Progressive decline of function in renal allografts with normal 1-year biopsies: Gene expression studies fail to identify a classifier

Walter D. Park, Dean Y. Kim, Martin L. Mai, Kunam Sudhakar Reddy, Thomas A Gonwa, Margaret S. Ryan, Loren P. Herrera Hernandez, Maxwell L. Smith, Xochiquetzal J Geiger, Sandor Turkevi-Nagy, Lynn D Cornell, Byron H. Smith, Walter K. Kremers, Mark D. Stegall

Research output: Contribution to journalArticlepeer-review

Abstract

Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c-statistic =.59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and.58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1-year biopsy and eGFR > 40) remains difficult.

Original languageEnglish (US)
JournalClinical Transplantation
DOIs
StateAccepted/In press - 2021

Keywords

  • genomics
  • glomerular filtration rate
  • kidney (allograft) function / dysfunction

ASJC Scopus subject areas

  • Transplantation

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