Prediction models for delayed graft function: external validation on The Dutch Prospective Renal Transplantation Registry.

Background: Delayed graft function (DGF) is a common complication after kidney transplantation in the era of accepting an equal number of brain- and circulatory-death donor kidneys in the Netherlands. To identify those cases with an increased risk of developing DGF, various multivariable algorithms have been proposed. The objective was to validate the reproducibility of four predictive algorithms by Irish et al. (A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transplant 2010;10:2279-2286) (USA), Jeldres et al. (Prediction of delayed graft function after renal transplantation. Can Urol Assoc J 2009;3:377-382) (Canada), Chapal et al. (A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors. Kidney Int 2014;86:1130-1139) (France) and Zaza et al. (Predictive model for delayed graft function based on easily available pre-renal transplant variables. Intern Emerg Med 2015;10:135-141) (Italy) according to a novel framework for external validation. Methods: We conducted a prospective observational study with data from the Dutch Organ Transplantation Registry (NOTR). Renal transplant recipients from all eight Dutch academic medical centers between 2002 and 2012 who received a deceased allograft were included (N = 3333). The four prediction algorithms were reconstructed from donor, recipient and transplantation data. Their predictive value for DGF was validated by c-statistics, calibration statistics and net benefit analysis. Case-mix (un)relatedness was investigated with a membership model and mean and standard deviation of the linear predictor. Results: The prevalence of DGF was 37%. Despite a significantly different case-mix, the US algorithm by Irish was best reproducible, with a c-index of 0.761 (range 0.756 - 0.762), and well-calibrated over the complete range of predicted probabilities of having DGF. The US model had a net benefit of 0.242 at a threshold probability of 0.25, compared with 0.089 net benefit for the same threshold in the original study, equivalent to correctly identifying DGF in 24 cases per 100 patients (true positive results) without an increase in the number of false-positive results. Conclusions: The US model by Irish et al. was generalizable and best transportable to Dutch recipients with a deceased donor kidney. The algorithm detects an increased risk of DGF after allocation and enables us to improve individual patient management.

Long-term cardiovascular outcome of renal transplant recipients after early conversion to everolimus compared to calcineurin inhibition: results from the randomized controlled MECANO trial.

Long-term data on cardiovascular (CV) outcome of renal transplant recipients (RTR) on mTOR-i (mammalian Target Of Rapamycin-inhibitors) are scarce. In a sub-study of the MECANO trial we investigated changes in intima media thickness (IMT), CV risk profile, Major Adverse CV Events (MACE) and survival in RTR on a mTORi versus CNI based regimen. Patients (enrolled 361) were treated with (basiliximab) and triple IS (CsA-Cyclosporine A-(C), MPS (M), prednisolone (P)). At M6 patients were randomized (n = 224) to the CsA group (C, P, N = 89), MPS group (M, P, N = 39) EVL group (Everolimus, P, N = 96). At week 2, M6 and M 24, IMT measurements of the Common Carotid Artery were performed. Cardiovascular risk factors were assessed at baseline, 6 and 24 months of follow-up. Seven years survival and MACE-free survival probability were calculated by the Cardiovascular Risk Calculator for RTR. After 7 years of follow-up, incidence of cardiovascular events and patient survival were assessed. Mean IMT at baseline (N = 192), was 0.64 ± 0.14 mm. At M6 (N = 158), 0.66 ± 0.15, M24 IMT was 0.68 ± 0.15 (N = 95). No significant differences between groups concerning IMT, true CV events and mortality, CV risk profile, predicted MACE/Mortality were found between mTORi and CNI-based regimen after 7 years of follow-up.

Stretching the Limits of Renal Transplantation in Elderly Recipients of Grafts from Elderly Deceased Donors.

An increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002-2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly donor, stratified by donor type. In multiple logistic regression analysis, elderly recipients of elderly DCD kidneys experienced more delayed graft function and acute rejection than did elderly recipients of young DBD kidneys (odds ratios 10.43 [95% confidence interval (95% CI), 5.75 to 18.91] and 2.78 [95% CI, 1.35 to 5.73], respectively). In Cox regression analysis, elderly recipients of elderly DCD kidneys had a 5-year mortality risk higher than that of elderly recipients of young DBD kidneys (hazard ratio, 1.86; 95% CI, 1.15 to 3.02). Elderly recipients of elderly kidneys had a 5-year mortality rate comparable to that of waitlisted elderly patients remaining on dialysis. Among elderly recipients, 63.8% of those who received elderly DCD kidneys, 45.5% of those who received elderly DBD kidneys, and approximately 26% of those who received young DBD or DCD kidneys had an eGFR<30 ml/min per 1.73 m2 (including primary nonfunction) after 1 year. In conclusion, improving donor selection and preservation is warranted if the allocation of elderly DCD grafts to elderly recipients is to be expanded.

Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy.

BACKGROUND: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). METHODS: A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV-associated nephropathy (BKVAN). RESULTS: From 6 months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) (P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group (P=.03). CONCLUSIONS: Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus.

Changes of perceived control after kidney transplantation: a prospective study.

AIMS: The aim of this study was to determine if kidney transplantation is associated with increases of perceived control and how changes of perceived control affect the course of psychological distress until 1 year after transplantation. BACKGROUND: Low levels of perceived control are associated with reduced well-being among dialysis patients. DESIGN: Prospective longitudinal cohort study. METHODS: Perceived control (Mastery Scale) and psychological distress (GHQ-12) were prospectively assessed before (T0; n = 470) and three (T1; n = 197), six (T2; n = 210) and twelve (T3; n = 183) months after transplantation. Differences between T1 and T0 perceived control were used to stratify the sample into three groups (control gain, stable control and control loss). Socio-demographic and clinical variables, including complications, were examined as potential correlates and the course of psychological was distress compared across groups. Data were collected between July 2008 - July 2013. RESULTS: Perceived control showed a small increase overall, with 35·1%, 50·0% and 14·9% reporting gain, stable level and loss respectively. Patients with secondary schooling were overrepresented in the control loss group. The course of psychological distress varied across perceived control change groups, with patients in the control gain group experiencing a significant reduction in psychological distress. CONCLUSION: A considerable number of patients report increased levels of perceived control after transplantation that are associated with a subsequent decrease in psychological distress. Results emphasize the importance of perceived control and could inform interventions to facilitate well-being after kidney transplantation.

Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients.

AIMS: This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). METHODS: Adult renal transplant recipients (n = 361) on cyclosporine-based immunosuppression were followed for the first 6 months after transplantation. The incidence of DGF and AR were documented as well as the prevalence of SCR at 6 months in surveillance biopsies. Demographic, transplant-related factors, pharmacological and pharmacogenetic factors (ABCB1, CYP3A5, CYP3A4, CYP2C8, NR1I2, PPP3CA and PPP3CB) were analysed in a combined approach in relation to the occurrence of DGF, AR and prevalence of SCR at month 6 using a proportional odds model and time to event model. RESULTS: Fourteen per cent of the patients experienced at least one clinical rejection episode and only DGF showed a significant effect on the time to AR. The incidence of DGF correlated with a deceased donor kidney transplant (27% vs. 0.6% of living donors). Pharmacogenetic factors were not associated with risk for DGF, AR or SCR. A deceased donor kidney and acute rejection history were the most important determinants for SCR, resulting in a 52% risk of SCR at 6 months (vs. 11% average). In a sub-analysis of the patients with AR, those treated with rejection treatment including ATG, significantly less frequent SCR was found in the 6-month biopsy (13% vs. 50%). CONCLUSIONS: Transplant-related factors remain the most important determinants of DGF, AR and SCR. Furthermore, rejection treatment with depleting antibodies effectively prevented SCR in 6-month surveillance biopsies.

Role of the vascular wall in sodium homeostasis and salt sensitivity.

Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume.

The Biobank of Nephrological Diseases in the Netherlands cohort: the String of Pearls Initiative collaboration on chronic kidney disease in the university medical centers in the Netherlands.

Despite advances in preventive therapy, prognosis in chronic kidney disease (CKD) is still grim. Clinical cohorts of CKD patients provide a strategic resource to identify factors that drive progression in the context of clinical care and to provide a basis for improvement of outcome. The combination with biobanking, moreover, provides a resource for fundamental and translational studies. In 2007, the Dutch government initiated and funded the String of Pearls Initiative (PSI), a strategic effort to establish infrastructure for disease-based biobanking in the University Medical Centres (UMCs) in the Netherlands, in a 4-year start-up period. CKD was among the conditions selected for biobanking, and this resulted in the establishment of the Biobank of Nephrological Diseases-NL (BIND-NL) cohort. Patients with CKD Stages 1-4 are eligible. The data architecture is designed to reflect routine care, with specific issues added for enrichment, e.g. questionnaires. Thus, the collected clinical and biochemical data are those required by prevailing guidelines for routine nephrology care, with a minimal dataset for all patients, and diagnosis-specific data for the diagnostic categories of primary and secondary glomerular disorders and adult dominant polycystic kidney disease, respectively. The dataset is supplemented by a biobank, containing serum, plasma, urine and DNA. The cohort will be longitudinally monitored, with yearly follow-up for clinical outcome. Future linking of the data to those from the national registries for renal replacement therapy is foreseen to follow the patients' lifeline throughout the different phases of renal disease and different treatment modalities. In the design of the data architecture, care was taken to ensure future exchangeability of data with other CKD cohorts by applying the data harmonization format of the Renal DataSHaPER, with a dataset based upon standardized indicator sets to facilitate collaboration with other CKD cohorts. Enrolment started in 2010, and over 2200 eligible patients have been enrolled in the different UMCs. Follow-up of enrolled patients has started, and enrolment will continue at a slower rate. The aggregation and standardization of clinical data and biosamples from large numbers of CKD patients will be a strategic resource not only for clinical and translational research, but also by its basis in routine clinical care for clinical governance and quality improvement projects.

Sodium intake and blood pressure in renal transplant recipients.

BACKGROUND: Hypertension is common among renal transplant recipients (RTR) and a risk factor for graft failure and mortality. Sodium intake is a well-established determinant of blood pressure (BP) in the general population. However, data in RTR are limited. International guidelines recommend a maximum daily sodium intake of 70 mmol. We investigated sodium intake in RTR as compared to healthy controls and its association with BP. METHODS: We included 660 RTR (age 53 ± 13 years, 58% male) and 201 healthy controls (age 54 ± 11 years, 46% male). Sodium intake was assessed from 24-h urine collections. The morning after completion of urine collection, BP was measured according to a strict protocol. RESULTS: Urinary sodium excretion was 156 ± 62 mmol/24 h in RTR and 195 ± 75 in controls (difference: P < 0.001), and 95% of RTR had a urinary sodium excretion >70 mmol/24 h. Systolic BP (SBP) and diastolic BP (DBP) were 136 ± 18 and 82 ± 11 mmHg, respectively. Sodium intake was positively associated with SBP (ß = 0.042 mmHg/mmol/24 h, P = 0.002) and DBP (ß = 0.023 mmHg/mmol/24 h, P = 0.007), independent of potential confounders. CONCLUSIONS: Although RTR had a lower sodium intake than healthy controls, their intake still exceeded current guidelines. Reduction of sodium intake to recommended amounts could reduce SBP by 4-5 mmHg. Better control of sodium intake may help to prevent graft failure and mortality due to hypertension among RTR.

Plasma bilirubin and late graft failure in renal transplant recipients.

Exogenous bilirubin has been shown to protect against oxidative stress in ischemia-reperfusion injury. Oxidative stress has been implicated in the pathophysiology of chronic transplant dysfunction leading to late graft failure after renal transplantation. We prospectively investigated whether high endogenous bilirubin is protective against development of late graft failure in renal transplant recipients (RTR). Baseline data were collected between August 2001 and July 2003 in nonicteric outpatient RTR with a functioning graft for >1 year. At baseline, bilirubin and liver enzymes were measured using routine assays on a Merck Mega analyzer. Graft failure was prospectively recorded until May 19 2009. During follow-up for 7.1 [6.2-7.2] years, 55 RTR developed graft failure. We found that circulating levels of bilirubin are inversely associated with late graft failure in RTR (HR = 0.29 [95% CI: 0.16-0.52], P < 0.001). This association was independent of potential confounders, including creatinine clearance, urinary protein excretion, calcineurin inhibitors, and gender (HR = 0.31 [95% CI: 0.15-0.62] P = 0.001). Our findings are consistent with a protective effect of increased endogenous bilirubin against development of late graft failure in RTR. If our findings are confirmed by other studies, intervention with endogenous or exogenous bilirubin may be of interest for long-term preservation of renal function in RTR.

Higher body mass index is associated with higher fractional creatinine excretion in healthy subjects.

BACKGROUND: Accurate glomerular filtration rate (GFR) measurement in normal to high range is important for epidemiological studies and workup for kidney donation. Creatinine-based equations perform poorly in this GFR range. Creatinine clearance (CrCl) provides a substitute, provided urine is collected accurately and tubular creatinine handling can be accounted for. The latter is poorly characterized in the normal GFR range. METHODS: Therefore, we studied performance of CrCl, fractional creatinine excretion (FE(creat)) and its determinants in 226 potential kidney donors (47% males, mean 53 ± 10 years). GFR was assessed as (125)I-iothalamate clearance, simultaneously with 2-h CrCl and 24-h CrCl. RESULTS: Mean GFR was 101 ± 18, 2-h CrCl 110 ± 20 and 24-h CrCl 106 ± 29 mL/min/1.73 m(2). Mean bias of 24 h CrCl was 7.4 [inter-quartile range -6.7 to 20.0] mL/min/1.73 m(2), precision (R(2)) 0.39 and 30% accuracy 82%. Mean FE(creat) was 110 ± 11%. FE(creat) correlated with body mass index (BMI) (r = 0.34, P < 0.001). Consequently, bias of 24-h CrCl increased from 2.7 (inter-quartile range -6.5 to 16.7) to 8.6 (inter-quartile range -5.8 to 20.5) and 12.6 (inter-quartile range 7.0 to 25.4) mL/min in subjects with BMI <25, 25-30 and >30 kg/m(2), respectively (P < 0.05). On multivariate analysis, BMI and gender were predictors of FE(creat). CONCLUSIONS: CrCl systematically overestimates GFR in healthy subjects. The overestimation significantly correlates with BMI, with higher FE(creat) in subjects with higher BMI. The impact of BMI on tubular creatinine secretion can be accounted for, when using CrCl for GFR assessment in the normal to high range, by the following formula: GFR = 24-h CrCl - (22.75 + 0.76 × BMI - 0.29 × mean arterial pressure (-6.11 if female).

Machine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death.

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heart-beating deceased ECDs--defined according to the United Network of Organ Sharing definition--were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P=0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P=0.04). One-year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P=0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys. (Current Controlled Trials number: ISRCTN83876362).

Body mass index and creatinine clearance are associated with steady-state serum concentrations of the cell damage marker S100B in renal transplant recipients.

BACKGROUND: S100B is a prominent cell damage marker which can lead to sustained pro-inflammatory signaling. The aim was to investigate cross-sectional associations of steady-state S100B concentrations, particularly with C-reactive protein (CRP), in renal transplant recipients (RTRs) and also to investigate prospectively whether S100B would predict graft failure or mortality. MATERIAL/METHODS: Outpatient RTRs with a graft functioning for >1 year were eligible for participation in this study. S100B was determined at baseline from serum. Mortality and the occurrence of graft failure were recorded until September 2007. Multivariable linear regression analyses were performed to identify potential determinants of S100B. Multivariable Cox regression analyses were performed to investigate S100B as a potential predictor of mortality or graft failure. RESULTS: Five hundred eighty-one RTRs participated in the study. The median S100B concentration was 0.19 (0.14-0.25) microg/l. Recipient age (beta=0.009, p=0.02), body mass index (BMI) (beta=0.021, p<0.001), and creatinine clearance (beta=-015, p<0.001) were independently associated with S100B. During follow-up, 95 RTRs (16.4%) died and 41 (7.1%) developed graft failure. S100B levels did not predict mortality or graft failure. CONCLUSIONS: BMI, creatinine clearance, and age are determinants of steady-state serum S100B concentrations in renal transplant recipients. The association of BMI with S100B suggests that S100B might be a new adipokine.

The effect of additional drug therapy as metaphylaxis in patients with cystinuria: a systematic review.

INTRODUCTION: To systematically review the effect of additional drug therapy as metaphylaxis in patients with cystinuria. EVIDENCE ACQUISITION: A literature search of three databases (MEDLINE, Embase and the Cochrane Library) was performed according to the PRISMA-guidelines enclosing articles published up to May 2019. A total of 1117 articles were screened. Thirty-four publications met the inclusion criteria for this review. EVIDENCE SYNTHESIS: Male-female ratio in the studied cohorts was 49.9% - 50.1%. The majority of studies showed a positive effect in reducing stone events and/or urinary cystine excretion. D-Penicillamine showed success in 13/14 (92%) studies, whereas Tiopronin-treatment showed a reduction in all (8/8; 100%) studies. All studies on Captopril (4/4) showed a decrease, however not all significant. The same is true for studies on Thiols in combination with Captopril (2/2). Furthermore, Tiopronin showed less side effects compared to D-penicillamine, respectively 30% and 37%. Captopril showed the least adverse events, with one event in nine patients. CONCLUSIONS: The evidence on benefit of additional drug therapy in patients with cystinuria is scarce. All studied medications showed an effect on stone event and urinary cystine excretion, when used in addition to hyperhydration, alkalization and a diet low on methionine. Based on this systematic review, no drug can be preferred over another. An important aspect in the choice of drug is the risk of side effects. Therefore, the choice of additional drug should be personalized for every patient where the risk of side effects should be taken into consideration.

Impact of Cold Ischemia Time on Outcomes of Deceased Donor Kidney Transplantation: An Analysis of a National Registry.

BACKGROUND: Cold ischemia time (CIT) is known to impact kidney graft survival rates. We compare the impact of CIT on graft failure and mortality in circulatory death versus brain death donor kidneys and how it relates to donor age. METHODS: We used the prospective Dutch Organ Transplantation Registry to include 2153 adult recipients of brain death (n = 1266) and circulatory death (n = 887) donor kidneys after static cold storage from transplants performed between 2005 and 2012. CIT was modeled nonlinearly with splines. Associations and interactions between CIT, donor type, donor age, 5-year (death-censored) graft survival, and mortality were evaluated. RESULTS: The median CIT was 16.2 hours (interquartile range 12.8-20), ranging from 3.4 to 44.7 hours for brain death and 4.7 to 46.6 hours for circulatory death donor kidneys. At >12 hours of CIT, we observed an increased risk of graft failure in kidneys donated after circulatory death versus after brain death. This risk rose significantly at >22 hours of CIT (hazard ratio 1.45; 95% confidence interval, 1.01-2.49; P = 0.043). Kidneys that came from 60-year-old circulatory death donors demonstrated elevated hazard risk at 19 hours of CIT, a shorter timeline than that for kidneys that came from brain death donors of the same age (hazard ratio 1.33; 95% confidence interval, 1.00-1.78; P = 0.045). The additional harmful effects of increased CIT in kidneys from circulatory-death donors were also found for death-censored graft failure but did not affect mortality rates in any significant way. CONCLUSIONS: The findings support the hypothesis that prolonged cold ischemia is more harmful for circulatory death donor kidneys that have already been subjected to a permissible period of warm ischemia. Efforts should be made to reduce CIT, especially for older circulatory death donor kidneys.

Urinary creatinine excretion reflecting muscle mass is a predictor of mortality and graft loss in renal transplant recipients.

BACKGROUND: Insulin resistance has been implicated to underlie both excess cardiovascular disease and chronic transplant dysfunction after renal transplantation. Skeletal muscle mainly determines peripheral insulin resistance, and could therefore affect outcome. METHODS: All transplant recipients at our outpatient clinic with a functioning graft more than 1 year were invited to participate between 2001 and 2003. Mortality and death censored graft loss were recorded until August 2007. We used 24 hr urine creatinine excretion as measure of muscle mass. Cox regression was used to analyze the prospective data. RESULTS: Six hundred four renal transplant recipients (age 51+/-12 years, 55% men) were studied. Creatinine excretion was 10.1+/-2.6 mmol/24 hr in women and 13.6+/-3.4 mmol/24 hr in men. During follow-up of 5.3 (4.7-5.7) years, 95 recipients died and 42 suffered graft loss. Determinants of creatinine excretion were weight, sex, age, height, cumulative prednisolone doses, and diabetes (r2=0.45). Creatinine excretion was associated with both mortality (3rd vs. 1st tertile Hazard ratio: 0.4 [95% confidence interval 0.2-0.7], P=0.003) and graft loss (3rd vs. 1st tertile Hazard ratio: 0.4 [95% confidence interval 0.1-0.9], P=0.03) independent of age, sex, serum creatinine, proteinuria, insulin resistance related factors, time after transplantation, and duration of dialysis. CONCLUSIONS: Creatinine excretion as measure of muscle mass is associated with mortality and graft loss after renal transplantation, independent of insulin resistance and its related factors. We speculate that preservation of muscle mass by stimulating exercise, sufficient diet, and less use of corticosteroids may be relevant for improving prognosis in renal transplant recipients.

Validation of the Prognostic Kidney Donor Risk Index Scoring System of Deceased Donors for Renal Transplantation in the Netherlands.

BACKGROUND: The prognostic Kidney Donor Risk Index (KDRI)-developed and internally validated in the United States-is a widely used tool to predict transplant outcome of a deceased donor kidney. The KDRI is currently used for longevity matching between donors and recipients in the United States. METHODS: We aimed to externally validate the KDRIdonor-only and KDRIfull as proposed by Rao et al (2009). KDRIdonor-only consist of 10 donor factors, and KDRIfull with an additional 4 transplant factors. We used the Dutch Organ Transplantation Registry to include 3201 adult recipients transplanted from 2002 to 2012. RESULTS: The median Dutch KDRI was 1.21 and comparable with the year 2012 in the United States (median of 1.24). The calibration-slope was 0.98 and 0.96 for the KDRIfull and KDRIdonor-only, respectively, indicating that predictions of graft failure were on average similar. The discriminative ability (Harrell C) of the KDRIfull and the KDRIdonor-only at 5 years was 0.63 (95% confidence interval [CI], 0.62-0.64), and 0.62 (95% CI, 0.61-0.63), respectively. We found misspecification of 3 KDRI factors: age (P = 0.002), weight (P = 0.017), and cold ischemia time (P < 0.001). Adding the use of inotropic drugs before donation (P = 0.040) and the interaction between circulatory-death donor kidneys and prolonged cold ischemic time (>24 hours vs 12 hours; P = 0.059) could improve predictive ability. CONCLUSIONS: The KDRI performs equal in the Dutch population. Discriminative ability of the KDRI indicates limited clinical use for adequate individualized decisions. An updated KDRI may contribute to a standardized policy meeting the growing demand of donor kidneys in the Eurotransplant region.

Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial.

BACKGROUND: The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown. METHODS: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies-one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation-were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization. RESULTS: This interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early steroid withdrawal group and the standard immunosuppression groups (43.2 mL/min per 1.73 m2 vs 45.0 mL/min per 1.73 m2, P = 0.408). There were also no significant differences in the secondary endpoints of death (1.0% vs 1.5%; P = 0.737), primary nonfunction (4.1% vs 1.5%, P = 0.159), graft failure (3.1% vs 1.5%, P = 0.370), rejection (18.6% vs 13.6%, P = 0.289), and discontinuation of study medication (19.6% vs 12.6%, P = 0.348). Treatment failure, defined as a composite endpoint of these individual secondary endpoints, was more common in the early steroid withdrawal group (P = 0.027), but this group had fewer serious adverse events and a more favorable cardiovascular risk profile. CONCLUSIONS: Based on these interim results, early steroid withdrawal is a safe short-term immunosuppressive strategy. Long-term outcomes, including a comparison with tacrolimus minimization after 6 months, will be reported in the final 2-year analysis.

No increase of melanoma after kidney transplantation in the northern part of The Netherlands.

One medical problem of renal transplant patients who receive immunosuppression therapy is the development of a malignancy during the long-term follow-up. Existing studies, however, are not in agreement over whether patients who undergo renal transplantation have an increased risk of melanoma. The aim of this study was to determine the risk of melanoma in renal transplantation patients in the northern part of The Netherlands. We linked a cohort of 1,125 patients who received a renal transplantation in the University Medical Centre Groningen between 1989 and 2003 with the Cancer Registry of the Comprehensive Cancer Centre North-Netherlands, to identify all the melanoma patients in this cohort. The risk for melanoma after renal transplantation was calculated using the Standardized Incidence Ratio and the absolute excess risk. With a mean follow-up of 7.26 +/- 4.48 years, one patient developed a melanoma after the renal transplantation; the number of melanoma patients was among the lowest compared with other studies. The absolute excess risk for melanoma after renal transplantation was 0.5/10,000 person-years. Although several epidemiologic studies have shown that the risk of melanoma is increased in renal transplantation patients who receive immunosuppression therapy to prevent allograft rejection, this significant increase was not found in this study. The low net immunosuppressive agents given might be responsible for this low number of melanomas.