Changes in co-morbidity pattern in patients starting renal replacement therapy in Europe-data from the ERA-EDTA Registry.

Background: Patients starting renal replacement therapy (RRT) for end-stage renal disease often present with one or more co-morbidities. This study explored the prevalence of co-morbidities in patients who started RRT in Europe during the period from 2005 to 2014. Methods: Using data from patients aged 20 years or older from all 11 national or regional registries providing co-morbidity data to the European Renal Association - European Dialysis and Transplant Association Registry, we examined the prevalence of the following co-morbidities: diabetes mellitus (DM) (primary renal disease and/or co-morbidity), ischaemic heart disease (IHD), congestive heart failure (CHF), peripheral vascular disease (PVD), cerebrovascular disease (CVD) and malignancy. Results: Overall, 70% of 7578 patients who initiated RRT in 2014 presented with at least one co-morbidity: 39.0% presented with DM, 25.0% with IHD, 22.3% with CHF, 17.7% with PVD, 16.4% with malignancy and 15.5% with CVD. These percentages differed substantially between countries. Co-morbidities were more common in men than in women, in older patients than in younger patients, and in patients on haemodialysis at Day 91 when compared with patients on peritoneal dialysis. Between 2005 and 2014 the prevalence of DM and malignancy increased over time, whereas the prevalence of IHD and PVD declined. Conclusions: More than two-thirds of patients initiating RRT in Europe have at least one co-morbidity. With the rising age at the start of RRT over the last decade, there have been changes in the co-morbidity pattern: the prevalence of cardiovascular co-morbidities decreased, while the prevalence of DM and malignancy increased.

Development of Kidney Transplant Fibrosis Is Inversely Associated With Plasma Marine Fatty Acid Level.

OBJECTIVE(S): We assessed associations between plasma levels of polyunsaturated fatty acids (PUFAs) and degree of inflammation and interstitial fibrosis in transplanted kidneys. DESIGN: The design of the study was single center cohort study. SUBJECTS: A study population of 156 patients who received a kidney transplant at Oslo University Hospital during 2010. MAIN OUTCOME MEASURE: Kidney transplant biopsies were obtained at 2 months and 1 year after transplantation. Degree of inflammation and interstitial fibrosis in the cortex of transplanted kidneys were estimated semi-quantitatively. Plasma phospholipid fatty acids levels were measured in a stable phase 2 months posttransplant. We used multivariate linear regression to assess associations between plasma levels of PUFAs and degree of inflammation and interstitial fibrosis at 2 months and 1 year postoperatively and change in degree of interstitial fibrosis during the first year after transplantation, adjusting for inflammation and fibrosis risk factors. RESULTS: Higher plasma marine n-3 PUFA levels were associated with less development of interstitial fibrosis in the kidney transplant (unstandardized ß-coefficient -1.12, standardized ß-coefficient -0.18, P = .03) during the first year after transplantation. Plasma levels of alpha linoleic acid, linoleic acid, and arachidonic acid were not associated with development of interstitial fibrosis. No associations were found between plasma levels of PUFAs and inflammation inside fibrotic areas or outside fibrotic areas in the kidney transplant at neither 2 months nor 1 year postoperatively. Linolenic acid levels in plasma were positively associated with change in renal function during the first year after transplantation. CONCLUSION: The inverse association between plasma marine n-3 PUFA levels and development of interstitial fibrosis during the first year after kidney transplantation suggests that marine fatty acid consumption might halt progression of fibrosis.

Plasma levels of marine n-3 polyunsaturated fatty acids and renal allograft survival.

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.

Calcineurin inhibitor avoidance with daclizumab, mycophenolate mofetil, and prednisolone in DR-matched de novo kidney transplant recipients.

BACKGROUND: Calcineurin inhibitor (CNI)-free regimens posttransplantation have been claimed to conserve graft function in addition to reduce the risk factors for cardiovascular and malignant disease in renal transplant recipients. METHODS: The primary aim of this prospective, open-label, randomized, parallel-group, single-center study was to compare the effect of complete CNI-avoidance posttransplant (daclizumab + mycophenolate mofetil + prednisolone: Dac-group, n=27) with the standard CNI-based immunosuppressive protocol at our transplant unit (cyclosporine A + mycophenolate mofetil + prednisolone: CsA-group, n=27) on renal function (glomerular filtration rate [GFR] determined as plasma clearance of 51Cr-EDTA) in a selected low immunogenic risk population (DR-matched, PRA-negative de novo cadaveric transplant recipients). RESULTS: There were no significant difference in GFR at week 10 (P=0.61), but GFR was significantly (P=0.029) lower in the Dac-group (52+/-20 ml/min) at month 12 than in the CsA-group (69+/-29 ml/min). One-year patient and graft survival did not differ between the two groups. Overall acute rejection rate was 70.4% (19/27) in the Dac-group and 29.6% (8/27) in the CsA-group (P=0.006). CONCLUSIONS: The strategy to select DR-matched, PRA-negative de novo cadaveric transplant recipients for a CNI-avoidance protocol was not successful. The incidence of acute rejection was unacceptable high even though anti-CD25 antibody induction as well as initial higher mycophenolate mofetil doses (3 g/day) were applied, and renal function was significantly lower in the CNI-avoidance patients at 1 year. Other strategies need to be examined for avoidance of CNI's in the early posttransplant period.