The role of residual renal function on potassium intake and excretion in patients on peritoneal dialysis.

BACKGROUND: Patients on chronic dialysis are at increased risk of developing disorders in potassium balance. The preservation of residual renal function (RRF), frequently observed in patients on peritoneal dialysis (PD), may contribute to better control of serum potassium. This study aimed to investigate the role residual renal function on potassium intake and excretion in PD patients. METHODS: In this cross-sectional study, dietary potassium was evaluated by the 3-day food record. Potassium concentration was determined in serum, 24 h dialysate, stool ample, and 24 h urine of patients with diuresis > 200 mL/day, who were considered non-anuric. RESULTS: Fifty-two patients, 50% men, 52.6 ± 14.0 years, and PD vintage 19.5 [7.0-44.2] months, were enrolled. Compared to the anuric group (n = 17, 33%), the non-anuric group (n = 35, 67%) had lower dialysate potassium excretion (24.8 ± 5.3 vs 30.9 ± 5.9 mEq/d; p = 0.001), higher total potassium intake (44.5 ± 16.7 vs 35.1 ± 8.1 mEq/d; p = 0.009) and potassium intake from fruit (6.2 [2.4-14.7] vs 2.9 [0.0-6.0]mEq/d; p = 0.018), and no difference in serum potassium (4.8 ± 0.6 vs 4.8 ± 0.9 mEq/L; p = 0.799) and fecal potassium (2.2 ± 0.5 vs 2.1 ± 0.7 mEq/L; p = 0.712). In non-anuric patients, potassium intake correlated directly with urinary potassium (r = 0.40; p = 0.017), but not with serum, dialysate, or fecal potassium. In the anuric group, potassium intake tended to correlate positively with serum potassium (r = 0.48; p = 0.051) and there was no correlation with dialysate or fecal potassium. CONCLUSION: The presence of residual renal function constitutes an important factor in the excretion of potassium, which may allow the adoption of a less-restrictive diet.

Gut microbiota profile of patients on peritoneal dialysis: comparison with household contacts.

BACKGROUND: Differences in patients gut microbiota composition with the potential for dysbiosis have been associated with chronic kidney disease (CKD). However, factors other than the disease itself, such as diet and cohabitation, have not been evaluated when gut microbiota of CKD patients was compared with that of healthy controls. The aim of this study was to compare the gut microbiota composition between patients on peritoneal dialysis (PD) and age-matched household contacts with normal renal function. METHODS: Fecal samples were collected from 20 patients [men: 70%; age: 53.5 years (48.2-66; median and interquartile range); length on PD: 14 months (5.2-43.5) and 20 controls. The region V4 of the 16S ribosomal RNA gene was PCR-amplified and sequenced on Illumina MiSeq platform. Dietary intake and diet quality were assessed by a 3-day food record and a diet quality index, respectively. RESULTS: No difference was found between the gut microbiota composition of patients and controls, assessed by alpha and beta diversities (p > 0.05) and genera differential abundance (p > 0.05). The most abundant phyla in both groups were Firmicutes (PD = 45%; Control: 47%; p = 0.65) and Bacteroidetes (PD = 41%; Control: 45%; p = 0.17). The phylum Proteobacteria, known as a potential marker of gut dysbiosis, was not different in proportions between groups (p > 0.05). No difference was observed regarding diet quality and dietary intake of fiber, protein and other nutrients (p > 0.05). CONCLUSION: Gut microbiota of patients on PD did not differ from household contacts. This result suggests that cohabitation and dietary intake might have outweighed the disease influence on gut microbiota composition of our PD patients.

Effect of Unripe Banana Flour on Gut-Derived Uremic Toxins in Individuals Undergoing Peritoneal Dialysis: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

In chronic kidney disease (CKD), the accumulation of gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole 3-acetic acid (IAA), has been associated with the burden of the disease. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating the gut microbiota and production of their metabolites. The aim of this study was to evaluate the effect of unripe banana flour (UBF-48% resistant starch, a prebiotic) on serum concentrations of IS, pCS, and IAA in individuals undergoing peritoneal dialysis (PD). A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch-12 g/day) for 4 weeks, or vice versa (4-week washout). The primary outcomes were total and free serum levels of IS, pCS, and IAA. Secondary outcomes were 24 h urine excretion and dialysis removal of IS, pCS, and IAA, serum inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α)], serum lipopolysaccharide LPS, and dietary intake. Of the 43 individuals randomized, 26 completed the follow-up (age = 55 ± 12 years; 53.8% men). UBF did not promote changes in serum levels of IS (p = 0.70), pCS (p = 0.70), and IAA (p = 0.74). Total serum IS reduction was observed in a subgroup of participants (n = 11; placebo: median 79.5 µmol/L (31-142) versus UBF: 62.5 µmol/L (31-133), p = 0.009) who had a daily UBF intake closer to that proposed in the study. No changes were observed in other secondary outcomes. UBF did not promote changes in serum levels of IS or pCS and IAA; a decrease in IS was only found in the subgroup of participants who were able to take 21g/day of the UBF.

Influence of bowel habits on gut-derived toxins in peritoneal dialysis patients.

BACKGROUND: Gut-derived uremic toxins have been associated with adverse outcomes in chronic kidney disease (CKD). Alterations in bowel habits, including constipation, seem to play an additional role in uremic toxicity. The aim of this study is to investigate the association of bowel habits with gut-derived uremic toxins and intestinal permeability in patients on automated peritoneal dialysis (APD). METHODS: This cross-sectional study enrolled 58 APD patients (age 52.5 ± 15.1 years; dialysis vintage 14.1 (6.0-36.5) months). Constipation was defined according to the Rome IV criteria. Bowel habits were assessed by the Bristol Stool Scale (BSS < 3 characterized by hard consistency of stools and/or low frequency of evacuation, a surrogate of slow intestinal transit time, and BSS ≥ 3, defining regular bowel habit). The total and free serum concentration of p-cresyl sulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA) were dosed by high-performance liquid chromatography. Lipopolysaccharide (LPS) and zonulin were assessed by ELISA and D(-)-lactate by colorimetric method. Dietary intake was assessed by the 3-day food records. RESULTS: No differences were observed in clinical, demographic, and dietary characteristics between constipated (n = 30) and non-constipated (n = 28) groups. A trend for higher total PCS (p = 0.07) and free PCS (p = 0.06) was found in constipated patients. Patients with BSS < 3 (n = 11) exhibited significantly higher levels of total and free PCS (p < 0.01) and total IAA (p = 0.04). Conversely, No difference was found in IS levels. Except for a lower serum level of D(-)-lactate in patients with BSS < 3 (p = 0.01), zonulin and LPS levels were not different. CONCLUSIONS: Disturbed bowel habits, mainly characterized by slow transit time, may play a role in the accumulation of uremic toxins, particularly PCS, in patients on automatized peritoneal dialysis.

In vitro effect of uremic serum on barrier function and inflammation in human colonocytes / Efeito in vitro do soro urêmico sobre a função de barreira e inflamação em colonócitos humanos

ABSTRACT Introduction: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). Methods: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. Results: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. Conclusion: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.

RESUMO Introdução: Tem sido sugerido que na doença renal crônica (DRC) a uremia pode causar alterações intestinais, tais como modificações na microbiota e danos à barreira intestinal, e que estas possíveis alterações podem ter uma relação importante com o estado inflamatório e a toxicidade urêmica apresentadas por pacientes com DRC. Objetivos: Avaliar o efeito in vitro do soro urêmico sobre a permeabilidade da monocamada de células epiteliais do intestino, inflamação e apoptose. Métodos: Pools de soro foram preparados a partir de soros de indivíduos saudáveis, pacientes em tratamento conservador e em hemodiálise (Pré e Pós-HD). As células T84 foram incubadas por 24 horas com os diferentes pools. Em seguida a TER foi medida e as células foram submetidas às seguintes análises: apoptose, produção de espécies reativas de oxigênio (EROs) e expressão de receptores toll-like (TLR) por citometria de fluxo e detecção de IL-6 no sobrenadante da cultura por ELISA. Resultados: Não foram encontradas diferenças, entre os grupos, com relação a TER, apoptose, EROs e expressão de TLR-2, TLR-4 e TLR-9. Já a secreção de IL-6 foi maior (p < 0,001) pelas células incubadas com soro pré-HD e pós-HD. Conclusão: Os resultados obtidos a partir deste modelo sugerem que a uremia per se parece não comprometer a integridade das células epiteliais do intestino. O aumento da secreção de IL-6 pelas células incubadas com soro HD (pré e pós) sugere um potencial efeito da uremia sobre a resposta inflamatória intestinal.

In vitro effect of uremic serum on barrier function and inflammation in human colonocytes.

INTRODUCTION: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). METHODS: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. RESULTS: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. CONCLUSION: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.