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

Clin Transplant. 2024 May;38(5):e15322. doi: 10.1111/ctr.15322.

Abstract

Introduction: The 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.

Methods: Retrospective 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.

Results: We 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.

Conclusion: In 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.

Keywords: cohort study; graft function; hyperparathyroidism; kidney biopsy; kidney transplantation; parathyroid hormone.

MeSH terms

  • Adult
  • Allografts* / pathology
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate*
  • Graft Rejection* / etiology
  • Graft Rejection* / pathology
  • Graft Survival*
  • Humans
  • Hyperparathyroidism* / etiology
  • Hyperparathyroidism* / pathology
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Postoperative Complications* / etiology
  • Prognosis
  • Retrospective Studies
  • Risk Factors

Substances

  • Parathyroid Hormone