Concurrent Renal-Limited Thrombotic Microangiopathy and Suspected Crystal Globulin Nephropathy: An Unusual Manifestation of Multiple Myeloma

Introduction: Renal involvement occurs in 20-50% of multiple myeloma (MM) patients. While cast nephropathy predominates, thrombotic microangiopathy (TMA) and crystal globulin nephropathy (CGN) represent rare manifestations, with concurrent presentation posing significant diagnostic and therapeutic challenges. Case Description: A 70-year-old Hispanic female with diabetes, hypertension, and CKD-3 presented with pathological fractures, extensive lytic lesions, acute kidney injury, significant proteinuria (4.5g/24h with 2.8 grams of albuminuria). Laboratory evaluation revealed IgG kappa monoclonal gammopathy with markedly elevated kappa-lambda ratio (54.7), confirming R-ISS stage III MM. Progressive azotemia necessitated hemodialysis initiation. Renal biopsy demonstrated renal-limited TMA, advanced diabetic nephropathy, acute tubular injury, and 50% interstitial fibrosis with tubular atrophy. Focal intraluminal eosinophilic, fuchsinophilic, weakly PAS-positive fibrillar material suggested concurrent CGN. Normal complement studies and negative Congo Red staining excluded complement-mediated disease and amyloidosis. Treatment included empiric eculizumab (discontinued after genetic analysis excluded complement-mediated disease) and CyBorD (cyclophosphamide, bortezomib, dexamethasone) plus daratumumab. This regimen yielded partial renal recovery with dialysis independence and partial hematologic response (kappa-lambda ratio reduction to 12 and proteinuria decreased to 2.26g). Discussion: This case illustrates the importance of comprehensive renal evaluation in MM patients with AKI. The unusual concurrence of renal-limited TMA and suspected CGN as the initial manifestations of MM underscores the necessity for early renal biopsy for definitive diagnosis, therapeutic guidance, and prognostic assessment.TMA(image 1) Arrow is pointing to deposit concerning for CGN(image 2)