Urinary Expression of Kidney Injury Markers in Renal Transplant Recipients

Abstract

Background and objectives: The outcome of renal transplantation after an episode of acute rejection is difficult to predict, even with an allograft biopsy. We examined whether urinary expression of specific biomarker mRNA could be used as a noninvasive prognostic marker in kidney transplant recipients.Design, setting, participants, & measurements: We studied 63 kidney transplant recipients who require graft biopsy because of progressive worsening of kidney function. The mRNA of neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 (KIM-1), IL-18, surfactant protein-C, and S100 calcium-binding proteins A8 and A9 in urinary sediment were quantified.Results: Urinary expressions of neutrophil gelatinase-associated lipocalin, KIM-1, and IL-18, but not other target genes, were significantly different between histologic groups (P < 0.0001 for all). After followed for an average of 39.7 ؎ 21.1 months, the rate of renal function decline significantly correlated with urinary KIM-1 expression (r ‫؍‬ ؊0.434, P ‫؍‬ 0.0004) but not other target genes. At 48 months, the graft survival rate for the high and low KIM-1 groups were 46.2 and 78.6%, respectively. After adjusting for confounding variables, each log of higher urinary KIM-1 expression conferred an ϳ2.9-fold higher risk of developing graft failure (95% confidence interval, 1.3-to 6.2-fold; P ‫؍‬ 0.006). The result remained similar when only patients with no acute cellular rejection were analyzed.Conclusions: In kidney allograft recipients, urinary KIM-1 expression provides prognostic information in relation to the rate of renal function decline, irrespective of the kidney pathology.

Urinary Biomarkers for The Prediction of Reversibility in Acute-on-Chronic Renal Failure

“…In contrast, our previous study in kidney transplant recipients found that urinary NGAL and IL-18 expression are associated with response to antirejection therapy [29]. The discrepancy is probably explained by the fact that cellular rejection is essentially an inflammatory condition, and the severity or reversibility could understandably assessed by urinary NGAL and IL-18 expression.…”

“…The discrepancy is probably explained by the fact that cellular rejection is essentially an inflammatory condition, and the severity or reversibility could understandably assessed by urinary NGAL and IL-18 expression. We also previously found that urinary KIM-1 expression correlates with the rate of renal function decline in kidney transplant patients with acute renal dysfunction, irrespective to the kidney pathology [29]. In the present study, our duration of observation was short and we could not determine whether urinary KIM-1 provides the same long-term prognostic information for non-transplant patients with acute-on-chronic renal failure.…”

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

“…In the past years, besides NGAL, several AKI and DGF biomarkers have been extensively investigated, including urinary KIM‐1, IL‐18, heat shock protein 72 (uHsp72), L‐FABP, calprotectin, CXCL9, CXCL10, CCL2, IL‐18, cystatin C, T‐cell immunoglobulin, and mucin domain‐3 (Tim‐3), tissue inhibitor of metalloproteinase 2 (TIMP‐2), insulin‐like growth factor‐binding protein 7 (IGFBP‐7) 57, 58, 59, 60, 61, 62, 63.…”

Inksto Transplantato Pažeidimo Biožymenys

“…Natyvinių inkstų pažeidimų atveju padidėjusi KIM-1 koncentracija leidžia prognozuoti dializių poreikį, o pacientams po inksto transplantacijos KIM-1 koncentracijos nustatymas šlapi-me leidžia prognozuoti transplantato funkcijos blogėjimo greitį, tačiau neleidžia diferencijuoti skirtingų transplantato pažeidimo priežasčių [14].…”