A 68-year-old man with known IgG lambda multiple myeloma presents with acute kidney injury (creatinine 4.8 mg/dL, up from 1.4 mg/dL) and nephrotic-range proteinuria. Renal biopsy shows PAS-positive, fractured casts within tubules surrounded by multinucleated giant cells. What is the primary pathogenic mechanism?

• A Deposition of monoclonal immunoglobulin in glomerular basement membrane causing membranous nephropathy
• B Tubulointerstitial inflammation from direct toxicity of filtered light chains on tubular epithelium
• C Renal vein thrombosis due to hypercoagulability from paraprotein
• D Intratubular obstruction by casts formed from monoclonal light chains complexed with Tamm-Horsfall protein ✓

Explanation

This describes light chain cast nephropathy (myeloma kidney). Filtered monoclonal light chains (usually kappa) bind Tamm-Horsfall protein in the distal tubule, forming obstructive casts with associated giant cell reaction. Rapid reduction of free light chains is key. Option A describes AL amyloidosis or light chain deposition disease, which present with nephrotic syndrome but different histology. Direct tubular toxicity is a separate mechanism.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.