Urine volume as an estimator of residual renal clearance and urinary removal of solutes in patients undergoing peritoneal dialysis.

In non-anuric patients undergoing peritoneal dialysis (PD), residual kidney function (RKF) is a main contributor to fluid and solute removal and an independent predictor of survival. We investigated if urine volume could be used to estimate renal clearances and removal of urea, creatinine, and phosphorus in PD patients. The observational, cross-sectional study included 93 non-anuric prevalent PD patients undergoing continuous ambulatory PD (CAPD; n = 34) or automated PD (APD; n = 59). Concentrations of urea, creatinine and phosphorus in serum and in 24-h collections of urine volume were measured to calculate weekly residual renal clearance (L/week) and removed solute mass (g/week). Median [interquartile range], 24-h urine output was 560 [330-950] mL and measured GFR (the mean of creatinine and urea clearances) was 3.24 [1.47-5.67] mL/min. For urea, creatinine and phosphorus, residual renal clearance was 20.60 [11.49-35.79], 43.02 [19.13-75.48] and 17.50 [8.34-33.58] L/week, respectively, with no significant differences between CAPD and APD. Urine volume correlated positively with removed solute masses (rho = 0.82, 0.67 and 0.74) and with weekly residual renal clearances (rho = 0.77, 0.62 and 0.72 for urea, creatinine, and phosphorus, respectively, all p < 0.001). Residual renal clearances and urinary mass removal rates for urea, creatinine, and phosphorus correlate strongly with 24-h urine volume suggesting that urine volume could serve as an estimator of typical values of residual solute removal indices in PD patients.

Resistant Starch Type-2 Supplementation Does Not Decrease Trimethylamine N-Oxide (TMAO) Plasma Level in Hemodialysis Patients.

Dysbiosis is recognized as a new cardiovascular disease (CVD) risk factor in hemodialysis (HD) patients because it is linked to increased generation in the gut of uremic toxins such as trimethylamine N-Oxide (TMAO) from dietary precursors (choline, betaine, or L-carnitine). Nutritional strategies have been proposed to modulate the gut microbiota and reduce the production of these toxins. This study aimed to evaluate the effect of amylose-resistant starch (RS) supplementation on TMAO plasma levels in HD patients.We conducted a randomized, double-blind, placebo-controlled trial (NCT02706808) with patients undergoing HD enrolled in a previous pilot study. The participants were allocated to RS or placebo groups to receive 16 g/d of RS or placebo for 4 weeks. Plasma TMAO, choline, and betaine levels were measured with LC-MS/MS. Fecal microbiome composition was evaluated by 16S ribosomal RNA sequencing, followed by a search for TMA-associated taxa. Anthropometric, routine biochemical parameters, and food intake were evaluated.Twenty-five participants finished the study, 13 in the RS group, and 12 in the placebo group. RS supplementation did not reduce TMAO plasma levels. Moreover, no significant alterations were observed in choline, betaine, anthropometric, biochemical parameters, or food intake in both groups. Likewise, RS was not found to exert any influence on the proportion of potential TMA-producing bacterial taxa in fecal matter.RS supplementation did not influence plasma TMAO, choline, betaine, or fecal taxa potentially linked to TMAO. Thus, RS does not seem to modify the TMA-associated bacterial taxa, precursors of TMAO.Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2021.1967814 .

Can nutritional interventions modulate the activation of the NLRP3 inflammasome in chronic kidney disease?

Inflammatory and innate immune responses triggered by pathogen-associated and other danger-associated signals emerging during infections, results in the activation of cytosolic inflammasomes. The nod-like receptor pyrin domain containing 3 (NLRP3) is one of the inflammasomes mediating such responses through the activation of caspase-1, which increases the production and release of pro-inflammatory cytokines, such as IL-1ß and IL-18 and induces programmed cell death through pyroptosis. NLRP3 is thought to play a crucial role in the underlying inflammatory responses in many lifestyles related chronic diseases. Consequently, research on the NLRP3 inflammasome has expanded dramatically in recent years. Although several studies have investigated the role of NLRP3 activation in chronic kidney disease (CKD), few studies have evaluated strategies to modulate its activation by means of interventions using non-pharmacological strategies. This review discusses some nutritional strategies (bioactive compounds, probiotics and caloric restriction) that have been shown to influence NLRP3 in experimental models of renal disease, and in CKD. It discusses how nutritional interventions could potentially dampen NLRP3 associated inflammatory burden, as part of nutritional strategies to prevent and treat CKD and its complications.

Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: A pilot randomized, double-blind, controlled study.

BACKGROUND & AIMS: Chronic kidney disease (CKD) patients have numerous complications associated with inflammation, which is a potential driver for cardiovascular disease. Curcumin, a compound of the curcuminoid class produced by the Curcuma longa, has been reported to activate nuclear factor erythroid factor 2-related (Nrf2) and inhibit nuclear factor kappa-B (NF-kB). Our aim was to evaluate the effects of curcumin juice on the expression of inflammatory transcription factors in hemodialysis (HD) patients. METHODS AND RESULTS: This double-blind randomized pilot study included 31 HD patients divided into two groups: curcumin group (receiving 100 mL of orange juice with 12 g of carrot and 2.5 g of turmeric after each dialysis session/week for 3 months) and control group (receiving the same juice without curcumin); 14 patients in each arm completed the study. The mRNA expression of Nrf2, NF-kB, NLRP3 inflammasome and IL-1ß in peripheral blood mononuclear cells (PBMC; using real-time quantitative polymerase chain reaction, qPCR) and routine biochemistries, food intake and anthropometrics were analyzed. After three months of supplementation, the curcumin group showed a significant decrease in NF-kB mRNA expression (AU) [from 1.08 (0.77-1.38) to 0.52 (0.32-0.95),p = 0.02] and in plasma high sensitivity C-reactive protein (hsCRP) levels [from 3.8 (2.5-6.8) to 2.0 (1.1-3.8) mg/L, p = 0.04]. There was no change in the other evaluated markers. CONCLUSION: Three months treatment with curcumin in CKD patients undergoing HD resulted in decreased markers of inflammation, NF-kB mRNA expression and hsCRP, suggesting that oral supplementation of curcumin may have an anti-inflammatory effect in this patient group. TRIAL REGISTRATION: Approved by the Ethics Committee of the Faculty of Medicine/UFF, number: 2.346.933. This study was registered within ClinicalTrials.gov under the number NCT03475017.

Vitamin D deficiency and treatment versus risk of infection in end-stage renal disease patients under dialysis: a systematic review and meta-analysis.

Background: Infections are common and can be fatal in patients undergoing long-term dialysis. Recent studies have shown conflicting evidence associating infection with vitamin D status or use of vitamin D and have not been systematically reviewed in this population. Methods: We searched PubMed, Web of Science, Cochrane Library, Embase and three Chinese databases from inception until December 2017 for interventional [non-randomized or randomized controlled trials (RCTs)], cohort and case-control studies on levels of serum 25-hydroxyvitamin D [25(OH)D] or use of vitamin D [supplemental nutritional vitamin D or vitamin D receptor activator (VDRA)] and infection (any infection, infection-required hospitalization or infection-related death or composite) in long-term dialysis patients. We conducted a meta-analysis on the relative risk (RR) of infection and level of 25(OH)D or use of vitamin D. Results: Of 2440 reports identified, 17 studies met inclusion criteria, all with moderate quality, with 6 cohort studies evaluating 25(OH)D serum concentrations (n = 5714) and 11 (2 RCTs and 9 observational studies) evaluating the use of vitamin D (n = 92 309). The risk of composite infection was 39% lower {relative risk [RR] 0.61 [95% confidence interval (CI) 0.41-0.89]} in the subjects with high or normal levels of 25(OH)D than in those with low levels. When compared with those who did not use vitamin D, the pooled adjusted risk for composite infection was 41% lower in those who used vitamin D [RR 0.59 (95% CI 0.43-0.81)]. Conclusions: High or normal serum levels of 25(OH)D and the use of vitamin D, particularly VDRA, were each associated with a lower risk of composite infection in long-term dialysis patients.

The value of the Brazilian açai fruit as a therapeutic nutritional strategy for chronic kidney disease patients.

Açai (Euterpe oleracea Mart.) fruit from the Amazon region in Brazil contains bioactive compounds such as α-tocopherol, anthocyanins (cyanidin 3-glycoside and cyanidin 3-rutinoside), and other flavonoids with antioxidant and anti-inflammatory properties. Moreover, the prebiotic activity of anthocyanins in modulating the composition of gut microbiota has emerged as an additional mechanism by which anthocyanins exert health-promoting effects. Açai consumption may be a nutritional therapeutic strategy for chronic kidney disease (CKD) patients since these patients present with oxidative stress, inflammation, and dysbiosis. However, the ability of açai to modulate these conditions has not been studied in CKD, and this review presents recent information about açai and its possible therapeutic effects in CKD.

Prognostic Value of Copeptin in Chronic Kidney Disease: From General Population to End-Stage Renal Disease.

Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is released in response to osmotic and non-osmotic stimuli and plays a key role in many physiologic and pathologic processes. The main function of AVP is the control of fluid homeostasis by inducing water conservation by the kidney, but it also stimulates arteriolar vasoconstriction and the release of adrenocorticotropic hormone (ACTH). These actions are mediated by different AVP receptors located on various target cells. Produced in hypothalamus from a larger precursor, pre-proAVP, AVP is produced in equimolar amounts to copeptin, a glycopeptide with yet unknown biologic function. Copeptin remains stable in plasma and its circulating concentrations correlate directly with those of AVP. Because AVP is unstable in isolated plasma or serum and its half-life is short, copeptin has become an easily measured surrogate marker reflecting vasopressin concentration. Recently, associations between high circulating copeptin and decline in glomerular filtration rate as well as greater risk of new-onset chronic kidney disease (CKD) have been reported. In addition, copeptin has been shown to be associated with increased risk of complications such as myocardial infarction, heart failure, diabetes mellitus and metabolic syndrome. In this brief review, studies on the prognostic value of copeptin measurement in the general population and in CKD are presented and discussed.

Circulating Alpha-Tocopherol and Insulin Sensitivity Among Older Men With Chronic Kidney Disease.

OBJECTIVE: Insulin resistance is common in individuals with chronic kidney disease (CKD) and may be partly explained by modifiable risk factors. In the general population, vitamin E supplementation has been suggested to improve both insulin sensitivity and secretion. We here explore the potential role of vitamin E as a modifiable risk factor for insulin resistance among individuals with CKD. DESIGN: Observational study. SETTING: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate ≥ 20 mg/minute from the third examination cycle of Uppsala Longitudinal Study of Adult Men. SUBJECTS: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate ≥ 20 µg/minute. METHODS: Serum α-, ß-, and γ-tocopherol concentrations were measured by high-performance liquid chromatography and expressed as µmol/total serum cholesterol and triglycerides (in mmol). Dietary vitamin E intake was estimated from 7-day food records. MAIN OUTCOME MEASURE: Insulin sensitivity index (M/I ratio) was measured by hyperinsulinemic-euglycemic glucose clamps. Univariate and multivariate regression models were fitted to assess the association between M/I and circulating concentrations of tocopherols. RESULTS: The mean serum concentration of α-, ß-, and γ- was 37.4 ± 6.58, 0.89 ± 0.23, and 4.32 ± 1.69 µmol/mmol, respectively. Median dietary vitamin E intake was 6.14 (interquartile range, 5.48-6.82) mg/day. In crude and fully-adjusted multivariate regression analyses, serum α-tocopherol levels were directly and strongly associated with M/I (standard ß = 0.17, P = .003). No such association was observed for dietary vitamin E, serum ß-, and γ-tocopherol concentrations. CONCLUSIONS: Serum α-tocopherol concentration associates with insulin sensitivity in nondiabetic older men with CKD.

Dietary fat modification in patients with chronic kidney disease: n-3 fatty acids and beyond.

Replacement of dietary saturated fat with unsaturated fat has been recommended for prevention of cardiovascular disease (CVD) in the general population. Less is known of the health risks in individuals with chronic kidney disease (CKD), of a diet with an unhealthy fat profile, in general characterized by insufficient polyunsaturated fatty acids (PUFA) and excess satu-rated fatty acids (SFA). The dietary intake of PUFA, both the n-3 and n-6 subfamilies, is increasingly gaining attention in CKD, owing to its broad cardioprotective effects. Conversely, dietary SFA may promote CVD in this vulnerable population. This review discusses the potential benefits of dietary fat modification in CKD patients, including plausible effects on renal function, albuminuria, lipoproteins, nutritional status, inflammation, thrombosis and clinical outcomes. Increasing evidence supports the concept that n-3 PUFA might have therapeutic potential in reducing proteinuria in CKD and reducing triglycerides and inflammation in dialysis patients. In addition, emerging evidence suggests that linoleic acid, a major n-6 PUFA derived from vegetable oils, may be beneficial for a number of CVD risk factors. Increased consumption of oily fish as part of plant-based diets with low content of SFA is likely to benefit patients who have CKD, or are at risk of developing CKD. Such recommendations are in line with the concept of a healthy "Mediterranean diet" and are in line with current dietary recommendations for CVD prevention in the community.

Determinants of fibroblast growth factor-23 and parathyroid hormone variability in dialysis patients.

BACKGROUND/AIMS: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined. METHODS: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored. RESULTS: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode. CONCLUSIONS: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients.

Reaching targets for mineral metabolism clinical practice guidelines and its impact on outcomes among Mexican chronic dialysis patients.

BACKGROUND AND AIMS: An increasing number of studies have been published concerning meeting targets of clinical guidelines for different aspects of the diagnosis and treatment of patients with end-stage renal disease. Most of these studies have shown that guideline recommendations are not always satisfied, and results outside target limits have been associated with high rates of mortality and morbidity. The objective of this study was to analyze the frequency of reaching mineral and bone metabolism-related guideline targets and its impact on clinical outcomes in Mexican chronic dialysis patients. METHODS: A cohort of prevalent peritoneal dialysis (PD) and hemodialysis (HD) patients were analyzed at baseline and followed for at least 16 months. Patients were on continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD), and HD and contracted HD modalities where patients received HD sessions outside institution facilities. RESULTS: We studied 753 patients. The percentage of patients within target limits for phosphorus was 35%, for calcium 32%, and for PTH 12%. The most frequent pattern was hyperphosphatamia, hypercalcemia, and low PTH. This was even more frequent in CAPD patients, probably due to the high percentage of diabetic patients. Hypercalcemia was found as an independent risk factor for mortality. CONCLUSIONS: The most important results suggest that guideline recommendations are not usually satisfied and that hypercalcemia, in addition to other traditional risk factors, is associated with high mortality rates. The study also detected some opportunities to improve the quality of treatment by reducing the calcium content of dialysis solutions and reducing the use of calcium carbonate as a phosphate binder.

Vitamin B6 and the immunity in kidney transplant recipients.

OBJECTIVE: The study aimed to determine vitamin B6 status in elderly (age ≥ 60 years) and younger (age <60 years) recipients of allogeneic kidney graft and to investigate associations between vitamin B6 status and immunity markers. DESIGN: A retrospective observational study. SETTING: The study was conducted at the Medical University of Gdansk, Poland. SUBJECTS: We recruited 34 kidney allograft recipients (17 males and 17 females) and allocated them into 2 groups: patients aged ≥ 60 years (18 patients) and those aged <60 years (16 patients). Exclusion criteria included patients receiving vitamin B6 supplementation or drugs known to influence vitamin B6 metabolism. MAIN OUTCOME MEASURE: Plasma levels of pyridoxal 5'-phosphate (PLP), pyridoxal, pyridoxine, pyridoxamine, pyridoxamine 5'-phosphate, and 4 pyridoxic acid were determined by high-performance liquid chromatography. Measured immunity markers were serum cytokines (interleukin-6, interleukin-10, and transforming growth factor-ß), levels of T-lymphocyte subsets, and the proliferative ability of peripheral blood mononuclear cells. RESULTS: Concentrations of all vitamin B6 vitamers in plasma (PLP, pyridoxal, pyridoxamine 5'-phosphate, pyridoxamine, pyridoxine, 4 pyridoxic acid) were comparable in the 2 studied groups. There were no cases of PLP deficiency in the study population, but 29% of patients had PLP concentrations more than the upper reference limit. Vitamin B6 vitamer concentrations were not influenced by gender, estimated glomerular filtration rate, and circulating phosphate concentration. There was no difference in immunity markers according to age. However, the plasma concentrations of vitamin B6 vitamers were inversely associated with levels of CD28(+) lymphocyte subsets, as well as with the proliferative response of peripheral blood mononuclear cells in both groups. CONCLUSIONS: No cases of vitamin B6 deficiency were found among kidney allograft recipients, and we report inverse links between vitamin B6 vitamer concentrations and markers of cellular immunity, suggesting that bioactive vitamin B6 concentration in kidney allograft recipients merits further investigation.

Improved plasma amino acids pattern following 12 months of supplemented low-protein diet in peritoneal dialysis patients.

BACKGROUND: Decreased plasma essential amino acid (EAA) levels, increased nonessential amino acid (NEAA) levels, and low EAA to NEAA ratio (E/NEAA) are common in peritoneal dialysis (PD) patients and may impact uremic complications. In the present study, we investigate the impact of keto acids-supplemented low-protein (sLP) diet on plasma amino acids (AAs) patterns in stable PD patients. METHODS: This is a supplemental analysis of a previously published prospective and randomized trial. Thirty-nine PD patients selected from the original population were divided to receive either low (LP: 0.6-0.8 g/kg ideal body weight [IBW]/d, n = 13), keto acids-supplemented low- (sLP: 0.6-0.8 g/kg IBW/d + 0.12 g/kg IBW/d of keto acids, n = 12), or high- (HP: 1.0-1.2 g/kg IBW/d, n = 14) protein diets and followed for 1 year. Plasma AA patterns were assessed at baseline and 12 months using high-performance liquid chromatography. RESULTS: Whereas there were no significant differences between the three groups at baseline, following 12 months, the E/NEAA had increased significantly in group sLP (0.58 +/- 0.16 to 0.83 +/- 0.20, p < 0.05), but was not different in either LP (0.62 +/- 0.20 to 0.72 +/- 0.13, p = ns) or HP (0.66 +/- 0.14 to 0.74 +/- 0.12, p = ns) group. This change in E/NEAA in group sLP was due to a significant decrease in NEAA concomitantly with maintained EAA levels, whereas in the other two groups, neither EAA nor NEAA changed significantly. CONCLUSIONS: A low-protein diet supplemented with keto acids significantly improved the pattern of plasma AA in prevalent PD patients.

Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality.

BACKGROUND: Histidine is considered as an antiinflammatory and antioxidant factor. Histidine deficiency may contribute to an impaired nutritional state in patients with chronic kidney disease (CKD). OBJECTIVE: We aimed to investigate the consequences of plasma histidine deficiency in CKD patients. DESIGN: CKD patients (n = 325; 203 M) with a median age of 54 y (range: 19-70 y) were evaluated shortly before the beginning of renal replacement therapy. The median glomerular filtration rate was 6.4 mL/min (range: 0.8-14.5 mL/min). Nutritional status was assessed by subjective global assessment. Survival was followed for up to 60 mo; 101 patients died. RESULTS: Plasma histidine concentrations were significantly lower in CKD patients with history of cardiovascular disease, presence of plaques, protein-energy wasting, and inflammation. Plasma histidine was negatively associated with age, C-reactive protein, interleukin-6, leukocytes, thrombocytes, fibrinogen, hepatocyte growth factor, adhesion molecules, insulin-like growth factor-1, and 8-hydroxy-2'-deoxyguanosine and was positively associated with handgrip strength, hemoglobin, S-albumin and fetuin-A. A multivariate regression analysis showed that histidine concentrations were independently associated with hepatocyte growth factor, hemoglobin, and fetuin-A. In unadjusted analysis, a low histidine concentration was associated with all-cause mortality (log rank chi-square test = 8.9; P = 0.002). After adjustment for age, sex, cardiovascular disease, inflammation, diabetes mellitus, serum S-albumin, and amino acid supplementation, the association between low histidine and mortality remained significant (hazard ratio: 1.55; 95% CI: 1.02, 2.40; P < 0.05). CONCLUSION: Low plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in CKD patients.

Homocysteine-lowering is not a primary target for cardiovascular disease prevention in chronic kidney disease patients.

The homocysteine (Hcy) theory states that total homocysteine (tHcy) is a risk factor for atherosclerosis. Chronic kidney disease (CKD) is one of the most frequent causes of hyperhomocysteinemia in the presence of high prevalence of cardiovascular disease (CVD). However, there is not yet any conclusive answer to the question whether Hcy may contribute to, or predict, cardiovascular events or mortality in CKD patients or whether it is just an innocent bystander biologically related to other potential risk factors for CVD. Moreover, tHcy levels in CKD are influenced by several commonly occurring confounding factors, such as inflammation and protein-energy wasting (PEW). These factors are also associated with morbidity and mortality and altogether this may explain why Hcy does not show up as a cardiovascular risk but in fact is reversely associated with clinical outcome. Thorough evaluation of such reverse association may not necessarily imply that the principles of Hcy being a contributor to vascular pathophysiology are different in CKD patients but rather indicate that other superimposed factors, such as PEW and inflammation, are more important. These confounders contribute significantly to the unacceptably high mortality rate in this patient population and may require nutritional and anti-inflammatory interventions to improve clinical outcome. So far, the results of recent folic acid intervention trials do not support the use of folic acid supplementation for lowering tHcy and improving survival in CKD patients. Although we are still waiting for the results from several ongoing controlled randomized trials in this area, future studies are needed to evaluate if thiol-exchange agents, besides folic acid, as part of a future multifactorial intervention regime targeting inflammation, PEW, oxidative stress as well as hyperhomocysteinemia may decrease CVD risk in this high-risk patient population.

Effect of repeated intravenous iron administration in haemodialysis patients on serum 8-hydroxy-2'-deoxyguanosine levels.

BACKGROUND: Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients. METHODS: Twenty-seven patients (62+/-14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht<30% and FTN<100 ng/ml; n=7); High FTN group (Ht>or=30% and FTN>or=100 ng/ml; n=11); and low FTN group (Ht>or=30% and FTN<100 ng/ml; n=9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks. RESULTS: At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2=0.47, P<0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22+/-0.07-0.50+/-0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52+/-0.20-0.58+/-0.28 ng/ml) and the low FTN group (0.39+/-0.11-0.36+/-0.11 ng/ml) (ANOVA for repeated measures P<0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner. CONCLUSIONS: Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.

Effect of high-dose thiamine and pyridoxine on advanced glycation end products and other oxidative stress markers in hemodialysis patients: a randomized placebo-controlled study.

OBJECTIVE: To study the effect of high doses of thiamine (250 mg/day) and pyridoxine (200 mg/day) supplementation on plasma levels of advanced glycation end products and other oxidative stress markers in hemodialysis patients. DESIGN: An interventional survey. SETTING: This study was conducted at an outpatient nephrology clinic. INTERVENTION AND PATIENTS: We performed a randomized placebo-controlled study over 8 weeks in 50 patients (53% men, age 52.9 +/- 3.4 years) on regular hemodialysis. MAIN OUTCOME MEASURES: The patients were divided into 2 groups of 25 patients in each arm. Before starting the study, the patients in both groups were matched by age, gender, inflammatory profile (plasma interleukin [IL]-6 and high-sensitivity C-reactive protein [hsCRP]), and nutritional status (subjective global assessment and protein nitrogen appearance). RESULTS: In all, 40 of 50 patients completed the study (19 patients in the vitamin group and 21 in the placebo group). Serum albumin, plasma hsCRP, IL-6, advanced oxidation protein products, pentosidine and 8-hydroxy-2'-deoxyguanosine were measured before and after treatment in each group. In both groups, over 8 weeks of follow-up, no significant differences could be observed in oxidative stress, inflammatory, or nutritional markers. CONCLUSIONS: There was no evidence showing that high doses of thiamine and pyridoxine affects oxidative stress in hemodialysis patients.

Novel approaches in an integrated therapy of inflammatory-associated wasting in end-stage renal disease.

It is increasingly apparent that end-stage renal disease (ESRD) patients carry an inflammatory burden, which may play a pivotal role in the evolution of not only wasting, but also the massive increase in the relative risk of cardiovascular disease (CVD). Thus wasting is strongly associated with a persistent systemic inflammatory response, CVD, and impaired patient survival in end-stage renal disease (ESRD), as well as in other chronic diseases. Evidence suggests that a facilitative interaction between inflammatory cytokines and other factors such as poor appetite, comorbidity, acidosis, anemia, and hormonal derangements may cause wasting in this patient group. Clearly, isolated interventions in the form of nutritional energy and protein supplementation have seldom proven to be very effective in improving nutritional status and outcome in ESRD patients, presumably because of the need to attack other causative factors. Therefore, new treatment strategies must be evaluated. Strategies such as multiple appetite stimulants, various "anti-inflammatory diets," and new potentially useful anti-inflammatory pharmacologic agents may be tested alone, or in combination, to evaluate if these new therapeutic modalities can improve the outcome of ESRD patients. As the etiology of wasting in ESRD is multifactorial, we propose that its treatment must include not one, but a number of concomitant measures to provide an integrated therapy against this devastating complication.

Plasma sulfur amino acids in relation to cardiovascular disease, nutritional status, and diabetes mellitus in patients with chronic renal failure at start of dialysis therapy.

Sulfur amino acids (sAAs) are potential candidates as risk factors for cardiovascular disease (CVD). However, we recently reported that chronic hemodialysis patients with CVD had a greater prevalence of malnutrition, hypoalbuminemia, and lower plasma total homocysteine (tHcy) levels than those without CVD. In this cross-sectional study, we examined the relationship of plasma sAAs to CVD and nutritional status in 151 patients with chronic renal failure (CRF) close to the start of regular dialysis treatment (33 +/- 7 days before the first dialysis treatment). Clinical signs of CVD were present in 32% of patients with CRF, 41% had malnutrition assessed by subjective global nutritional assessment (SGNA) score, and 26% had diabetes mellitus (DM). Plasma tHcy levels were high in 91% of patients, as were plasma total cysteine (tCys) levels, whereas plasma methionine (Met) and taurine (Tau) levels were normal. Patients with CRF who had CVD were older, more often malnourished, and had lower tHcy and serum albumin (s-albumin) levels and a greater frequency of DM than those without CVD. Plasma tCys, Met, and Tau levels did not differ between patients with CRF with and without CVD. The tCys-tHcy ratio was higher in patients with CVD and related to SGNA score and DM. Moreover, this ratio, but not tHcy or tCys level, correlated with age and triglyceride, total cholesterol, and apolipoprotein B levels. Malnutrition and hypoalbuminemia were associated with low plasma sAA levels (tHcy, Met, and Tau); tCys was related to s-albumin level, but not SGNA score. Among patients with diabetes, sAA levels did not differ between patients with and without CVD or between malnourished and well-nourished patients. In conclusion, patients with CRF at the start of dialysis treatment with CVD were more often diabetic, malnourished, and had lower s-albumin and tHcy levels and a higher tCys-tHcy ratio than patients with no CVD. tCys-tHcy ratio, but not tHcy or tCys levels per se, was related to cardiovascular risk factors, suggesting that cysteine may have a role in the development of CVD. Malnutrition, hypoalbuminemia, and DM in patients with CRF influence sAA levels, mainly plasma tHcy, which should be considered when evaluating hyperhomocysteinemia as a cardiovascular risk factor.