Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality. However, most analyses have included control groups less healthy than the living donor population and have had relatively short follow-up periods. Here we compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation. All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval 1.11-1.52) for donors compared with controls. There was a significant corresponding increase in cardiovascular death to 1.40 (1.03-1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37-29.6). The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors. Immunological renal disease was the cause of ESRD in the donors. Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have lately become the recommended treatment in patients with type 2 diabetes and high cardiovascular risk. Patients with posttransplant diabetes mellitus (PTDM) also have high cardiovascular risk. The aim of this study was to investigate the safety and efficacy of empagliflozin in renal transplant recipients with PTDM. RESEARCH DESIGN AND METHODSForty-nine renal transplant recipients were included in an investigator-initiated, single-center, prospective, double-blind study and randomized to receive either 10 mg empagliflozin or placebo once daily for 24 weeks. Patients transplanted >1 year ago, diagnosed with PTDM, with stable renal function (estimated glomerular filtration rate [eGFR] >30 mL/min/1.73 m 2 ), and with stable immunosuppressive therapy were studied. RESULTS Forty-four renal transplant recipients (22 empagliflozin/22 placebo, 34 males) completed the study. Median (interquartile range) change in glycated hemoglobin (HbA 1c ) was significantly reduced with empagliflozin compared with placebo: 20.2% (20.6, 20.1) (22.0 mmol/mol [26.5, 21.0]) vs. 0.1% (20.1, 0.4) (1.0 mmol/mol [20.75, 3.8]) (P = 0.025). The magnitude of glucose reduction was dependent on GFR and baseline HbA 1c. The treatment also resulted in a significant reduction in body weight of 22.5 kg (24.0, 20.05) compared with an increase of 1.0 kg (0.0, 2.0) in the placebo group (P = 0.014). There were no significant differences between the groups in adverse events, immunosuppressive drug levels, or eGFR. CONCLUSIONSEmpagliflozin appeared safe and improved glycemic control in renal transplant recipients with PTDM compared with placebo. A concomitant reduction in body weight was seen.Posttransplant diabetes mellitus (PTDM) is a serious condition that may follow renal transplantation. In the early posttransplant period, hyperglycemia is common in renal transplant recipients mainly due to high doses of immunosuppressive therapy (1,2). However, 10-20% of renal transplant recipients without a prior history of diabetes develop persisting hyperglycemia after renal transplantation, defined as PTDM (3-6).

Background Preliminary data suggest that COVID-19 has reduced access to solid organ transplantation. However, the global consequences of the COVID-19 pandemic on transplantation rates and the effect on waitlisted patients have not been reported. We aimed to assess the effect of the COVID-19 pandemic on transplantation and investigate if the pandemic was associated with heterogeneous adaptation in terms of organ transplantation, with ensuing consequences for waitlisted patients.Methods In this population-based, observational, before-and-after study, we collected and validated nationwide cohorts of consecutive kidney, liver, lung, and heart transplants from 22 countries. Data were collected from Jan 1 to Dec 31, 2020, along with data from the same period in 2019. The analysis was done from the onset of the 100th cumulative COVID-19 case through to Dec 31, 2020. We assessed the effect of the pandemic on the worldwide organ transplantation rate and the disparity in transplant numbers within each country. We estimated the number of waitlisted patient life-years lost due to the negative effects of the pandemic. The study is registered with ClinicalTrials.gov, NCT04416256.Findings Transplant activity in all countries studied showed an overall decrease during the pandemic. Kidney transplantation was the most affected, followed by lung, liver, and heart. We identified three organ transplant rate patterns, as follows: countries with a sharp decrease in transplantation rate with a low COVID-19-related death rate; countries with a moderate decrease in transplantation rate with a moderate COVID-19-related death rate; and countries with a slight decrease in transplantation rate despite a high COVID-19-related death rate. Temporal trends revealed a marked worldwide reduction in transplant activity during the first 3 months of the pandemic, with losses stabilising after June, 2020, but decreasing again from October to December, 2020. The overall reduction in transplants during the observation time period translated to 48 239 waitlisted patient life-years lost.Interpretation We quantified the impact of the COVID-19 pandemic on worldwide organ transplantation activity and revealed heterogeneous adaptation in terms of organ transplantation, both at national levels and within countries, with detrimental consequences for waitlisted patients. Understanding how different countries and health-care systems responded to COVID-19-related challenges could facilitate improved pandemic preparedness, notably, how to safely maintain transplant programmes, both with immediate and non-immediate life-saving potential, to prevent loss of patient life-years.

PurposeTo identify patient characteristics that influence tacrolimus individual dose requirement in kidney transplant recipients.MethodsData on forty-four 12-h pharmacokinetic profiles from 29 patients and trough concentrations in 44 patients measured during the first 70 days after transplantation (1,546 tacrolimus whole blood concentrations) were analyzed. Population pharmacokinetic modeling was performed using NONMEM 7.2®.ResultsStandardization of tacrolimus whole blood concentrations to a hematocrit value of 45 % improved the model fit significantly (p < 0.001). Fat-free mass was the best body size metric to predict tacrolimus clearance and volume of distribution. Bioavailability was 49 % lower in expressers of cytochrome P450 3A5 (CYP3A5) than in CYP3A5 nonexpressers. Younger females (<40 years) showed a 35 % lower bioavailability than younger males. Bioavailability increased with age for both males and females towards a common value at age >55 years that was 47 % higher than the male value at age <40 years. Bioavailability was highest immediately after transplantation, decreasing steeply thereafter to reach its nadir at day 5, following which it increased during the next 55 days towards an asymptotic value that was 28 % higher than that on day 5.ConclusionsHematocrit predicts variability in tacrolimus whole blood concentrations but is not expected to influence unbound (therapeutically active) concentrations. Fat-free mass, CYP3A5 genotype, sex, age and time after transplant influence the tacrolimus individual dose requirement. Because hematocrit is highly variable in kidney transplant patients and increases substantially after kidney transplantation, hematocrit is a key factor in the interpretation of tacrolimus whole blood concentrations.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-013-1584-7) contains supplementary material, which is available to authorized users.

Background. Kidney transplantation generally improves long-term survival in patients with end-stage renal disease. However, in patients older than 70 years of age, only limited data are available that directly compare the potential survival benefit of transplantation versus dialysis.Methods. All patients aged above 70 years who started dialysis between 1990 and 2005 and were waitlisted for kidney transplantation were included in the study. They were categorized according to time periods of inclusion (1990–99 vs 2000–05). Survival rates of altogether 286 dialysis patients were analyzed with a Kaplan–Meier model, as well as with a time-dependent Cox model. Comparisons were made between those who received a transplant and those who did not, and further between the two time periods.Results. Median age at inclusion was 73.6 years (interquartile range 72.3–75.6). Two hundred and thirty-three patients (81%) received a kidney transplant during follow-up. Transplant recipients experienced an increased mortality in the first year after transplantation when compared to waitlisted patients. Patients starting dialysis between 1990 and 1999 had no significant long-term benefit of transplantation; HR for death 1.01 (0.58–1.75). In contrast, there was a substantial long-term benefit of transplantation among those starting dialysis after 2000; HR for death 0.40 (0.19–0.83), P = 0.014.Conclusions. Survival after kidney transplantation in patients over 70 years has improved during the last decade and offers a survival advantage over dialysis treatment. Our experience supports the use of kidney transplantation in this age group if an increased early post-operative risk is accepted. This transplant policy may be challenged for priority reasons.