Immunoglobulin A Deposits In Renal Allografts: A Prospective Longitudinal Single-Center Study

Abstract

Aims and ObjectivesTo describe the prevalence of IgA deposits in renal allografts in a cohort of renal transplant recipients and to analyse their management strategies and histopathology.To assess graft function and proteinuria after 1 year of follow up. Materials and MethodsA Prospective longitudinal follow up study carried out in VPS Lakeshore Hospital and Research Centre, Kochi, Kerala over a period of five years (July 2015 to June 2020). Kidney transplant recipients with allograft biopsies that reported IgA deposits (IgAD) on immunofluorescence were included in the study. Light microscopy and immunofluorescence studies were performed. MEST-C Scoring was done in patients with pathogenic IgA deposits. Treatment strategies included increased baseline steroid dosage, rituximab administration and plasma exchange. Clinical details and management strategies were analysed and patients were followed up for 1 year after diagnosis. Changes in graft function (S. Creatinine) and proteinuria (Urine Protein/Creatinine ratio) was analysed. Clinico-pathological correlation with the MEST-C scores was also done. ResultsOut of 1036 kidney transplants done in the study period, 760 graft biopsies were performed. 64 cases had post transplant deposition of IgA (8%). Mean age was 45±11.25SD years. The study had 51 males and 13 females. Induction immunosuppression comprised of rabbit antithymocyte globulin in 29 (45%) patients and basiliximab in 35 (54%). Maintenance immunosuppression in all comprised of tacrolimus, mycophenolate mofetil and steroids. There were 2 groups: Group A (pathogenic IgAD) and Group B (incidental IgAD). Group A had 46 cases (71.9%), out of which 8 had ‘active’ IgA nephropathy (endocapillary proliferation, crescents and IgA vasculitis), and 38 had ‘inactive’ IgA deposits. In patients with active deposits, 3 had cellular crescents (18%, 30% and 23%), all 8 had endocapillary proliferation and 2 had vasculitis. Group B had 18 cases (28.1%), comprising T cell mediated rejections (5), antibody mediated rejection (8), BK virus nephropathy (1) and interstitial fibrosis and tubular atrophy (4). In Group A, 22 (47.8%) presented with graft dysfunction, 8 (17.3%) with isolated proteinuria and 14 (30.4%) patients presented with a combination. 2 (4.3%) patients had neither. 14 (30.4%) presented within 1 month of renal transplant. In patients of group A, at the end of 1 year of treatment, mean S. Creatinine reduced to 1.68mg/dl from 1.84mg/dl and the mean protein/creatinine ratio reduced from 1.2 to 0.5. (±1.17). In patients with ‘active IgA’ lesions, at the end of 1 year of treatment mean S. Creatinine increased slightly to 1.68mg/dl (±0.47SD) from 1.48mg/dl (±0.52SD) and the mean protein/creatinine ratio reduced from 2.32 (±1.56SD) to 1.05. (±1.70SD). In the 16 patients with IgA deposits and proteinuria, at the end of 1 year of treatment mean S. Creatinine decreased to 1.41 ±0.32 SD mg/dl from 1.47±0.37SD mg/dl and the mean protein/creatinine ratio reduced from 1.12±1.31 SD to 0.39±0.75 SD. In the remaining 22 patients with acute tubular injury, at the end of 1 year mean S. Creatinine decreased to 1.92 ±0.32 SD mg/dl from 2.1±0.8SD mg/dl and the mean protein/creatinine ratio reduced from 1.1±1.31 SD to 0.66±1.45 SD. In MEST-C scoring analysis, all scores were 0 in 20 (43.4%) biopsies, only M1 score in 11 (23.9%) biopsies, only E1 score in 10 biopsies (21.7%), S1 in 13 (28.2%) cases. ConclusionsImmunoglobulin A deposits occur commonly after transplant, these may represent recurrence, de novo IgA or donor derived IgA deposits. Although commonly benign, some may cause significant graft dysfunction and graft loss. IgA deposition can present as varying combinations of graft dysfunction and proteinuria. Active IgA pathologies may occur early in the post transplant course, may have significant graft dysfunction and need proactive management. There is correlation between segmental sclerosis and proteinuria. Evidence for efficacy of Rituximab, plasma exchange and prolonged courses of steroids is wanting, however some benefit is possible. Long term follow up is essential.