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Hypertension and diabetes are contraindications for living kidney donation in young candidates. However, little is known about the long-term outcomes of women who had these pregnancy-related complications and subsequently became donors. In the general population, gestational hypertension (GHtn), preeclampsia/eclampsia, and gestational diabetes (GDM) are associated with long-term risks.Donors with the specified predonation complication were matched to contemporary control donors with pregnancies without the complication using nearest neighbor propensity score matching. Propensity scores were estimated using logistic regression with covariates for gravidity, blood pressure, glucose, body mass index, age, and creatinine at donation, donation year, race, relationship with recipient, and family history of disease. Long-term incidence of hypertension, diabetes, cardiovascular disease, and reduced renal function (estimated glomerular filtration rate [eGFR]30, eGFR45 mL/min/1.73 m 2 ) were compared between groups using proportional hazards models.Of 1862 donors with predonation pregnancies, 48 had preeclampsia/eclampsia, 49 had GHtn without preeclampsia, and 43 had GDM. Donors had a long interval between first pregnancy and donation (median, 18.5 y; interquartile range, 10.6-27.5) and a long postdonation follow-up time (median, 18.0; interquartile range, 9.2-27.7 y). GHtn was associated with the development of hypertension (hazard ratio, 1.89; 95% confidence interval, 1.26-2.83); GDM was associated with diabetes (hazard ratio, 3.04; 95% confidence interval, 1.33-6.99). Pregnancy complications were not associated with eGFR30 or eGFR45 mL/min/1.73 m 2 .Our data suggest that women with predonation pregnancy-related complications have long-term risks even with a normal donor evaluation. Donor candidates with a history of pregnancy-related complications should be counseled about these risks.

Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney.We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG):100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250).Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04).Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

BACKGROUND Glomerular size in renal allografts is impacted by donor-recipient factors and response to injury. In serial biopsies of patients with well-functioning grafts, increased glomerular size correlates with better survival. However, no previous study has addressed the association of glomerular size at the time of a for-cause biopsy and clinical/histopathologic markers of injury, or effect on long-term graft outcome. METHODS Two cohorts of kidney transplant recipients enrolled in the Deterioration of Kidney Allograft Function study were evaluated. The prospective cohort (PC, n = 581): patients undergoing first for-cause kidney biopsy 1.7 ± 1.4 (mean ± SD) y posttransplant; and the cross-sectional cohort (CSC, n = 446): patients developing new-onset renal function deterioration 7.7 ± 5.6 y posttransplant. Glomerular planar surface area and diameter were measured on all glomeruli containing a vascular pole. Kidney biopsy was read centrally in a blinded fashion according to the Banff criteria. RESULTS Glomerular area was significantly higher in the CSC than the PC; time from transplant to indication biopsy was associated with glomerular area in both cohorts (P values ≤ 0.001). Glomerular area was associated with indices of microvascular inflammation (glomerulitis, peritubular capillary infiltrates; P values ≤ 0.001) and segmental glomerulosclerosis (P value < 0.0001). In the CSC, higher glomerular area was associated with higher estimated glomerular filtration rate (P value ≤ 0.001) and increased graft survival after accounting for microvascular inflammation (adjusted hazard ratio = 0.967; 95% confidence interval: 0.948-0.986; hazard ratio in biopsies without evidence of diabetes or antibody mediated rejection = 0.919, 95% confidence interval: 0.856-0.987). CONCLUSIONS Glomerular size is associated with histopathologic features present at the time of indication biopsy and with increased graft survival in the CSC.

Hormonal replacement therapy is administered to many brain-dead organ donors to improve hemodynamic stability. Previous clinical studies present conflicting results with several randomized studies reporting no benefit.Consecutive adult donors (N = 199) were randomized to receive high-dose levothyroxine, high-dose methylprednisolone, both (Combo), or no hormonal therapy (Control). Vasopressor requirements using the vasoactive-inotropic score (VIS) were assessed at baseline, 4 h, and at procurement. Crossover to the Combo group was sufficient to require separate intention-to-treat and per-protocol analyses.In the intention-to-treat analysis, the mean (±SD) reduction in VIS from baseline to procurement was 1.6 ± 2.6, 14.9 ± 2.6, 10.9 ± 2.6, and 7.1 ± 2.6 for the levothyroxine, methylprednisolone, Combo, and Control groups, respectively. While controlling for the baseline score, the reduction in VIS was significantly greater in the methylprednisolone and Combo groups and significantly less in the levothyroxine group compared with controls. Results were similar in the per-protocol analysis.High-dose methylprednisolone alone or in combination with levothyroxine allowed for significant reduction in vasopressor support in organ donors. Levothyroxine alone offered no advantage in reducing vasopressor support. Organ yield, transplantation rates, and recipient outcomes were not adversely affected.

Background About half of late kidney allograft losses are attributed to death with function (DWF), a poorly characterized outcome. An ongoing question is whether DWF is a consequence of chronic allograft dysfunction. Using the prospective Long-term Deterioration of Kidney Allograft Function study database, we sought to better define the impact, phenotype, and clinical course of DWF in the current era. Methods Three thousand five hundred eighty-seven kidney recipients with functional grafts at 90 days post-transplant were followed prospectively for a median of 5.2 years. Results Characteristics at transplantation in those with DWF (N = 350, 9.8%) differed from those who otherwise lost their grafts (death-censored graft failure [DC-GF], N = 295, 8.2%) or maintained function (N = 2942, 82.0%); DWF patients were older, sicker, and had been on dialysis longer, with more preexisting cardiovascular disease, whereas DC-GF patients experienced more early rejection, more acute rejection after 90 days, and a clinically significant decrease in kidney function before graft failure. In contrast, the clinical course after transplantation in DWF patients did not differ before death from those who maintained function throughout. Conclusions DWF and DC-GF in kidney transplant recipients represent differing clinical phenotypes occurring in distinct patient populations. Reducing the impact of DWF requires better definition of causes and clinical course and then trials of therapies to improve outcomes. Composite endpoints in clinical trials that group DWF and DC-GF together may obscure important clinical findings.

Background Identifying kidney allograft recipients who are predisposed to acute rejection (AR) could allow for optimization of clinical treatment to avoid rejection and prolong graft survival. It has been hypothesized that a part of this predisposition is caused by the inheritance of specific genetic variants. There are many publications reporting a statistically significant association between a genetic variant, usually in the form of a single-nucleotide polymorphism (SNP), and AR. However, there are additional publications reporting a lack of this association when a different cohort of recipients is analyzed for the same single-nucleotide polymorphism. Methods In this report, we attempted to validate 75 common genetic variants, which have been previously reported to be associated with AR, using a large kidney allograft recipient cohort of 2390 European Americans and 482 African Americans. Results Of those variants tested, only 1 variant, rs2910164, which alters the expression of the microRNA MIR146A, was found to exhibit a significant association within the African American cohort. Suggestive variants were found in the genes CTLA and TLR4. Conclusions Our results show that most variants previously reported to be associated with AR were not validated in our cohort. This shows the importance of validation when reporting the associations with complex clinical outcomes such as AR. Additional work will need to be done to understand the role of MIR146A in the risk of AR in kidney allograft recipients.

Recent changes in policies guiding allocation of transplant kidneys are predicted to increase sharing between distant geographic regions. The potential exists for an increase in cold ischemia time (CIT) with resulting increases in delayed graft function (DGF) and transplant-related costs (TRC). We sought to explore the impact of CIT on metrics that may influence TRC.Between 2006 and 2014, 81 945 adult solitary deceased donor kidney transplants were performed in the United States; 477 (0.6%) at our institution. Regression models were constructed to describe the relationship between CIT on DGF and length of stay (LOS). Using hospital accounting data, we created regression models to evaluate the effect of DGF on LOS and TRC.In multivariable models, longer CIT was associated with an increased rate of DGF (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.38-1.44) and increased LOS (OR, 1.04; 95% CI, 1.02-1.05). Recipients at our institution who developed DGF had longer LOS (OR, 1.71; 95% CI, 1.50-1.95), suggesting that the effect is partially mediated by DGF. After adjusting for LOS, neither CIT nor DGF were independently associated with increased TRC. However, an increased LOS resulted in an increase in TRC by US $3422 (95% CI, US $3180 to US $3664) per additional day, indicating that the effect of CIT on TRC is partially mediated through LOS.The prolongation of CIT is associated with an increase in DGF rates and LOS, resulting in increased TRC. This study raises the need to balance increased access of traditionally underserved populations to kidney transplant with the inadvertent increase in TRC.

BACKGROUND The rate of measured glomerular filtration rate (GFR) change in kidney donor years after donation has not been adequately addressed. Whether this change is accelerated in the setting of 1 kidney is also understudied. METHODS Two hundred fourteen randomly selected donors underwent serial GFR measurements of nonradioactive iohexol. Estimated GFR at each visit was calculated using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease study equations. RESULTS Glomerular filtration rate visits were 4.8 ± 1.3 years apart and the second occurring 16.9 ± 9.1 years after donation. Most (97.7%) were white, 60.8% female, and 78.5% were related to their recipient. Most, 84.6%, had a GFR of 60 mL/min per 1.73 m or higher, 14.0% had a GFR between 45 and 60 mL/min per 1.73 m, and 1.4% had a GFR less than 45 mL/min per 1.73 m. Between visits 1 and 2, 56.5% had a GFR decline, 36.0% increase, and in 7.5%, there was no change. Overall, GFR declined at a rate of -0.42 mL/min per 1.73 m per year. Of GFR estimating models, only Chronic Kidney Disease Epidemiology Collaboration-Creatinine equation produced a slope that was steeper than measured GFR. CONCLUSIONS Nearly 2 decades postdonation GFR declined at a rate similar to that seen in the general population, and in one third, GFR continues to increase.

BACKGROUND Infants (age, < 2 years) with end-stage renal disease (ESRD) have increased morbidity and mortality. We evaluated our long-term outcomes of kidney transplants (KTx) in infants. METHODS Between 1984 and 2014, 136 infants underwent KTx. We examined trends in survival rates and complications by era (1984-1993 [era 1], 1994-2003 [era 2], 2004-2014 [era 3]). RESULTS Patients were 92.6% white and 70.6% males. Posttransplant (Tx) initial length of hospital stay declined 37% over the 30-year period (P

BACKGROUND Short- and intermediate-term results have been reported after rapid discontinuation of prednisone (RDP) in kidney transplant recipients. Yet there has been residual concern about late graft failure in the absence of maintenance prednisone. METHODS From October 1, 1999, through June 1, 2015, we performed a total of 1553 adult first and second kidney transplants-1021 with a living donor, 532 with a deceased donor-under our RDP protocol. We analyzed the 15-year actuarial overall patient survival (PS), graft survival (GS), death-censored GS (DCGS), and acute rejection-free survival (ARFS) rates for RDP compared with historical controls on maintenance prednisone. RESULTS For living donor recipients, the actuarial 15-year PS rates were similar between groups. But RDP was associated with increased GS (P = 0.02) and DCGS (P = 0.01). For deceased donor recipients, RDP was associated with significantly better PS (P < 0.01), GS (P < 0.01) and DCGS (P < 0.01). There was no difference between groups in the rate of acute or chronic rejection, or in the mean estimated glomerular filtration rate at 15 years. However, RDP-treated recipients had significantly lower rates of avascular necrosis, cytomegalovirus, cataracts, new-onset diabetes after transplant, and cardiac complications. Importantly, for recipients with GS longer than 5 years, there was no difference between groups in subsequent actuarial PS, GS, and DCGS. CONCLUSIONS In summary, at 15 years postkidney transplant, RDP did not lead to decreased in PS or GS, or an increase in graft dysfunction but as associated with reduced complication rates.

The development of minimally invasive surgical approaches to donor nephrectomy (DN) has been driven by the potential advantages for the donor, with questions remaining about long-term outcomes.All living DN performed from June 1963 through December 2014 at the University of Minnesota were reviewed. Outcomes were compared among 4 DN techniques.We performed 4286 DNs: 2759 open DN (ODNs), 1190 hand-assisted (HA) laparoscopic DNs (LDNs), 203 pure LDN (P-LDNs), and 97 robot-assisted-LDN. Laparoscopic DN was associated with an older (P0.001) and heavier (P0.001) donor population. Laparoscopic DN was associated with a higher probability of left kidney procurement (P0.001). All 3 LDN modalities required a longer operative time (P0.001); robot-assisted-LDN took significantly longer than HA-LDN or P-LDN. Laparoscopic DN decreased the need for intraoperative blood transfusion (P0.001) and reduced the incidence of intraoperative complications (P0.001) and hospital length of stay (P0.001). However, LDN led to a significantly higher rate of readmissions, both short-term (30 day, P0.001) and long-term (30 day, P0.001). Undergoing HA-LDN was associated with a higher rate of an incisional hernia compared with all other modalities (P0.001). For recipients, LDN seemed to be associated with lower rates of graft failure at 1 year compared with ODN (P = 0.002). The odds of delayed graft function increased for kidneys with multiple arteries procured via P-LDN compared with HA-LDN (OR 3 [1,10]) and ODN (OR 5 [2, 15]).In our experience, LDN was associated with decreased donor intraoperative complications and hospital length of stay but higher rates of readmission and long-term complications.

Background Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies. Methods We studied postdonation outcomes in 46 segmental pancreas living donors. Surgical complications, risk factors (RF) for development of diabetes mellitus (DM) and quality of life were studied. A risk stratification model (RSM) for DM was created using predonation and postdonation RFs. Recipient outcomes were analyzed. Results Between January 1, 1994 and May 1, 2013, 46 LDSPTx were performed. Intraoperatively, 5 (11%) donors received transfusion. Overall, 9 (20%) donors underwent splenectomy. Postoperative complications included: 6 (13%) peripancreatic fluid collections and 2 (4%) pancreatitis episodes. Postdonation, DM requiring oral hypoglycemics was diagnosed in 7 (15%) donors and insulin-dependent DM in 5 (11%) donors. RSM with three predonation RFs (oral glucose tolerance test, basal insulin, fasting plasma glucose) and 1 postdonation RF, greater than 15% increase in body mass index from preoperative (Δ body mass index >15), predicted 12 (100%) donors that developed postdonation DM. Quality of life was not significantly affected by donation. Mean graft survival was 9.5 (±4.4) years from donors without and 9.6 (±5.4) years from donors with postdonation DM. Conclusions LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using RSM and predonation counseling on life style modifications postdonation.

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are a significant cause of morbidity and mortality in transplant recipients and are often transmitted from the donor organ.In a pilot prospective, randomized, double-blinded, placebo-controlled trial, we studied whether 14 days of pretransplant donor treatment with valganciclovir (valG) versus placebo reduced donor-to-recipient transmission, making posttransplant recipient prophylaxis more effective in reducing EBV and CMV disease.Seventeen D+ R- donor-recipient pairs were enrolled: 7 and 10 donors were randomized to valG and placebo, respectively. At study initiation, no donor had detectable CMV replication, five had EBV replication (two in valG, three in placebo group): EBV replication was undetectable during valG treatment, but resumed on stopping valG. Valganciclovir was tolerated without side effects or leukopenia. All recipients received routine posttransplant viral prophylaxis with valG. For recipients, viremia-free survival time, incidence, range, peak, and duration of CMV and EBV viremia were not significantly different between groups. There was no disease in the valG group but two serious viral diseases occurred in the placebo group (one CMV; one EBV-related posttransplant lymphoproliferative disorder). In the case of posttransplant lymphoproliferative disorder, the EBV DNA from the donor's oral wash and the recipient's lymphoid tissue biopsy had identical latent membrane protein 1 (LMP-1) sequence variations from the reference EBV strain, making it highly probable that the recipient's virus was of donor origin.Based on this pilot trial, we recommend an adequately powered study to determine if pretransplant donor treatment with valG can reduce posttransplant CMV and EBV disease with merely routine posttransplant recipient viral prophylaxis.

Background The performance of glomerular filtration rate (GFR) equations incorporating both cystatin C (CysC) and serum creatinine (Creat) in living kidney donors has not been studied before. Methods From a population of 3,698 living kidney donors, 257 donors were randomly selected to undergo GFR measurement (mGFR) by the plasma disappearance of iohexol. GFR was estimated with the Modification of Diet in Renal Disease (MDRD) equation and the Chronic Kidney Disease Epidemiology Collaboration study eGFR(CKD-EPI-Creat) in 257 donors and the two newly developed equations using CysC with and without Creat, eGFR(CKD-EPI-CysC) and eGFR(CKD-EPI-Creat+CysC), in 215 donors. Results Mean mGFR was 71.8±11.8 mL/min/1.73 m. The eGFR(MDRD) exhibited least and only negative bias and the three other models were comparable in terms of bias. The eGFR(CKD-EPI-Creat+CysC) equation was most precise; r=0.64. Both eGFR(MDRD) and eGFR(CKD-EPI-Creat+CysC) had high percentage (94.4% and 92.6%, respectively) of estimates falling within 30% of mGFR versus estimates by eGFR(CKD-EPI-Creat) and eGFR(CKD-EPI-CysC) equations (87.2% and 85.1%, respectively). The eGFR(MDRD) was by far most accurate in identifying those with mGFR less than 60 mL/min/1.73 m whereas the CKD-EPI models were extremely accurate in classifying those with mGFR greater than or equal to 60 mL/min/1.73 m. Conclusions eGFR(CKD-EPI-Creat+CysC) equation provides comparable accuracy to the eGFR(MDRD) in overall estimation of mGFR, but with higher precision. However, eGFR(CKD-EPI-Creat+CysC) clearly misses many of those with a post-donation GFR less than 60 mL/min/1.73 m and therefore eGFR(MDRD) is preferable in detecting donors with GFR less than 60 mL/min/1.73 m.

The identification of biomarkers that can measure the biological age of an allograft could aid in optimizing the allocation of the allograft to specific recipients to maximize the life of each transplanted organ. Older kidneys have been shown to be more susceptible to chronic graft dysfunction (CGD) and graft failure (GF) when compared with younger kidneys after transplantation (1, 2). Older kidneys have a faster progression of tubular atrophy and tubular loss when compared younger kidneys (3) as well as having an increased incidence of delayed graft function (4), and this is felt to be an intrinsic feature of the older donated kidney. This has become an important issue, as older kidney allografts are increasingly being used in transplantation along with the poorer outcomes associated with these older kidneys, especially when transplanted into young recipients (5). Cellular replicative senescence, due to aging, is thought to play an important role in loss of graft function and this senescence may be linked to telomere length (TL) (6). Additionally, it has been suggested that younger recipients have a higher risk of acute rejection (AR) events than older recipients (7, 8), although these results are controversial (9). This reduced risk for AR in older recipients may be due to an older immune system that is less responsive, resulting in a lower risk of AR. Progressively shorter TL in immune cells due to aging in recipients may be a reason reduced immune response potentially making TL a better predictor of AR than chronological age. The aging of tissues and organs is a controlled biological process. Somatic cells have been shown to have a limited replicative capacity (10) and this is thought to be associated, in part, with the reduction in TL as chromosome replication occurs with each cell division (11). Telomeres consist of multiple copies (100s–1000s) of short (6 nucleotide) repeats at the end of all chromosomes, playing a protective role against chromosome deterioration. With every round of DNA replication in somatic cells, TL is reduced and this progressive shorting is thought to have a fundamental role in cell senescence. TL is thought to reflect the remaining replicative potential of a population of cells (10). TL is heritable and shortens throughout life, making TL a potential marker for the “biological age” of a tissue (12). The analysis of TL as a predictive marker of transplant outcome has been previously reported. It has been shown that TL may be a marker of treatment-related mortality in hematopoietic stem cell transplantation (13). A study by Bansal et al. (14) found that reduced TL was associated with reduced kidney function, but the significance was lost after adjustment for age. A modest significance associating TL and variation in serum creatinine levels in transplanted kidneys has also been reported (15). Using senescence-associated β-galactosidase (SA-β-Gal) enzyme as a marker, donor age appeared to be the major determinant factor in replicative senescence, as seen in higher expression of SA-β-Gal in donor kidneys with chronic allograft nephropathy (16). It was found that TL was significantly shorter in SA-β-Gal–expressing cells. Additionally, ischemia-reperfusion during transplantation of primate kidneys was associated with a more rapid decrease in TL (17). It has also been shown that TL shortens more rapidly in transplanted human liver allografts than in untransplanted livers resulting in a shorter than expected life for liver allografts, as would be predicted by the chronological age of the donor (18). Because of this progressive decrease in the TL, individuals who obtain a kidney from a donor with shorter than normal telomeres may be at greater risk for reduced graft survival and more susceptible to age associated disease, including allograft dysfunction. The DeKAF Genomics study contains a large number of recipient/living donor pairs along with clinical outcomes (19). We hypothesized that the biological age of the allograft, as estimated using TL from peripheral blood DNA, would be more reflective of risk for transplant outcomes than the chronological age of the allograft. We investigated if TL, in either the recipient or the donor, is associated with kidney allograft outcome.

Living kidney donors have donation-related out-of-pocket costs (direct costs) and/or ongoing daily expenses while losing income (indirect costs). Yet there is little information about how much of a subjective burden these constitute for the donors.From December 2003 through December 2014, we surveyed donors 6 months postdonation to determine their financial burden related to donation (on a scale of 1 to 10) and what resources were used to cover expenses.Of 1136 surveyed, 796 (70%) responded. Among respondents, mean age at donation was 43.6 ± 10.6 years, 64% were women, 96% were white, and 53% were related by blood to their recipient. Overall, 26% scored their financial burden as 5 or higher; 8% scored it as 8 or higher. Increased expenses were associated with a higher reported burden; however, significant burden was reported by some with no out-of-pocket expenses (presumably due to lost wages and continuing expenses). The burden was scored as 5 or higher by 27% of those employed outside the home (n = 660), 15% homemakers, 13% retirees, 40% students; 28% unemployed; and 26% whose occupation was unknown. Over half (51%) of those receiving a local or (means-tested) national grant still reported moderate to severe burden. Besides grants, donors used a variety of sources to help offset expenses: dipped into savings, borrowed from friends or family, took out a loan, and/or had a fundraiser. Those with the highest burden reported using the most additional sources.Donors should not have to incur costs or a financial burden to donate; the transplant community should strive to make donation financially neutral.

The upper age limit to receive a kidney transplant has progressively risen, but the outcomes of elderly (ages ≥65 years) transplant recipients remain understudied. We therefore evaluated mortality, graft failure, and predictors of these outcomes in this population.Three cohorts of recipients transplanted between 1963 and 2012 (ages50 years [n=2900], 50-64 years [n=1218], and ≥65 years [n=364] at transplantation) were compared for allograft and patient outcomes. Three similar age cohorts transplanted after 2000 (n=1410) were studied separately to address era effect.Death-censored graft survival was higher in recipients ages ≥65 years: 5, 10, and 15 years was 90.7%, 80.4%, and 73.7%; for ages 50-64 years, it was 87.2%, 77.6%, and 71.5%; and for ages50 years was 79.8%, 70.3%, and 60.8%. Risk factors for graft failure in those ages ≥65 years included panel-reactive antibody10%, congestive heart failure (CHF), delayed graft function, and cellular rejection. The 5-, 10-, and 15-year patient survival rate was 69.7%, 36.0%, and 14.0% for those ages ≥65 years; 76.4%, 54.8%, and 34.0% for those ages 50-64 years; and 81.7%, 66.7%, and 52.2% for those ages50 years. For the entire cohort of elderly recipients, coronary artery disease and CHF were associated with mortality, and in those recipients transplanted after 2000, the risk factors for mortality were coronary artery disease, graft failure, peripheral vascular disease, and cause of end-stage renal disease listed as other. For graft failure, only CHF and cellular rejection were associated with this outcome.The overall outcomes of transplantation in elderly kidney transplant recipients ages ≥65 years are excellent, but the risk factors for mortality and graft failure are distinctly different than those observed in younger recipients.

Defining living donor (LD)-related risk factors affecting kidney transplant outcome will allow better donor selection and more educated informed consent when there is more than one potential donor. We studied risk factors in a large cohort at a single institution.We reviewed 1632 recipients who underwent LD kidney transplantation at the University of Minnesota between January 1, 1990, and October 1, 2009. Using Cox regression, we studied the effect of donor and recipient risk factors on patient and graft survival. We specifically examined the effect of donor age and human leukocyte antigen (HLA) matching because these are variables that may help clinical decision making when multiple potential donors exist.Mean donor age was 40.6 years for all transplants; 180 (11%) donors were 55 years or older, and 24 (1.5%) donors were older than 65 years. Mean number of HLA mismatches (per transplant) was 2.9 (29.2% of recipients had one to two HLA mismatches, 39.8% had three to four HLA mismatches, and 25% had five to six HLA mismatches). Donor age more than 65 years, five to six HLA mismatches, delayed graft function, and acute rejection were independent predictors of decreased patient and graft survival. When controlling for recipient age, donor age more than 65 years remained a risk factor for worse outcome.Our data suggest that advanced donor age (65 years) and degree of HLA mismatch (≥5) are independent donor-related risk factors associated with worse outcome. When multiple potential LDs exist, it may be ideal to attempt to use a donor younger than 65 years and with less than five HLA mismatches.

Recurrent glomerulonephritis (GN) remains an important cause of kidney allograft loss and whether rapid discontinuation of steroids (RDS) is associated with a higher risk of recurrence is not known.We studied recurrence rate, and graft and patient survival in four groups of recipients: 216 recipients with GN transplanted under RDS (group 1), 978 concurrent non-GN recipients transplanted under RDS (group 2), 260 historic comparator group transplanted for GN between 1994 and 1999 with steroid maintenance (group 3), and 950 recipients who were also transplanted between 1994 and 1999 for non-GN and also maintained on steroids (group 4). Regression analysis adjusting for donor and recipient factors, steroid and sirolimus use, and also GN type was used to address factors associated with recurrent disease.The 1-, 5-, and 7-year recurrence rate in the GN group under RDS was 6.7%, 13.7%, and 19.2% and in historic GN recipients maintained on steroids it was 2.4%, 3.8%, and 5.3%, respectively (P0.0001). RDS was associated with a higher adjusted risk of recurrent disease for all GN types (hazard ratio 4.86; 95% confidence interval 2.34-10.07; P0.0001). Graft and patient survival were similar in the two GN groups and both were highest among all groups. Notably, death-censored graft survival was not different among the groups.Steroid avoidance may be associated with a higher rate of recurrent GN but no apparent increase in risk of graft loss. This group of recipients needs to be studied more carefully, in larger numbers, and for a longer time period.

BACKGROUND The CYP4503A5*1 genotype is associated with lower tacrolimus concentrations. Although its effect is important, it incompletely explains the variability in tacrolimus concentrations and has a relatively low minor allele frequency in whites relative to African Americans (AA). METHODS We studied clinical and recipient genetic correlates of dose-normalized tacrolimus troughs (n=12,277) in the first 6 months posttransplant using a customized single-nucleotide polymorphism chip with 2722 variants in a large, ethnically diverse (144 AA and 551 non-AA) adult kidney transplant population through a seven-center consortium. RESULTS During the 6-month study, AAs had consistently lower median (interquartile range) troughs than non-AAs, 6.2 (4.4-8.4) ng/mL vs. 8.3 (6.4-10.4) ng/mL (P

Background. Acute rejection (AR) is associated with worse renal allograft outcomes. Therefore, this study investigated single-nucleotide polymorphisms (SNPs) to identify genetic variants associated with AR, accounting for center variation, in a multicenter, prospective, observation study. Methods. We enrolled patients from six transplant centers, five in the United States and one in Canada. A total of 2724 SNPs were genotyped. We accounted for center variation in AR rates by stratifying by transplant center and using novel knowledge discovery methods. Results. There was significant center variation in AR rates across the six transplant sites (P