When the Hoof Beats Don't Sound Right: A Case of Renal Amyloidosis in a Patient with Newly Diagnosed Type 1 Diabetes

Introduction: Proteinuria is a common manifestation in patients (pts) with longstanding diabetes mellitus (DM) and is often attributed to diabetic kidney disease (DKD). However, not all proteinuria in DM pts is due to DKD, and failure to consider alternative diagnoses may lead to missed opportunities for intervention. This case underscores the importance of the temporal relationship between the onset of DM and development of proteinuria. We present a patient with presumed DKD who was found to have renal amyloidosis due to multiple myeloma (MM). Case Description: A 59-year-old male with a two-year history of type 1 DM without microvascular complications presented to the nephrology clinic for proteinuria. His serum creatinine (Cr) had increased from 1.3 mg/dL to 3.5 mg/dL, and the urine albumin to creatinine ratio was 529 mcg/kg. Further evaluation was done with a urine protein creatinine ratio (UPCR) of 5.0 g, serum lambda free light chain (FLC) of 3999.3 mg/L, and kappa FLC of 19.1 mg/L. Kidney biopsy showed positive Congo red-positive staining of mesangial areas on light microscopy, +1 lambda LC staining of the mesangium, and randomly arranged fibrils measuring 9-12 nm on electron microscopy, consistent with lambda LC renal amyloidosis. With MM therapy and stem cell transplant, Cr decreased to 2.0 mg/dL & UPCR to 0.1 g. Discussion: DKD remains the most common cause of CKD and proteinuria in pts with type 1 DM. However, it should not preclude a thorough evaluation for alternative causes of kidney disease. In this case, the onset of proteinuria shortly after the diagnosis of DM raised suspicion. Renal amyloidosis is a rare but important consideration in pts with nephrotic-range proteinuria. Clues such as rapid progression of proteinuria, absence of retinopathy and systemic symptoms should prompt consideration of a non-diabetic etiology. A key diagnostic point in this case was the recognition that the timeline of kidney disease did not align with typical DKD, which ultimately led to the correct diagnosis. This highlights the cognitive bias of diagnostic anchoring, where early assumptions based on a pt’s known conditions can lead to premature closure of the differential diagnosis. A thorough and critical review of the pt’s history, particularly the sequence of events, remains one of the most powerful diagnostic tools for nephrologists.