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Background: Previous reports suggest increased risk of hypertension and cardiovascular mortality after kidney donation. In this study we investigate the occurrence of ischaemic heart disease and cerebrovascular disease, diabetes and cancer in live kidney donors compared with healthy controls eligible for donation., Methods: Different diagnoses were assessed in 1029 kidney donors and 16 084 controls. The diagnoses at follow-up were self-reported for the controls and registered by a physician for the donors. Stratified logistic regression was used to estimate associations with various disease outcomes, adjusted for gender, age at follow-up, smoking at baseline, body mass index at baseline, systolic blood pressure at baseline and time since the donation., Results: The mean observation time was 11.3 years [standard deviation (SD) 8.1] for donors versus 16.4 years (SD 5.7) for controls. The age at follow-up was 56.1 years (SD 12.4) in donors versus 53.5 years (SD 11.1) in controls and 44% of donors were males versus 39.3% in the controls. At follow-up, 35 (3.5%) of the donors had been diagnosed with ischaemic heart disease versus 267 (1.7%) of the controls. The adjusted odds ratio for ischaemic heart disease was 1.64 (confidence interval 1.10-2.43; P = 0.01) in donors compared with controls. There were no significant differences for the risks of cerebrovascular disease, diabetes or cancer., Conclusions: During long-term follow-up of kidney donors, we found an increased risk of ischaemic heart disease compared with healthy controls. This information may be important in the follow-up and selection process of living kidney donors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA-EDTA.)

Kidney transplant recipients (KTRs) are at increased risk of developing renal cell carcinoma (RCC). The cancer can be encountered at different steps in the transplant process. RCC found during work-up of a transplant candidate needs treatment and to limit the risk of recurrence usually a mandatory observation period before transplantation is recommended. An observation period may be omitted for candidates with incidentally discovered and excised small RCCs (<3 cm). Likewise, RCC in the donor organ may not always preclude usage if tumor is small (<2 to 4 cm) and removed with clear margins before transplantation. After transplantation, 90% of RCCs are detected in the native kidneys, particularly if acquired cystic kidney disease has developed during prolonged dialysis. Screening for RCC after transplantation has not been found cost-effective. Treatment of RCC in KTRs poses challenges with adjustments of immunosuppression and oncologic treatments. For localized RCC, excision or nephrectomy is often curative. For metastatic RCC, recent landmark trials in the nontransplanted population demonstrate that immunotherapy combinations improve survival. Dedicated trials in KTRs are lacking. Case series on immune checkpoint inhibitors in solid organ recipients with a range of cancer types indicate partial or complete tumor response in approximately one-third of the patients at the cost of rejection developing in ~40%., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Endothelial dysfunction is an early and potentially reversible stage in the atherosclerotic process. We assessed endothelial dysfunction noninvasively in kidney transplant recipients (KTRs) and evaluated the association with mortality and graft outcomes., Methods: Flow-mediated dilation (FMD) was measured in arteria brachialis by ultrasound, with baseline diameters obtained at rest and maximal diameters obtained during reactive hyperemia occurring after 5 min of forearm occlusion. FMD% is the percentage difference of flow-mediated dilation relative to baseline. Endpoints on mortality and graft outcomes were collected from The Norwegian Renal Registry. The distribution of risk according to FMD levels was assessed in Cox regression using a restricted cubic spline function. FMD was dichotomized using receiver operating characteristic analysis to identify optimal cut points at maximal sensitivity and specificity., Results: From a total of 269 KTRs in 2012, 152 (56.5%) were eligible and examined 10 wk after transplantation, and 145 had successful FMD measurements. During a mean follow-up of 6.5 y, 26 patients died, 11 lost their graft, and 34 experienced either graft loss or death. Mortality increased with lower FMD levels until about 5% dilation and did not change with further reduction in FMD% ( P for nonlinearity <0.01). An optimal cut point of FMD ≤5.36% defined impaired endothelial function and FMD% below this level, was associated with fatal outcome, hazard ratio (HR), 9.80 (1.29-74.62), P = 0.03, uncensored graft loss, HR, 7.80 (1.83-33.30), P = 0.01, but an association with death-censored graft loss was lost after adjusting for pulse pressure, HR, 4.58 (0.55-37.92), P = 0.16., Conclusions: We found that impaired FMD is strongly associated with mortality in KTRs., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by multiorgan dysfunction. Since individuals with FD usually experience progressive clinical disease manifestations, their health-related quality of life (HRQOL) is expected to change over time. However, there is limited longitudinal research examining HRQOL outcomes in individuals with FD. We aimed to: assess longitudinal outcomes in HRQOL in adults with FD; examine the physical- and mental HRQOL trajectories at the initial registration (baseline), 3-5 year, and 7-13 year follow-ups; and evaluate the possible associations of age, sex and medical complications with the physical- and mental HRQOL trajectories., Methods: Forty-three individuals with FD (53% female) who were aged 18 to 81 years at baseline attended clinical follow-up visits between 2006 and 2020. Medical records were extracted retrospectively. Demographics and the 36-item Short-Form Health Survey (SF-36) were recorded at scheduled visits, except for the last data collection which was prospectively obtained in 2020. The physical (PCS) and mental (MCS) composite scores (SF-36) were chosen as outcome measures., Results: The eight SF-36 domain scores were stable over a span of 13 years, and only physical- and social functioning domains worsened clinically over this follow-up period. Mean baseline SF-36 domain scores were all significantly lower (decreased HRQOL) in the FD sample compared with Norwegian population norms. Two hierarchical linear models were run to examine whether demographics and medical complications (measured at the last clinical visit) predicted physical and mental HRQOL trajectories. Age above 47 years (p < 0.001), male sex (p = 0.027), small fibre neuropathy (p < 0.001), renal dysfunction (p < 0.001), and cerebrovascular events (p = 0.003) were associated with lower HRQOL over time. No significant interactions were found between the time of follow up and the abovementioned predictors of HRQOL., Conclusions: Overall HRQOL trajectories remained stable between baseline, 3-5 year, and 7-13 year follow-ups, with the majority of individuals reporting decreased physical and mental HRQOL. Medical complications in combination with older age and male sex are important predictors of lower HRQOL in FD. Awareness of this relationship is valuable both for health care providers and for patients. The findings provide indicators that can guide treatment decisions to improve physical and mental HRQOL outcomes., (© 2021. The Author(s).)

Health-related quality of life (HRQOL) is reduced in Fabry disease (FD) and associated with clinical disease manifestations, but few have used Fabry-specific severity scores to study how disease burden interferes with quality of life. We investigated how the Fabry DS3, consisting of four somatic domains and one patient-reported item, associates with HRQOL, while also evaluating fatigue, pain and psychological distress as possible predictors. Thirty-six adults with FD completed the Short-form Health Survey (SF-36), the hospital anxiety and depression scale (HADS), the brief pain inventory (BPI) and reported fatigue on a visual analog scale. Clinical data were collected from the last multidisciplinary hospital visit. Using correlation and hierarchical linear regression analyses, we examined associations between demographic, clinical and self-reported predictors and the SF-36 physical (PCS) and mental (MCS) component summary scores. Males scored lower than the general population in all SF-36 domains ( P  < .05). General health and social functioning were reduced in females. Before including self-reported symptom scores, DS3 showed associations with PCS ( P  = .009). Our fully adjusted model explained 66% of the variation in PCS, where education ( P  = .040) and fatigue ( P  = .002) retained significance. With HADS depression score ( P  = .001) as the sole significant factor, our regression model explained 56% of the variation in MCS. The DS3 score has implications for HRQOL in FD. Low education and fatigue represent major barriers to physical well-being, while depression strongly influences mental quality of life. Fatigue should be recognized as an important endpoint in future FD trials. Increased efforts to diagnose and treat affective disorders are warranted., Competing Interests: The results reported in the current manuscript should not lead to financial gain or loss for any organization or company from which the authors have received fees/salaries. Hege K. Pihlstrøm and Ketil R. Heimdal have received honoraria for work as consultants for Amicus Therapeutics and Sanofi Genzyme. Trond G. Jenssen has received honoraria for work as a consultant for Takeda and Sanofi Genzyme. Charlotte von der Lippe, Mina S. Weedon‐Fekjær, Birgitte L. Bjerkely, Kristin Ørstavik, Per Mathisen, Dag O. Dahle and Olga K. Solberg declare that they have no conflict of interest, apart from grants received by NKSD for conduction of the study., (© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov]., Competing Interests: The authors have declared that no competing interests exist.

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Kidney donors may be at increased risk of end-stage renal disease and premature mortality. Elevated blood pressure after donation may contribute to the increased risks. In this cohort study, we have assessed long-term risk for the development of hypertension in kidney donors compared to a control group potentially eligible as donors. Follow-up data were obtained from previous living kidney donors. A healthy control group with baseline assessment from similar time periods as the donor nephrectomies was selected. Hypertension was defined as blood pressure >140/90, use of blood pressure medication, or established diagnosis of hypertension. Stratified logistic regression was used to estimate risk of hypertension at follow-up, adjusted for systolic blood pressure at baseline, age at follow-up, time since donation/baseline, gender, smoking at baseline, and BMI at baseline. A total of 368 donors (36%) had hypertension at follow-up, and 241 of these (23%) were using blood pressure medication. In adjusted stratified logistic regression analyses, odds ratio for hypertension was significantly increased (1.25, 95% confidence interval 1.12-1.39, P < 0.001) in donors compared with controls. Kidney donors appear to be at increased long-term risk for hypertension compared with healthy controls. This finding supports regular follow-up of blood pressure in kidney donors., (© 2020 Steunstichting ESOT.)

Purpose: Until recently, it has been believed that donating a kidney not represents any risk for development of cardiovascular disease. However, a recent Norwegian epidemiological study suggests that kidney donors have an increased long-term risk of cardiovascular mortality. The pathophysiological mechanisms linking reduced kidney function to cardiovascular disease are not known. Living kidney donors are screened for cardiovascular morbidity before unilateral nephrectomy, and are left with mildly reduced glomerular filtration rate (GFR) after donation. Therefore, they represent an unique model for investigating the pathogenesis linking reduced GFR to cardiovascular disease and cardiovascular remodelling. We present the study design of Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate (CENS), which is an investigator-initiated prospective observational study on living kidney donors. The hypothesis is that living kidney donors develop cardiovascular remodelling due to a reduction of GFR. Materials and methods: 60 living kidney donors and 60 age and sex matched healthy controls will be recruited. The controls will be evaluated to fulfil the Norwegian transplantation protocol for living kidney donors. Investigations will be performed at baseline and after 1, 3, 6 and 10 years in both groups. The investigations include cardiac magnetic resonance imaging, echocardiography, bone density scan, flow mediated dilatation, laser Doppler flowmetry, nailfold capillaroscopy, office blood pressure, 24-h ambulatory blood pressure, heart rate variability and investigation of microbiota and biomarkers for inflammation, cardiovascular risk and the calcium-phosphate metabolism. Conclusions: The present study seeks to provide new insight in the pathophysiological mechanisms linking reduced kidney function to cardiovascular disease. In addition, we aim to enlighten predictors of adverse cardiovascular outcome in living kidney donors. The study is registered at Clinical-Trials.gov (identifier: NCT03729557).

Background: Patients with diabetes mellitus treated with successful pancreas transplantation (PTX) normalize hyperglycemia, but are exposed to immunosuppressive drugs that may impair endothelial function. This study aimed to evaluate endothelial function in single PTX recipients., Methods: Flow-mediated dilatation (FMD) in the brachial artery was measured by ultrasound 8 weeks after transplantation in single PTX (n = 27) and compared with healthy controls (n = 58), simultaneous pancreas and kidney recipients (n = 9), and kidney transplant recipients with (n = 41) and without (n = 95) diabetes mellitus. Adjustments for age, gender, blood pressure, and body mass index were included in a linear regression model. Changes in FMD from before to 1 year after transplantation were assessed in a subgroup of PTX recipients (n = 9)., Results: Flow-mediated dilatation% in PTX recipients was not inferior to healthy controls (8.7 ± 3.6 vs 7.7 ± 3.3, P = .06) and simultaneous pancreas and kidney recipients (6.7 ± 4.5, P = .24) in an adjusted model, and superior to kidney recipients with and without diabetes (3.0 ± 3.0 and 4.8 ± 3.3, respectively, both P < .005). FMD% improved significantly from eight weeks to one year after PTX, mean 7.9 ± 4.2% vs 11.8 ± 4.8% (N = 9; P = .03)., Conclusion: Flow-mediated dilatation is well preserved in patients undergoing pancreas transplantation and is not impaired when immunosuppressive drugs are introduced., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the general population, small increases in blood pressure are associated with increased mortality. In kidney donors this association is less certain. We therefore assessed long-term overall and cardiovascular mortality in donors who were hypertensive at the time of donation compared with normotensive donors. Hypertension was defined as blood pressure >140/90 mmHg or use of antihypertensive drugs. Adequate records available in 2131 donors revealed that 140 were hypertensive and 1991 were normotensive. Multivariable regression analyses were performed for overall and cardiovascular mortality. Hypertensive donors were significantly older (mean 57.7 vs. 46.9 years), more were males (44.3% vs. 41.5%), had higher body mass index (26.4 vs. 24.7) and lower estimated glomerular filtration rate (91.8 vs. 101.2 ml/min/1.73 m 2 ). After a median observation time of 20.8 years (interquartile range 11) 71 hypertensive donors had died and 26 of the deaths were cardiovascular. Multivariable analysis did not suggest a generalizable association between hypertension and long-term overall mortality [hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.9-1.5, P = 0.34] or cardiovascular mortality (HR 1.1, 95% CI 0.7-1.8, P = 0.55). These data may support the use of older healthy kidney donors with hypertension at donation., (© 2019 Steunstichting ESOT.)

Background: There is no consensus on how, when, or at what intensity exercise should be performed after heart transplantation (HTx). We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in the maintenance state after HTx, but studies have not investigated HIT effects in the de novo HTx state. We hypothesized that HIT could be introduced early after HTx and that it could lead to clinically meaningful increases in exercise capacity and health-related quality of life., Methods: This multicenter, prospective, randomized, controlled trial included 81 patients a mean of 11 weeks (range, 7-16 weeks) after an HTx. Patients were randomized 1:1 to 9 months of either HIT (4×4-minute intervals at 85%-95% of peak effort) or moderate-intensity continuous training (60%-80% of peak effort). The primary outcome was the effect of HIT versus moderate-intensity continuous training on the change in aerobic exercise capacity, assessed as the peak oxygen consumption (Vo 2 peak). Secondary outcomes included tolerability, safety, adverse events, isokinetic muscular strength, body composition, health-related quality of life, left ventricular function, hemodynamics, endothelial function, and biomarkers., Results: From baseline to follow-up, 96% of patients completed the study. There were no serious exercise-related adverse events. The population comprised 73% men, and the mean±SD age was 49±13 years. At the 1-year follow-up, the HIT group demonstrated greater improvements than the moderate-intensity continuous training group; the groups showed significantly different changes in the Vo 2 peak (mean difference between groups, 1.8 mL·kg - 1·min - 1), the anaerobic threshold (0.28 L/min), the peak expiratory flow (11%), and the extensor muscle exercise capacity (464 J). The 1.8-mL·kg - 1·min - 1 difference was equal to ≈0.5 metabolic equivalents, which is regarded as clinically meaningful and relevant. Health-related quality of life was similar between the groups, as indicated by results from the Short Form-36 (version 2), Hospital Anxiety and Depression Scale, and a visual analog scale., Conclusions: We demonstrated that HIT was a safe, efficient exercise method in de novo HTx recipients. HIT, compared with moderate-intensity continuous training, resulted in a clinically significantly greater change in exercise capacity based on the Vo 2 peak values (25% versus 15%), anaerobic threshold, peak expiratory flow, and muscular exercise capacity., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier NCT01796379.

There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high-risk patients (quartile 4) with genetic low-risk participants (quartile 1). A 27-SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

A serum test called T 50 assesses the overall propensity for calcification of the blood and is associated with cardiovascular outcomes. We aimed to examine T 50 over time in kidney transplant recipients and also address any effects of ibandronate. Serum samples taken from kidney transplant patients included in a prospective, randomized placebo controlled study of ibandronate were analyzed in retrospect. Adequate analyses were performed at baseline (approximately 3 weeks after transplantation) in 129 patients, at 10 weeks in 127 patients and at 1 year in 123 patients. There were no statistical differences between ibandronate and placebo treatment in terms of T 50 at 10 weeks (P = .094) or at 1 year (P = .116). Baseline T 50 was a significant covariate (P < .0001) for T 50 scores at 10 weeks and 1 year. In the total cohort, there was a highly significant (P < .0001) increase in T 50 of 26.6% after 10 weeks and T 50 remained stable after 1 year. T 50 change was inversely correlated to phosphate of -0.515 (P < .0001) and to change in serum albumin (P < .03). We found that T 50 increased from baseline to 10 weeks after transplantation with no further change after 1 year. Ibandronate had no effect on T 50 ., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Kidney transplantation in recipients with a previous malignancy is often deferred 2 to 5 years after cancer treatment due to fear of cancer recurrence. In Norway, the required waiting period has been 1 year., Methods: We compared patient and graft survival of recipients with pretransplant cancer to the outcomes of matched recipients without such cancer (comparators) using Cox regression., Results: From 1963 to 2010, 377 (6.4%) of 5867 recipients had a pretransplant cancer. During a median follow-up of 6.8 years, 256 recipients died, 35 (13.7%) from recurrent cancer and 27 (10.5%) from de novo cancer. Uncensored and death-censored graft loss occurred in 263 and 46 recipients, respectively. All-cause mortality was similar as in comparators (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.93-1.20]; P = 0.40), death-censored graft loss was lower (HR, 0.63; 95% CI, 0.47-0.84; P = 0.002), and uncensored graft loss was similar (HR, 0.99; 95% CI, 0.87-1.12; P = 0.87). Cancer mortality was higher than in comparators (HR, 1.97; 95% CI, 1.51-2.56; P < 0.001), particularly during the first 5 years of follow-up (HR, 3.44; 95% CI, 2.36-5.03; P < 0.01). Waiting period was not associated with recurrent cancer mortality or all-cause mortality (both P > 0.45). Results were similar within cancer subgroups, with most data in patients with a history of kidney cancer, prostate cancer, urothelial cancer, and skin squamous cell carcinoma., Conclusions: Kidney transplant recipients with a pretransplant cancer had a similar overall patient and graft survival as recipients without such cancer. Cancer mortality was increased, particularly during the first 5 years after transplantation. A short waiting period was not associated with mortality.

In stable renal transplant recipients with hyperparathyroidism, previous studies have indicated that vitamin D agonist treatment might have anti-proteinuric effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory effects. Early introduction of paricalcitol in de novo renal transplant recipients might reduce proteinuria and prevent progressive allograft fibrosis. We performed a single-center, prospective, randomized, open-label trial investigating effects of paricalcitol 2 μg/day added to standard care. Participants were included 8 weeks after engraftment and followed for 44 weeks. Primary end point was change in spot urine albumin/creatinine ratio. Exploratory microarray analyses of kidney biopsies at study end investigated potential effects on gene expression. Secondary end points included change in glomerular filtration rate (GFR), pulse wave velocity (PWV), and endothelial function measured by peripheral arterial tonometry as reactive hyperemia index (RHI). Seventy-seven de novo transplanted kidney allograft recipients were included, 37 receiving paricalcitol. Paricalcitol treatment lowered PTH levels (P = 0.01) but did not significantly reduce albuminuria (P = 0.76), change vascular parameters (PWV; P = 0.98, RHI; P = 0.33), or influence GFR (P = 0.57). Allograft gene expression was not influenced. To summarize, in newly transplanted renal allograft recipients, paricalcitol reduced PTH and was well tolerated without negatively affecting kidney function. Paricalcitol did not significantly reduce/prevent albuminuria, improve parameters of vascular health, or influence allograft gene expression., (© 2017 Steunstichting ESOT.)

Background: Previous reports indicate that posttransplantation diabetes mellitus (PTDM) is associated with overall renal graft loss, but not death-censored graft loss., Methods: In this single-center retrospective cohort study of 2749 adult Norwegian renal transplant recipients, transplanted between 1999 and 2011, we estimated overall and death-censored renal graft loss hazard ratios in patients diagnosed with PTDM, impaired glucose tolerance and diabetes before transplantation, using multivariable Cox proportional hazard regression analysis., Results: A total of 893 renal grafts were lost during the study period, either due to recipient death (n = 540) or death-censored graft loss (n = 353).When the observational time started at time of transplantation, diabetes before transplantation was associated with both overall and death-censored graft loss. Pretransplantation diabetes was also associated with a steeper decline in renal graft function, a higher risk of acute rejections and more renal grafts lost due to acute rejection.In patients with a functional renal graft 1 year after transplantation, PTDM was associated with overall graft loss (hazard ratio, 1.46; 95% confidence interval, 1.13-1.88; P < 0.001), but not death-censored graft loss (hazard ratio, 1.25; 95% confidence interval, 0.80-1.96; P = 0.33). We found no significant associations between PTDM and change in renal function during the first 5 years or acute rejection risk during the first year after renal transplantation.Impaired glucose tolerance was not associated with either overall or death-censored graft loss., Conclusions: The present study confirms previous findings of an increased risk of overall but not death-censored renal graft loss in renal transplant recipients with PTDM. Longstanding diabetes might increase the risk of acute rejections.

Background: Calcific uremic arteriolopathy (CUA), also referred to as calciphylaxis, is a rare and serious complication of kidney failure with limited treatment options. Kidney transplantation (KTX) restores kidney function and is hence a potential treatment option for CUA. We present 3 patients who had their CUA lesions successfully healed after urgent KTX., Methods: Data were retrospectively retrieved from hospital records at our national transplant center., Results: All 3 patients had previously been kidney transplanted and had experienced graft loss and were in stage 5 kidney failure when CUA developed. One patient was on warfarin treatment for pulmonary embolism. Skin lesions developed in the lower limbs in all 3 patients. Multidisciplinary care including intensified hemodialysis did not induce any clinically relevant improvement of the lesions. The recipients were enlisted on a clinically urgent waitlist for KTX and received a deceased donor kidney after 2 to 4 weeks. All recipients experienced good graft function. The lesions healed completely within 6 weeks in 2 patients. In the third patient, partial healing occurred after 2 months and complete healing was achieved 4 months after transplantation., Conclusions: These cases indicate that urgent KTX may contribute to an efficient treatment for end-stage renal disease patients with CUA., Competing Interests: The authors declare no funding or conflicts of interest.

Background/objectives: Cardiovascular (CV) disease is the leading cause of death after renal transplantation. Marine n-3 polyunsaturated fatty acids (PUFAs) exert potential cardio-protective metabolic effects and might reduce CV morbidity and mortality in renal transplant recipients (RTRs)., Subjects/methods: In this cross-sectional study of 1990 Norwegian RTRs, transplanted between 1999 and 2011, associations between plasma phospholipid marine n-3 PUFA levels and various CV risk markers at 10 weeks after transplant were evaluated., Results: Higher plasma marine n-3 PUFA levels were associated with lower resting heart rate (rHR), lower fasting plasma glucose (fPG) levels, lower plasma triglyceride levels and higher plasma high-density lipoprotein (HDL) cholesterol levels. Plasma levels of eicosapentaenoic acid, but not docosahexaenoic acid, showed a positive association with plasma HDL cholesterol levels. Plasma marine n-3 PUFA levels were not associated with plasma low-density lipoprotein cholesterol levels, pulse wave velocity or systolic and diastolic blood pressure. A negative association between plasma marine n-3 PUFA levels and CV mortality was weakened by additional adjustment for plasma triglyceride levels and rHR. The ratio of n-6 to n-3 PUFAs showed similar associations with CV risk markers as absolute plasma marine n-3 PUFA levels., Conclusions: This is the first study in RTRs showing that marine n-3 PUFAs are negatively associated with rHR and fPG in addition to beneficial effects on plasma HDL cholesterol and triglyceride levels. Especially, effects on autonomic nervous function and triglyceride metabolism might contribute to explain the lower CV mortality risk with higher plasma marine n-3 PUFA levels previously shown in this cohort.

Introduction: There is an uncertainty whether total inflammation in early protocol kidney graft biopsies is associated with fibrosis progression. We investigated whether total inflammation, both in fibrotic and non-fibrotic areas, at week 6 would predict fibrosis progression at one yr post-transplant., Methods: We included 156 single adult ABO compatible kidney recipients with adequate week 6 and one yr transplant protocol biopsies (312 biopsies). Biopsies were scored according to the current Banff criteria. In addition, fibrosis and inflammation in fibrotic and non-fibrotic areas were scored in a 10-grade semi-quantitative eyeballing system from 0% to 100%., Results: Fibrosis increased significantly from week 6 to one yr both by the 10-grade scoring system from 0.69 ± 1.07 to 1.45 ± 1.86, (mean ± SD), p < 0.001 and by Banff interstitial fibrosis (ci) scoring 0.81 ± 0.65 to 1.13 ± 0.87, p < 0.001. The 10-grade scoring system detected a larger proportion of fibrosis progressors than the Banff scoring 40.4% vs. 35.5%, p < 0.001. No significant positive association was found between inflammation at week 6 and progression of fibrosis in either of the scoring systems., Conclusions: Total inflammation in kidney transplant biopsies at week 6 did not predict progression of fibrosis at one yr post-transplant., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Current diagnostic criteria for post-transplantation diabetes mellitus (PTDM) are either fasting plasma glucose ≥7.0 mmol/l (≥126 mg/dl) or postchallenge plasma glucose ≥11.1 mmol/l (≥200 mg/dl) 2 h after glucose administration [oral glucose tolerance test (OGTT) criterion]. In this retrospective cohort study of 1632 renal transplant recipients (RTRs) without known diabetes mellitus at the time of transplantation, we estimated mortality hazard ratios for patients diagnosed with PTDM by either conventional glucose criteria or the proposed glycated haemoglobin (HbA1c) criterion [HbA1c ≥6.5% (≥48 mmol/mol)]. During a median follow-up of 7.0 years, 311 patients died. Compared with nondiabetic patients and after adjustment for confounders, patients diagnosed with PTDM based on chronic hyperglycaemia early after transplantation (manifest PTDM) or by the OGTT criterion at 10 weeks post-transplant suffered a higher mortality risk (HR 1.59, 95% CI 1.06-2.38, P = 0.02 and HR 1.56, 95% CI 1.04-2.38, P = 0.03, respectively). In contrast, patients diagnosed with PTDM by the HbA1c criterion at 10 weeks or between 10 weeks and 1 year post-transplant were not associated with mortality (HR 0.96, 95% CI 0.61-1.51, P = 0.86 and 1.58, 95% CI 0.74-3.36, P = 0.24 respectively). After adjustment for confounders and competing risks, only patients with manifest PTDM had a significantly higher cardiovascular mortality risk (subdistributional HR 2.31, 95% CI 1.19-4.47, P < 0.001). Since many cases with PTDM were only identified by the OGTT, we recommend monitoring fasting plasma glucose early after renal transplantation followed by an OGTT at 2-3 months post-transplant in patients without overt diabetes mellitus., (© 2016 Steunstichting ESOT.)

Background: Marine n-3 polyunsaturated fatty acids (PUFAs) may exert beneficial effects on inflammation, fibrosis, endothelial function, lipid profile and blood pressure that may prevent graft loss., Methods: In this observational cohort study in Norwegian renal transplant recipients (n = 1990), transplanted between 1999 and 2011, associations between plasma marine n-3 PUFA levels and graft loss were assessed by multivariable Cox proportional hazard regression analysis. Plasma phospholipid fatty acid composition was determined by gas chromatography and individual fatty acids recorded as weight percentage (wt%) of total fatty acids in a stable phase 10 weeks after transplantation., Results: During a median follow-up time of 6.8 years, 569 (28.6%) renal allografts were lost, either due to patient death (n = 340, 59.8% of graft loss) or graft loss in surviving patients (n = 229, 40.2%). Plasma marine n-3 PUFA levels ranged from 1.35 to 23.87 wt%, with a median level of 7.95 wt% (interquartile range 6.20-10.03 wt%). When adjusting for established graft loss risk factors, there was a 11% reduced risk of graft loss for every 1.0 wt% increase in marine n-3 PUFA level [adjusted hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.84-0.93], and a 10% reduced risk of graft loss in surviving patients (adjusted HR 0.90; 95% CI 0.84-0.97)., Conclusion: High levels of plasma marine n-3 PUFAs were associated with better renal allograft survival., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Calcification of the vasculature is associated with cardiovascular disease and death in kidney transplant recipients. A novel functional blood test measures calcification propensity by quantifying the transformation time (T50 ) from primary to secondary calciprotein particles. Accelerated T50 indicates a diminished ability of serum to resist calcification. We measured T50 in 1435 patients 10 weeks after kidney transplantation during 2000-2003 (first era) and 2009-2012 (second era). Aortic pulse wave velocity (APWV) was measured at week 10 and after 1 year in 589 patients from the second era. Accelerated T50 was associated with diabetes, deceased donor, first transplant, rejection, stronger immunosuppression, first era, higher serum phosphate and lower albumin. T50 was not associated with progression of APWV. During a median follow-up of 5.1 years, 283 patients died, 70 from myocardial infarction, cardiac failure or sudden death. In Cox regression models, accelerated T50 was strongly and independently associated with both all-cause and cardiac mortality, low versus high T50 quartile: hazard ratio 1.60 (95% confidence interval [CI] 1.00-2.57), ptrend   = 0.03, and 3.60 (95% CI 1.10-11.83), ptrend   = 0.02, respectively. In conclusion, calcification propensity (T50 ) was strongly associated with all-cause and cardiac mortality of kidney transplant recipients, potentially via a cardiac nonAPWV-related pathway. Whether therapeutic improvement of T50 improves outcome awaits clarification in a randomized trial., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We evaluated 167 patients without diabetes 8-10 weeks after kidney transplantation, performing oral glucose tolerance tests and measuring VAT content from dual-energy X-ray absorptiometry scans. Median VAT weight in normal glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg, impaired glucose tolerance patients 1.3 kg and patients with post-transplant diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups). Percentage VAT of total body fat was associated with fasting (R(2) = 0.094, P < 0.001) and 2-h glucose concentration (R(2) = 0.062, P = 0.001), while BMI was only associated with 2-h glucose concentration (R(2) = 0.029, P = 0.028). An association between BMI and 2-h glucose concentration was lost in adjusted models, as opposed to the associations between VAT as percentage of total body fat and glucose concentrations (R(2) = 0.132, P < 0.001 and R(2) = 0.097, P = 0.001, respectively for fasting and 2-h glucose concentration). In conclusion, VAT is more closely related to impaired glucose metabolism than BMI after kidney transplantation. The association with central obesity should encourage additional studies on lifestyle interventions to prevent PTDM., (© 2015 Steunstichting ESOT.)

Background: The association between aortic stiffness and all-cause mortality in kidney transplant recipients (KTRs) is uncertain, and aortic stiffness has not yet been incorporated into risk prediction tools., Methods: During 2007 to 2012, we measured carotid-femoral pulse wave velocity (PWV; SphygmoCor apparatus) 8 weeks after transplantation. The association between PWV and mortality was assessed in a Cox regression analysis adjusting for seven risk factors from a previously validated model. Internal validation was performed by bootstrap resampling, and discrimination and overfitting evaluated by Harrell's C and the calibration slope., Results: Of 1497 KTRs, 1040 (69%) had a valid PWV measurement. During a median follow-up of 4.2 years, 82 patients died. The association between PWV and mortality showed a ceiling effect, and PWV was truncated at 12 m/sec. Each 1 m/sec increase in PWV, up to 12 m/sec, was associated with mortality, hazard ratio (HR) 1.36 (95% CI, 1.14-1.62; P = 0.001). An interquartile range increase (3.8 m/sec) tripled the hazard of mortality, HR, 3.21 (95% CI, 1.63-6.31), similar to the effect of being approximately 20 years older (interquartile range increase (21.6 years); HR, 3.06 [95% CI, 1.87-5.29]). The PWV improved model discrimination with an increase in Harrell's C from 0.76 to 0.78; C difference, 0.024 (95% CI, 0.005-0.043; P = 0.01). Overfitting was moderate with a calibration slope of 0.89, and the final model was adjusted accordingly. A spreadsheet version is presented to estimate expected 5-year survival., Conclusions: The PWV is a strong risk factor for mortality in KTRs.

Background and Objectives: Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants., Design, Setting, Participants, & Measurements: In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation., Results: There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality., Conclusions: Higher plasma phospholipid marine n-3 polyunsaturated fatty acid levels were independently associated with better patient survival., (Copyright © 2015 by the American Society of Nephrology.)

Background: Posttransplant diabetes mellitus (PTDM) is usually detected 2 to 3 months after transplantation by fasting plasma glucose (fPG) ≥ 7.0 mmol/L (≥ 126 mg/dL) and/or 2 hr post-challenge plasma glucose ≥ 11.1 mmol/L (≥ 200 mg/dL) during an oral glucose tolerance test (OGTT). Recently, glycosylated hemoglobin (HbA1c) of 6.5% or higher (≥ 47.5 mmol/mol) has been proposed as an alternative diagnostic criterion (the HbA1c criterion). We aimed to assess the sensitivity of applying the HbA1c criterion alone or in combination with a single measurement of fPG of 7.0 mmol/L or higher (≥ 126 mg/dL) at 10 weeks after transplantation as screening tests for the diagnosis of PTDM., Methods: From 1999 to 2011, measurements of fPG, HbA1c, and OGTT were performed in 1,619 nondiabetic renal transplant recipients., Results: The HbA1c criterion detected 38.0% of patients with PTDM diagnosed with the standard diagnostic criteria. The specificity was 86.3%. When the HbA1c threshold value was lowered to 6.2% (44.3 mmol/mol), sensitivity increased to 57.8% with a corresponding reduced specificity of 80.4%. A combination of the HbA1c criterion and fPG of 7.0 mmol/L or higher (126 mg/dL) at 10 weeks after transplantation improved diagnostic precision with a sensitivity of 77.7% and a specificity of 96.1%., Conclusion: The proposed diagnostic HbA1c criterion failed to detect most cases of PTDM, and one of four cases of PTDM was detected by OGTT alone. This indicates that the HbA1c threshold value likely needs to be lowered for renal transplant recipients and supports continued use of OGTT as a diagnostic tool for detection of PTDM.

Background: Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study., Methods: We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years., Results: Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P=0.004), and with graft loss (6% increased risk per 10 units; P<0.001), but not with major cardiovascular events. Parathyroid hormone above the upper limit of normal (65 pg/mL) indicated a 46% (P=0.006) higher risk of death and an 85% higher risk of graft loss (P<0.001) compared with low/normal values., Conclusions: Hyperparathyroidism is an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.

Background: Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated., Methods: We analyzed SDMA in the placebo arm of the Assessment of Lescol in Renal Transplantation study, a randomized controlled trial of fluvastatin in RTR. Mean follow-up was 5.1 years. Patients were grouped into quartiles based on SDMA levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analyzed in 925 RTR using univariate and multivariate survival analyses., Results: In univariate analysis, SDMA was significantly associated with renal graft loss, all-cause death, and major cardiovascular events. After adjustment for established risk factors including estimated glomerular filtration rate, an elevated SDMA-level (4th quartile, >1.38 μmol/L) was associated with renal graft loss; hazard ratio (HR), 5.51; 95% confidence interval (CI), 1.95-15.57; P=0.001, compared to the 1st quartile. Similarly, SDMA in the 4th quartile was independently associated with all-cause mortality (HR, 4.56; 95% CI, 2.15-9.71; P<0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR, 2.86; 95% CI, 0.99-8.21; P=0.051)., Conclusion: In stable RTR, an elevated SDMA level is independently associated with increased risk of all-cause mortality and renal graft loss.

Unlabelled: Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores., Methods: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models., Results: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05)., Conclusions: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The association between serum uric acid and kidney graft and recipient survival is uncertain. During 2000-2011, we measured serum uric acid at week 10 after transplantation. Of 2748 transplanted patients, 2200 (80.1%) attended this visit. After a median follow-up of 7.4 yr, 378 patients had died, 143 from a cardiovascular cause, and 185 patients lost their graft. The third quintile of uric acid levels (357-405 μM) had the lowest mortality risk and was used as reference group. In Cox proportional hazard models adjusting for graft and patient characteristics, the fifth quintile of uric acid levels (>474 μM) was independently associated with cardiovascular mortality (hazard ratio [HR] = 2.87 [1.55-5.32], p = 0.001) and all-cause mortality (HR = 1.57 [1.09-2.25], p = 0.02). Also, the lowest quintile of uric acid levels (<309 μM) showed a trend toward increased risk of cardiovascular mortality (HR = 1.79 [0.90-3.58], p = 0.10) and all-cause mortality (HR = 1.31 [0.89-1.93], p = 0.18). The increased risk at low uric acid levels was confined to diabetic recipients. Uric acid was not associated with death-censored graft loss. In conclusion, uric acid has a J-shaped association with cardiovascular and all-cause mortality in kidney transplant recipients., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It is well established that post-transplantation anemia (PTA) in renal transplant recipients (RTRs) is associated with reduced graft survival. However, there is an uncertainty of the effect of PTA on cardiovascular events and all-cause mortality. We examined prospectively in a large cohort of erythropoietin-naive patients the effects of PTA on cardiovascular morbidity, patient survival, and graft survival., Methods: A prospective cohort study of RTRs (n = 2102) included in the ALERT study. Cox regression models were used to evaluate the impact of PTA on study endpoints: first occurrence of a major adverse cardiac event, all-cause death, and the incidence of death-censored graft loss. Mean follow-up was 6.7 yr. All endpoints were adjudicated by an independent endpoint committee., Results: Twenty-nine percent of women and 30% of men were anemic. Hemoglobin levels were not associated with any effect on cardiovascular morbidity and mortality (HR 0.97 [0.90-1.05] per g/dL, p = 0.48) or all-cause death (HR 0.96 [0.90-1.03] per g/dL, p = 0.24) after extensive multivariate adjustments for clinical and demographic factors. Hemoglobin levels were negatively associated with graft loss (HR 0.86 [0.80-0.92] per g/dL, p < 0.001)., Conclusions: PTA was not associated with an increased incidence of cardiovascular morbidity and mortality or all-cause mortality., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Endothelial dysfunction is prevalent in renal transplant recipients, but it is uncertain if there is an association with graft loss or mortality., Methods: Since 1997, we have measured endothelial function noninvasively by forearm laser Doppler flowmetry in several small trials. These tests were pooled for the current analysis. We used Cox proportional hazard models to adjust for patient and graft characteristics. Due to significant heterogeneity between tests conducted before or after day 90 after transplantation, these were examined separately., Results: In the 175 patients examined after day 90 after transplantation, an endothelial function score below the median predicted graft loss (hazard ratio [HR], 1.85 [1.09-3.16]; P=0.02) and death-censored graft loss (HR, 2.63 [1.18-5.84]; P=0.02) but not all-cause mortality (HR, 1.20 [0.62-2.30]; P=0.58). In 140 patients examined before day 90 after transplantation, no association was found., Conclusion: Endothelial dysfunction identified more than 90 days after transplantation was associated with renal graft loss.

Background: In patients with chronic kidney disease, vascular calcification contributes to increased cardiovascular (CV) morbidity and mortality. CV risk remains high after successful renal transplantation. Osteoprotegerin (OPG) is a glycoprotein, involved in the regulation of the vascular calcification process. Previous studies have shown that elevated OPG is predictive of mortality in high-risk populations. The aim of this study was to investigate the prognostic value of OPG for graft function, CV events and all-cause death, in a large transplant cohort., Methods: OPG was measured at baseline in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) study, a randomized placebo-controlled intervention study comparing fluvastatin and placebo. Patients were followed for 6.7 years with evaluation of pre-specified end points, graft loss, graft function, CV events and death., Results: OPG was analysed in 1889 renal transplant recipients, with a mean value of 4.69 ± 1.85 pg/L. The number of renal and CV events increased by quartiles of OPG. In the multivariate analysis, OPG in the fourth as compared to first quartile was an independent predictor of graft failure or doubling of serum creatinine [hazard ratio (HR) 2.20 (1.56-3.11), P < 0.001], major CV events [HR 2.40 (1.58-3.64), P < 0.001], cardiac mortality [HR 2.80 (1.32-5.94), P = 0.007] and all-cause mortality [HR 2.31 (1.53-3.49), P < 0.001]., Conclusion: In a large cohort of kidney transplant patients with long-term follow-up, OPG was independently associated with renal events, CV events and mortality.

Background: There are concerns regarding potential long-term risks to the living kidney donor. Cardiovascular mortality has not been evaluated. The aim of this study was to assess overall and cardiovascular mortality in previous kidney donors compared with a general population sample., Methods: All live kidney donors in Norway in the period 1963-2007 were included. Controls matched 3:1 for age, gender and year of birth were provided by Statistics, Norway. Cause of death was retrieved from the death master file. Vital status as of 1 January 2010 was provided for all participants, and cause of death was available until 1 January 2008. Comparative survival analyses were performed by Kaplan-Meier curves and log-rank test. Age-stratified death rates were calculated and compared with a selected group with a health status hypothetically allowing donation., Results: There were 2269 living kidney donors in the study period. At donation, mean age was 47.6 + 12.6 years, 41.3% were male. Median observation time was 14.3 years. A total of 324 donors died during the study period. Causes of death were similar for donors and controls. By Kaplan-Meier analysis, overall and cardiovascular mortality was lower for previous kidney donors than for matched controls (P < 0.001 and P = 0.004, respectively). Age-stratified death rates were elevated for the oldest group of donors., Conclusions: Overall and cardiovascular mortality results are partially reassuring. However, the seemingly elevated mortality rate among the oldest donors requires further study.

Renal function is thoroughly evaluated before live kidney donation. However, some donors experience impaired recovery of renal function after donation. Our aim was to assess estimated glomerular filtration rate (eGFR) and mean relative (%) increase in creatinine one yr after donor nephrectomy. The study was based on retrospective data from kidney donors during the period 1997-2009. Pre-operative and one-yr follow-up data were available for 721 of 1067 donors. Mean relative increase in creatinine and eGFR were stratified by gender, body mass index (BMI), and age at donation. At one yr post-donation, overweight (BMI > 5 kg/m(2) ) women 50 yr or older experienced the lowest eGFR of 49.6 ± 8.8 mL/min/1.73 m(2) . Men younger than 50 yr with normal weight (BMI < 25 kg/m(2) ) had the highest eGFR of 66.6 ± 10.4 mL/min/1.73 m(2) . Overweight men 50 yr or older had the highest relative increase in creatinine of 49.4% compared to pre-donation. Men under 50 yr with normal weight had the smallest increase in creatinine of 35.2%. In multivariate analysis, older age (p < 0.001), male gender (p < 0.001), and overweight (p = 0.01) were associated with relative increase in creatinine after donation. Potential donors should be offered counseling regarding overweight, as this is a modifiable risk factor., (© 2011 John Wiley & Sons A/S.)

Background: Although short-term graft survival has improved substantially in renal transplant recipients, long-term graft survival has not improved over the last decades. The lack of knowledge of specific causes and risk factors has hampered improvements in long-term allograft survival. There is an uncertainty if inflammation is associated with late graft loss., Methods: We examined, in a large prospective trial, the inflammation markers high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) and their association with chronic graft dysfunction. We collected data from the Assessment of Lescol in Renal Transplant trial, which recruited 2102 maintenance renal transplant recipients., Results: Baseline values were hsCRP 3.8 ± 6.7 mg/L and IL-6 2.9 ± 1.9 pg/mL. Adjusted for traditional risk factors, hsCRP and IL-6 were independently associated with death-censored graft loss, the composite end points graft loss or death and doubling of serum creatinine, graft loss or death., Conclusion: The inflammation markers hsCRP and IL-6 are associated with long-term graft outcomes in renal transplant recipients.