Effect of Oat ß-Glucan Supplementation on Chronic Kidney Disease: A Feasibility Study.

OBJECTIVE: Dietary supplementation with grains containing high ß-glucan fiber has been shown to attenuate the progression of chronic kidney disease (CKD) and vascular calcification in animal models. The aim of this study was to investigate the feasibility of consuming an oat ß-glucan supplement and to assess its effects on certain uremic toxins and markers of mineral metabolism in patients with CKD. DESIGN: This is a 20-week, nonrandomized, single-center, pretest-posttest study. Twenty-eight subjects with CKD stages 3-4 were enrolled. The mean age was 67.6 ± 8.9 years, and the mean estimated glomerular filtration rate was 35 ± 14 mL/min/1.73 m2. Subjects received a dietary supplement containing 3 g of oat ß-glucan per day for 12 weeks. The 4-week period before the start of the intervention was used as a baseline comparison for each subject. The primary outcome was pre-post supplement changes in plasma levels of two uremic toxins: trimethylamine N-oxide (TMAO) and asymmetric dimethylarginine. Secondary outcomes were pre-post supplement changes in serum calcium, phosphorus, and Klotho levels. Repeated-measures analysis of variance was used to test the differences in outcomes over the three-month-long intervention. RESULTS: Serum levels of TMAO decreased by a median of -17% (interquartile range: -46%, 7%) at the end of the intervention. A nonstatistically significant change was observed for asymmetric dimethylarginine (median -0.6% [-12%, 20%]) and serum Klotho (median -3% [-8%, 7%]). There were no changes in serum levels of calcium and phosphorus. One month after discontinuation of ß-glucan therapy, TMAO levels increased by a median of 16% (-12%, 36%) but remained slightly below the pretreatment levels. Eight subjects experienced side effects and discontinued the treatment. CONCLUSION: A diet supplemented with ß-glucan is safe and potentially efficacious in lowering serum concentrations of TMAO in patients with CKD. Larger trials with longer follow-up times are needed to determine whether such reductions translate into clinical benefits.

Acid Load and Phosphorus Homeostasis in CKD.

BACKGROUND: The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) in vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS: Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimated from food frequency questionnaire responses, and serum bicarbonate concentration < 22 mEq/L. OUTCOME & MEASUREMENTS: 24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations. RESULTS: Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P<0.05). Serum phosphorus concentration was also higher with higher net acid excretion and lower serum bicarbonate concentration (each P=0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion (P<0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but not FGF-23, concentration (P=0.2) was 26% (95% CI, 13%-40%) higher in participants with a serum bicarbonate concentration <22 versus ≥22 mEq/L (P<0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available. LIMITATIONS: Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion. CONCLUSIONS: In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.

Current status of bicarbonate in CKD.

Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been tested very little, especially with respect to standard clinical outcomes. On the basis of fundamental research and small alkali supplementation trials, correcting metabolic acidosis has a strikingly broad array of potential benefits. This review summarizes the published evidence on the association between serum bicarbonate and clinical outcomes. We discuss the role of alkali supplementation in CKD as it relates to retarding kidney disease progression, improving metabolic and musculoskeletal complications.

Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency is highly prevalent among patients with chronic kidney disease (CKD). The benefits and harms of vitamin D supplementation (ergocalciferol or cholecalciferol) were assessed in patients with nondialysis-dependent CKD, dialysis-dependent CKD, and renal transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE (1966 to September 2009), SCOPUS (September 2009), and nephrology conference proceedings were searched for relevant observational and randomized controlled trials (RCTs). Treatment effects were summarized as mean differences (MDs) with 95% confidence intervals (CIs) using a random effects model. Separate analyses were conducted for observational studies and RCTs. RESULTS: Twenty-two studies (17 observational and 5 RCTs) were included. There was a significant improvement in 25-hydroxyvitamin D (MD 24.1 ng/ml, 95% CI 19.6 to 28.6) and an associated decline in parathyroid hormone (PTH) levels (MD -41.7 pg/ml, 95% CI -55.8 to -27.7) among observational studies. PTH reduction was higher in dialysis patients. Among RCTs, there was a significant improvement in 25-hydroxyvitamin D (MD 14 ng/ml, 95% CI 5.6 to 22.4) and an associated decline in PTH levels (MD -31.5 pg/ml, 95% CI -57 to -6.1). A low incidence of hypercalcemia and hyperphosphatemia was reported with vitamin D supplementation. Cardiovascular and skeletal effects of vitamin D supplementation have not been studied. Included studies were mostly of low to moderate quality. CONCLUSIONS: Available evidence from low-to-moderate quality observational studies and fewer RCTs suggests that vitamin D supplementation improves biochemical endpoints. However, whether such improvements translate into clinically significant outcomes is yet to be determined.

Availability of weight-loss supplements: Results of an audit of retail outlets in a southeastern city.

The sale of nonprescription weight-loss products accounts for millions of dollars spent by Americans trying to lose weight, yet there is little evidence for effectiveness and there are multiple safety concerns. The purpose of this study was to determine what products, and ingredients within products, were available at retail outlets in a metropolitan area. A purposive sampling strategy identified 73 retail outlets. An audit form was used to collect information from product labels. The audit identified 402 products containing 4,053 separate ingredients. The mean number of ingredients per product was 9.9+/-8.96 (range = 1 to 96). A database search was conducted regarding evidence for effectiveness, safety precautions, and side effects for the 10 ingredients that appeared most often across products. Modest evidence of effectiveness exists for green tea (Camellia sinensis), chromium picolinate, and ma huang (Ephedra major). For the remaining seven (ginger root [Zingiber officinale], guarana [Paullinia cupana], hydroxycitric acid [Garcinia cambogia], white willow [Salix alba], Siberian ginseng [Eleutherococcus senticosus], cayenne [Capsicum annuum], and bitter orange/zhi shi [Citrus aurantium]), inadequate or negative evidence exists. Although precautions and contraindications were found for all 10 ingredients, the strongest concerns in the literature appear for ma huang, bitter orange, and guarana. Our audit revealed numerous weight-loss products available to consumers, yet there is little evidence to support the effectiveness of the top 10 ingredients identified and many potential adverse reactions; therefore, food and nutrition professionals should discuss dietary supplement use with their clients.