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BACKGROUND: The arteriovenous fistula (AVF) provides an effective vascular access for hemodialysis; however, the associated hemodynamic effects may alter cardiac structure and function. The objective of this study is to evaluate the effect of AVF closure on functional and structural echocardiographic findings. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: In a single center between 2003 and 2006, we enrolled 25 consecutive hemodialysis patients with AVF malfunction who underwent AVF closure and conversion to a tunneled central venous catheter because of exhaustion of alternative vascular sites and 36 matched controls with a well-functioning AVF. PREDICTOR: AVF closure. OUTCOMES & MEASUREMENTS: Outcomes were changes in findings on echocardiograms obtained before and 6 months after AVF closure for patients in the AVF-closure group and at baseline and 6 months later for controls. Echocardiographic measurements included left ventricular (LV) internal diastolic diameter, interventricular septum thickness, diastolic posterior wall thickness, LV mass (LVM), LVM index (LVMi), and LV ejection fraction (LVEF). Dialysis modality and scheme were unchanged. RESULTS: In the AVF-closure group, LVM decreased from 225 +/- 55 to 206 +/- 51 g (P < 0.001) and LVMi decreased from 135 +/- 40 to 123 +/- 35 g/m(2) (P < 0.001). LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness decreased significantly, whereas LVEF increased from 56% +/- 7% to 59% +/- 6% (P < 0.001). No significant changes were observed in controls. In patients with AVF closure, LV morphologic characteristics showed a decrease in both eccentric and concentric hypertrophy in favor of normalization or a pattern of concentric remodeling. No significant changes were observed in controls. LIMITATIONS: Use of matched rather than randomized controls. CONCLUSIONS: Closure of an AVF determines a significant decrease in LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness. This is associated with significant improvement in LVEF, a significant decrease in LVM and LVMi, and a more favorable shift of cardiac geometry toward normality. [ABSTRACT FROM AUTHOR]

BACKGROUND: A supplemented very-low-protein diet (sVLPD) seems to be safe when postponing dialysis therapy. STUDY DESIGN: Prospective multicenter randomized controlled study designed to assess the noninferiority of diet versus dialysis in 1-year mortality assessed by using intention-to-treat and per-protocol analysis. SETTING & PARTICIPANTS: Italian uremic patients without diabetes older than 70 years with glomerular filtration rate of 5 to 7 mL/min (0.08 to 0.12 mL/s). INTERVENTION: Randomization to an sVLPD (diet group) or dialysis. The sVLPD is a vegan diet (35 kcal; proteins, 0.3 g/kg body weight daily) supplemented with keto-analogues, amino acids, and vitamins. Patients following an sVLPD started dialysis therapy in the case of malnutrition, intractable fluid overload, hyperkalemia, or appearance of uremic symptoms. OUTCOMES & MEASUREMENTS: Mortality, hospitalization, and metabolic markers. RESULTS: 56 patients were randomly assigned to each group, median follow-up was 26.5 months (interquartile range, 40), and patients in the diet group spent a median of 10.7 months (interquartile range, 11) following an sVLPD. Forty patients in the diet group started dialysis treatment because of either fluid overload or hyperkalemia. There were 31 deaths (55%) in the dialysis group and 28 deaths (50%) in the diet group. One-year observed survival rates at intention to treat were 83.7% (95% confidence interval [CI], 74.5 to 94.0) in the dialysis group versus 87.3% (95% CI, 78.9 to 96.5) in the diet group (log-rank test for noninferiority, P < 0.001; for superiority, P = 0.6): the difference in survival was -3.6% (95% CI, -17 to +10; P = 0.002). The hazard ratio for hospitalization was 1.50 for the dialysis group (95% CI, 1.11 to 2.01; P < 0.01). LIMITATIONS: The unblinded nature of the study, exclusion of patients with diabetes, and incomplete enrollment. CONCLUSION: An sVLPD was effective and safe when postponing dialysis treatment in elderly patients without diabetes.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Background.The nephronophthisis-medullary cystic disease (NPH/MCD) complex represents a heterogeneous group of hereditary tubulointerstitial nephritis. The most common variant is juvenile recessive NPH, for which a gene locus (NPH1) has been mapped on chromosome 2q13. MCD is a less common dominant condition usually recognized later in life, which resembles NPH in many aspects, still presenting remarkable clinical differences. Nothing is known about the chromosome locus of MCD. [ABSTRACT FROM PUBLISHER]

Background: Malnutrition in haemodialysis (HD) patients has been referred to underdialysis with low protein intake, and to acidosis. However, the separate effects of underdialysis and acidosis on nutrition have not been clearly demonstrated. To evaluate the role of the dialysis dose and of metabolic acidosis on nutrition, we measured the predialysis serum HCO3, pH, serum albumin, PCRn, Kt/V, and BMI in 81 uraemic patients on maintenance bicarbonate, HD for 93±80 months. Patients with chronic liver diseases, malignancies, and cachexia were excluded. [ABSTRACT FROM PUBLISHER]

Background: Very low-protein intake during chronic kidney disease (CKD) improves metabolic disorders and may delay dialysis start without compromising nutritional status, but concerns have been raised on a possible negative effect on survival during dialysis. This study aimed at evaluating whether a very low-protein diet during CKD is associated with a greater risk of death while on dialysis treatment., Methods: This is an historical, cohort, controlled study, enrolling patients at dialysis start previously treated in a tertiary nephrology clinic with a very low-protein diet supplemented with amino acids and ketoacids (s-VLPD group, n = 184) or without s-VLPD [tertiary nephrology care (TNC) group, n = 334] and unselected patients [control (CON) group, n = 9.092]. The major outcome was survival rate during end-stage renal disease associated to s-VLPD treatment during CKD. The propensity score methods and Cox regression model were used to match groups at the start of dialysis to perform survival analysis and estimate adjusted hazard ratio (HR)., Results: In s-VLPD, TNC and CON groups, average age was 67.5, 66.0 and 66.3 years, respectively (P = 0.521) and male prevalence was 55, 55 and 62%, respectively (P = 0.004). Diabetes prevalence differed in the three groups (P < 0.001), being 18, 17 and 31% in s-VLPD, CON and TNC, respectively. A different prevalence of cardiovascular (CV) disease was found (P < 0.001), being similar in TNC and CON (31 and 25%) and higher in s-VLPD (41%). Median follow-up during renal replacement therapy (RRT) was 36, 32 and 36 months in the three groups. Adjusted HR estimated on matched propensity patients was 0.59 (0.45-0.78) for s-VLPD versus CON. Subgroup analysis showed a lower mortality risk in s-VLPD versus matched-CON in younger patients (<70 years) and those without CV disease. No significant difference in HRs was found between s-VLPD and TNC., Conclusion: s-VLPD during CKD does not increase mortality in the subsequent RRT period., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.

Background: Strict control of serum calcium and phosphate concentrations is paramount to prevent secondary hyperparathyroidism in haemodialysis (HD) patients. Standard intermittent low-flux HD (Lf-HD) is not sufficient to reach this goal. The aim of this study was to evaluate the effect of on-line haemodiafiltration (Ol-HDF) on serum calcium (sCa), phosphate (sPO4) and parathyroid hormone (PTHint) concentrations., Methods: Of the 220 patients screened, 65 met the inclusion criteria for the study; 30 of whom agreed to participate in the study (Study group), the others were considered as the control group (Controls). Protocol for Study the group consisted of 6 months conventional Lf-HD (Period 1) and 6 months of post-dilutional Ol-HDF (Period 2). Controls continued their usual Lf-HD and were followed for 12 months. The main variables evaluated at the start and at the end of each period were sCa, sPO(4) and PTHint., Results: The switchover from Lf-HD to Ol-HDF resulted in a significant reduction of sPO4 (from 5.1 ± 1.0 to 4.0 ± 0.7; P < 0.0001) and PTHint concentrations (from 307 ± 167 to 194 ± 98; P < 0.0001), no significant changes were found in both sCa concentrations (from 9.1 ± 0.7 to 8.9 ± 0.6) and phosphate binder dose. Kt/Vurea increased significantly, and beta(2) microglobulin concentrations decreased significantly. In the Controls, no significant variations of the same variables were observed over time, except for a significant increase in sevelamer intake., Conclusion: This study supports the idea that Ol-HDF could be better than Lf-HD in controlling mineral metabolism in HD patients.

We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 × 10⁻²⁶ and 4.84 × 10⁻⁹ and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures.

Background: Dialysis increases patient life expectancy but is associated with clinically severe and costly complications. Health and economic benefits could derive from postponing dialysis with a supplemented very low-protein diet (sVLPD)., Methods: An economic evaluation was conducted to compare benefits and costs of sVLPD versus dialysis in elderly CKD5 patients. Data from 57 patients aged >or=70 years, with glomerular filtration rate (GFR) 5-7 mL/min, previously participating in a clinical trial demonstrating non-inferior mortality and morbidity of starting sVLPD compared to dialysis treatment, were analysed: 30 patients were randomized to dialysis and 27 to sVLPD. A cost-benefit analysis was conducted, in the perspective of the National Health Service (NHS). Direct medical and non-medical benefits and costs occurring in 3.2 mean years of follow-up were quantified: time free from dialysis, cost of dialysis treatment, hospitalization, drugs, laboratory/instrumental tests, medical visits and travel and energy consumption to receive dialysis. Prices/tariffs valid in 2007 were used, with an annual discount rate of 5% applied to benefits and costs occurring after the first year. Sensitivity analyses were conducted to identify how estimates could vary in different contexts of applications. Results are reported as net benefit, expressed as mean euro/patient (patient-year)., Results: The opportunity to safely postpone initiation of dialysis of 1 year/patient on average translated into an economic benefit to the NHS, corresponding to 21 180 euro/patient in the first, 6500 euro/patient in the second and 682 euro/patient in the third year of treatment, with a significant net benefit in favour of sVLPD even in a worst-case hypothesis., Conclusion: The initiation of sVLPD in elderly CKD5 subjects is a safe and beneficial strategy for these patients and allows them to gain economic resources that can be allocated to further health care investments.

Background: The effect of the correction of metabolic acidosis (MA) on serum albumin concentrations (sAlbs) in hemodialysis (HD) patients is controversial. This study evaluated the role of the correction of MA on sAlb concentrations, normalized protein catabolic rate (nPCR), and the effect of the concomitant inflammatory status, in a group of acidotic HD patients., Methods: The correction of MA by oral supplementation with sodium bicarbonate, and the evaluation of its effect on sAlb, nPCR, and high-sensitivity C-reactive protein (hsCRP), were performed in 29 patients on bicarbonate dialysis for a median of 30 months. Other variables included pre-HD arterial pH, serum bicarbonate, serum creatinine, serum Na, body weight, interdialytic weight gain, pre-HD systolic and diastolic blood pressure, and Kt/V., Results: Serum bicarbonate and pH increased significantly (P < .0001), from 19.1 +/- 0.7 mmol/L to 24.6 +/- 1.1 mmol/L and from 7.33 +/- 0.03 to 7.39 +/- 0.02, respectively (all values with +/- are SD). The nPCR decreased from 1.13 +/- 0.14 g/kg/day to 1.05 +/- 0.14 g/kg/day (P < .0001). The other variables did not change significantly. In 17 patients with high-sensitivity C-reactive protein <10 mg/L, sAlb increased from 3.7 +/- 0.3 g/dL to 4.0 +/- 0.3 g/dL (P < .01), whereas in 12 with high-sensitivity C-reactive protein >or=10 mg/L, sAlb did not change (3.5 +/- 0.17 g/dL vs. 3.4 +/- 0.13 g/dL; P = NS)., Conclusions: Oral sodium bicarbonate supplementation is effective in correcting MA in HD patients and does not affect interdialytic weight gain, plasma Na, and blood pressure. The correction of MA is effective in reducing protein catabolism (nPCR) in both inflamed and less inflamed HD patients, but increases sAlb only in patients without inflammation. In inflamed patients, the correction of MA is not sufficient per se to improve sAlb concentrations.