Serum indoxyl sulfate is associated with mortality in hospital-acquired acute kidney injury: a prospective cohort study.
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ABSTRACT: Background
Protein-bound uremic toxins are associated with poor outcomes in patients with chronic kidney disease. The aim of this study is to investigate the relationship between indoxyl sulfate (IS), a protein-bound solute, and 90-day mortality in patients with acute kidney injury.Methods
Adults with hospital-acquired AKI (HA-AKI) were enrolled in this prospective cohort study between 2014 and 2015, according to the KDIGO creatinine criteria. The primary end point was all-cause death during follow-up.Results
The mean serum IS level in patients with HA-AKI was 2.74?±?0.75??g/ml, which was higher than that in healthy subjects (1.73?±?0.11??g/ml, P?ConclusionsSerum IS levels were significantly elevated in patients with HA-AKI compared to those in healthy subjects and critically ill patients and were associated with a worse prognosis of HA-AKI.Trial registration
www.clinicaltrials.gov NCT 00953992. Registered 6 August 2009.
SUBMITTER: Wang W
PROVIDER: S-EPMC6376694 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Publications
Serum indoxyl sulfate is associated with mortality in hospital-acquired acute kidney injury: a prospective cohort study.
Wang Wenji W Hao Guihua G Pan Yu Y Ma Shuai S Yang Tianye T Shi Peng P Zhu Qiuyu Q Xie Yingxin Y Ma Shaojun S Zhang Qi Q Ruan Hong H Ding Feng F
BMC nephrology 20190214 1
<h4>Background</h4>Protein-bound uremic toxins are associated with poor outcomes in patients with chronic kidney disease. The aim of this study is to investigate the relationship between indoxyl sulfate (IS), a protein-bound solute, and 90-day mortality in patients with acute kidney injury.<h4>Methods</h4>Adults with hospital-acquired AKI (HA-AKI) were enrolled in this prospective cohort study between 2014 and 2015, according to the KDIGO creatinine criteria. The primary end point was all-cause ...[more]
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Project description:BACKGROUND:Hospital-acquired acute kidney injury (AKI) is associated with increased mortality and resource consumption. Little is known about the association of AKI with short-term hospital readmissions. STUDY DESIGN:Retrospective cohort study. SETTING & PARTICIPANTS:We investigated whether adult survivors of hospital-acquired AKI were at increased odds for early hospital readmission. PREDICTOR:The peak-to-nadir serum creatinine difference during the index hospitalization was used to define AKI according to the KDIGO (Kidney Disease: Improving Global Outcomes) classification and staging system. MEASUREMENTS:Multivariable logistic regression analyses examined the association of AKI with 30-, 60-, and 90-day hospital readmission, adjusting for age, sex, race, Charlson-Deyo comorbidity index score, acute hospital-related factors, common causes of hospitalization, and baseline estimated glomerular filtration rate. RESULTS:3,345 (15%) of 22,001 included patients experienced AKI during the index hospitalization. Compared to the non-AKI group, the AKI group had a significantly higher 30-day hospital readmission rate (11% vs 15%; P<0.001), which persisted at 60 and 90 days. The AKI group also was more likely to be readmitted to the hospital within 30 days for cardiovascular-related conditions, mainly heart failure (P<0.001) and acute myocardial infarction (P=0.01). AKI associated independently with higher odds of 30-day hospital readmission (OR, 1.21; 95% CI, 1.08-1.36), which persisted at 60 (OR, 1.15; 95% CI, 1.03-1.27) and 90 days (adjusted OR, 1.13; 95% CI, 1.02-1.25). Results were attenuated in a propensity score-matched cohort of 5,912 patients. LIMITATIONS:Single-center study of mild forms of AKI; ascertainment bias and outcome misclassification due to the use of administrative codes. CONCLUSIONS:Our results suggest that survivors of hospital-acquired AKI experience higher odds of early hospital readmission. Transitions of care services may be warranted for such patients to prevent readmissions and reduce health care costs.
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Project description:The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.
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Project description:IntroductionIn patients with cirrhosis, differences between acute kidney injury (AKI) at the time of hospital admission (community-acquired) and AKI occurring during hospitalization (hospital-acquired) have not been explored. We aimed to compare patients with hospital-acquired AKI (H-AKI) and community-acquired AKI (C-AKI) in a large, prospective study.MethodsHospitalized patients with cirrhosis were enrolled (N = 519) and were followed for 90 days after discharge for mortality. The primary outcome was mortality within 90 days; secondary outcomes were the development of de novo chronic kidney disease (CKD)/progression of CKD after 90 days. Cox proportional hazards and logistic regressions were used to determine the independent association of either AKI for primary and secondary outcomes, respectively.ResultsH-AKI occurred in 10%, and C-AKI occurred in 25%. In multivariable Cox models adjusting for significant confounders, only patients with C-AKI had a higher risk for mortality adjusting for model for end-stage liver disease-Na: (hazard ratio 1.64, 95% confidence interval [CI] 1.04-2.57, P = 0.033) and adjusting for acute on chronic liver failure: (hazard ratio 2.44, 95% CI 1.63-3.65, P < 0.001). In univariable analysis, community-acquired-AKI, but not hospital-acquired-AKI, was associated with de novo CKD/progression of CKD (odds ratio 2.13, 95% CI 1.09-4.14, P = 0.027), but in multivariable analysis, C-AKI was not independently associated with de novo CKD/progression of CKD. However, when AKI was dichotomized by stage, C-AKI stage 3 was independently associated with de novo CKD/progression of CKD (odds ratio 4.79, 95% CI 1.11-20.57, P = 0.035).DiscussionCompared with H-AKI, C-AKI is associated with increased mortality and de novo CKD/progression of CKD in patients with cirrhosis. Patients with C-AKI may benefit from frequent monitoring after discharge to improve outcomes.
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Project description:BACKGROUND:Intestinal dysbiosis has been documented in humans with chronic kidney disease (CKD) and is thought to contribute to production of the uremic toxins indoxyl sulfate (IS) and p-cresol sulfate (pCS). Characteristics of the fecal microbiome in cats with CKD and correlation to serum concentrations of uremic toxins are unknown. OBJECTIVES:To characterize the fecal microbiome and measure serum IS and pCS concentrations of cats with CKD in comparison to healthy older cats. ANIMALS:Thirty client-owned cats with CKD (International Renal Interest Society stages 2-4) and 11 older (?8 years) healthy control cats. METHODS:Prospective, cross-sectional study. Fecal samples were analyzed by sequencing of 16S rRNA genes and Escherichia coli quantitative PCR (qPCR). Serum concentrations of IS and pCS measured using liquid chromatography tandem mass spectrometry. RESULTS:Cats with CKD had significantly decreased fecal bacterial diversity and richness. Escherichia coli qPCR showed no significant difference in bacteria count between control and CKD cats. Cats with stage 2 (P?=?.01) and stages 3 and 4 (P?=?.0006) CKD had significantly higher serum IS concentrations compared to control cats. No significant difference found between stage 2 and stages 3 and 4 CKD. The pCS concentrations were not significantly different between CKD cats and control cats. CONCLUSIONS AND CLINICAL IMPORTANCE:Decreased fecal microbiome diversity and richness is associated with CKD in cats. Indoxyl sulfate concentration is significantly increased with CKD, and cats with stage 2 CKD may suffer from a similar uremic toxin burden as do cats with later stage disease.
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Project description:The disease burden and outcomes of community-acquired (CA-) and hospital-acquired acute kidney injury (HA-AKI) are not well understood. The aim of the study was to investigate the incidence, outcomes, and risk factors of AKI in a large Taiwanese adult cohort.This retrospective cohort study examined 734,340 hospital admissions from a group of hospitals within an organization in Taiwan between January 1, 2010 and December 31, 2014. Patients with AKI at discharge were classified as either CA- or HA-AKI based on the RIFLE (risk, injury, failure, loss of function, end stage of kidney disease) classification criteria. Outcomes were in-hospital mortality, dialysis, recovery of renal function, and length of stay. Risks of developing AKI were determined using multivariate logistic regression based on demographic and baseline clinical characteristics and nephrotoxin use before admission.AKI occurred in 1.68% to 2% hospital discharges among adults without and with preexisting chronic kidney disease (CKD), respectively. The incidence of CA-AKI was 17.25 and HA-AKI was 8.14 per 1000 admissions. The annual rate of CA-AKI increased from 12.43 to 19.96 per 1000 people, but the change in HA-AKI was insignificant. Comparing to CA-AKI, those with HA-AKI had higher levels of in-hospital mortality (26.07% vs 51.58%), mean length of stay (21.25 ± 22.35 vs 35.84 ± 34.62 days), and dialysis during hospitalization (1.45% vs 2.06%). Preexisting systemic diseases, including CKD were associated with increased risks of CA-AKI, and nephrotoxic polypharmacy increased risk of both CA- and HA-AKI.Patients with HA-AKI had more severe outcomes than patients with CA-AKI, and demonstrated different spectrum of risk factors. Although patients with CA-AKI with better outcomes, the incidence increased over time. It is also clear that optimal preventive and management strategies of HA- and CA-AKI are urgently needed to limit the risks in susceptible individuals.
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Project description:BackgroundElevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients.MethodsThis prospective, multicenter, open-label study enrolled patients with CKD stages 3-5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA.ResultsA total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0.406, P < 0.001) and increased with increasing CKD stages (stage 3, 0.21 ± 0.21 mg/dL; stage 4, 0.54 ± 0.52 mg/dL; stage 5, 1.15 ± 054 mg/dL; P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P < 0.001) and up to 8 weeks (31.9 ± 33.7% reduction from baseline, P < 0.001). This reduction effect was noted regardless of age, kidney function, or diabetes. No severe adverse effects were reported. Gastrointestinal symptoms were the most commonly reported adverse effects. In total, 21 patients withdrew from the study, with dyspepsia due to heavy pill burden as the most common reason. The medication compliance rate was 84.7 ± 21.2% (min 9%, max 101%) for 8 weeks among those who completed the study.ConclusionsOSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported.Trial registrationClinical Research Information Service ( KCT0001875 . 14 December 2015.).
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