Clinically adjudicated deceased donor acute kidney injury and graft outcomes

Background: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association. Methods: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes. Results: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI. Conclusion: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization

Use of urine biomarker-derived clusters to predict the risk of chronic kidney disease and all-cause mortality in HIV-infected women

BackgroundAlthough individual urine biomarkers are associated with chronic kidney disease (CKD) incidence and all-cause mortality in the setting of HIV infection, their combined utility for prediction remains unknown.MethodsWe measured eight urine biomarkers shown previously to be associated with incident CKD and mortality risk among 902 HIV-infected women in the Women's Interagency HIV Study: N-acetyl-β-d-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), alpha-1 microglobulin (α1m), interleukin 18, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, liver fatty acid-binding protein and α-1-acid-glycoprotein. A group-based cluster method classified participants into three distinct clusters using the three most distinguishing biomarkers (NAG, KIM-1 and α1m), independent of the study outcomes. We then evaluated associations of each cluster with incident CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2) by cystatin C) and all-cause mortality, adjusting for traditional and HIV-related risk factors.ResultsOver 8 years of follow-up, 177 CKD events and 128 deaths occurred. The first set of clusters partitioned women into three groups, containing 301 (Cluster 1), 470 (Cluster 2) and 131 (Cluster 3) participants. The rate of CKD incidence was 13, 21 and 50% across the three clusters; mortality rates were 7.3, 13 and 34%. After multivariable adjustment, Cluster 3 remained associated with a nearly 3-fold increased risk of both CKD and mortality, relative to Cluster 1 (both P < 0.001). The addition of the multi-biomarker cluster to the multivariable model improved discrimination for CKD (c-statistic = 0.72-0.76, P = 0.0029), but only modestly for mortality (c = 0.79-0.80, P = 0.099). Clusters derived with all eight markers were no better for discrimination than the three-biomarker clusters.ConclusionsFor predicting incident CKD in HIV-infected women, clusters developed from three urine-based kidney disease biomarkers were as effective as an eight-marker panel in improving risk discrimination

Use of urine biomarker-derived clusters to predict the risk of chronic kidney disease and all-cause mortality in HIV-infected women

BACKGROUND: Although individual urine biomarkers are associated with chronic kidney disease (CKD) incidence and all-cause mortality in the setting of HIV infection, their combined utility for prediction remains unknown. METHODS: We measured eight urine biomarkers shown previously to be associated with incident CKD and mortality risk among 902 HIV-infected women in the Women's Interagency HIV Study: N-acetyl-β-d-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), alpha-1 microglobulin (α1m), interleukin 18, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, liver fatty acid-binding protein and α-1-acid-glycoprotein. A group-based cluster method classified participants into three distinct clusters using the three most distinguishing biomarkers (NAG, KIM-1 and α1m), independent of the study outcomes. We then evaluated associations of each cluster with incident CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2) by cystatin C) and all-cause mortality, adjusting for traditional and HIV-related risk factors. RESULTS: Over 8 years of follow-up, 177 CKD events and 128 deaths occurred. The first set of clusters partitioned women into three groups, containing 301 (Cluster 1), 470 (Cluster 2) and 131 (Cluster 3) participants. The rate of CKD incidence was 13, 21 and 50% across the three clusters; mortality rates were 7.3, 13 and 34%. After multivariable adjustment, Cluster 3 remained associated with a nearly 3-fold increased risk of both CKD and mortality, relative to Cluster 1 (both P < 0.001). The addition of the multi-biomarker cluster to the multivariable model improved discrimination for CKD (c-statistic = 0.72–0.76, P = 0.0029), but only modestly for mortality (c = 0.79–0.80, P = 0.099). Clusters derived with all eight markers were no better for discrimination than the three-biomarker clusters. CONCLUSIONS: For predicting incident CKD in HIV-infected women, clusters developed from three urine-based kidney disease biomarkers were as effective as an eight-marker panel in improving risk discrimination

First post-operative urinary kidney injury biomarkers and association with the duration of AKI in the TRIBE-AKI cohort

10.1371/journal.pone.0161098PLoS ONE118e016109

Association of perioperative plasma neutrophil gelatinase-associated lipocalin levels with 3-year mortality after cardiac surgery: A prospective observational cohort study

10.1371/journal.pone.0129619PLoS ONE106e012961