Acute on Chronic Thrombotic Microangiopathy with Evidence of Dense Deposit Disease

Introduction: A 66-year-old Asian male with a background of Raynaud’s disease, dyslipidemia, and hypertension presented with abdominal pain, haematuria, and acute kidney injury (AKI) on chronic kidney disease (CKD). Urine dip revealed +3 proteinuria and +4 haematuria. His history included digital gangrene (2020), treated with Iloprost. Urology investigations were unremarkable. Case Description: Initial exam showed fatigue, shortness of breath, BP 220/110, and bilateral leg edema. Blood tests showed creatinine 354 (eGFR 15), low albumin (20), Hb 69, elevated CRP (74), and LDH (295). Immunology showed low IgG/IgM, presence of IgG lambda paraprotein, but negative ANA, ANCA, anti-GBM, and antiphospholipid antibodies. C3 and C4 were normal. A kidney biopsy revealed mesangiolysis, GBM reduplication, crescent formation, and fibrin deposits—features suggestive of thrombotic microangiopathy (TMA). Anti–Factor H antibody was detected. Diagnosis: paraprotein-driven C3 glomerulopathy (C3G) with overlapping atypical HUS (aHUS). Treatment included Bortezomib (6 cycles) for paraproteinemia and Eculizumab 1.2g biweekly. After 3 months, creatinine improved to 160 then rose to 250, while proteinuria decreased (uPCR from 990 to 129). However, LDH remained elevated, raising concerns about persistent TMA or insufficient treatment of dense deposit disease (DDD). Complement pathways were markedly suppressed. Management involved increasing Eculizumab to 1.5g biweekly and repeating relevant markers and biopsy was considered. After 7 months, the patient improved clinically: no SOB or edema, BP 154/80, stable renal function (creatinine 145, eGFR 43), significantly reduced proteinuria (uPCR 57.2), and normalization of C3/C4. Anti-FH antibodies were no longer detected. Serum immunoglobulins remained low. Kappa/lambda ratio mildly elevated (1.72). Discussion: Was aHUS driven by paraproteinemia or vice versa? Should autologous bone marrow transplant be considered if paraprotein rises? Duration of Eculizumab treatment remains unclear. Ongoing uncertainty between DDD and aHUS as primary pathology.