Mini-Oral Presentation

Biopsy-proven recurrent IgA nephropathy after kidney transplantation in a multi-ethnic Southeast Asian cohort

Presenter

Hersharan Sran (SG)

Senior Consultant · National University Centre for Organ Transplantation · National University Hospital, Singapore · Singapore

Profile

Authors

Ada Pei Yu Ng^1,2, Hersharan Kaur Sran^1,2, Emmett Tsz Yeung Wong^1,2, Matthew Ross D'Costa^1,2, Zi Yun Chang^1,2, A Vathsala^1,2

Affiliations

¹ National University Hospital

² National University of Singapore

Abstract

IgA nephropathy (IgAN) is a leading cause of end-stage kidney disease (ESKD) and may recur after kidney transplantation. Incidence is higher in Asians, suggesting a genetic predisposition, although ethnicity has not been consistently associated with post-transplant recurrence. HLA DRB1*04, DRB1*15, DQB1*02, DQB1*03, and DQB1*04 have been associated with IgAN in Asian cohorts, and DRB1*11 with recurrence in kidney transplant recipients (KTR). We aim to identify risk factors for recurrent IgAN in a multi-ethnic Southeast Asian cohort.
This retrospective single-center study included consecutive deceased- and living-donor KTR with biopsy-proven native IgAN transplanted between 1 January 2010 and 31 December 2020. Induction immunosuppression consisted of non-lymphocyte-depleting, lymphocyte-depleting or none based on immunological risk. Maintenance therapy included corticosteroids, a calcineurin inhibitor and an anti-metabolite. HLA alleles were obtained from clinical laboratory typing or imputed when missing. Recurrence was defined as biopsy-proven mesangial IgA deposition in the allograft. Data were obtained from electronic records.
60 KTR were included: 42 (70%) Chinese, 8 (13.3%) Malays, 8 (13.3%) Indians, and 2 (3.3%) Others (Table 1). Over a median follow-up of 9.2 (IQR 6.9–11.6) years, 12 (20%) developed recurrence; 1 had graft loss contributed by sepsis-related acute kidney injury at 8.5 years post-transplant. Median time to recurrence was 7.1 (3.5–9.4) years. KTR with recurrence had a shorter time from diagnosis to ESKD (p=0.006) and were younger at transplant (p=0.0007). HLA mismatch and immunosuppression were not associated with recurrence. HLA DQB1*02 (OR 7.50, p=0.025) and DRB1*10 (p=0.006) were associated with recurrence on univariable analysis. Living-donor transplantation was associated with recurrence (OR 7.21, p=0.047) on univariable analysis. In multivariable logistic regression including living-donor status, time from diagnosis to transplantation and HLA DQB1*02, only shorter time to transplantation (OR 0.64 per year, p<0.0001) and HLA DQB1*02 (OR 23.38, p=0.014) remained independently associated with recurrence, while living-donor was not significant (p=0.76). Post-transplant estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR) were similar between groups (Table 2). Kaplan-Meier analysis showed no significant difference in patient or death-censored graft survival.

Table 1: Clinical characteristics and factors associated with IgAN recurrence

Table 2: Post Transplant Clinical Outcomes

In our multi-ethnic Southeast Asian cohort, IgAN recurrence was associated with shorter time to ESKD and younger age at transplant. Independent predictors were shorter time to transplantation and DQB1*02, supporting a role of disease biology and genetic risk in post-transplant recurrence. Despite recurrence, graft function was preserved with no difference in patient or graft survival.