What is the diagnostic approach and treatment plan for a patient suspected of having Chronic Kidney Disease (CKD), particularly those with risk factors such as diabetes, hypertension, and family history of kidney disease?

Diagnosis of Chronic Kidney Disease

CKD is diagnosed when either eGFR <60 mL/min/1.73 m² or albuminuria ≥30 mg/g persists for at least 3 months, confirmed by repeat testing. 1, 2

Diagnostic Criteria

Both serum creatinine (to calculate eGFR) and urine albumin-to-creatinine ratio (ACR) must be measured—testing only one parameter is insufficient for comprehensive CKD diagnosis. 1, 3, 2

• CKD requires either decreased kidney function (eGFR <60 mL/min/1.73 m²) OR evidence of kidney damage (primarily albuminuria ≥30 mg/g) present for >3 months 2
• The 3-month duration requirement distinguishes CKD from acute kidney injury 2
• Following incidental detection of elevated ACR, hematuria, or low eGFR, repeat tests to confirm CKD presence 1, 2

Initial Laboratory Testing

Essential Tests for All Suspected CKD Patients

• Serum creatinine with eGFR calculation using the 2021 race-free CKD-EPI equation 1, 3, 2
• Spot urine albumin-to-creatinine ratio (first morning specimen preferred): normal ≤30 mg/g, microalbuminuria 30-300 mg/g, macroalbuminuria >300 mg/g 3
• Confirm persistent albuminuria by repeating in 2 of 3 samples if initial values are elevated 3

Additional Baseline Tests

• Complete blood count with differential to assess for anemia (hemoglobin <13.5 g/dL in males defines anemia in CKD) 3
• Comprehensive metabolic panel including electrolytes, calcium, phosphorus, bicarbonate 2, 4
• Urinalysis with microscopy to evaluate for casts, cells, and crystals 2, 4
• Serum ferritin and transferrin saturation (TSAT): ferritin <25 ng/mL indicates absolute iron deficiency, TSAT <20% suggests inadequate iron availability 3

Confirming Chronicity (≥3 Months Duration)

Proof of chronicity can be established by: 1, 2

• Review of past GFR measurements or serum creatinine levels 1
• Review of past albuminuria/proteinuria measurements and urine microscopy 1
• Imaging findings such as reduced kidney size (<9 cm in adults is definitely abnormal) and cortical thinning 1
• Kidney biopsy showing fibrosis and atrophy 1
• Medical history of conditions known to cause CKD (diabetes >5 years, longstanding hypertension) 1
• Repeat measurements within and beyond the 3-month point 1

Do not assume chronicity based on a single abnormal eGFR and ACR, as this could represent acute kidney injury or acute kidney disease. 1

CKD Staging System

GFR Categories 1, 2

• G1: ≥90 mL/min/1.73 m² (normal or high, with other evidence of 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 1, 2

• A1: <30 mg/g (normal to mildly increased)
• A2: 30-300 mg/g (moderately increased)
• A3: >300 mg/g (severely increased, including nephrotic syndrome >2200 mg/24h)

Determining CKD Cause

History and Risk Factor Assessment 1, 2

• Diabetes mellitus (screen Type 1 diabetes patients 5 years after diagnosis; Type 2 at diagnosis) 1, 2
• Hypertension (present in 91% of CKD patients) 1
• Family history focusing on kidney disease, dialysis, transplantation, early-onset hypertension, cerebral aneurysms, liver cysts (to evaluate for autosomal dominant polycystic kidney disease) 3
• Age >60 years, cardiovascular disease, obesity 1, 5
• US ethnic minority status: African American, American Indian, Hispanic, Asian or Pacific Islander 1
• Medication history particularly nephrotoxins (NSAIDs, certain antibiotics, contrast agents) 2, 6

Additional Diagnostic Tests Based on Clinical Context 2

• Serologic testing for autoimmune diseases (ANA, ANCA, anti-GBM antibodies)
• Complement levels (C3, C4)
• Hepatitis B/C and HIV serology
• Serum and urine protein electrophoresis (if multiple myeloma suspected)

Imaging Studies

Renal Ultrasound 1, 3, 2

• Differentiates acute kidney injury from CKD by determining renal size and cortical thickness 1
• Renal length <9 cm in adults is definitely abnormal 1
• Normal-sized kidneys do not exclude CKD—renal size is initially preserved in diabetic nephropathy and infiltrative disorders 1
• Increased echogenicity is a nonspecific finding present in only 10.3% of CKD patients 1
• Ultrasound has minimal impact on diagnosis and management in CKD patients with diabetes or hypertension 1

When Ultrasound Is Indicated 1

• Prior history of stones or obstruction
• Suspected renal artery stenosis
• Frequent urinary tract infections
• Family history of autosomal dominant polycystic kidney disease
• Evaluation of "a couple of cysts" requires distinguishing simple cysts from early ADPKD 3

Cardiovascular Assessment

• 12-lead ECG is mandatory for all hypertensive CKD patients to assess for left ventricular hypertrophy and arrhythmias 3
• Blood pressure measurement (office and home monitoring) as hypertension is both cause and consequence of CKD 3

Monitoring Frequency After CKD Diagnosis

Based on GFR Stage 1, 3

• GFR 45-60 (Stage 3a): Monitor eGFR and ACR every 6 months; electrolytes, bicarbonate, hemoglobin, calcium, phosphorus, PTH at least yearly 1, 3
• GFR 30-44 (Stage 3b): Monitor eGFR every 3 months; electrolytes, bicarbonate, calcium, phosphorus, PTH, hemoglobin, albumin every 3-6 months 1, 3
• GFR <30 (Stage 4-5): Monitor every 3 months or more frequently; refer to nephrologist 1, 3
• All confirmed CKD patients: Annual monitoring minimum 3

Nephrology Referral Criteria

Refer to nephrologist when: 1, 2, 7

• eGFR <30 mL/min/1.73 m² (Stage 4 CKD or worse)
• Persistent urine ACR >300 mg/g or protein-to-creatinine ratio >500 mg/g
• Rapid decline in kidney function (eGFR decline >5 mL/min/1.73 m² per year)
• Uncertainty about CKD etiology (heavy proteinuria, active urine sediment, absence of diabetic retinopathy in diabetic patients, duration of Type 1 diabetes <10 years with albuminuria)
• Difficult management issues (anemia, secondary hyperparathyroidism, metabolic bone disease, resistant hypertension, electrolyte disturbances)

Screening Recommendations

Who to Screen 1, 5

Screen adults with risk factors including diabetes, hypertension, cardiovascular disease, family history of kidney disease, age >60 years, obesity 1, 5

• The U.S. Preventive Services Task Force found insufficient evidence for screening asymptomatic adults without risk factors 1
• The American College of Physicians recommends against screening asymptomatic adults without diabetes or hypertension 1
• However, screening adults with diabetes and hypertension for CKD is now considered cost-effective with availability of SGLT2 inhibitors 1

Screening Frequency 2, 7

• At least annual screening with serum creatinine, urine ACR, and urinalysis for patients with diabetes, hypertension, or cardiovascular disease 7

Enhanced GFR Assessment When Needed

If eGFR based on creatinine is potentially inaccurate (extremes of muscle mass, malnutrition, cirrhosis), measure cystatin C and calculate eGFRcr-cys (combined creatinine-cystatin C equation) for more accurate assessment. 1, 4