What are the causes of chronic kidney disease when the kidneys are normal-sized on ultrasound?

Chronic Kidney Disease with Preserved Kidney Size: Causes

Diabetic kidney disease is the most common cause of CKD with normal-sized kidneys, as both renal size and parenchymal thickness remain preserved until end-stage renal failure, unlike most other chronic kidney diseases that lead to atrophy and shrinkage. 1, 2

Primary Causes Maintaining Normal Kidney Size

Diabetic Nephropathy (Most Common)

• Diabetic kidney disease uniquely preserves kidney size throughout disease progression, distinguishing it from virtually all other chronic kidney diseases that cause atrophy 1, 2, 3
• This occurs in both type 1 diabetes (typically after 10 years) and type 2 diabetes (may be present at diagnosis) 1
• Accounts for 30-40% of CKD cases in developed countries 1
• Up to 30% of patients with presumed diabetic kidney disease have other causes on biopsy, making kidney biopsy necessary when atypical features are present 1

Infiltrative and Inflammatory Disorders

• Infiltrative diseases maintain kidney size while reducing function 1, 4
• These include amyloidosis, sarcoidosis, and lymphoma 3
• Normal kidney size does not exclude advanced CKD in these conditions 1, 4

Primary Glomerular Diseases (Early Stages)

• Minimal change disease causes significant proteinuria with normal kidney morphology 1
• Primary focal segmental glomerulosclerosis (FSGS) maintains normal size in early stages 1
• IgA nephropathy and membranous nephropathy are less likely to show sonographic abnormalities 5
• Proliferative glomerulonephritis may show enlarged kidneys initially before eventual atrophy 5

Polycystic Kidney Disease (Early Stages)

• Early autosomal dominant polycystic kidney disease can present with declining function before massive enlargement occurs 1
• Eventually progresses to bilaterally enlarged kidneys with multiple cysts 3, 6

HIV-Associated Nephropathy (HIVAN)

• Can present with normal or enlarged kidneys despite significant dysfunction 3

Diagnostic Approach

Confirm CKD Diagnosis and Chronicity

• CKD requires either eGFR <60 mL/min/1.73 m² OR UACR ≥30 mg/g persisting for at least 3 months 1
• Review historical eGFR/creatinine trends to distinguish from acute kidney injury 1
• If duration unclear, repeat testing in 2-4 weeks 1

Clinical History Red Flags

• Diabetes duration >10 years (type 1) or present at diagnosis (type 2) strongly suggests diabetic nephropathy 1
• Absence of diabetic retinopathy with significant proteinuria suggests non-diabetic kidney disease requiring biopsy 1
• Family history of kidney disease points to genetic disorders (Alport syndrome, thin basement membrane disease, APOL1-related nephropathy) 1
• Systemic symptoms (rash, arthritis, hearing loss) indicate vasculitis or hereditary conditions 1

Essential Laboratory Evaluation

• Measure both eGFR and UACR immediately—both provide independent prognostic information 1
• Hepatitis B and C serologies when infectious etiology considered 1
• Autoimmune workup: complement levels (C3, C4), ANA, ANCA, anti-GBM antibodies for glomerulonephritis 1
• Serum/urine protein electrophoresis with immunofixation and serum free light chains to exclude monoclonal gammopathies 1

Ultrasound Interpretation Pitfalls

• Normal kidney length (≥9 cm) indicates early-stage disease before substantial fibrosis develops but does NOT exclude advanced CKD 1, 4
• Increased echogenicity is nonspecific and present in only 10.3% of CKD patients 7
• Ultrasound has minimal diagnostic impact in diabetic or hypertensive CKD with normal-sized kidneys 7
• Assess corticomedullary differentiation—preservation suggests earlier stage disease 4

Indications for Kidney Biopsy

KDIGO 2024 endorses kidney biopsy when the underlying cause is uncertain or results will influence management 1

Specific Biopsy Indications with Normal-Sized Kidneys:

• Diabetic patients with atypical features: absence of retinopathy, short disease duration, rapid eGFR decline, active urinary sediment, or nephrotic-range proteinuria without retinopathy 1
• Suspicion of primary glomerulonephritis (hematuria with proteinuria, active sediment) 1
• Nephrotic syndrome (UACR >3000 mg/g with hypoalbuminemia and edema) 1
• Rapidly progressive kidney function loss 1
• Persistent diagnostic uncertainty despite comprehensive evaluation 1

Nephrology Referral Criteria

Refer to nephrology when any of the following are present:

• eGFR <30 mL/min/1.73 m² 1
• UACR ≥300 mg/g with ongoing increase despite optimal therapy 1
• eGFR decline >5 mL/min/1.73 m² per year 1
• Unclear etiology or atypical clinical features 1
• Difficulty managing CKD complications (anemia, mineral-bone disorder, resistant hypertension, hyperkalemia) 1
• Consideration of kidney biopsy to clarify diagnosis 1

Common Pitfalls to Avoid

• Never assume normal kidney size excludes significant CKD—diabetic nephropathy and infiltrative disorders are major exceptions 1, 4, 2
• Do not skip albuminuria testing—eGFR and UACR provide independent prognostic information 1
• Do not rely on increased echogenicity alone—it is insensitive (only 10.3% of CKD) and nonspecific 7
• Do not assume all diabetic patients have diabetic nephropathy—30% have other causes on biopsy 1
• Dehydration can cause artifactual ultrasound findings—correct before interpreting 7