Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the
high-risk genotype on postdonation renal function in black living kidney ...donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as
high-risk (two risk alleles;
=19; 14%) or low-risk (one or zero risk alleles;
=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the
high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m
;
=0.04). At a median of 12 years after donation, donors with the
high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m
;
=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m
per year,
=0.02). Two donors developed ESRD; both carried the
high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by
genotype, we did not find a difference between groups in the rate of eGFR decline (
=0.39) or any statistical interaction by
status (
=0.92). In conclusion,
high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between
high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.
Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk ...factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.
The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition’s actual cause. To improve ...phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown.
Cross-sectional analysis from multicenter prospective cohort.
Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation.
(1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin NGAL, liver-type fatty acid-binding protein L-FABP, interleukin 18 IL-18, and kidney injury molecule 1 KIM-1) measured at organ procurement.
Histologic acute tubular injury.
Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1.
The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population.
Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.
Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this ...study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m(2) In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.
Although some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long-term outcomes, a causal relationship remains controversial. We ...investigated this relationship using an instrumental variables model (IVM), a quasi-randomization technique for drawing causal inferences.
We identified 80,690 adult, deceased-donor, kidney-only transplant recipients from the Scientific Registry of Transplant Recipients between 1997 and 2010. We used cold ischemia time (CIT) as an instrument to test the hypothesis that DGF causes death-censored graft failure and mortality at 1 and 5 years after transplantation, controlling for an array of characteristics known to affect patient and graft survival. We compared our IVM results with a multivariable linear probability model.
DGF occurred in 27% of our sample. Graft failure rates at 1 and 5 years were 6% and 22%, respectively, and 1-year and 5-year mortality rates were 5% and 20%, respectively. In the linear probability model, DGF was associated with increased risk of both graft failure and mortality at 1 and 5 years (P<0.001). In the IVM, we found evidence suggesting a causal relationship between DGF and death-censored graft failure at both 1 year (13.5% increase; P<0.001) and 5 years (16.2% increase; P<0.001) and between DGF and mortality at both 1 year (7.1% increase; P<0.001) and 5 years (11.0% increase; P<0.01). Results were robust to exclusion of lower quality as well as pumped kidneys and use of a creatinine-based definition for DGF.
Instrumental variables analysis supports a causal relationship between DGF and both graft failure and mortality.
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.
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.
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.
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.
Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to ...determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate ≤ 20 mL/min/1.73 m2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI.
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