Marine n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Kidney Transplant Recipients: A Randomized, Placebo-Controlled Trial.

Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student's t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (-0.020 ± 0.08 vs. -0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. -0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.

Cardiovascular Risk Factors are Inversely Associated With Omega-3 Polyunsaturated Fatty Acid Plasma Levels in Pediatric Kidney Transplant Recipients.

OBJECTIVES: High plasma levels of the omega-3 fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid, and docosapentaenoic acid associates with positive outcomes in adult renal transplant recipients. However, data from pediatric populations are scarce. The aim of the study was to assess the fatty acid profile in a pediatric renal transplantation cohort and to examine the associations between plasma omega-3 fatty acids and cardiovascular disease (CVD) risk factors. METHODS: In this cross-sectional study comprising 53 children (median age, 12.2 years; 32 boys) with a renal transplant, we assessed the prevalence of CVD risk factors as well as markers of end organ damage: carotid intima-media thickness (cIMT) and left ventricular mass index. The associations between plasma omega-3 fatty acids and CVD risk factors were assessed. RESULTS: Twenty-five (47%) patients were preemptively transplanted. Seventy-six percent had dyslipidemia and 51% had hypertension. The mean left ventricular mass index was 40.4 ± 14.3 g/m2.7, and 14% had left ventricular hypertrophy. The mean cIMT was 0.41 ± 0.04 mm. In a multivariate linear regression, EPA levels were inversely associated to blood pressure (ß coeff. = -0.37, P = .007), triglycerides (ß coeff. = -0.44, P = .01), and high-density lipoprotein cholesterol (ß coeff. = -0.41, P = .01). CONCLUSION: EPA levels are inversely associated with components of the metabolic syndrome, which may provide support for specific dietary advice or supplementation in this patient population. cIMT is less pronounced in our cohort than in comparable cohorts with lower rate of preemptive transplantations. Our results need replication in prospective cohorts.

Effects of marine n-3 fatty acid supplementation in renal transplantation: A randomized controlled trial.

Marine n-3 fatty acids (FAs) may exert beneficial effects on inflammation, fibrosis, and endothelial function, which could preserve renal graft function. In this randomized controlled trial, 132 Norwegian renal transplant recipients received either 2.6 g of marine n-3 FAs or olive oil (control) daily for 44 weeks, in addition to standard care. Thirty patients did not complete the trial. The primary endpoint was change (Δ) in measured glomerular filtration rate (mGFR) during follow-up. We found no significant difference in Δ mGFR between the marine n-3 FA group and controls (6.7 vs 3.8 mL/min per 1.73 m2 , P = .15). Significant beneficial effects from marine n-3 FA supplementation were, however, seen in secondary endpoints plasma triglycerides, plasma high-sensitivity C-reactive protein, and brachial artery flow-mediated dilation. In the per-protocol population, the renal graft indices percent interstitial fibrosis and Chronic Allograft Damage Index also were significantly lower in the marine n-3 FA group. The cumulative incidence of adverse events did not differ between the marine n-3 FA group (n = 218) and controls (n = 240). In conclusion, marine FA supplementation did not improve renal function compared with controls, but was safe, lowered plasma triglyceride and high-sensitivity C-reactive protein levels, and improved endothelial function (Clinical.Trials.gov identifier NCT01744067).

Paricalcitol supplementation during the first year after kidney transplantation does not affect calcification propensity score.

BACKGROUND: Cardiovascular complications are common in kidney transplant patients and calcification propensity of blood, measured as T50, is associated with cardiovascular outcomes. Paricalcitol supplementation affects calcium/phosphate homeostasis and may affect calcification propensity. To assess this hypothesis we measured T50 in kidney transplant recipients participating in a randomized study comparing paricalcitol versus no treatment during the first year after kidney transplantation. METHODS: Stored serum samples from 76 kidney transplant recipients (paricalcitol n = 37, no treatment n = 39) were analyzed. Analyses were performed at inclusion (8 weeks after transplantation) and repeated one year after transplantation. RESULTS: There were no statistically significant differences in T50 between the paricalcitol and placebo groups, neither at baseline (p = 0.56) nor at 1 year (p = 0.61). Also, there were no significant changes in T50 over time in either group or when pooling all data (p <  0.20). In multivariate regression analysis, out of 16 potentially relevant covariates, comprising clinical and biochemical parameters, only plasma PTH and T50 at baseline were significantly correlated to T50 after one year. (p <  0.03 and p < 0.01, respectively). CONCLUSIONS: Calcium propensity measured as T50 score remained unchanged with paricalcitol treatment in kidney transplant recipients, and was not changed over time during the study period of one year. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01694160 , registered 23 September 2012.

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 n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Renal Transplant Recipients.

OBJECTIVE: Renal transplant recipients (RTR) suffer high rates of bone loss and increased risk of fracture. Marine n-3 polyunsaturated fatty acids (n-3 PUFA), found mainly in fish and seafood, may have beneficial effects on bone and are positively associated with bone mineral density (BMD) in healthy elderly. The aim of this study was to investigate if this association prevails despite the more complex causes of bone loss in RTR. DESIGN, SUBJECTS, AND METHODS: A total of 701 RTR were included in a cross-sectional analysis. BMD of lumbar spine, proximal femur, and distal forearm were measured by dual energy x-ray absorptiometry scan, and blood samples were drawn in the fasting state for measurement of plasma fatty acid composition 10 weeks posttransplant. Multiple linear regression analysis was used to assess the association between plasma marine n-3 PUFA levels and BMD. RESULTS: Mean age was 52.2 years, and two-thirds were men. Based on femoral neck T-scores, 26% of patients were osteoporotic and 52% osteopenic. Z-scores increased significantly across quartiles of marine n-3 PUFA levels, and marine n-3 PUFA was a positive predictor of BMD at total hip and lumbar spine after multivariate adjustment. No association was found between n-6 PUFA content and BMD. CONCLUSIONS: Plasma marine n-3 PUFA levels were positively associated with BMD at the hip and lumbar spine 10 weeks posttransplant.

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.