n-3 polyunsaturated fatty acids and adiponectin in patients with end-stage renal disease.

BACKGROUND AND AIM: In subjects without kidney disease, adiponectin appears to have anti-inflammatory, anti-diabetic, and anti-atherogenic effects. n-3 polyunsaturated fatty acids (PUFA) from seafood have several beneficial effects in patients with endstage renal disease (ESRD) and the aim of the present study was to assess the effect of n-3 PUFA supplementation on plasma adiponectin levels in ESRD patients. METHODS: In a double blinded intervention trial, 162 ESRD patients (mean age 67 years  ± 13, 56 women and 106 men) undergoing chronic hemodialysis were randomized to 1.7 g n-3 PUFA daily or placebo for 3 months. Adiponectin, plasma lipids and lipoproteins were measured at baseline and after the intervention period. RESULTS: At baseline, adiponectin was positively correlated to HDL-cholesterol (r = 0.55, p < 0.001) and inversely correlated to plasma triglycerides, body mass index (BMI) and high sensitive C-reactive protein (Hs-CRP) (r = -0.32, p < 0.01, r = -0.43, p < 0.01, and r = -0.21, p < 0.01, respectively). Furthermore, adiponectin was inversely correlated to the plasma levels of the two major n-3 PUFA docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (r = -0.19, p < 0.001, and r = -0.30, p < 0.001, respectively). Baseline plasma adiponectin levels were high in both groups but after 3 months of supplementation no significant change was observed in the groups. Thus, n-3 PUFA supplementation did not change adiponectin levels. CONCLUSION: We found an elevated plasma adiponectin level, which was inversely associated with plasma levels of DHA and EPA at baseline. Supplementation with n-3 PUFAs for 3 months did not change adiponectin levels. The negative result in this study may be related to a relatively low dose and future studies with higher dose and longer duration are needed to explore this mechanism.

The Effect of n-3 Fatty Acids on Small Dense Low-Density Lipoproteins in Patients With End-Stage Renal Disease: A Randomized Placebo-Controlled Intervention Study.

OBJECTIVE: Patients with end-stage renal disease (ESRD) have a high risk of cardiovascular disease. Small dense low-density lipoprotein (sdLDL) particles are particularly atherogenic. Marine n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on numbers of sdLDL particles, and the aim of this study was to investigate the effect of n-3 PUFA on plasma levels of sdLDL in patients with ESRD. METHODS: ESRD patients with cardiovascular disease (n = 161) on chronic hemodialysis were randomized to treatment with 1.7 g of n-3 PUFA (n = 81) or 2 g of placebo (olive oil; n = 80) for 3 months. The study was double-blinded. Densities of LDL and percentages of sdLDL (sdLDL%) of total LDL were measured before and after intervention. On the basis of sdLDL%, patients were classified as having lipid pattern A, I (intermediate), or B defined by a successive increase in sdLDL concentration and decrease in lipid particle size. RESULTS: n-3 PUFAs significantly reduced triglycerides. However, LDL cholesterol remained unchanged. In the n-3 group, the LDL density did not change significantly during follow-up. Similarly, the LDL density remained unchanged in the placebo group. In the n-3 group, the sdLDL% was 34% at baseline and unchanged at follow-up. At baseline 71% had LDL pattern A, 9% had pattern I, and 20% had pattern B, and none of these patterns were significantly changed by n-3 PUFA supplementation. CONCLUSION: Dietary supplementation with 1.7 g of n-3 PUFA had no effect on LDL density or sdLDL levels in patients with ESRD.

Human kidney graft survival correlates with structural parameters in baseline biopsies: a quantitative observational cohort study with more than 14 years' follow-up.

This prospective cohort study evaluates associations between structural and ultrastructural parameters in baseline biopsies from human kidney transplants and long-term graft survival after more than 14 years' follow-up. Baseline kidney graft biopsies were obtained prospectively from 54 consecutive patients receiving a kidney transplant at a single institution. Quantitative measurements were performed on the baseline biopsies by computer-assisted light microscopy and electron microscopy. Stereology-based techniques estimated the fraction of interstitial tissue, the volume of glomeruli, mesangial fraction, and basement membrane thickness of glomerular capillaries. The fraction of occluded glomeruli and scores according to the Banff classification were achieved. Kidney graft survival was analyzed by Kaplan-Meier estimates and Cox regression. Association to long-term kidney function was also analyzed. The long-term surviving kidney transplants were characterized at implantation by less arteriolar hyaline thickening (P < 0.001) and less interstitial fibrosis (P = 0.001), as well as a lower fraction of occluded glomeruli (P = 0.004) and lower glomerular volume (P = 0.03). At the latest follow-up, eGFR was decreased by 12 ml/min/1.73 m2 per unit increase in the score for arteriolar hyalinosis at implantation (P = 0.02), and eGFR was decreased by 19 ml/min/1.73 m2 per 106 µm3 increase in glomerular volume at baseline (P = 0.03). The unbiased Cavalieri estimate of glomerular volume and the ultrastructural parameters are the first to be evaluated in a cohort study with prospective follow-up for more than 14 years. The study shows that baseline biopsies from human kidney grafts contain extraordinary long-term prognostic information, and it highlights the importance of these intrinsic graft factors.

The effect of n-3 fatty acids on levels of methylarginines in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a very high mortality mainly caused by cardiovascular disease (CVD). It has been suggested that plasma concentrations of asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide synthase inhibitor, are markedly elevated in patients with ESRD. Elevation of ADMA is linked to CVD and an adverse prognosis. Supplementation with n-3 fatty acids has previously been shown to prevent CVD, but there is very little data regarding the effect of n-3 fatty acids on levels of ADMA. METHODS: Patients with ESRD and documented CVD were randomized to treatment with 1.7 g of n-3 fatty acids (n=103, 34% women) or olive oil (n=103, 38% women) for three months. ADMA, symmetric dimethyl arginine (SDMA), L-arginine, and the relative content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in serum phospholipids were measured before and after treatment. RESULTS: ADMA was normally distributed with a mean value of 0.56+/-0.13 micromol/L (range 0.21-1.01) and only 14/206 (6.8 %) had elevated levels of ADMA. SDMA was generally elevated with a mean value of 1.88+/-0.64 micromol/L (range 0.67-4.56). Supplementation with n-3 fatty acids for three months did not change plasma levels of ADMA, SDMA or L-arginine. CONCLUSIONS: The present data do not support a beneficial effect of n-3 fatty acids on methylarginines in patients with ESRD.

The effect of desmopressin on renal water and solute handling in desmopressin resistant monosymptomatic nocturnal enuresis.

PURPOSE: We sought to evaluate the effect of desmopressin on renal water and solute handling in children with monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria compared to healthy controls. MATERIALS AND METHODS: A total of 12 patients with enuresis and nocturnal polyuria, normal bladder reservoir function and no response to desmopressin, and 10 age matched controls were enrolled in the study. Children were admitted to the hospital for a 48-hour protocol comprising urine collections and blood sampling. Sodium and water intake was standardized. During the second night children received 40 mug intranasal desmopressin. Parameters characterizing the renal water and solute handling were measured and compared between baseline nights and nights with desmopressin. RESULTS: Desmopressin markedly reduced nocturnal urine output in patients with enuresis, minimizing sodium, urea and overall solute excretion, despite the fact that these children were unresponsive to desmopressin at home. This effect on renal sodium handling was not mediated by atrial natriuretic peptide, angiotensin II, aldosterone or renin. Desmopressin did not influence urinary prostaglandin E(2) excretion. The antinatriuretic effect was seen only in patients with enuresis, and it was directly correlated with the reduction in urine output. CONCLUSIONS: Children with nocturnal enuresis and nocturnal polyuria who do not exhibit adequate response to desmopressin at home seem to respond well to the agent at the clinic. The effect of desmopressin in children with enuresis seems largely dependent on reductions in the amount of sodium excreted. Sodium regulating hormones remained unaffected by desmopressin, indicating a possible direct effect of the agent on renal sodium handling.

The effect of n-3 fatty acids on lipids and lipoproteins in patients treated with chronic haemodialysis: a randomized placebo-controlled intervention study.

BACKGROUND: Patients with end-stage renal disease (ESRD) have an increased mortality, mainly due to cardiovascular disease (CVD). ESRD is accompanied by several lipid abnormalities, which may be responsible for part of the increased risk of CVD in this population. n-3 polyunsaturated fatty acids (PUFA) lower plasma triglycerides in patients with normal renal function. The aim of the present study was to examine the effect of n-3 PUFA on serum lipid and lipoproteins in patients treated with chronic haemodialysis (HD). METHODS: In a double-blind randomized placebo-controlled design, patients with documented CVD, treated with HD for a minimum of 6 months, were randomized to treatment with n-3 PUFA or a control treatment (olive oil). A dietary intake of n-3 PUFA was assessed with a dietary questionnaire. Plasma lipids and lipoproteins and the content of n-3 PUFA in serum phospholipids were measured at baseline and after 3 months. RESULTS: Two hundred and six patients were included. Serum phospholipid levels of n-3 PUFA were significantly higher in patients reporting a high fish intake compared to patients reporting a low fish intake. After 3 months, a significant decrease was seen in serum triglycerides in the n-3 PUFA group compared to the control group (P = 0.01). No significant effect was seen on total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, Lp(a) or apoB. CONCLUSION: In patients treated with HD, consumption of fish increases levels of n-3 PUFA. Additional supplementation with n-3 PUFA for 3 months further increases levels of n-3 PUFA and lowers serum triglycerides, but does not significantly affect other plasma lipids or lipoproteins.

The effect of n-3 fatty acids on heart rate variability in patients treated with chronic hemodialysis.

OBJECTIVE: The aim of the present study was to address the effect of n-3 polyunsaturated fatty acids (PUFAs) on heart rate variability (HRV) in patients treated with chronic hemodialysis. DESIGN: We performed a randomized, placebo-controlled intervention trial. SETTING: The study took place at two hospital-based dialysis centers. PATIENTS: Thirty patients with documented cardiovascular disease who were treated with hemodialysis for at least 6 months were included. INTERVENTION: Treatment consisted of 1.7 g of n-3 PUFA or a control treatment (olive oil). MAIN OUTCOME MEASURE: The outcome measure was 24-hour Holter recordings with time domain HRV measurements at baseline and after 3 months of treatment. Blood samples were obtained to assess the content of n-3 PUFA in serum phospholipids before and after treatment. RESULTS: n-3 PUFA did not significantly affect time domain parameters of HRV, compared with a control group. CONCLUSION: We conclude that treatment with n-3 PUFA does not increase HRV in patients treated with chronic hemodialysis, a result that may have been compromised by a small sample size.

The content of docosahexaenoic acid in serum phospholipid is inversely correlated with plasma homocysteine levels in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) have a high morbidity and mortality from cardiovascular disease. An elevated homocysteine level is an independent predictor of cardiovascular events in patients with ESRD. Interestingly, some studies have found an inverse relationship between the content of marine n-3 polyunsaturated fatty acids (PUFAs) and homocysteine levels, but data are ambiguous. In patients with ESRD, we hypothesized that serum phospholipid n-3 PUFA content would inversely correlate with homocysteine levels in plasma and that supplementation with n-3 PUFA would reduce plasma homocysteine levels. In a double-blind, randomized, controlled design, 206 patients with documented cardiovascular disease and treated with hemodialysis for a minimum of 6 months were randomized to treatment with daily supplement of 1.7 g n-3 PUFA or placebo (olive oil) for 3 months. The content of n-3 PUFA in serum phospholipids and homocysteine levels in plasma were measured at baseline and after 3 months of intervention. A dietary questionnaire was filled out at baseline, and study participants were divided into groups of low, intermediate, and high fish intake. Docosahexaenoic acid was inversely correlated with homocysteine at baseline (coefficient = -0.161; P = .03). Homocysteine was not related to self-reported fish intake. Supplementation with n-3 PUFA did not reduce homocysteine levels compared with placebo (mean ± SD difference, -0.3 ± 7.8 versus 0.3 ± 7.1; P = .58). The content of docosahexaenoic acid in serum phospholipids is inversely correlated with plasma homocysteine levels, and supplementation with n-3 PUFA does not reduce homocysteine levels in patients with ESRD.

Blood tacrolimus levels and calcineurin phosphatase activity early after renal transplantation.

The toxicity of tacrolimus (FK) despite therapeutic levels (trough) has led us to investigate its relationship with the inhibition of calcineurin (CaN) in recently transplanted renal patients. Twenty-one patients taking FK had blood drawn on day 3 and 14 at 0,1,2,3,4 and 6h. CaN activity was measured by its ability to cleave 32P from a previously radiolabeled phosphorylated 19-amino acid peptide. Radioactivity was quantitated and results were converted to units CaN. FK concentration was measured simultaneously. Maximal suppression of CaN occurred after 2h on both days. Unlike FK levels, CaN activity returned to predose levels by 6h. Comparing mean CaN activity at time 0 with each subsequent time showed statistical significance at hours 1, 2 and 3 on each day. Comparing mean FK concentrations, similarly, revealed statistical significance at all hours. Area under CaN activity curve (AUCCaN) vs. mean FK levels failed to show significance. However, comparing AUCCaN with mean CaN activity was significant throughout. CaN capacity at time 0 and 6h (day 14) resulted in the best estimate of CaN inhibition. Prior to steady-state (day 3), the best estimate occurred at 2h. No single FK concentration seemed to be a reliable indicator of CaN inhibition.