Patients who develop proteinuria experience increases in urinary copper excretion. Manuela Yepes Calderon, PhD, and colleagues conducted a prospective cohort study to examine whether proteinuria in kidney transplant recipients is associated with urinary copper excretion. The researchers also sought to determine if there is an association between urinary copper excretion and the biomarker of tubular damage urinary liver-type fatty acid-binding protein (u-LFABP) and the development of graft failure. Results were reported during a poster session at the American Society of Nephrology Kidney Week 2022 in a poster titled Urinary Copper Excretion Is Associated With Graft Failure in Kidney Transplant Recipients.
The study included kidney transplant recipients with a functioning allograft ≥1 year posttransplant. Urinary copper was measured in 24-hour urine samples by coupled plasma mass spectrometry. The researchers conducted multivariable linear regression and Cox regression analyses.
The study cohort included 693 kidney transplant recipients. Of those, 57% were male, and mean age was 53 years. Baseline copper excretion was 23.57 µg. There was a direct association between copper and proteinuria independent of graft function (Std ß 0.45; P<.01) and with u-LFABP independent of proteinuria (Std ß 0.34; P<.001).
Median follow-up was 5.3 years. During follow-up, 12% of the cohort (n=83) developed graft failure. There was an association between being on the third tertile of urinary copper excretion and an increased risk of graft failure (hazard ratio, 2.94; 95% CI, 1.34-6.45; P<.001). The association was independent of adjustment by multiple potential confounders. The association was significantly mediated by u-LFABP, accounting for 46% of the total effect.
“We concluded that in kidney transplant recipients, proteinuria is associated with increased copper excretion, and this is further associated with the risk of graft failure apparently by enhancing tubular damage,” the researchers said. “Further studies seem warranted to elucidate whether copper-targeted interventions may decrease the burden of graft failure on kidney transplant recipients.”
Source: Yepes Calderon M, Kremer D, Knobbe TJ, et al. Urinary copper excretion is associated with graft failure in kidney transplant recipients. FR-PO810. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2022; November 4, 2022; Orlando, Florida.