Can Chronic Kidney Disease (CKD) have normal corticomedullary differentiation?

Can CKD Have Normal Corticomedullary Differentiation?

Yes, CKD can absolutely present with normal corticomedullary differentiation (CMD), particularly in early stages (Stages 1 and 2) and in specific disease etiologies such as diabetic kidney disease, even with advanced dysfunction. 1, 2

Early-Stage CKD with Preserved CMD

• Stages 1 and 2 CKD routinely maintain normal CMD because these stages are defined by the presence of kidney damage (proteinuria, structural changes, or imaging abnormalities) with normal or only mildly decreased GFR (≥60 mL/min/1.73 m²), meaning structural architecture remains largely intact. 1

• Patients in Stage 1 have GFR ≥90 mL/min/1.73 m² with evidence of kidney damage, while Stage 2 patients have GFR 60-89 mL/min/1.73 m², both of which can show preserved CMD on imaging. 1

Specific Etiologies with Preserved CMD Despite CKD

Diabetic kidney disease is the most important cause of CKD that maintains normal kidney size and CMD despite progressive dysfunction, accounting for 30-40% of CKD cases and being the leading cause of end-stage kidney disease in the United States. 2

• Diabetic nephropathy typically presents with normal-sized kidneys and preserved CMD, particularly in type 2 diabetes where kidney size is initially maintained despite declining function. 2

• Ultrasound findings of normal-sized kidneys with preserved CMD do not exclude CKD, particularly in diabetic nephropathy and infiltrative disorders. 2

Other causes that can maintain normal CMD include:

• Minimal change disease can cause significant proteinuria and kidney dysfunction while maintaining normal kidney morphology on imaging. 2
• Primary focal segmental glomerulosclerosis (FSGS) can cause progressive CKD with normal-sized kidneys and CMD, especially in early stages. 2
• Early polycystic kidney disease can show kidney function decline with relatively normal-appearing kidneys. 2
• Infiltrative disorders can maintain kidney size and CMD while reducing function. 2

Relationship Between Serum Creatinine and CMD Loss

Research demonstrates a clear threshold effect for CMD loss based on severity of renal dysfunction:

• Serum creatinine levels above 3.0 mg/dL (265 μmol/L) result in loss of CMD on unenhanced T1-weighted MRI, independent of the cause of elevated creatinine. 3

• Patients with mildly elevated creatinine (1.5-2.9 mg/dL) show variable CMD preservation—approximately 50% maintain CMD on unenhanced imaging, while all maintain CMD on gadolinium-enhanced imaging. 3

• Serum creatinine levels above 10.0 mg/dL (884 μmol/L) result in loss of CMD even on gadolinium-enhanced imaging, representing severe advanced CKD. 3

Critical Clinical Pitfalls

The most dangerous pitfall is assuming that normal CMD on imaging excludes CKD or indicates preserved kidney function. This is particularly problematic in diabetic patients where:

• Up to 30% of patients with diabetic kidney disease have other causes of CKD on kidney biopsy, requiring tissue diagnosis when clinical presentation is atypical. 2

• Kidney biopsy may be necessary to definitively diagnose the cause of CKD when kidneys appear normal on imaging, as imaging alone cannot distinguish between various etiologies. 2

Do not rely on imaging alone for CKD diagnosis or staging—the diagnosis requires:

• Persistent albuminuria (UACR >30 mg/g) for at least 3 months, OR 2, 4
• eGFR <60 mL/min/1.73 m² for at least 3 months, regardless of kidney size or CMD appearance 2, 4

Diagnostic Algorithm

When evaluating a patient with suspected CKD:

1. Measure both eGFR and UACR at baseline, as CKD can be diagnosed by either abnormality regardless of imaging findings. 1, 2

2. Repeat testing to confirm persistence for at least 3 months before making a definitive CKD diagnosis, avoiding testing during urinary tract infections which cause false-positive proteinuria. 4

3. **Consider nephrology referral when eGFR <30 mL/min/1.73 m²** or with significant albuminuria (ACR >300 mg/g), even if imaging shows normal CMD. 4

4. In diabetic patients with normal CMD but declining eGFR or increasing albuminuria, maintain high suspicion for diabetic kidney disease and optimize blood pressure control and consider SGLT2 inhibitors to reduce CKD progression. 2