid hormone (PTH)
- 25-hydroxyvitamin D
- Iron studies
Consider kidney biopsy when: 1
- Etiology is uncertain despite thorough evaluation
- Atypical features suggest non-diabetic kidney disease in diabetic patients (up to 30% have alternative diagnoses on biopsy) 2
- Rapidly progressive kidney function decline
- Active urine sediment with glomerular hematuria
- Results would change management decisions
Monitoring Frequency
Tailor monitoring intensity to risk stratification based on combined GFR and albuminuria categories: 2
- Low risk (G1-G2 with A1): Annual monitoring
- Moderate risk (G3a with A1, or G1-G2 with A2): Every 6 months
- High risk (G3b with A1, G3a with A2, or any stage with A3): Every 3-4 months
- Very high risk (G4-G5 or rapidly declining function): Monthly to quarterly with nephrology co-management
Nephrology Referral Indications
Refer to nephrology when any of the following are present: 2, 4
- eGFR <30 mL/min/1.73 m² (stage G4-G5)
- UACR >300 mg/g with or without reduced eGFR
- Rapidly declining eGFR (>5 mL/min/1.73 m² per year)
- Continuously increasing albuminuria despite optimal management
- Uncertainty about etiology or atypical features
- Difficulty managing CKD complications (anemia, mineral bone disorder, metabolic acidosis, resistant hypertension)
- Acute kidney injury superimposed on CKD
- Hereditary kidney disease suspected
Common Pitfalls to Avoid
Never use serum creatinine alone - always calculate eGFR using validated equations. 1, 7, 2 Serum creatinine can remain within normal range until 50% of kidney function is lost. 3
Do not skip albuminuria testing - eGFR and UACR provide independent prognostic information and both are required for complete CKD assessment. 2
Do not assume normal-sized kidneys exclude CKD - diabetic kidney disease, minimal change disease, and early-stage focal segmental glomerulosclerosis commonly present with preserved kidney size. 2
Avoid discontinuing ACE inhibitors or ARBs for minor creatinine increases (<30%) in the absence of volume depletion or hyperkalemia. 2
Never combine ACE inhibitors with ARBs - this increases adverse events without additional benefit. 2
Consider initiation of CKD-specific treatments at first presentation if CKD is deemed likely based on clinical indicators, even before 3-month chronicity is confirmed. 1 Early intervention with SGLT2 inhibitors, RAS blockade, and blood pressure control can slow progression and reduce cardiovascular events. 1