A Watch-and-Wait Can Turn Nephrotoxic: A Case of Chronic Lymphocytic Leukemia-Associated Granulomatous Acute Interstitial Nephritis

Introduction: Chronic lymphocytic leukemia (CLL) infiltrates the kidneys in up to 90% of autopsies but rarely causes end-stage renal disease. Granulomatous acute interstitial nephritis (AIN) is uncommon, seen in only 0.5–0.9% of biopsies. CLL-related renal dysfunction may result from diverse mechanisms including acute tubular necrosis, leukemic infiltration, and cryoglobulinemia. We present a case of progressive renal failure in newly diagnosed CLL, with biopsy revealing granulomatous AIN and mesangial IgA deposits. Case Description: A 66-year-old male with hypertension and hyperlipidemia presented with acute renal insufficiency (Cr 3.4; baseline 0.92), anemia, and leukocytosis. Renal ultrasound revealed left hydronephrosis. Serum protein electrophoresis revealed an M spike and low IgG kappa on immunofixation (kappa/lambda (K/L) ratio 3.24); urine protein electrophoresis was negative for Bence Jones protein. Kidney biopsy showed granulomatous AIN with mesangial IgA deposits—findings consistent with granulomatous AIN and likely incidental IgA nephropathy, given previously normal renal function. Bone marrow biopsy confirmed CLL in a hypocellular marrow (35% cellularity) with monoclonal B cells on flow cytometry and no excess plasma cells. Next-generation sequencing was unremarkable. Two months later, labs showed K/L ratio of 2.57, M spike of 0.05, and low IgG lambda. Due to worsening renal function, he required temporary hemodialysis, later discontinued after partial improvement. He was started on zanubrutinib and high-dose steroids with some response. Creatinine remained elevated (3.1–3.6) with persistent hypercalcemia. Repeat labs showed a K/L ratio of 1.29 and M spike of 0.17. Discussion: This case highlights an unusual renal manifestation of CLL. While leukemic renal infiltration is typically subclinical, this patient developed acute renal failure with biopsy showing granulomatous AIN and concurrent IgA nephropathy. The absence of leukemic cells in renal tissue suggests an immune-mediated or paraneoplastic mechanism. Unlike previous cases, which often involve direct infiltration, this presentation responded partially to CLL-directed therapy and corticosteroids. The case underscores the importance of recognizing atypical CLL presentations and the diagnostic value of early kidney biopsy in guiding management to potentially prevent irreversible renal injury.