The Effect of Acute Aerobic Exercise on Biomarkers of Renal Health and Filtration in Moderate-CKD.

Purpose: Efficacy of exercise to improve renal health and filtration remains understudied in adults with moderate-stages (stages G3a-b) of chronic kidney disease (CKD). Acute exercise may contribute clinically relevant information for exercise-related augmentation of renal health and filtration in CKD. Urine epidermal growth factor (uEGF) and cystatin C (CyC) are proposed to be more direct biomarkers of renal health and filtration. This study aimed to determine the influence of continuous moderate-intensity exercise (CMIE) and high-intensity interval exercise (HIIE) on traditional and novel biomarkers of renal health and filtration in moderate-stages of CKD. Methods: Twenty CKD participants completed 30 minutes of both CMIE and HIIE. Blood and urine samples were obtained pre, 1-hour, and 24-hours post-exercise. Traditional-serum creatinine (sCr) urine creatinine, novel-uEGF, uEGF ratio (uEGFr), and CyC. Estimates of glomerular filtration rate (eGFR)-modification of diet in renal disease (MDRD) and the CKD-Epidemiology (CKD-EPI)-responses were compared pre, 1 hr, and 24 hr post-exercise. Results: Relative to pre-exercise measures, uEGF remained unchanged in both exercise conditions. However, uEGFr was 5.4% greater 24-hours after HIIE (P = .05), while uEGFr remained unchanged with CMIE. sCr decreased 6 to 19% 1-hour post-exercise in both conditions (P = .009). On average renal filtration increased in eGFR-MDRD (7.2 ± 2.0 ml/min/1.73 m2) (P = .007) and eGFR-CKD-EPI (8.6 ± 2.3 ml/min/1.73 m2) 1-hour post-exercise (P = .009). Conclusion: By clinical estimates, renal filtration in CKD was not normalized but transiently improved regardless of exercise condition, with HIIE eliciting transient improvements in renal health.

The Influence of an Acute Bout of Aerobic Exercise on Vascular Endothelial Function in Moderate Stages of Chronic Kidney Disease.

Chronic kidney disease (CKD) is directly influenced by the deleterious effects of systemic inflammation and oxidative stress. The vascular endothelium may transiently respond to aerobic exercise and improve post-exercise vascular renal function in moderate stages of CKD. Brachial artery flow-mediated dilation (FMD) is a nitric-oxide-dependent measure of endothelial function that is transiently potentiated by exercise. The purpose of the study was to determine the acute influence of a single bout of high-intensity interval exercise (HIIE) or steady-state moderate-intensity exercise (SSE) on endothelial dysfunction in moderate stages of CKD. Twenty participants (n = 6 men; n = 14 women) completed 30 min of SSE (65%) and HIIE (90:20%) of VO2reserve in a randomized crossover design. FMD measurements and blood samples were obtained before, 1 h, and 24 h post-exercise. FMD responses were augmented 1 h post-exercise in both conditions (p < 0.005). Relative to pre-exercise measures, total antioxidant capacity increased by 4.3% 24 h post-exercise (p = 0.012), while paraoxonase-1 was maintained 1 h and elevated by 6.1% 24 h after SSE, but not HIIE (p = 0.035). In summary, FMD can be augmented by a single episode of either HIIE or SSE in moderate stages of CKD. Modest improvements were observed in antioxidant analytes, and markers of oxidative stress were blunted in response to either SSE or HIIE.

Metabolic Health, Obesity, and Cardiovascular Disease: 2015-2016 National Health and Nutrition Examination Survey.

BACKGROUND: The metabolically unhealthy normal weight (MUN) and metabolically healthy obese (MHO) phenotypes are abnormal metabolic states. The purpose of this study was to report the frequency of the strictly defined MHO and MUN phenotypes and the association between metabolic phenotype and 10-year Framingham cardiovascular disease (CVD) risk score using a sample taken from the 2015-2016 National Health and Nutrition Examination Survey. METHODS: A cross-sectional sample of 2,316 participants age 18-79 years with complete metabolic health information were selected from the 2015-2016 dataset and included in the present analysis. Metabolic health was defined as the absence of all metabolic abnormalities as outlined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index ≥30 kg/m2 or waist > 88.9 cm for females or > 101.6 cm for males. RESULTS: Frequency of the MHO phenotype was 5.5% and the MUN was 44.3%. After adjustment for all covariates, Framingham CVD risk score was higher in the MUN (b = 1.74,p < 0.001) and metabolically unhealthy obese (b = 3.32,p < 0.001) phenotypes that used BMI to define obesity, and the MHO phenotype had a slight protective effect (b = -2.25,p < 0.001) when waist circumference was used as the measure of obesity. CONCLUSIONS: Metabolically unhealthy phenotypes had higher CVD risk, while the MHO phenotype was not at any greater risk than the metabolically healthy normal weight.

Rhabdomyolysis and acute renal failure in a sickle cell trait athlete: a case study.

This case study reports the clinical details and pathologic mechanisms of a nonfatal case of rhabdomyolysis secondary to heat exhaustion and sickle cell trait (SCT) resulting in acute renal failure. A 19-year-old African American male college football player collapsed after running 5 intervals of 300 m during a preseason conditioning test. After 17 days of treatment, the athlete was released from the hospital to a short-term noncritical care facility for further treatment and dialysis. Scientific literature reports that at least 15 college football players with SCT have died as a result of a sickling crisis after intense physical exertion. This case study presents the clinical importance of prompt medical treatment and sustained low-efficiency dialysis in treating rhabdomyolysis and its sequelae after collapse in an SCT athlete.

Effects of Uric Acid on Lipid Levels in CKD Patients in a Randomized Controlled Trial.

BACKGROUND: Few studies have been conducted that compared lipid levels and uric acid in CKD or End-Stage Renal Disease (ESRD) patients with most using animal models. The purpose of the study was to explore effects on lipids while controlling uric acid levels in CKD patients. METHODS: Twenty-four CKD patients (N = 24) volunteered to participate in this study. The study was conducted using a double-blind, randomized, placebo controlled experimental protocol. The experimental group was prescribed 300 mg of allopurinol PO daily by their treating physician and followed prospectively for 8-weeks. The control group consumed a similar pill once a day for 8-weeks. RESULTS: ANCOVA revealed significant differences in total cholesterol (P = 0.009) and Apo B (P = 0.006) with lower levels in the allopurinol group. A trend emerged with LDL (P = 0.052) with lower levels in the allopurinol group. No significant differences were discovered in triglycerides (P = 0.403), HDL (P = 0.762) and total Cholesterol/HDL Ratio (P = 0.455). CONCLUSIONS: After statistically controlling for compliance and inflammation significant differences between groups were observed for total cholesterol and Apo B. In both instances the allopurinol group had lower concentrations than the placebo group. Similarly, a trend was observed in LDL with the allopurinol group having lower concentrations than the placebo group.

The effects of fish oil supplementation on markers of inflammation in chronic kidney disease patients.

OBJECTIVE: One prevalent characteristic of all stages of chronic kidney disease (CKD) is excessive production of proinflammatory cytokines. Fish oil (FO) supplementation has been reported to lower levels of proinflammatory cytokines. The benefits of FO for an extensive range of populations and a variety of health concerns are apparent, yet the anti-inflammatory benefits for nondialysis CKD patients are not as well documented. Therefore, the purpose of this study was to investigate the effects of the daily consumption of FO (1,400 mg eicosapentaenoic acid + 1,000 mg docosahexaenoic acid) on interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) for 8 weeks in nondialysis CKD patients. DESIGN, SETTING, AND SUBJECTS: In this double-blind, randomized, placebo-controlled intervention, the effect of 8 weeks of FO administration on IL-1ß, IL-6, and TNF-α levels in nondialysis CKD patients were evaluated. INTERVENTION: Thirty-one nondialysis CKD patients (17 = FO; 14 = placebo) randomly received either FO dietary supplementation 2.4 g/day (1,400 mg eicosapentaenoic acid + 1,000 mg docosahexaenoic acid) or placebo (safflower oil) for 8 weeks. MAIN OUTCOME MEASURES: IL-1ß, IL-6, and TNF-α were all measured as markers of inflammation. RESULTS: One-way analysis of variance revealed no significant differences in IL-6 (P = .06), IL-1ß (P = .18), and TNF-α (P = .20) between groups in pretest values. Additionally, no pretest differences existed between groups for age (P = .549), weight (P = .324), waist circumference (P = .086), gender (P = .591), and ethnicity (P = .875). Covariance was calculated using compliance, age, gender, ethnicity, body weight, and waist circumference as covariates. No significant differences were discovered between groups after FO supplementation for IL-6 (P = .453) and TNF-α (P = .242). A significant difference was discovered for IL-1ß (P = .050) with lower levels in the FO group. CONCLUSIONS: The results of this study are in agreement with some previous studies that suggest that FO supplementation has no effect on plasma proinflammatory cytokines TNF-α or IL-6, but does have an effect on IL-1ß in nondialysis CKD patients.

Reverse epidemiology of lipid-death associations in a cohort of end-stage renal disease patients.

BACKGROUND AND AIMS: Cardiovascular disease is the leading cause of death among end-stage renal disease (ESRD) patients with hypercholesterolemia as a major cause. A few studies have demonstrated counter-intuitive findings known as reverse epidemiology where normal levels of cholesterol are associated with higher levels of mortality. The purpose of this study was to determine if there are reverse epidemiological associations between lipid risk factors and mortality in ESRD patients. METHODS: ESRD (n = 438) patients were recruited from 4 outpatient dialysis units. Patients were tracked for 36 months until study completion or death with mortality status as the outcome measure. RESULTS: Analysis of covariance revealed significant differences at posttest and reverse epidemiological effects for total cholesterol (p = 0.0001), low-density lipoprotein cholesterol (LDL) (p = 0.023), LDL particle number (p = 0.0001), LDL size (p = 0.009), triglycerides (p = 0.0001), and very low-density lipoprotein cholesterol (p = 0.036). A step-wise linear regression revealed weak, but significant predictors of mortality with total cholesterol (ß = 0.263, p = 0.017) and LDL (ß = -0.177, p = 0.045). A Cox death hazard ratio revealed LDL size as a significant predictor of mortality in this study. CONCLUSIONS: Our study discovered reverse epidemiology in a number of lipid variables. Additionally regression revealed that LDL and total cholesterol were predictors of mortality with lower levels being more predictive of death.

LDL particle size and number compared with LDL cholesterol and risk categorization in end-stage renal disease patients.

BACKGROUND: Few studies have been conducted that make comparisons between traditional measures of cholesterol and cholesterol subfractions, and only one study has compared low-density lipoprotein cholesterol (LDL-C) particle number, LDL-C particle size and LDL-C among end-stage renal disease (ESRD) patients. The purpose of this study was to examine the relationships between cholesterol measures and differences in risk stratification when using ATP-III guidelines compared with cholesterol particle number and size in ESRD patients. METHODS: ESRD patients (n=1,092) from clinics associated with the Central Texas Nephrology Associates were recruited to participate in this study. RESULTS: LDL particle size categorized more patients at-risk when compared with LDL-C, non-HDL-C and triglycerides. Pearson correlation coefficients revealed a strong significant correlation between LDL-C and LDL particle number (r2=0.908, p=0.0001) and a significant correlation between LDL particle number and LDL particle size (r2=-0.290, p=0.0001). A significant but weak correlation existed between LDL-C and LDL particle size (r2=0.107, p=0.0001). A significant correlation existed between LDL particle number and triglycerides (r2=0.335, p=0.0001) and a significant inverse relationship between LDL particle size and triglycerides (r2=-0.500, p=0.0001). CONCLUSIONS: Our study seems to suggest that using LDL particle size may help to identify those who would not be considered at-risk using LDL-C, non-HDL-C or triglycerides alone, and can be used as a further screening measure that may be more predictive of coronary heart disease outcomes.

Malnutrition, inflammation, and lipids in a cohort of dialysis patients.

BACKGROUND: This study aimed to determine if there is an association between lipid levels, serum albumin, and C-reactive protein (CRP) levels in patients on dialysis. METHODS: Lipid profiles, albumin, and CRP levels were collected after a 12-hour fast from patients with end-stage renal disease (N = 105) who were on chronic hemodialysis. Patients were placed in an albumin group (>or= 3.8 g/dL) or a hypoalbumin group (< 3.8 g/dL), a high-risk CRP group (> 3 mg/dL) or a low-risk CRP group (

The effects of lowering uric acid levels using allopurinol on markers of metabolic syndrome in end-stage renal disease patients: a pilot study.

OBJECTIVE: Allopurinol was administered to end-stage renal disease (ESRD) patients with elevated uric acid levels presenting with symptoms of gout and also had risk factors of metabolic syndrome. The primary aim of this pilot study was to examine the effects of lowering uric acid levels using allopurinol on lipoprotein markers of metabolic syndrome in patients. METHODS: The study was conducted using a prospective open-label protocol. End-stage renal disease patients (n=12) (mean age: 45.8+/- 13.6 years) undergoing chronic hemodialysis were recruited through their treating physician to participate in this study. All patients had ESRD and were prescribed allopurinol (300 mg/bid) for gout over a 3-month period. Pre-allopurinol and post-allopurinol data was obtained on low-density lipoprotein (LDL) cholesterol, LDL particle number, LDL particle size, high-density lipoprotein (HDL) cholesterol, large HDL particle number, total cholesterol, triglycerides, large very-low density lipoprotein (VLDL) particle number, and uric acid. Changes in lipid values were measured using a one-sample exact Wilcoxon rank sum test. RESULTS: Significant changes occurred in the primary outcome measures of serum uric acid levels (-3.53 mg/dL, p=0.01), LDL cholesterol (-14.00 mg/dL, p=0.04), and triglycerides (32.67 mg/dL, p=0.01). Trends were observed in lipid markers that warrant further investigation. CONCLUSION: Novel findings of our study suggest that lowering uric acid in ESRD patients may help to reduce the risk of cardiovascular disease in this population. It should be noted than an increase in triglycerides may mitigate the reduction in risk.

Effect of over-the-counter fish-oil administration on plasma Lp(a) levels in an end-stage renal disease population.

OBJECTIVE: This study sought to examine the effect of n-3 supplementation on lipoprotein(a) (Lp(a)) levels in end-stage renal disease (ESRD) patients undergoing chronic hemodialysis. DESIGN: The present study was conducted using a double-blind, permuted-randomized, controlled experimental protocol. SETTING: This study took place at the Central Texas Nephrology Associates Dialysis Clinic (Waco, TX). PATIENTS: Patients with ESRD and associated with the Central Texas Nephrology Associates who were undergoing chronic hemodialysis participated in this study. INTERVENTION: Patients with ESRD were followed prospectively while receiving supplements of fish oil (treatment, eicosapentaenoic acid, 0.96g/day, and docosahexaenoic acid, 0.6g/day) or corn oil (control subjects) for 6 months. After a 12-hour fast, participants donated 12mL of blood for analysis of Lp(a) at baseline and at 6 months. MAIN OUTCOME MEASURE: The comparison of Lp(a) concentration by group at 6 months was the primary outcome measure of the study. RESULTS: Our study suggests that fish-oil supplementation did not decrease levels of Lp(a) (P=.66), compared with control subjects. CONCLUSION: We failed to show a significant effect of 6 months of over-the-counter fish-oil supplementation on Lp(a) status in an ESRD population, although results from this study support findings from other studies suggesting that African Americans have higher Lp(a) concentrations than persons of Caucasian decent.

Effects of omega-3 fatty acid supplementation on lipid levels in endstage renal disease patients.

OBJECTIVE: Our purpose was to determine if over-the-counter fish oil improves the cardiovascular-disease risk profile of endstage renal disease patients. DESIGN: This study used a double-blind, permuted-block, randomized, placebo-controlled design. The experimental intervention consisted of fish-oil concentrate supplementation, whereas corn-oil capsules were used as a control. Compliance follow-ups were performed 3 times per week. SETTING: Patients of Central Texas Nephrology Associates clinics were eligible for this study. PATIENTS: Exclusion criteria comprised a life-expectancy of less than 6 months, pregnancy, a history of hemodialysis or medication noncompliance, or age below 18 years. The final sample size was 87 patients. The attrition rate was 9%. INTERVENTION: Participants in the experimental group consumed six 1-g soft-gel capsules of fish-oil concentrate each day for 6 months. The control group consumed corn-oil capsules, following the same protocol. Venous blood samples were acquired before and after the intervention. MAIN OUTCOME MEASURE: We assessed a number of serum lipid indicators. RESULTS: There were significant supplement/time interactions in low-density lipoprotein cholesterol (LDL) levels (P = .0001) and LDL particle number (P = .0001). Repeated-measures analysis of variance revealed significant time trends in high-density lipoprotein cholesterol (P = .012) and LDL (P = .001). High-density lipoprotein cholesterol levels significantly decreased in the control group, and increased in the fish-oil group, at 6 months, and LDL levels increased significantly in both groups. CONCLUSIONS: The analysis indicates mixed results with respect to cardiovascular disease risk. Further research is needed to assess the benefits of an over-the-counter fish-oil supplement in the renal population.

Fish oil supplementation lowers C-reactive protein levels independent of triglyceride reduction in patients with end-stage renal disease.

BACKGROUND: Inflammation has been identified as a marker for cardiovascular disease. The purpose of this study is to examine the effects of fish oil fatty acid supplementation on C-reactive protein (CRP) levels. METHODS: The study uses a double-blind, permuted-randomized, and placebo-controlled experimental protocol. Patients are randomly placed into a fish oil group or a control group. Thirty-three patients in the experimental and control groups ingest 2 soft-gel pills (1 g each) of fish oil supplements containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or placebo at each meal. Patients follow the supplementation protocol for 6 months. Analysis of variance (ANOVA) is used to measure pretest and posttest differences in the variable of interest. A Kolmogorov-Smirnov test for normality is used to test whether CRP levels are normally distributed. RESULTS: The Kolmogorov-Smirnov test for CRP finds a P value of .273 (KS = .997), revealing that the distribution is normal. ANOVA reveals no statistically significant difference between groups at baseline for CRP (F = 4.118, P = .053). ANOVA reveals a significant main effect (F = 4.29, P = .048) for CRP, with the EPA/DHA group having a significant change in values from pretest (16 mg/dL, standard deviation [SD] = 13.80) to posttest (10.22 mg/dL, SD = 7.87). The placebo group's CRP levels do not change significantly from pretest (13.37, standard deviation [SD] = 7.94) to posttest (13.67, SD = 7.07). An observed power calculation using Cohen's D with a computed alpha of .05 is .588. CONCLUSIONS: The study demonstrates that consuming 960 mg/d of EPA and 600 mg/d of DHA can lower CRP.

Omega-3 fatty acid supplementation and total homocysteine levels in end-stage renal disease patients.

AIM: Elevated total homocysteine (tHcy) levels are commonplace among end-stage renal disease (ESRD) patients increasing risk for poor cardiovascular outcomes. Specifically, when plasma levels become significantly elevated, tHcy levels appear to contribute to vascular damage and premature atherosclerosis. The purpose of this study was to examine the effect of an over-the-counter omega-3 (n-3) fatty acid supplementation on tHcy levels in ESRD patients undergoing chronic haemodialysis. METHODS: The present study was conducted using a double-blind, permuted-randomized and placebo-controlled experimental protocol. ESRD patients were followed prospectively while supplementing n-3 or corn oil (n-6) prospectively for 6 months. PATIENTS: Sixty-nine patients were recruited that had previously demonstrated compliance with dialysis and medication. Following a 12 h fast, participants donated 12 mL of blood for analysis of tHcy at baseline and at 6 months. RESULTS: The results of this study using regression models revealed no differences in age and gender regarding homocysteine levels at the post-test with P-values of 0.6818, 0.6709 and 0.3331 for each regression model. The study findings also revealed that daily administration of 6 g of n-3 fatty acids containing 160 mg of eicosapentaenic acid (0.96 g/day) and 100 mg of docosahexaenoic acid (0.6 g/day) had no effect on tHcy levels when compared with control. CONCLUSION: Potential reasons for this non-significant result may be found in a dose-response relationship, advancement of disease progression in our sample population, or potentially the lack of a significant relationship between fish oil and tHcy. Future studies should address whether a dose-response relationship between n-3 fatty acid supplementation and tHcy levels exists, and how stage of disease progression affects intervention success or failure.

Effects of omega-3 fatty acid supplementation on vascular access thrombosis in polytetrafluorethylene grafts.

OBJECTIVE: The purpose of this study was to investigate the effects of orally administered over-the-counter omega-3 (n-3) fatty acid supplements on primary patency of polytetrafluoroethylene (PTFE) grafts. DESIGN: This study was conducted with a triple-blind, permuted-block, randomized, placebo-controlled experimental design. SETTING: Dialysis clinics with patients who, in accordance with physician diagnosis, needed a new PTFE graft. PATIENTS AND OTHER PARTICIPANTS: Patients on long-term hemodialysis with newly placed PTFE grafts who were unable to receive a native arteriovenous fistula. INTERVENTION: Patients were followed prospectively for 8 months after they had been placed into an n-3 fatty acid or control group and were monitored for primary patency. MAIN OUTCOME VARIABLE: Primary patency of the PTFE graft. RESULTS: The n-3 fatty acid group had a mean PTFE graft primary patency rate of 254.2 days (SEM = 51.8), and the control group had a mean PTFE graft primary patency rate of 254.1 days (SEM = 34.6), revealing no significant difference in survival time between groups. CONCLUSIONS: No significant differences in primary patency rates were noted in the experimental and control groups.