Evolution of renal function and urinary biomarker indicators of inflammation on serial kidney biopsies in pediatric kidney transplant recipients with and without rejection

Abstract

Urinary CXCL10 and metabolites are biomarkers independently associated with TCMR. We sought to test whether these biomarkers fluctuate in association with histological severity of TCMR over short time frames. Forty-nine pairs of renal biopsies obtained 1-3 months apart from 40 pediatric renal transplant recipients were each scored for TCMR acuity score (i + t; Banff criteria). Urinary CXCL10:Cr and TCMR MDS were obtained at each biopsy and were tested for association with changes between biopsies in acuity, estimated GFR (ΔeGFR), and 12-month ΔeGFR. Sequential biopsies were obtained 1.8 ± 0.8 months apart. Biopsy 1 was usually obtained under protocol (75%), and 62% percent had evidence of TCMR. Using each biopsy pair for comparison, ΔeGFR did not predict change in acuity. By contrast, change in acuity was significantly correlated with change in urinary CXCL10:Cr (ρ 0.45, P = .003) and MDS (ρ 0.29, P = .04) between biopsies. The 12-month ΔeGFR was not predicted by TCMR acuity or CXCL10:Cr at Biopsy 2; however, an inverse correlation was seen with urinary MDS (ρ -0.35; P = .02). Changes in eGFR correlate poorly with evolving TCMR acuity on histology. Urinary biomarkers may be superior for non-invasive monitoring of rejection, including histological response to therapy, and may be prognostic for medium-term function.

Keywords: acute rejection; biomarkers; chemokines; graft survival; histopathology; metabolomics; pediatric.