Serum total indoxyl sulfate and clinical outcomes in hemodialysis patients: results from the Japan Dialysis Outcomes and Practice Patterns Study.
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ABSTRACT: Background
Uremic toxins are associated with various chronic kidney disease-related comorbidities. Indoxyl sulfate (IS), a protein-bound uremic toxin, reacts with vasculature, accelerating atherosclerosis and/or vascular calcification in animal models. Few studies have examined the relationship of IS with clinical outcomes in a large cohort of hemodialysis (HD) patients.Methods
We included 1170 HD patients from the Japan Dialysis Outcomes and Practice Patterns Study Phase 5 (2012-15). We evaluated the associations of serum total IS (tIS) levels with all-cause mortality and clinical outcomes including cardiovascular (CV)-, infectious- and malignancy-caused events using Cox regressions.Results
The median (interquartile range) serum tIS level at baseline was 31.6 μg/mL (22.6-42.0). Serum tIS level was positively associated with dialysis vintage. Median follow-up was 2.8 years (range: 0.01-2.9). We observed 174 deaths (14.9%; crude rate, 0.06/year). Serum tIS level was positively associated with all-cause mortality [adjusted hazard ratio per 10 μg/mL higher, 1.16; 95% confidence interval (CI) 1.04-1.28]. Association with cause-specific death or hospitalization events, per 10 μg/mL higher serum tIS level, was 1.18 (95% CI 1.04-1.34) for infectious events, 1.08 (95% CI 0.97-1.20) for CV events and 1.02 (95% CI 0.87-1.21) for malignancy events after adjusting for covariates including several nutritional markers.Conclusions
In a large cohort study of HD patients, serum tIS level was positively associated with all-cause mortality and infectious events.
SUBMITTER: Yamamoto S
PROVIDER: S-EPMC8023193 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC10470217 | biostudies-literature
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| S-EPMC7609896 | biostudies-literature
Project description:Background and objectivesIndoxyl sulfate and p-cresyl sulfate are important representatives of the protein-bound uremic retention solutes. Serum levels of p-cresyl sulfate and indoxyl sulfate are linked to cardiovascular outcomes and chronic kidney disease progression, respectively. They share important features such as the albumin-binding site, low dialytic clearance, and both originate from protein fermentation. Whether serum concentrations are related is, however, not known.Design, setting, participants, & measurementsIn an observational study in 75 maintenance hemodialysis patients, we studied agreement between indoxyl sulfate and p-cresyl sulfate serum concentrations, dialytic reduction rates, and dialytic clearances. Concentrations were determined by HPLC. Dialytic clearances were determined from total spent dialysate collections. In vitro spiking experiments were performed to explore protein binding characteristics.ResultsIndoxyl sulfate and p-cresyl sulfate total serum concentrations were not related (r = 0.02, P = 0.9), whereas free serum concentrations were only moderately related (r = 0.53, P < 0.001). Indoxyl sulfate and p-cresyl sulfate share the same albumin binding site, for which they are competitive binding inhibitors. Intriguingly, indoxyl sulfate and p-cresyl sulfate reduction rates (r = 0.91, P < 0.001) and dialytic clearances (r = 0.97, P < 0.001) correlated tightly.ConclusionsIndoxyl sulfate and p-cresyl sulfate serum concentrations are not associated, suggesting different metabolic pathways. Indoxyl sulfate and p-cresyl sulfate are both valid markers to monitor behavior of protein-bound solutes during dialysis. Finally, they are competitive binding inhibitors for the same albumin binding site.
| S-EPMC2798868 | biostudies-literature
Project description:IntroductionIn China, a quarter of patients are undergoing 2-times weekly hemodialysis. Using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we tested the hypothesis that whereas survival and hospitalizations would be similar in the presence of residual kidney function (RKF), patients without RKF would fare worse on 2-times weekly hemodialysis.MethodsIn our cohort derived from 15 units randomly selected from each of 3 major cities (total N = 45), we generated a propensity score for the probability of dialysis frequency assignment, estimated a survival function by propensity score quintiles, and averaged stratum-specific survival functions to generate mean survival time. We used the proportional rates model to assess hospitalizations. We stratified all analyses by RKF, as reported by patients (urine output <1 vs. ≥1 cup/day).ResultsAmong 1265 patients, 123 and 133 were undergoing 2-times weekly hemodialysis with and without evidence of RKF. Over 2.5 years, adjusted mean survival times were similar for 2- versus 3-times weekly dialysis groups: 2.20 versus 2.23 and 2.20 versus 2.15 for patients with and without RKF (P = 0.65). Hazard ratios for hospitalization rates were similar for 2- versus 3-times weekly groups, with (1.15, 95% confidence interval = 0.66-2.00) and without (1.10, 95% confidence interval 0.68-1.79]) RKF. The normalized protein catabolic rate was lower and intradialytic weight gain was not substantially higher in the 2- versus 3-times weekly dialysis group, suggesting greater restriction of dietary sodium and protein.ConclusionIn our study of patients in China's major cities, we could not detect differences in survival and hospitalization for those undergoing 2- versus 3-times weekly dialysis, regardless of RKF. Our findings indicate the need for pragmatic studies regarding less frequent dialysis with associated nutritional management.
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Project description:BackgroundHemodialysis (HD) patients are commonly prescribed phosphate binders (PBs) to manage serum phosphorus levels, as hyperphosphatemia is strongly associated with poorer survival. Nonadherence with the PB prescription is associated with elevated serum phosphorus levels. We studied associations between patient satisfaction with their PB and serum phosphorus levels and mortality rates.MethodsAdult HD patients in Germany, Italy, Spain and the UK in the Dialysis Outcomes and Practice Patterns Study were administered a survey instrument in late 2017. Patients were asked about their satisfaction with their PBs, as measured through three questions (difficulty, inconvenience and dissatisfaction) on a 5-point Likert scale, with each dichotomized into average worst versus good responses. These were used as predictors in linear regression models of continuous serum phosphorus levels and in Cox proportional hazards models of mortality, with adjustments for demographics, comorbidities and laboratory values.ResultsPatients having greater difficulty, inconvenience and dissatisfaction with their PB had higher serum phosphorus levels in adjusted models {+0.21 mg/dL [95% confidence interval (CI) ±0.23], +0.30 (±0.21) and 0.36 (±0.22), respectively}, and higher odds of having serum phosphorus levels ≥6.0 mg/dL. Measures of dissatisfaction were also associated with an elevated risk of mortality, with adjusted hazard ratios of 2.2 (95% CI 1.3-3.6), 1.6 (1.0-2.6) and 1.7 (1.1-2.7), respectively; this association was not strongly affected by adjustment for baseline serum phosphorous level.ConclusionsSelf-reported difficulty, inconvenience and dissatisfaction in taking one's prescribed PBs were associated with elevated serum phosphorus levels and serum phosphorus levels above clinically meaningful thresholds. While the mechanism for the association with mortality is unclear, patient-reported satisfaction should be considered when attempting to manage patient serum phosphorus levels.
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| S-EPMC5520979 | biostudies-literature
Project description:BackgroundThe Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin-mortality association and relative influence of IV iron and inflammation in the USA, where ferritin levels have recently increased dramatically, and in Europe and Japan, where ferritin levels are lower and anemia management practices differ.MethodsData from 18 261 patients in Phases 4 and 5 (2009-15) of the international Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, were analyzed. Using Cox regression, we modeled the association between baseline ferritin and 1-year mortality with restricted cubic splines and assessed the impact of potential confounders.ResultsMedian ferritin levels were 718 ng/mL in the USA, 405 in Europe and 83 in Japan. High ferritin levels were associated with elevated mortality (relative to region-specific medians) in all three regions. The strength of this association was attenuated more by adjustment for malnutrition and inflammation than by IV iron and erythropoiesis-stimulating agent dose in each region.ConclusionThe utility of high ferritin as a biomarker for clinical risk due to excess iron stores may be limited, although caution regarding IV iron dosing to higher upper ferritin targets remains warranted. Research to resolve biomarker criteria for iron dosing, and whether optimal anemia management strategies differ internationally, is still needed.
| S-EPMC6275147 | biostudies-literature
Project description:Beside the phosphate binding effect, non-calcium non-aluminum phosphate binder, namely sevelamer hydrochloride (SH), has many other effects in dialysis patients. It can absorb many other compounds, decrease low-density lipoprotein cholesterol (LDL-C) level, and attenuate the progression of vascular calcification; it has been reported to have anti-inflammatory effect. However, it is not clear whether it has any effect on uremic toxins, i.e. serum indoxyl sulfate (IS) and p-cresyl sulfate, (PCS) in hemodialysis (HD) patients. This study was carried out to appraise the effect of sevelamer on serum IS and PCS in HD patients.Five adult HD patients from a single medical center were enrolled in this study; these patients were treated with 800 mg of sevelamer thrice per day for 3 months; a series of biochemical parameters, serum IS and PCS were monitored concurrently.There was a significant reduction in the mean level of phosphate from 7.20 ± 0.70 mg/dL (mean ± SD) before treatment to 5.40 ± 0.50 mg/dL (mean ± SD) after treatment, total cholesterol from 151.00 ± 37.40 mg/dL (mean ± SD) before treatment to 119.20 ± 29.40 mg/dL (mean ± SD) after treatment, and PCS from 31.30 ± 10.60 mg/L (mean ± SD) before treatment to 19.70 ± 10.50 mg/L (mean ± SD) after treatment. On the contrary, this treatment had no effect on IS.A statistically significant reduction of serum phosphate and PCS in HD patients treated with SH suggests that beside the action of lowering serum phosphate, sevelamer may have an important role in the treatment of uremic syndrome by decreasing the uremic toxin.
| S-EPMC5544481 | biostudies-other
Project description:BackgroundHemodialysis patients are exposed to disease- and treatment-related stresses, and use various coping strategies to deal with these stresses. Although some studies have reported the association of coping strategies with mortality or health-related quality of life (QOL) in some populations, the effect of coping strategies on clinical outcomes in hemodialysis patients remains unclear. We investigated the association in a longitudinal design among Japanese hemodialysis patients.MethodsWe examined Japanese hemodialysis patients who participated in the Dialysis Outcomes and Practice Patterns Study (DOPPS) IV, which was conducted between 2009 and 2012. The exposure variable was stress coping strategy, as assessed using subscales in Coping Strategies Inventory Short Form: problem-focused engagement, problem-focused disengagement, emotion-focused engagement, and emotion-focused disengagement. Hazard ratios were estimated using Cox proportional hazard model for all-cause mortality and mean differences for change in health-related QOL in 1 year were estimated using a regression model.ResultsAmong 1,354 patients, only problem-focused engagement was significantly associated with longer survival; other subscales were not associated with all-cause mortality after adjustment for potential confounding factors. In terms of health-related QOL, the subscale of problem-focused engagement was also associated with improvement in physical functioning and mental health among 1,045 patients. Emotion-focused disengagement was associated with deterioration in mental health, but not with change in physical functioning. The other subscales were not associated with change in physical functioning or mental health.ConclusionsAmong hemodialysis patients, "problem-focused engagement" coping strategies were associated with longer survival and also with improvement in physical functioning and mental health. To achieve greater longevity and improve QOL in hemodialysis patients under ongoing stresses, problem-focused engagement should be encouraged.
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