In a patient with chronic kidney disease who has normal‑sized kidneys on ultrasound, how should I evaluate the underlying cause and manage the condition?

Chronic Kidney Disease with Normal-Sized Kidneys: Evaluation and Management

In a patient with CKD and normal-sized kidneys on ultrasound, you must immediately suspect diabetic kidney disease, infiltrative disorders, or early-stage glomerular disease—and proceed with systematic laboratory evaluation including urinary albumin-to-creatinine ratio (UACR), comprehensive metabolic panel, and serologic testing, as normal kidney size does NOT exclude significant CKD or guide etiology. 1, 2

Why Normal Kidney Size Matters (and Why It Doesn't)

Normal-sized kidneys (≥9 cm in adults) indicate that the disease process is either:

• Relatively early in its course before significant fibrosis and atrophy have occurred 3
• A specific disease that preserves kidney size despite functional decline, most commonly diabetic nephropathy, infiltrative disorders (amyloidosis, lymphoma), minimal change disease, or early focal segmental glomerulosclerosis 1, 4

Critical pitfall: The American College of Radiology explicitly states that normal-sized kidneys with preserved parenchymal thickness do NOT exclude CKD, particularly in diabetic nephropathy and infiltrative disorders. 1, 2 Small kidneys (<9 cm) suggest advanced irreversible disease, but normal size tells you nothing definitive about severity or cause. 3, 5

Algorithmic Approach to Evaluation

Step 1: Confirm CKD Diagnosis and Establish Chronicity

Measure both eGFR and UACR immediately on all patients, as CKD is diagnosed by either abnormality (eGFR <60 mL/min/1.73 m² OR UACR ≥30 mg/g) persisting ≥3 months. 3

Establish chronicity by: 3

• Reviewing past eGFR and creatinine measurements
• Reviewing past urinalysis results for proteinuria or hematuria
• Checking medical history for conditions causing CKD (diabetes, hypertension, glomerulonephritis)
• If duration unclear, repeat testing in 2-4 weeks to distinguish CKD from acute kidney injury 4

Do not assume chronicity from a single abnormal test—this could represent acute kidney injury or acute kidney disease. 3

Step 2: Determine the Underlying Cause

The most common causes of CKD with normal-sized kidneys are: 4

• Diabetic kidney disease (most common, especially type 2 diabetes where kidney size is initially preserved) 1, 4
• Hypertensive nephrosclerosis (particularly with long-standing uncontrolled hypertension) 4
• Glomerular diseases: minimal change disease, primary FSGS, IgA nephropathy 1, 4
• Infiltrative disorders: amyloidosis, light chain deposition disease, lymphoma 1
• Early polycystic kidney disease (before massive cyst expansion) 1

Systematic evaluation includes: 3, 4

Clinical history:

• Duration of diabetes (typically >10 years in type 1, but may be present at diagnosis in type 2) 4
• Hypertension history and control (70% of patients with elevated creatinine have hypertension) 4
• Family history of kidney disease (suggests genetic causes like Alport syndrome, thin basement membrane disease, or APOL1-related disease) 3, 4
• Medication exposure: NSAIDs, lithium, calcineurin inhibitors, aminoglycosides 4
• Systemic symptoms: rash, arthritis, hearing loss (suggests vasculitis or Alport syndrome) 3

Laboratory evaluation: 3, 4

• Urinalysis with microscopy: Look for dysmorphic RBCs, RBC casts (glomerulonephritis), WBCs (interstitial nephritis), or crystals
• UACR quantification: Severely increased albuminuria (≥300 mg/g) strongly suggests diabetic nephropathy or glomerular disease 4
• Complete metabolic panel: Assess for hyperkalemia, metabolic acidosis, hyperphosphatemia 4
• Hemoglobin A1c and fasting glucose (if diabetes suspected) 4
• Hepatitis B and C serologies 3
• Complement levels (C3, C4), ANA, ANCA, anti-GBM antibodies (if glomerulonephritis suspected) 3
• Serum and urine protein electrophoresis with immunofixation, serum-free light chains (to exclude myeloma or monoclonal gammopathy of renal significance) 3

Imaging beyond ultrasound:

• Ultrasound has already been performed and shows normal kidney size
• Measure parenchymal thickness at upper pole, mid-kidney, and lower pole—preserved thickness supports early disease 1
• Assess for hydronephrosis (requires urgent intervention if present) 2
• Check cortical echogenicity—increased echogenicity suggests parenchymal disease but is nonspecific and insensitive (present in only 10.3% of CKD patients) 2, 6
• No routine follow-up ultrasound is needed unless renal function deteriorates, symptoms develop, or obstruction is suspected 2

Step 3: Consider Kidney Biopsy

KDIGO 2024 guidelines suggest kidney biopsy as an acceptable, safe diagnostic test when clinically appropriate to establish cause and guide treatment. 3

Specific indications for biopsy in CKD with normal-sized kidneys: 4

• Diabetic patients with atypical features: Absence of diabetic retinopathy, short diabetes duration (<5 years in type 1), rapidly declining eGFR, active urinary sediment (RBC casts, dysmorphic RBCs), or nephrotic-range proteinuria without retinopathy
• Up to 30% of patients with presumed diabetic kidney disease have other causes on biopsy 4
• Suspected glomerulonephritis (hematuria with proteinuria, active sediment)
• Nephrotic syndrome (UACR >3000 mg/g with hypoalbuminemia and edema)
• Rapidly progressive kidney function decline
• Uncertainty about diagnosis despite thorough evaluation

Step 4: Risk Stratification Using eGFR and UACR

The combination of eGFR and albuminuria determines progression risk and monitoring intensity. 4

Risk categories: 4

• Low risk: eGFR ≥60 with UACR <30 mg/g → Monitor annually
• Moderate risk: eGFR 45-59 with UACR 30-300 mg/g → Monitor 2 times/year
• High risk: eGFR 30-44 with UACR 30-300 mg/g, OR eGFR 45-59 with UACR >300 mg/g → Monitor 3 times/year
• Very high risk: eGFR <30, OR any eGFR with UACR >300 mg/g → Monitor 4 times/year and refer to nephrology

Step 5: Screen for CKD Complications

At eGFR <60 mL/min/1.73 m² (Stage 3), systematically screen for: 4

• Anemia: Complete blood count
• Mineral bone disease: Serum calcium, phosphate, intact PTH, 25-hydroxyvitamin D (PTH begins rising when eGFR falls below 60) 4
• Metabolic acidosis: Serum bicarbonate
• Hyperkalemia: Serum potassium (monitor closely if on ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists) 4
• Cardiovascular risk: Lipid panel, blood pressure monitoring

Management Priorities

Blood Pressure Control

Target BP <130/80 mmHg in all CKD patients. 4

For patients with UACR ≥30 mg/g: Initiate ACE inhibitor or ARB regardless of blood pressure, as these reduce albuminuria and slow CKD progression. 4

For patients with UACR ≥300 mg/g: ACE inhibitor or ARB is mandatory even if BP is normal. 4

Do not combine ACE inhibitors with ARBs—this increases adverse events without additional benefit. 4

Diabetes Management (if applicable)

Optimize glucose control with HbA1c target 6.5-7% (individualize based on hypoglycemia risk). 4

SGLT2 inhibitors are strongly recommended for patients with diabetes and CKD (eGFR ≥20 mL/min/1.73 m²) to reduce CKD progression and cardiovascular events. 4

Cardiovascular Risk Reduction

Initiate statin therapy for all CKD patients, as cardiovascular mortality risk is 5-10 times higher than progression to end-stage kidney disease. 4

Nephrotoxin Avoidance

Avoid NSAIDs, aminoglycosides, and contrast agents when possible. 4, 7

Adjust drug dosing for many antibiotics, oral hypoglycemic agents, and other renally cleared medications. 7

Nephrology Referral Indications

Refer to nephrology when: 3, 4

• eGFR <30 mL/min/1.73 m²
• UACR ≥300 mg/g with continuously increasing albuminuria despite optimal management
• Rapidly declining eGFR (>5 mL/min/1.73 m² per year)
• Uncertainty about etiology or atypical features
• Difficulty managing CKD complications (anemia, mineral bone disease, resistant hypertension, hyperkalemia)
• Consideration of kidney biopsy

Common Pitfalls to Avoid

Do not rely on kidney size alone to determine disease severity or reversibility—normal-sized kidneys can have advanced CKD, particularly in diabetic nephropathy. 1, 2

Do not skip albuminuria testing—eGFR and UACR provide independent prognostic information for cardiovascular events, CKD progression, and mortality. 4

Do not assume diabetic kidney disease without confirming typical features—30% of diabetic patients with CKD have other causes on biopsy. 4

Do not discontinue ACE inhibitors/ARBs for minor creatinine increases (<30%) in the absence of volume depletion. 4

Do not interpret increased renal echogenicity as definitive evidence of CKD—it is present in only 10.3% of CKD patients and is nonspecific. 2