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

KEY POINTS: Kidney involvement in patients with multiple myeloma has many different findings in kidney histology. Persistent dialysis requirement is a major cause of mortality. The rapid initiation of modern myeloma therapy is essential to prevent the need for dialysis and reduce mortality. BACKGROUND: Acute or CKD affects 20%-40% of patients with multiple myeloma (MM). While the negative prognostic effect of kidney involvement is established, the specific effect of different histological patterns remains poorly understood. We aimed to characterize the clinical outcomes associated with distinct kidney histologies in patients with MM. METHODS: We retrospectively analyzed 193 patients with MM who underwent kidney biopsy, comparing outcomes with 62 patients with MM without kidney disease. Patients were categorized by histological findings: cast nephropathy (CN, n =120), lightchain (AL) amyloidosis ( n =19), monoclonal Ig deposition disease (MIDD, n =8), and other renal disease ( n =46). We evaluated kidney function, dialysis requirements, treatment responses, and survival across histological subtypes and treatment modalities (conventional therapy versus 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 per 1.73 m 2 , respectively). Nephrotic-range proteinuria (>3.5 g/24 hours per Kidney Disease Improving Global Outcomes) was observed in the AL amyloidosis group (median 3910 mg/24 hours). KRT was initiated in 42.5% of patients. The proportion achieving KRT independence was 42.4% in the CN group and 50% in the other renal disease 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 with those never requiring KRT (12.7 versus 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 patients with MM, 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.