Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors: Observational study.
ABSTRACT: Donor nephrectomy in living-donor kidney transplantation may result in hyperfiltration injury in remnant kidney; however, its clinical implication in partial recovery of kidney function (PRKF) in remnant kidney and chronic kidney disease (CKD) progression remains unclear. Thus, we investigated the effect of PRKF on CKD development in the residual kidney and the utility of cystatin-C (Cys-C) in evaluating renal function in living-donor kidney transplantation donors.The electronic medical records and laboratory results of 1648 kidney transplant (KT) donors and 13,834 healthy nondonors between January 2006 and November 2014 were reviewed. The predictors of PRKF and CKD diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria were evaluated by multivariate analysis. CKD risk was compared between KT donors and healthy nondonors using Cox proportional hazard regression analysis following propensity score matching (PSM).The incidence of PRKF for KT donors was 49.3% (813). CKD incidence was 24.8% (408) in KT donors and 2.0% (277) in healthy nondonors. The predictors of PRKF were, male sex (odds ratio [OR], 17.32; 95% confidence interval [CI] 9.16-32.77), age (OR, 1.02; 95% CI, 1.00-1.04; P?
Project description:Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, high-risk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation.To compare the risk of ESRD in kidney donors with that of a healthy cohort of nondonors who are at equally low risk of renal disease and free of contraindications to live donation and to stratify these comparisons by patient demographics.A cohort of 96,217 kidney donors in the United States between April 1994 and November 2011 and a cohort of 20,024 participants of the Third National Health and Nutrition Examination Survey (NHANES III) were linked to Centers for Medicare & Medicaid Services data to ascertain development of ESRD, which was defined as the initiation of maintenance dialysis, placement on the waiting list, or receipt of a living or deceased donor kidney transplant, whichever was identified first. Maximum follow-up was 15.0 years; median follow-up was 7.6 years (interquartile range [IQR], 3.9-11.5 years) for kidney donors and 15.0 years (IQR, 13.7-15.0 years) for matched healthy nondonors.Cumulative incidence and lifetime risk of ESRD.Among live donors, with median follow-up of 7.6 years (maximum, 15.0), ESRD developed in 99 individuals in a mean (SD) of 8.6 (3.6) years after donation. Among matched healthy nondonors, with median follow-up of 15.0 years (maximum, 15.0), ESRD developed in 36 nondonors in 10.7 (3.2) years, drawn from 17 ESRD events in the unmatched healthy nondonor pool of 9364. Estimated risk of ESRD at 15 years after donation was 30.8 per 10,000 (95% CI, 24.3-38.5) in kidney donors and 3.9 per 10,000 (95% CI, 0.8-8.9) in their matched healthy nondonor counterparts (P?<?.001). This difference was observed in both black and white individuals, with an estimated risk of 74.7 per 10,000 black donors (95% CI, 47.8-105.8) vs 23.9 per 10,000 black nondonors (95% CI, 1.6-62.4; P?<?.001) and an estimated risk of 22.7 per 10,000 white donors (95% CI, 15.6-30.1) vs 0.0 white nondonors (P?<?.001). Estimated lifetime risk of ESRD was 90 per 10,000 donors, 326 per 10,000 unscreened nondonors (general population), and 14 per 10,000 healthy nondonors.Compared with matched healthy nondonors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small. These findings may help inform discussions with persons considering live kidney donation.
Project description:The Organ Procurement and Transplantation Network gives priority in kidney allocation to prior live organ donors who require a kidney transplant. In this study, we analyzed the effect of this policy on facilitating access to transplantation for prior donors who were wait-listed for kidney transplantation in the United States. Using 1:1 propensity score-matching methods, we assembled two matched cohorts. The first cohort consisted of prior organ donors and matched nondonors who were wait-listed during the years 1996-2010. The second cohort consisted of prior organ donors and matched nondonors who underwent deceased donor kidney transplantation. During the study period, there were 385,498 listings for kidney transplantation, 252 of which were prior donors. Most prior donors required dialysis by the time of listing (64% versus 69% among matched candidates; P=0.24). Compared with matched nondonors, prior donors had a higher rate of deceased donor transplant (85% versus 33%; P<0.001) and a lower median time to transplantation (145 versus 1607 days; P<0.001). Prior donors received higher-quality allografts (median kidney donor risk index 0.67 versus 0.90 for nondonors; P<0.001) and experienced lower post-transplant mortality (hazard ratio, 0.19; 95% confidence interval, 0.08 to 0.46; P<0.001) than matched nondonors. In conclusion, these data suggest that prior organ donors experience brief waiting time for kidney transplant and receive excellent-quality kidneys, but most need pretransplant dialysis. Individuals who are considering live organ donation should be provided with this information because this allocation priority will remain in place under the new US kidney allocation system.
Project description:Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 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 APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m2; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m2; P=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 m2 per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 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 APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.
Project description:<h4>Rationale & objective</h4>Live kidney donation is associated with a small increased risk for kidney disease and hypertension in African American donors. We investigated a possible association between donor family history of end-stage kidney disease (ESKD) and their postdonation kidney function and the development of hypertension. We tested whether this association was modified by kidney donation.<h4>Study design</h4>Retrospective cohort.<h4>Setting & participants</h4>Former African American live kidney donors between 1993 and 2010. Healthy nondonors were selected from the Coronary Artery Disease in Young Adults (CARDIA) Study.<h4>Exposure</h4>Family history of ESKD in a first-degree relative.<h4>Outcomes</h4>Kidney function and blood pressure ≥ 140/90 mm Hg or use of antihypertensive medications at follow-up.<h4>Analytical approach</h4>Donors were grouped based on family history of ESKD. Outcomes were first compared between donor groups and then between donors and healthy nondonors matched for demographics, follow-up time, and family history. A mixed-effect model was used to compare outcomes.<h4>Results</h4>Of 179 donors, 139 (78%) had a first degree relative with ESKD. Predonation characteristics were similar between the 2 groups. At a median follow-up of 11 years postdonation, there was no difference in postdonation estimated glomerular filtration rates (68 ± 19 vs 69 ± 13 mL/min/1.73 m<sup>2</sup>; <i>P</i> = 0.71) and the presence of albuminuria (<i>P</i> = 0.16). There was a trend toward a higher incidence of hypertension (51% vs 35%; <i>P</i> = 0.08) among donors with a family history of ESKD than for those without. Although there was no difference in annual change in estimated glomerular filtration rate (<i>P</i> = 0.17), the risk for hypertension was higher in donors than nondonors (relative risk, 2.44 [95% CI, 1.56-3.84]), but there was no interaction by family history (<i>P</i> = 0.11).<h4>Limitations</h4>Retrospective small study. Lack of data across donor-recipient specific biological relationship.<h4>Conclusions</h4>Family history of ESKD is not associated with postdonation kidney function among African American kidney donors. Live kidney donation is associated with an increased risk for hypertension among African Americans, independent of donor family history of ESKD.
Project description:Background:The prevalence of chronic kidney disease (CKD) in African American individuals is high but whether this applies to native populations in sub-Saharan Africa is unclear. Methods:In a cross-sectional study, we assessed the prevalence and risk factors of CKD in rural and urban adults in South Kivu, Democratic Republic of Congo. Glomerular filtration rate (GFR) was estimated using the CKD-Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or both markers (eGFRcr-cys), without ethnic correction factor. CKD was defined as an eGFR <60 ml/min per 1.73 m2 and/or albuminuria (albumin-to-creatinine ratio ?30 mg/g). Results:A total of 1317 participants aged 41.1 ± 17.1 years (730 rural, 587 urban) were enrolled. The prevalence of hypertension (20.2%; 95% confidence interval [CI], 18-22.3), diabetes mellitus (4.3%; 95% CI, 3.2-5.4) and obesity (8.9%; 95% CI, 7.4-10.5) was higher in urban than rural participants (all P < 0.05). HIV infection prevalence was 0.41% (95% CI, 0.05-0.78). The prevalence of eGFRcr <60 ml/min per 1.73 m2 was 5.4% (95% CI, 4.2-6.7). The prevalence of albuminuria was 6.6% (95 % CI, 5.1-8.1). The overall prevalence of CKD was 12.2% (95% CI, 10.2-14.2) according to CKD-EPIcr. Factors independently associated with CKD-EPIcr were older age (adjusted odds ratio [aOR], 1.05 [1.04-1.07]), urban residence (aOR 1.86 [1.18-2.95]), female sex (aOR 1.66 [1.04-2.66]), hypertension (aOR 1.90 [1.15-3.12]), diabetes (aOR 2.03 [1.02-4.06]), and HIV infection (10.21 [2.75-37.85]). The results based on eGFRcys or eGFRcr-cys were largely consistent with the preceding. Conclusion:Overall, the burden of CKD is substantial (>11%), predominantly in the urban area, and largely driven by classic risk factors (gender, aging, HIV, hypertension, and diabetes).
Project description:Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies.We conducted a retrospective cohort study of living kidney donors involving 85 women (131 pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy nondonors from the general population (788 pregnancies after cohort entry). Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow-up through linked health care databases until March 2013. Donors and nondonors were matched with respect to age, year of cohort entry, residency (urban or rural), income, number of pregnancies before cohort entry, and the time to the first pregnancy after cohort entry. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia. Secondary outcomes were each component of the primary outcome examined separately and other maternal and fetal outcomes.Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4 for preeclampsia). There were no significant differences between donors and nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low birth weight (6% and 4%, respectively). There were no reports of maternal death, stillbirth, or neonatal death among the donors. Most women had uncomplicated pregnancies after donation.Gestational hypertension or preeclampsia was more likely to be diagnosed in kidney donors than in matched nondonors with similar indicators of baseline health. (Funded by the Canadian Institutes of Health Research and others.).
Project description:Chronic kidney disease is characterized by stiffening, thinning, dilatation, and increased circumferential wall stress of large arteries, associated with increased cardiovascular risk. Kidney transplantation (KT) reverses many pathological features of chronic kidney disease and improves life expectancy; however, longitudinal studies exploring the impact of KT on recipient large arteries are scarce.This study was designed to appraise arterial changes following KT. Carotid-femoral pulse wave velocity, carotid remodeling (circumferential wall stress and carotid internal diameter), and stiffness were measured in 161 consecutive recipients receiving either a living (n=49) or a deceased (n=112) donor allograft, at 3 and 12 months after transplantation. Mean pulse wave velocity decreased from 10.8 m/s (95% confidence interval, 10.5-11.2 m/s) (at month 3) to 10.1 m/s (95% confidence interval, 9.8-10.5 m/s) (at month 12) (P<0.001). After multivariate adjustment, pulse wave velocity reduction from month 3 to month 12 was significantly larger in the living donor allograft KT (P<0.001). Circumferential wall stress decreased, 70 kPa (95% confidence interval, 68-72 kPa) to 64 kPa (95% confidence interval, 62-67 kPa), as well as carotid internal diameter and carotid stiffness (P<0.001 for all). Reductions in circumferential wall stress, diameter, and stiffness were significantly larger in the living donor allograft KT (P<0.001). When deceased donor allograft patients were classified into standard and expanded criteria donors, changes in both pulse wave velocity and circumferential wall stress were blunted in expanded criteria donors. Changes were independent of graft function and blood pressure changes.Large-artery stiffness and maladaptive carotid artery remodeling of chronic kidney disease is partially reversed within 12 months of KT and appears unrelated to renal function. Improvements were independently associated with live organ donation. Our data suggest that expanded criteria donors may hamper vascular recovery.
Project description:<h4>Background</h4> Favorable long-term and short-term graft survival and patient survival after kidney transplantation (KT) from deceased donors with acute kidney injury (AKI) have been reported. However, few studies have evaluated effects of donor AKI status on graft outcomes after KT in Asian population. Thus, the purpose of this study was to evaluate graft function after KTs from donors with AKI compared to matched KTs from donors without AKI using a multicenter cohort in Korea. <h4>Methods</h4> We analyzed a total of 1,466 KTs collected in Korean Organ Transplant Registry between April 2014 and December 2017. KTs from AKI donors (defined as donors with serum creatinine level ≥ 2 mg/dL) and non-AKI donors (275 cases for each group) were enrolled using a 1:1 propensity score matching. Graft outcomes including graft and patient survival, delayed graft function (DGF), rejection rate, and serially measured estimated glomerular filtration rate (eGFR) were evaluated. <h4>Results</h4> After propensity matching, KTs from AKI donors showed higher rate of DGF (44.7% vs. 24.0%, p < 0.001). However, the rejection rate was not significantly different between the two groups (KTs from AKI donors vs. KTs from non-AKI donors). eGFRs measured after 6 months, 1 year, 2 years and 3 years were not significantly different by donor AKI status. With median follow-up duration of 3.52 years, cox proportional hazards models revealed hazard ratio of 0.973 (95% confidence interval [CI], 0.584 to 1.621), 1.004 (95% CI, 0.491 to 2.054) and 0.808 (95% confidence interval [CI], 0.426 to 1.532) for overall graft failure, death-censored graft failure and patient mortality, respectively, in KTs from AKI donors compared to KTs from non-AKI donors as a reference. <h4>Conclusions</h4> KTs from AKI donors showed comparable outcomes to KTs from non-AKI donors, despite a higher incidence of DGF. Results of this study supports the validity of using kidneys from deceased AKI donors in Asian population.
Project description:BACKGROUND:The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS:Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS:The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3?months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS:The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.
Project description:BACKGROUND:Minority groups are affected by significant disparities in kidney transplantation (KT) in Veterans Affairs (VA) and non-VA transplant centers. However, prior VA studies have been limited to retrospective, secondary database analyses that focused on multiple stages of the KT process simultaneously. Our goal was to determine whether disparities during the evaluation period for KT exist in the VA as has been found in non-VA settings. METHODS:We conducted a multicenter longitudinal cohort study of 602 patients undergoing initial evaluation for KT at 4 National VA KT Centers. Participants completed a telephone interview to determine whether, after controlling for medical factors, differences in time to acceptance for transplant were explained by patients' demographic, cultural, psychosocial, or transplant knowledge factors. RESULTS:There were no significant racial disparities in the time to acceptance for KT [Log-Rank ? = 1.04; P = 0.594]. Younger age (hazards ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.99), fewer comorbidities (HR, 0.89; 95% CI, 0.84-0.95), being married (HR, 0.81; 95% CI, 0.66-0.99), having private and public insurance (HR, 1.29; 95% CI, 1.03-1.51), and moderate or greater levels of depression (HR, 1.87; 95% CI, 1.03-3.29) predicted a shorter time to acceptance. The influence of preference for type of KT (deceased or living donor) and transplant center location on days to acceptance varied over time. CONCLUSIONS:Our results indicate that the VA National Transplant System did not exhibit the racial disparities in evaluation for KT as have been found in non-VA transplant centers.