Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients

PLoS One. 2016 Dec 30;11(12):e0167929. doi: 10.1371/journal.pone.0167929. eCollection 2016.

Abstract

Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

MeSH terms

  • Adolescent
  • Allografts / metabolism*
  • Allografts / pathology*
  • Biomarkers / metabolism*
  • Calcification, Physiologic / physiology*
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Female
  • Fibroblast Growth Factors / metabolism
  • Fibrosis / metabolism*
  • Fibrosis / pathology*
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / pathology
  • Kidney Transplantation / methods
  • Male
  • Phosphates / metabolism*
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology
  • Retrospective Studies
  • Vitamin D / metabolism

Substances

  • Biomarkers
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23

Grant support

This work was funded by grants from NCCR kidney.ch to SdS and AP and Swiss National Foundation to SdS.