Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction

Abstract

AbstractIntroductionThe causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford‐Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time‐zero graft biopsies.MethodsRetrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre‐transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post‐transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation.ResultsWe included 325 KTRs (56% female, age 38 ± 13 years, follow‐up 4.2 years [IQR: 2.7‐5.8]). Based on pre‐transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre‐transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67–1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88–1.60]) criteria. Similarly, there were no differences when using 1 year post‐transplant iPTH cut‐offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata.ConclusionIn young KTRs who received a healthy graft, no association was found between increased pre‐ and post‐transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.