leptin and Delayed-Graft-Function

Based on evidence that leptin and adiponectin are removed from circulation primarily by the kidney, we designed a study to examine the longitudinal changes of these adipokines during the first week after kidney transplantation (KTx) and to test the hypothesis that higher levels of leptin and/or adiponectin could be early biomarkers of delayed graft function (DGF=dialysis requirement during the first post-transplant week) and acute rejection.. Repeated-measures prospective study.. Forty consecutive adult patients with end-stage renal disease who were undergoing KTx. Leptin and adiponectin were measured in blood samples that were collected before (day-0) and after KTx (days-1, 2, 4 and 7). Linear mixed-models, receiver operating characteristic and area under curve (AUC-ROC) were used.. At post-transplant day-1, leptinemia and adiponectinemia declined 43% and 47%, respectively. At all times studied after KTx, the median leptin levels were significantly higher in patients developing DGF (n=18), but not adiponectin levels. Shortly after KTx (day-1), leptin values were significantly higher in DGF recipients in contrast to patients with promptly functioning kidneys, approximately two times higher when controlling for gender and BMI. The leptin reduction rate between pre-tranplant and one-day after KTx moderately predicted DGF (AUC=0.73). On day-1, serum leptin predicted DGF (AUC-ROC=0.76) with a performance slightly better than serum creatinine (AUC-ROC=0.72), even after correcting for BMI (AUC-ROC=0.73). Separating this analysis by gender showed that the performance of leptin in predicting DGF for male gender (AUC-ROC=0.86) improved.. Kidney graft function is an independent determinant of leptin levels, but not of adiponectin. Leptin levels at day-1 slightly outperformed serum creatinine in predicting the occurrence of DGF, and more accurately in male gender. No significant association was detected with acute rejection.

Topics: Adiponectin; Adult; Biomarkers; Cohort Studies; Delayed Graft Function; Early Diagnosis; Female; Hospitals, Urban; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Portugal; Postoperative Period; Prospective Studies; Sensitivity and Specificity; Up-Regulation

Serum creatinine (SCr) alone does not allow for the early diagnosis of delayed graft function (DGF) following kidney transplantation (KTx).. The diagnostic utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum leptin, malondialdehyde (MD.A), and cystatin C (CysC) for the early detection of DGF was previously evaluated by our group in a prospective cohort study of 40 consecutive adults undergoing KTx. Because no single biomarker achieved adequate sensitivity or specificity for practical purposes, this study was designed to evaluate the combined use of new markers with SCr. Urine and blood samples were collected 8-to-12h after KTx (day-1). Logistic regression was used to combine the biomarkers, and receiver operating characteristic curves and areas under the curve (AUC-ROC) were generated.. Eighteen recipients developed DGF (dialysis requirement during the first post-transplant week). On day-1, the AUC for SCr to predict DGF was 0.73, 0.88 for uNGAL, 0.90 for MDA, 0.76 for leptin, and 0.91 for CysC. Adding new biomarkers to SCr enhanced the performance of DGF prediction, and the best combination was achieved with SCr, MDA, and CysC (AUC=0.96, sensitivity=100%; specificity=86%).. A combination of graft damage biomarkers outperformed SCr in the early diagnosis of DGF, and the best performance was achieved by a triple-marker approach, using SCr, MDA, and CysC.

Topics: Acute-Phase Proteins; Adult; Area Under Curve; Biomarkers; Creatinine; Cystatin C; Delayed Graft Function; Early Diagnosis; Female; Humans; Kidney; Kidney Function Tests; Kidney Transplantation; Leptin; Lipocalin-2; Lipocalins; Male; Malondialdehyde; Middle Aged; Prospective Studies; Proto-Oncogene Proteins; Renal Dialysis; ROC Curve; Sensitivity and Specificity