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.

Impact of superimposed nephrological care to guidelines-directed management by primary care physicians of patients with stable chronic kidney disease: a randomized controlled trial.

BACKGROUND: Optimal clinical care of patients with chronic kidney disease (CKD) requires collaboration between primary care physicians (PCPs) and nephrologists. We undertook a randomised trial to determine the impact of superimposed nephrologist care compared to guidelines-directed management by PCPs in CKD patients after hospital discharge. METHODS: Stage 3b-4 CKD patients were enrolled during a hospitalization and randomised in two arms: Co-management by PCPs and nephrologists (interventional arm) versus management by PCPs with written instructions and consultations by nephrologists on demand (standard care). Our primary outcome was death or rehospitalisation within the 2 years post-randomisation. Secondary outcomes were: urgent renal replacement therapy (RRT), decline of renal function and decrease of quality of life at 2 years. RESULTS: From November 2009 to the end of June 2013, we randomised 242 patients. Mean follow-up was 51 + 20 months. Survival without rehospitalisation, GFR decline and elective dialysis initiation did not differ between the two arms. Quality of life was also similar in both groups. Compared to randomised patients, those who either declined to participate in the study or were previously known by nephrologists had a worse survival. CONCLUSION: These results do not demonstrate a benefit of a regular renal care compared to guided PCPs care in terms of survival or dialysis initiation in CKD patients. Increased awareness of renal disease management among PCPs may be as effective as a co-management by PCPs and nephrologists in order to improve the prognosis of moderate-to-severe CKD. TRIAL REGISTRATION: This study was registered on June 29, 2009 in clinicaltrials.gov (NCT00929760) and adheres to CONSORT 2010 guidelines.

Olfactory function improves following hemodialysis.

Olfactory function has been shown to be affected in chronic kidney disease; however, studies are contradictory and little is known on the effects of dialysis. To resolve these issues we tested olfactory function in 24 healthy controls and in 28 patients with chronic kidney disease receiving hemodialysis (20 patients) or peritoneal dialysis (the other 8). As assays for olfactory function we measured smell identification, n-butanol and acetic acid thresholds, Kt/V urea, percentage reduced urea, and weights before and after dialysis. Olfactory function was also self-rated by the participants. Compared to healthy controls, predialysis olfactory function was moderately but significantly decreased in the two dialysis groups, with hemodialysis patients being more affected. Patients self-rated olfactory function similar to that of healthy controls, suggesting that patients are unaware of the olfactory decrease. Olfactory function was significantly improved by one hemodialysis session. Neither body mass index, total volume loss, nor any other dialysis parameter correlated with olfactory function or its restitution following hemodialysis. The observed pattern of improvement suggests underlying mixed peripheral and central mechanisms. Thus, olfactory dysfunction in patients with chronic kidney disease is readily reversible by hemodialysis.

Humoral and cellular rejection after combined liver-kidney transplantation in low immunologic risk recipients.

Combined liver-kidney transplantation is considered a low risk for immunologic complication. We report an unusual case of identical ABO liver-kidney recipient without preformed anti-human leukocyte antigen (HLA) antibodies, transplanted across a T- and B-cell-negative cross-match and complicated by early acute humoral and cellular rejection, first in the liver then in the kidney. While analyzing the immunologic complications in our cohort of 12 low-risk combined liver-kidney recipients, only one recipient experienced a rejection episode without detection of anti-HLA antibody over time. Although humoral or cellular rejection is rare after combined kidney-liver transplantation, our data suggest that even in low-risk recipients, the liver does not always systematically protect the kidney from acute rejection. Indeed, the detection of C4d in the liver should be carefully followed after combined liver-kidney transplantation.

Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation.

Anti-human leukocyte antigen (HLA) antibody could lead to humoral rejection and a decrease in graft survival after kidney transplantation. A recent report has suggested that islet transplantation alone is associated with a high rate of sensitization. The withdrawal of the immunosuppressive therapy because of the progressive nonfunction of the islets could explain the high rate of sensitization. Because the specific risk of immunization of multiple islet infusions remains unknown, we studied the immunization rate in our cohort of multiple islet infusions transplant recipients. De novo anti-HLA antibodies were analyzed in 37 patients after islets alone (n=8), islet-after-kidney (n=13), and simultaneous islet-kidney (n=16) transplantation by solid phase assays over time. The rate of immunization was 10.8% that is comparable with the risk of immunization after kidney transplantation alone. Multiple islet infusions do not represent a specific risk for the development of anti-HLA antibodies after combined kidney-islets transplantation.

Nonphosphate-binding effects of sevelamer--are they of clinical relevance?

Sevelamer is an ion-exchanging resin that binds phosphate in the gut. Because it does so without increasing the calcium load, treatment with sevelamer may lead to less vascular calcification and better survival in chronic kidney disease patients. However, the results of available clinical studies have not been consistent; recent observations challenge the hypothesis that the extra calcium load inherent in calcium-based phosphate binder therapy increases cardiovascular mortality by accelerating vascular calcification. This reemphasizes the fact that we still lack detailed understanding on the complex relationships between vascular calcification, bone metabolism, vascular disease and outcome in the context of uremia. Thus, the role of phosphate binders may be more complex than initially anticipated and not limited to the extra calcium load. Even if detailed mechanisms of action for sevelamer are not yet clearly established (except for its lipid-lowering action), sevelamer may have a number of additional nonphosphate-lowering actions (including lipid lowering as well as improvement in endothelial function, modulation of inflammation and oxidative stress and binding of uremic toxin absorption). Whether these potentially very interesting pleiotropic effects of sevelamer may be translated into significant clinical benefits remains to be established.

Increase in bone mineral density after successful parathyroidectomy for tertiary hyperparathyroidism after renal transplantation.

BACKGROUND: Few studies have reported changes of bone mineral density (BMD) after parathyroidectomy in patients with persistent hyperparathyroidism after renal transplantation (3 HPT). PATIENTS AND METHODS: We retrospectively analyzed 14 patients who underwent successful parathyroidectomy for 3 HPT and who had available BMD data before and after parathyroidectomy. RESULTS: Median follow-up time was 26 months (IQR: 16.8-40.2). Serum calcium levels decreased significantly after parathyroidectomy (2.32 +/- 0.09 versus 2.66 +/- 0.16 mmol/l; p < 0.01), as did PTH levels (5.1 +/- 3.0 versus 27.8 +/- 23.7 pmol/l; p < 0.01). Nine patients (64%) had a steroid-free immunosuppression at follow-up. Mean increase in BMD was 9.5 +/- 8.0% for the spine and 9.5 +/- 7.9% for the hip (p < 0.01 for both sites). Patients with osteoporosis (T-score

Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab.

A 22-year-old patient whose primary kidney disease was focal segmental glomerulosclerosis (FSGS) developed severe recurrence of proteinuria (up to 57 g/24 h) immediately after a haploidentic living donor kidney transplantation despite pre-operative plasmapheresis. The immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil, basiliximab and steroids. He underwent 10 plasmapheresis sessions in the first 3-week post-transplantation. In addition, he received 2 i.v. doses of rituximab (RTX) 600 mg (375 mg/m(2)) on days 7 and 15. Proteinuria decreased below nephrotic range at day 14 and serum creatinine returned progressively to normal values. A short course of oral ciclophosphamide (100 mg/j) was administrated between days 22 and 40 and three additional plasmapheresis sessions on days 34, 39 and 49. This strategy allowed obtaining sustained full remission of the nephrotic syndrome (NS) and excellent graft function, which persists over 2 years after transplantation. No notable adverse events related to RTX or plasmapheresis were observed. This case suggests that RTX associated with plasmapheresis may be an effective treatment of recurrent NS because of FSGS.