Rare Case of C3 Glomerulopathy in Castleman Disease

Introduction: Castleman’s disease (CD) is an uncommon lymphoproliferative disorder characterized by focal or generalized lymphadenopathy. Renal injuries are related to glomerular pathologies including AA amyloidosis, TMA and MPGN. Case Description: We report a 66 year old male with multi-centric HHV-associated CD, HIV on HAART, CKD 3A who presented to the hospital with fatigue and chills for several weeks. Physical exam was pertinent for abdominal distension and 1-2+ lower extremity edema. Admission labs were notable for anemia with hemoglobin 6.6g/dL, platelets 66, LDH 287 Units/L, Haptoglobin 124 mg/dL, rare schistocytes on peripheral smear and an AKI with Creatinine 2.17 mg/dL from prior baseline of 1.4 mg/dL and potasium 5.0 mmol/L. Urinalysis showed 1+ protein, 3+ blood, >50 RBC and RBC casts. 24-hour urine protein was 398 mg/g. Serological workup showed mildly positive ANA (1:80), dsDNA, anti-GBM antibodies, ANCA and complements (C3 and C4) were normal. UPEP largely unremarkable and SPEP showed abnormal restricted peak in gamma region and polyconal increase in gamma globulins. FLC ratio was 1.33. Viral serologies were reactive for Hep A, Hep B core IgG and IgM. HIV RNA was <20. Renal ultrasound showed nephromegaly – 15 cms, stable echogenic focus on right kidney and no hydronephrosis. Due to progressive renal dysfunction, renal replacement therapy was initiated. Renal biopsy showed membranoproliferative pattern (MPGN) of glomerular injury, IF showed C3 (3+) staining in mesangium and capillary loops and was negative for IgG, IgA, IgM. Kappa and lambda light chains show similar staining throughout. IF was checked on paraffin after protease digestion and was negative for immunoglobulins. The diagnosis was consistent with C3 glomerulopathy. Patient was initiated on IV Solu-Medrol and transitioned to Prednisone (1mg/kg/day) per Hematology due to CD-related bicytopenia. Patient was discharged on maintenance dialysis, noted to have renal recovery within a week with 24 hour creatinine clearance of 60 ml/min and dialysis was discontinued. Discussion: To our knowledge, this is the first reported case of C3 glomerulopathy in CD, Our patient had complete renal recovery with steroid monotherapy. MMF and Cytoxan are other alternatives that could be considered in C3 glomerulopathy patients.