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Background and Aims With rising demand for kidney transplantation and the kidney donor pool lagging behind, the acceptance criteria for donor kidneys are expanding. Hence, reliable pre-transplant assessment of organ quality has become a top priority. Estimating the risk of adverse outcomes at the time of kidney allocation is challenging and particularly relevant for recipients of kidneys from older donors. The existing kidney donor risk index (KDRI) has been criticized for heavily depending on donor age. Therefore, the aim of the current study was to develop and validate a prediction model for adverse outcome after kidney transplantation from deceased donors aged 50 years or older and compare this model’s performance to the KDRI. Method We utilized the Dutch kidney transplant registry (NOTR) and identified patients who received a kidney from a deceased donor aged 50 years or older between 2006 and 2019. These recipients were included for model development and temporal validation. The prediction model was externally validated on the United States organ transplantation registry (OPTN), in which we selected patients that were transplanted between 2006 and 2017. Potential pre-transplant predictors were selected by an expert panel of nephrologists and surgeons. The predicted adverse outcome was defined as a composite of graft failure, recipient mortality or CKD stage 4/5 within 1 year of transplantation. A logistic regression model was developed, internally validated and shrunk for optimism through bootstrapping. Missing data were multiply imputed in 10-fold, non-linear continuous predictors were modelled with restricted cubic splines and clinically relevant interaction terms were included. The KDRI was validated on the same NOTR and OPTN cohorts for graft survival within 1 year. The developed model and the KDRI were recalibrated to the baseline risk of outcome in external validation. Model performance was assessed by discrimination and calibration. Results The model was developed on 2510 patients of whom 823 experienced an adverse outcome within the first year. The temporal validation cohort contained 837 patients of whom 230 had an adverse outcome and the US external validation cohort consisted of 31987 patients with 6758 adverse outcomes. Selected donor predictors were: age, gender, BMI, cause of death, CPR, inotropes use, serum creatinine, hypertension, hypotension, diabetes, smoking, left/right kidney, warm ischemic time, cold ischemic time and proteinuria. Recipient predictors were: age, gender, BMI, diabetes, cardiovascular comorbidity, primary kidney disease, dialysis duration, number of previous kidney transplantations, HLA mismatches and PRA. Discrimination of the adverse outcome model was moderate, yet considerably better than discrimination of the KDRI (see table). The adverse outcome model’s calibration and distribution of predicted risks were good in both the NOTR and OPTN (see figure). Conclusion A prediction model was developed and extensively validated for adverse outcome after kidney transplantation from older deceased donors. Despite the use of advanced and robust methodology, its discriminatory capacity was limited. However, the adverse outcome model showed good calibration and performed considerably better than the KDRI in this population of suboptimal donors. This model could potentially assist nephrologists in deciding whether to accept or decline a specific kidney from an older deceased donor.

Background. FTY720 (fingolimod), a novel immunomodulator, has demonstrated potential for prevention of acute rejection in combination with cyclosporine.Methods. This study evaluated FTY720 2.5 mg versus mycophenolate mofetil (MMF) in a combination regimen with standard tacrolimus and corticosteroids in de novo renal transplant recipients for the composite efficacy within 6 months of transplantation.Results. Incidence of treated biopsy-proven acute rejection was 22.9% with FTY720 and 18.5% with MMF. Increased incidence of macular oedema, transient decrease in heart rate and low rate of infections were seen in the FTY720 arm.Conclusion. FTY720 combined with tacrolimus and steroids did not show a significant therapeutic advantage over MMF for the prevention of acute rejection in de novo renal transplant recipients. © The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

In 1991 and 1992 Pneumocystis carinii pneumonia (PCP) was diagnosed in 28 renal transplant recipients. The incidence of PCP in our renal transplant centre was remarkably increased from 1.1% before 1991 to 11.5% in 1991-1992. We compared 28 PCP patients with a control group of 27 renal transplant recipients, matched for transplantation day and without an episode of PCP. The mean age was significantly higher in the PCP group (50 ± 13 versus 38 ± 13 years). We observed no differences in basic immunosuppressive and rejection treatment nor in antibiotic consumption, number of hospitalization days, and incidence of CMV infection. In March 1993 we introduced PCP prophylaxis. More than 140 renal transplant recipients received co-trimoxazole, starting 1 day after transplantation and continued for a period of 4 months. To the time of writing no one in this group had developed PCP.

The possible presence of lithium transport beyond the proximal tubule was examined by measuring lithium excretion after administration of triamterene, a potassium-sparing diuretic, exclusively acting in the cortical collecting tubule. Eight young and healthy volunteers were studied on two occasions during maximal water diuresis. After obtaining baseline values triamterene (100 mg orally) or placebo was administered, and measurements continued for 4 hours. Creatinine clearance was used as a marker of glomerular filtration rate, and phosphate excretion was used as an additional marker of proximal sodium transport. Compared to placebo (P), triamterene (T) caused a significant increase in fractional excretion of sodium (P, 0.74 +/- 0.08%; T, 1.73 +/- 0.24%, mean +/- SEM; P less than 0.01), and lithium (P, 21.2 +/- 1.3%; T, 27.5 +/- 1.5%; P less than 0.01), whereas fractional excretion of phosphate remained unchanged (P, 9.8 +/- 1.3%; T, 9.4 +/- 1.5%; P = NS). These results indicate that lithium is transported in the cortical collecting tubule, and provide further evidence that the use of lithium as a marker of purely proximal tubular sodium transport is of limited value.

The prevalence of hypertension was studied in renal transplant recipients followed for at least 1 year. Twenty-eight patients with a transplant renal artery stenosis, all with hypertension, were excluded from further study. Hypertension was present at 1 year after transplantation in 48.3% of 329 cadaveric renal graft recipients, treated with azathioprine. These hypertensive patients had experienced more rejection episodes. The prevalence of hypertension was higher in patients with (n = 237) than in those without (n = 92) host kidneys in situ (57.8% and 23.9% respectively, P less than 0.001). In patients with host kidney, the prevalence of hypertension was higher in patients with glomerulonephritis (n = 108) than in those in whom interstitial nephritis (n = 63) was the original renal disease (71.3% and 42.8 respectively, P less than 0.001). In 41 patients initially treated with cyclosporin and in 42 recipients of a kidney from a living donor, the prevalence of hypertension was not clearly lower than in the azathioprine-treated patients. In 30 patients without host-kidneys who did not experience acute rejections, only three had hypertension. In all three patients a specific cause for the hypertension was found. In hypertensive patients, blood pressure decreased gradually in the years following transplantation. In conclusion, besides transplant renal artery stenosis, the main determinants of the prevalence of hypertension after renal transplantation are host kidneys original renal disease, and rejection.