Paraoxonase 1 arylesterase activity and mass are reduced and inversely related to C-reactive protein in patients on either standard or home nocturnal hemodialysis.

UNLABELLED: Human serum paraoxonase (PON1) activity is reduced in standard hemodialysis (SHD) (4 hours, 3 days/week) patients. Home nocturnal hemodialysis (HNHD) (8 hours, 6 days/week), provides a greater dialysis dose resulting in a greater clearance of metabolites. Whether improvements in the metabolic milieu of HNHD patients results in different PON1 activity levels compared to SHD patients is unclear. We determined serum PON1 mass and arylesterase activities in a group of HNHD patients and compared them to SHD patients and a group of healthy controls (HC). PATIENTS AND METHODS: We measured PON1 arylesterase activity and mass, C-reactive protein (CRP), cystatin C, total and high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins A-I and B in 15 HNHD, 15 SHD and 15 HC participants. RESULTS: PON1 arylesterase activity (p < 0.001) and mass (p < 0.05) were significantly higher in HC participants compared to SHD and HNHD participants, although no significant differences were noted between HD groups. CRP (p < 0.05) was significantly higher in SHD compared to HC participants and there were no significant differences noted between HD groups. Cystatin C (p < 0.001) was significantly different among the 3 groups. There were no significant differences noted in any lipoprotein parameters among the groups. PON1 activity (r = -0.636, p < 0.001) and mass (r = -0.425, p = 0.019) were inversely correlated with CRP in HD patients. CONCLUSION: PON1 is reduced in HNHD patients compared to HC subjects, independent of the concentration of HDL cholesterol. Within subjects on HD, the combination of increased CRP and reduced PON1 may identify subjects at a high risk for cardiovascular complications.

Dietary fiber effects in chronic kidney disease: a systematic review and meta-analysis of controlled feeding trials.

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) is a major health concern associated with increased risk of cardiovascular disease, morbidity and mortality. Current CKD practice guidelines overlook dietary fiber, which is chronically low in the renal diet. However, increasing dietary fiber has been proposed to ameliorate the progress of CKD. We therefore conducted a systematic review and meta-analysis on the effect of dietary fiber intake on serum urea and creatinine as classical markers of renal health in individuals with CKD. SUBJECTS/METHODS: We searched MEDLINE, EMBASE, CINHAL and the Cochrane Library for relevant clinical trials with a follow-up ⩾7 days. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean difference (MD) with 95% confidence intervals (95% CIs). Heterogeneity was assessed by the Cochran Q statistic and quantified by I(2). RESULTS: A total of 14 trials involving 143 participants met the eligibility criteria. Dietary fiber supplementation significantly reduced serum urea and creatinine levels in the primary pooled analyses (MD, -1.76 mmol/l (95% CI, -3.00, -0.51), P<0.01 and MD, -22.83 mmol/l (95% CI, -42.63, -3.02), P=0.02, respectively) with significant evidence of interstudy heterogeneity only in the analysis of serum urea. CONCLUSIONS: This is the first study to summarize the potential beneficial effects of dietary fiber in the CKD population demonstrating a reduction in serum urea and creatinine, as well as highlighting the lack of clinical trials on harder end points. Larger, longer, higher-quality clinical trials measuring a greater variety of uremic toxins in CKD are required (NCT01844882).

Threonine kinetics in preterm infants fed their mothers' milk or formula with various ratios of whey to casein.

BACKGROUND: Plasma threonine concentrations are elevated in infants fed formula containing a whey-to-casein protein ratio of 60:40 compared with concentrations in infants fed formula containing a ratio of 20:80 or human milk (60:40). OBJECTIVE: We studied whether degradation of excess threonine was lower in formula-fed infants than in infants fed their mothers' milk. DESIGN: Threonine kinetics were examined in 17 preterm infants (gestational age: 31+/-2 wk: birth weight: 1720+/-330 g) by using an 18-h oral infusion of [1-13C]threonine at a postnatal age of 21+/-11 d and weight of 1971+/-270 g. Five infants received breast milk. Formula-fed infants (n = 12) were randomly assigned to receive 1 of 3 formulas (5.3 g protein/MJ) that differed only in the whey-to-casein ratio (20:80, 40:60, and 60:40). RESULTS: Threonine intake increased significantly in formula-fed infants with increasing whey content of the formula (48.5, 56.4, and 63.2 micromol.kg(-1).h(-1), respectively; pooled SD: 2.2; P = 0.0001), as did plasma threonine concentrations (228, 344, and 419 micromol/L, respectively; pooled SD: 75; P = 0.03). Despite a generous threonine intake by infants fed breast milk (58.0+/-16.0 micromol.kg(-1).h(-1), plasma threonine concentrations remained low (208+/-41 micromol/L). Fecal threonine excretion and net threonine tissue gain, estimated by nitrogen balance, did not differ significantly among groups. Threonine oxidation did not differ significantly among formula-fed infants but was significantly lower in formula-fed infants fed than in infants fed breast milk (17.1% compared with 24.3% of threonine intake, respectively). CONCLUSION: Formula-fed infants have a lower capacity to oxidize threonine than do infants fed breast milk.

Isotopic enrichment of amino acids in urine following oral infusions of L-[1-(13)C]phenylalanine and L-[1-(13)C]lysine in humans: confounding effect of D-[13C]amino acids.

Urine sampling of the free amino acid pool serves to reflect plasma enrichment and is used as a noninvasive means to determine isotope enrichment in studies of amino acid metabolism. We determined the effect of D-[13C]phenylalanine and D-[13C]lysine content of tracers on urinary amino acid enrichment following oral infusion of L-[13C]phenylalanine in 18 preterm infants and L-[1-(13)C]lysine in seven healthy adult females. Urinary [13C]phenylalanine enrichment was higher (P < .0001) for L-[13C]phenylalanine containing 0.4% D-[13C]phenylalanine (28.6 +/- 7.1) versus L-[1-(13)C]phenylalanine that contained undetectable D-[13C]phenylalanine (10.2 +/- 1.5). D-[13C]phenylalanine, measured by chiral column gas chromatography-mass spectrometry (GC-MS), accounted for 10% to 30% (20.5% +/- 7%) of total phenylalanine in the urine of infants who received 0.4% D-[13C]phenylalanine, and was absent from the urine of infants receiving tracer with undetectable [13C]phenylalanine. Urinary L-[13C]phenylalanine enrichment did not differ between tracer groups (9.8 +/- 1.5 and 9.8 +/- 2.5). In adult females, the use of L-[1-(13)C]lysine (1.6% D-lysine) resulted in a higher (P < .02) urine total L,D-[13C]lysine enrichment compared with plasma enrichment (40.8 +/- 4.1 v 11.1 +/- 0.7). This study demonstrates the significant presence of D-[13C]amino acids in urine that originate as contaminants from commercially manufactured tracers, as a result of renal tubular discrimination of D-amino acids. A tracer containing detectable amounts of D-[13C]isomer cannot be recommended for any study in which urine will be used to reflect enrichment in the arterial plasma pool.

Effect of taurine supplements on fat absorption in cystic fibrosis.

Patients with cystic fibrosis have an increased proportion of glycine conjugated bile acids with diminished tauroconjugates which could contribute to fat malabsorption. Twenty-two CF children with documented steatorrhea were supplemented with taurine capsules (30 mg/kg/day) and placebo during separate 6-month treatment periods. Alteration of the glycine/taurine conjugation pattern was verified in two patients who showed a predominance of tauroconjugates as a result of taurine supplementation. On taurine, steatorrhea was reduced (p less than 0.05) by 17.6 +/- 9.7% in 19 patients who completed the study as was the excretion of long-chain saturated fatty acids. There was no change in linoleic acid (C 18:2) excretion. In the 10 patients with a more severe degree of steatorrhea the decrease in fat loss approached 20% and a close relationship was found (r = 0.84, p less than 0.01) between the extent of the fatty acid loss on placebo and the decrease of this loss on taurine. A linear relationship was found between the percentage decrease of individual fatty acids and their log solubility in water. No change was found in the daily excretion of bile acids, neutral sterols, and nitrogen. Fasting plasma fatty acids, cholesterol, and triglycerides were also unchanged. Monitoring of growth over the two 6-month periods revealed a marginal (p less than 0.1) increase of weight velocity expressed as a percentage expected for age (83.4 +/- 11.3----117.1 +/- 16.5). The increase in height velocity in response to taurine showed a more modest trend (95.3 +/- 7.8----110.7 +/- 10.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans.

The threonine dehydrogenase (TDG) pathway is a significant route of threonine degradation, yielding glycine in experimental animals, but has not been accurately quantitated in humans. Therefore, the effect of a large excess of dietary threonine, given either as free amino acid (+Thr) or as a constituent of protein (+P-Thr), on threonine catabolism to CO(2) and to glycine was studied in six healthy adult males using a 4-h constant infusion of L-[1-(13)C]threonine and [(15)N]glycine. Gas chromatography-combustion isotope ratio mass spectrometry was used to determine [(13)C]glycine produced from labeled threonine. Threonine intakes were higher on +Thr and +P-Thr diets compared with control (126, 126, and 50 micromol x kg(-1) x h(-1), SD 8, P < 0.0001). Threonine oxidation to CO(2) increased threefold in subjects on +Thr and +P-Thr vs. control (49, 45, and 15 micromol x kg(-1) x h(-1), SD 6, P < 0.0001). Threonine conversion to glycine tended to be higher on +Thr and +P-Thr vs. control (3.5, 3.4, and 1.6 micromol x kg(-1) x h(-1), SD 1.3, P = 0.06). The TDG pathway accounted for only 7-11% of total threonine catabolism and therefore is a minor pathway in the human adult.