The Swiss Kidney Stone Cohort: A Longitudinal, Multicentric, Observational Cohort to Study Course and Causes of Kidney Stone Disease in Switzerland.

BACKGROUND: Kidney stone disease has a high prevalence worldwide of approximately 10% of the population and is characterized by a high recurrence rate. Kidney stone disease results from a combination of genetic, environmental, and lifestyle risk factors, and the dissection of these factors is complex. METHODS: The Swiss Kidney Stone Cohort (SKSC) is an investigator-initiated prospective, multicentric longitudinal, observational study in patients with kidney stones followed with regular visits over a period of 3 years after inclusion. Ongoing follow-ups by biannual telephone interviews will provide long-term outcome data. SKSC comprises 782 adult patients (age >18 years) with either recurrent stones or a single stone event with at least one risk factor for recurrence. In addition, a control cohort of 207 individuals without kidney stone history and absence of kidney stones on a low-dose CT scan at enrolment has also been recruited. SKSC includes extensive collections of clinical data, biochemical data in blood and 24-h urine samples, and genetic data. Biosamples are stored at a dedicated biobank. Information on diet and dietary habits was collected through food frequency questionnaires and standardized recall interviews by trained dieticians with the Globodiet software. CONCLUSION: SKSC provides a unique opportunity and resource to further study cause and course of kidney disease in a large population with data and samples collected of a homogeneous collective of patients throughout the whole Swiss population.

Gut microbiota associations with chronic kidney disease: insights into nutritional and inflammatory parameters.

Introduction: The gut barrier, comprising gut microbiota, plays a pivotal role in chronic kidney disease (CKD) progression and nutritional status. This study aimed to explore gut barrier alterations in hemodialyzed (HD) patients, non-HD (NHD) CKD patients, and healthy volunteers. Methods: Our cross-sectional study enrolled 22 HD patients, 11 NHD patients, and 11 healthy volunteers. We evaluated fecal microbiota composition (assessed via bacterial 16S rRNA gene sequencing), fecal IgA levels, surrogate markers of gut permeability, serum cytokines, appetite mediators, nutritional status, physical activity, and quality of life. Results: HD patients exhibited significant alterations in fecal microbiota composition compared to healthy volunteers, with observed shifts in taxa known to be associated with dietary patterns or producing metabolites acting on human host. In comparison to healthy volunteers, individuals with HD patients exhibited elevated levels of inflammatory markers (CRP, IL-6 and TNF-α), glucagon-like peptide-2, and potential anorexigenic markers (including leptin and peptide YY). NHD patients had increased levels of CRP and peptide YY. Overall fecal microbiota composition was associated with height, soft lean mass, resting energy expenditure, handgrip strength, bone mineral content and plasma albumin and TNF-α. Discussion: Compared to healthy volunteers, HD patients have an altered fecal microbiota composition, a higher systemic inflammation, and a modification in plasma levels of appetite mediators. While some differences align with previous findings, heterogeneity exists likely due to various factors including lifestyle and comorbidities. Despite limitations such as sample size, our study underscores the multifaceted interplay between gut microbiota, physiological markers, and kidney function, warranting further investigation in larger cohorts.

Gut barrier and microbiota changes with glycine and branched-chain amino acid supplementation in chronic haemodialysis patients.

BACKGROUND: We have previously shown that glycine increases fat-free mass in chronic haemodialysis patients with features of malnutrition as compared with branched-chain amino acids (BCAAs). This multicentre randomized double-blind crossover study evaluates the impact of these amino acids on the gut barrier and microbiota. METHODS: Haemodialysis patients were included if they had plasma albumin <38 g/L or weight loss >5% of dry body weight, and daily dietary intakes <30 kcal/kg and <1 g protein/kg. They consumed glycine or BCAA (7 g twice daily) for 4 months and underwent a 1 month washout period, before crossover of supplementations. Faecal microbiota (16S rRNA gene sequencing) and immunoglobulin A (IgA), serum levels of cytokines, surrogate markers of intestinal permeability, appetite mediators, and endocannabinoids were obtained at the start and end of each supplementation. Supplementations were compared by multiple mixed linear regression models, adjusted for age, sex, month of supplementation (0 and 4 in each period), and period (Period 1: first 4 months; Period 2: last 4 months). Microbiota comparisons were performed using principal coordinate analysis and permutational multivariate analysis of variance, Shannon diversity index estimate and analysis of composition of microbiomes analysis, and Wilcoxon tests. RESULTS: We analysed 27 patients compliant to the supplementations. Multiple mixed linear regression models were significant only for interleukin-6 (P = 0.002), glucagon-like peptide 1 (P = 0.028), cholecystokinin (P = 0.021), and peptide YY (P = 0.002), but not for the other outcomes. The significant models did not show any impact of the type of supplementation (P < 0.05 in all models). Principal coordinate analysis and permutational multivariate analysis of variance (P = 0.0001) showed strong microbiota clustering by subject, but no effect of the amino acids. Bacterial alpha diversity and zero-radius operational taxonomic unit richness remained stable, whatever the supplementation. Lacticaseibacillus paracasei (0.030; Q1-Q3 0.008-0.078 vs. 0.004; Q1-Q3 0.001-0.070) and Bifidobacterium dentium (0.0247; Q1-Q3 0.002-0.191 vs. 0.003; Q1-Q3 0.001-0.086) significantly decreased with the BCAA supplementation. CONCLUSIONS: The BCAA and glycine supplementations had no impact on the serum levels of cytokines, appetite mediators, intestinal permeability, endocannabinoids, or faecal IgA. Overall faecal microbiota composition and microbial diversity did not change with the glycine or BCAA supplementation but decreased the abundance of L. paracasei and B. dentium.

Glycine increases fat-free mass in malnourished haemodialysis patients: a randomized double-blind crossover trial.

BACKGROUND: Protein energy wasting is associated with negative outcome in patients under chronic haemodialysis (HD). Branched-chain amino acids (BCAAs) may increase the muscle mass. This post hoc analysis of a controlled double-blind randomized crossover study assessed the impact of BCAAs on nutritional status, physical function, and quality of life. METHODS: We included 36 chronic HD patient features of protein energy wasting as plasma albumin <38 g/L, and dietary intakes <30 kcal/kg/day and <1 g protein/kg/day. Patients received either oral BCAA (2 × 7 g/day) or glycine (2 × 7 g/day) for 4 months (Period 1), followed by a washout period of 1 month, and then received the opposite supplement (Period 2). The outcomes were lean body mass measured by dual-energy X-ray absorptiometry, fat-free mass index measured by bioelectrical impedance, resting energy expenditure, dietary intake and appetite rating, physical activity and function, quality of life, and blood parameters. Analyses were performed by multiple mixed linear regressions including type of supplementation, months, period, sex, and age as fixed effects and subjects as random intercepts. RESULTS: Twenty-seven patients (61.2 ± 13.7 years, 41% women) were compliant to the supplementations (consumption >80% of packs) and completed the study. BCAA did not affect lean body mass index and body weight, but significantly decreased fat-free mass index, as compared with glycine (coeff -0.27, 95% confidence interval -0.43 to -0.10, P = 0.002, respectively). BCAA and glycine intake had no effect on the other clinical parameters, blood chemistry tests, or plasma amino acids. CONCLUSIONS: Branched-chain amino acid did not improve lean body mass as compared with glycine. Unexpectedly, glycine improved fat-free mass index in HD patients, as compared with BCAA. Whether long-term supplementation with glycine improves the clinical outcome remains to be demonstrated.

[Nephrology]. / Néphrologie.

Increasing the nightly dialysate flow is efficient to increase the dialyse dose but has to be weighted against the possible negative impact of impaired sodium removal and increased glucose absorption. Mixing osmotic agents is an interesting option to tackle the challenge of ultrafiltration management and glucose exposure. High volume peritoneal dialysis is a possible alternative to hemodialysis in some case of acute kidney injury. Except relief of pain experienced during exchange with standard solutions, the others possible effects of more biocompatible peritoneal dialysis solutions need to be tested in further studies.

Assessment of health status in chronic hemodialysis patients.

BACKGROUND: We compared three ways of assessing health status in chronic hemodialysis patients: generic questionnaire compared with population norms, disease-specific questionnaire, and open questions. METHODS: Hemodialysis patients (n=83) treated in Geneva canton, Switzerland, answered the Kidney Disease Quality of Life (KDQOL-SF) questionnaire, which combines 12 disease-specific scales with the generic Short-Form 36 (SF36) health survey, and open questions about the most disturbing and most positive aspects of having end-stage renal disease. SF36 scores were compared with those of the general population, and generic health scales were correlated with dialysis-specific scales. RESULTS: Hemodialysis patients had significantly lower scores than general population controls on 7 of 8 SF36 scales, especially physical functioning (-1.2 standard deviation (SD) units, p<0.001) and general health (-1.2 SD, p<0.001), but their mental health was similar (-0.2 SD, p=0.13). All 12 KDQOL dialysis-specific scores correlated significantly with the SF36 mental summary score, but only 6 correlated significantly with the SF36 physical summary score. Open comments suggested that dialysis itself is the chief problem confronting dialysis patients, but also that the predicament of end-stage renal disease may have a positive impact on the lives of some patients. CONCLUSIONS: While physical problems are the biggest difference between dialysis patients and controls, disease-specific scales and open comments highlighted the importance of psychosocial and treatment-related problems among hemodialysis patients. Generic and disease-specific questionnaires, and open comments provide different information about the health status of dialysis patients.

Survival after parathyroidectomy in patients with end-stage renal disease and severe hyperparathyroidism.

BACKGROUND: Patients with end-stage renal disease (ESRD) and secondary hyperparathyroidism (SHPT) are at high risk of mortality. Whether an increased risk of death persists after a parathyroidectomy (PTX) is not clearly established. SUBJECTS AND METHODS: The survival of 40 patients with ESRD and SHPT who underwent PTX was compared with that of 664 ESRD patients. RESULTS: From first dialysis, a lower mortality rate was found in the group of patients who underwent PTX than in the nonoperated ESRD group (hazard ratio: 0.23; 95% CI: 0.14-0.37). The patients who underwent PTX were younger, had a longer time on dialysis, and had a higher prevalence of kidney transplantation. The mean number of comorbidities was lower (Charlson score 4.2 +/- 2.1 versus 6.4 +/- 2.9, p < 0.001). Then, we randomly selected two matched controls for each PTX case (80 controls, 40 PTX) who had at least an equivalent mean duration of dialysis between the first dialysis and PTX of the PTX group. In a univariate model, there was a trend for PTX being associated with prolonged survival. The mortality was higher both among those at an advanced age and those with a high Charlson score. Adjustments for these covariates made the effect of PTX no more significant. CONCLUSIONS: The risk of death of patients with severe SHPT leading to PTX differed from that of nonoperated subjects. The apparent differences in survival may be related to the number and severity of associated comorbidities. ESRD patients who undergo PTX may represent a subset of healthier subjects.

Safety of low-dose spironolactone administration in chronic haemodialysis patients.

BACKGROUND: Prevention of cardiovascular diseases is essential in chronic haemodialysis patients. Recently, low-dose spironolactone has been shown to decrease cardiovascular mortality in patients with severe heart failure. However, since haemodialysis patients are prone to hyperkalaemia, a known side effect of spironolactone, this treatment is not used in this population. We performed a study to assess whether low-dose spironolactone (3 x 25 mg/week) could be administered without inducing hyperkalaemia in haemodialysis patients. METHODS: The study design included a 2-week baseline period, followed by a 4-week treatment period in which doses of spironolactone were started at 12.5 mg three times/week for 2 weeks, then increased to 25 mg three times/week, and followed by a 2-week wash-out period. Fourteen patients receiving low-dose spironolactone after each dialysis were compared with 21 haemodialysis patients (control group). RESULTS: Low-dose spironolactone did not change mean serum potassium (4.9 +/- 0.7 vs 4.9 +/- 0.3 mmol/l: control). The mean plasma canrenone level induced by administration of spironolactone 25 mg three times/week in the 14 treated patients was 13 +/- 5.3 ng/ml. Serum aldosterone was not significantly modified by the administration of spironolactone in these patients [before, median 0.35; interquartile range (IQR) 0.11-2.83 nmol/l vs after, median 0.22; IQR 0.12-0.60 nmol/l, NS]. Dietary potassium intake and the use of ion-exchange resin, angiotensin-converting enzyme inhibitors and beta-blockers were similar for the two groups throughout the study. CONCLUSION: This non-randomized and non-blinded study shows that administration of 25 mg spironolactone thrice weekly is not associated with an increased frequency of hyperkalaemia in haemodialysis patients when they are carefully monitored. More studies are required, however, before concluding that spironolactone administration is safe in the chronic haemodialysis population.