Impact of Kidney Histology and Choice of Treatment on Survival in Patients with Multiple Myeloma

Background: Acute or chronic kidney disease (CKD) affects 20-40% of multiple myeloma (MM) patients. While the negative prognostic effect of kidney involvement is established, the specific impact of different histological patterns remains poorly understood. We aimed to characterize the clinical outcomes associated with distinct kidney histologies in MM patients. Methods: We retrospectively analyzed 193 MM patients who underwent kidney biopsy, comparing outcomes with 62 MM patients without kidney disease. Patients were categorized by histological findings: cast nephropathy (CN, n=120), AL amyloidosis (n=19), monoclonal immunoglobulin deposition disease (MIDD, n=8), and other renal diseases (ORD, n=46). We evaluated kidney function, dialysis requirements, treatment responses, and survival across histological subtypes and treatment modalities (conventional therapy vs. modern agents including proteasome inhibitors, CD38 antibodies, and autologous stem cell transplantation). Results: The CN and MIDD groups had the lowest median eGFR at biopsy (13.0 and 25.5 ml/min/1.73 m 2 , respectively). Nephrotic-range proteinuria (>3.5 g/24h per KDIGO) was observed in the AL amyloidosis group (median 3910 mg/24h). Kidney replacement therapy (KRT) was initiated in 42.5% of patients. The proportion achieving KRT independence was 42.4% in the CN group and 50% in the ORD group, whereas none in the AL amyloidosis or MIDD groups recovered sufficient native kidney function. Modern combination therapy significantly improved renal outcomes, with 100% of patients receiving triple therapy showing renal response. KRT dependency was the strongest predictor of mortality: patients remaining on KRT had significantly shorter survival compared to those never requiring KRT (12.7 vs 56.2 months, p<0.001). The extent of improvement in kidney function did not influence survival; only dialysis status was prognostically relevant. Conclusions: Kidney histology determines distinct clinical trajectories in MM patients, with CN showing potential for dialysis reversibility. Modern combination therapies significantly improve renal outcomes. The requirement for ongoing KRT, was the primary predictor of overall survival.