An Observational Study on Thrombotic Microangiopathy in Renal Transplant Recipients - A Tertiary Care Centre Experience. Dr Sarang Vijayan Senior Resident Department of Nephrology Nizams Institute of Medical Sciences

Introduction Thrombotic microangiopathy (TMA) is a well documented, but rare and serious complication of kidney transplantation. It can be the histological manifestation of many etiological factors; mainly associated with Calcineurin inhibitor (CNI) toxicity and Antibody mediated rejection (AMR). Rarely it can be a manifestation of recurrence of disease or associated with viral infections. TMA in post transplant patients have varied clinical course and outcome, but usually associated with poor prognosis.

Aim of the study To study the clinical profile, etiology and immediate as well as long term outcome of patients with biopsy proven Thrombotic microangiopathy in transplanted kidneys.

Materials and methods All post-transplant patients presented with acute graft dysfunction having biopsy proven Thrombotic microangiopathy in last three years were included. Those patient’s baseline characteristics including native kidney disease, induction given, maintenance immunosuppression and donor details were analyzed. The episode of TMA which led to acute graft dysfunction was evaluated in detail and patient was followed up and outcomes assessed.

Baseline Characteristics Total cases (TMA) Total transplants percentage All transplants 10 145 6.9 Live transplant 9 89 10.2 Deceased donor transplant 1 57 1.85

Membranous nephropathy Gender No of cases Male 9 Female 1 NKD No of Cases IgAN 2 Membranous nephropathy 1 FSGS Presumed CGN 4 Presumed CIN Onset of TMA No of Cases <7 days 4 7 days – 1 month nil 1 month – 6 months > 6 months 2

Baseline characteristics parameters Mean SD Min Max Age (years) 29.4 14.6 18 45 Duration (months) 13.4 24.6 2 Days 76 Months Serum creatinine (mg/dl) 3.71 2.6 2.3 6.5 Hemoglobin (g/dl) 9.7 2.9 7.4 12.1 Platelet count 1.38 0.86 0.6 2.1 Baseline characteristics

Donor Characteristics DONOR AGE – MEAN -45.5 < 30Y -NIL 30-39 -2 40-49 -5 50-59 -3 >60 –NIL MEAN S CREATININE 0.84 ± 0.4 DONOR GFR MEAN GFR – 89.6 ± 44 ≥ 90 -4 81 -90 -1 71 -80 - 5 AGE GROUP NO <30 NIL 30-39 2 40-49 5 50-59 3 >60 GFR NO ≥ 90 4 81-90 1 71-80 5

TMA - Etiology

DIAGN0SIS OCCURENCE TAC LEVELS IV MP PE IV IG RITUX ATG TAC STOP/ REDUCE CASE 1 TAC TOXICITY 6 M 6.84 YES 3 NO STOPPED CASE 2 ?RECCURRENC POD3 12.94 5 50 DECREASED CASE 3 AMR 3M 7.83 75 500 SAME CASE 4 POD6 7.19 4 20 INCREASED CASE 5 6M 7.9 CASE 6 37 M CASE 7 5M 8.11 CASE 8 POD2 CASE 9 TAC TOXICITY 76M CASE 10 COMBINED REJECTION 8 125 150

Immediate Outcome

Final Outcome

MILD GRAFT DYSFUNCTION CASE DIAGNOSIS FINAL OUTCOME TIME INTERVAL TX (MONTHS) TIME INTERVAL TMA (MONTHS) CASE 1 TAC TOXICITY MILD GRAFT DYSFUNCTION 26 21 CASE 2 ?RECCURRENCE GRAFT AND PATIENT LOSS 3 CASE 3 AMR 4 <1 CASE 4 NORMAL GRAFT FUNCTION 24 CASE 5 GRAFT LOSS 9 1 CASE 6 39 CASE 7 8 CASE 8 CASE 9 TAC TOXICITY 92 16 CASE 10 COMBINED REJECTION

Discussion The incidence of TMA in our study was 6.9% (10 out of 145). Other studies have also showed similar incidence ranging from 4 -14%.1,2 Most common cause of post transplant TMA identified was CNI toxicity which is the same in most recent studies.3 Thrombotic microangiopathy was more common in Live related renal transplant than deceased donor transplant unlike other studies which showed more risk in DDRT. 4 TMA in post renal transplant has poor prognosis with 70% of patients ended up in graft loss in long term.

Post renal transplant TMA ACUTE CNI TOXICITY ACUTE ABMR Recent initiation/increase in dose of CNI Predominant tubular abnormalities, mainly prominent vacuolations. Eccentric vascular hyalinosis C4d negative DSA negative Recent decrease in immunosuppression Extensive arteritis usually involving entire vascular tree Associated glomerulitis and/or peritubular capillaritis C4d positive DSA positive

References Radha S, Tameem A, Sridhar G, Aiyangar A, Rajaram KG, Prasad R, et al. Thrombotic microangiopathy in renal allografts. Indian journal of nephrology 2014;24(1). Karthikeyan V, Parasuraman R. Outcome of Plasma Exchange Therapy in Thrombotic Microangiopathy After Renal Transplantation. American Journal of Transplantation 2003; 3: 1289–1294 Ardalan MR. Review of Thrombotic Microangiopathy (TMA), and Post- Renal Transplant TMA. Saudi J Kidney Dis Transpl 2006;17:235-44 Young BA, Marsh CL, Alpers CE, Davis CL. Cyclosporine-Associated Thrombotic Microangiopathy/Hemolytic Uremic Syndrome Following Kidney and Kidney-Pancreas Transplantation. American journal of kidney diseases,1996;561–71.