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Alteration of Skin Microbiome in CKD Patients Is Associated With Pruritus and Renal Function.

ABSTRACT: Dysbiotic gut microbiome in chronic kidney disease (CKD) patients has been extensively explored in recent years. Skin microbiome plays a crucial role in patients with skin diseases or even systemic disorders. Pruritus is caused by the retention of uremic solutes in the skin. Until now, no studies have investigated the role of skin microbiome in CKD and its association with pruritus. Here, we aim to examine the bacterial profile of skin microbiome in CKD and whether it is correlated to pruritus. A total of 105 CKD patients and 38 healthy controls (HC) were recruited. Skin swab was used to collect skin samples at the antecubital fossa of participants. Bacterial 16S rRNA genes V3-V4 region was sequenced on NovaSeq platform. On the day of skin sample collection, renal function was assessed, and numeric rating scale was used to measure pruritus severity. Principal coordinate analysis (PCoA) revealed a significant difference in bacterial composition between the groups of CKD and HC. A depletion of bacterial diversity was observed in CKD patients. Akkermansia, Albimonas, Escherichia-Shigella, etc. showed significant higher abundance in CKD patients, whereas Flavobacterium, Blastomonas, Lautropia, etc. significantly declined in patients. Escherichia-Shigella achieved an acceptable diagnostic biomarker with area under the curve (AUC) value of 0.784 in the receiver operating characteristics (ROC) curve. In addition, CKD patients with pruritus (P-CKD) had a different bacterial community comparing to those without pruritus (non-P-CKD) and HC group. Several bacterial genera showing significant difference between P-CKD and non-P-CKD/HC, such as Oribacterium, significantly declined in P-CKD patients than that in the HC group, and Methylophaga significantly increased in P-CKD patients compared to that in HC subjects. Escherichia-Shigella was positively associated with the levels of pruritus severity, blood urea nitrogen (BUN), uric acid, and urine protein; Oribacterium was negatively associated with pruritus severity, whereas it was positively associated with estimated glomerular filtration rate (eGFR) and 24-h urine volume. The dysbiotic of skin microbiome in CKD patients and its association with pruritus and renal function shed a light on skin probiotics.

SUBMITTER: Tian Y

PROVIDER: S-EPMC9274276 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rationale & objectiveItching is a frequent symptom experienced by people with chronic kidney disease (CKD). We investigated the associations of CKD-associated pruritus (CKD-aP) with clinical outcomes.Study designThis was a longitudinal cohort study.Setting & participantsPatients from Brazil, France, and the United States enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) from 2013 to 2021, an international prospective cohort study of adults with nondialysis dependent CKD, and an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 were included.ExposureCKD-aP was self-reported by response to the question: "During the past 4 weeks, to what extent were you bothered by itchy skin?"OutcomesThe outcomes were as follows: CKD progression, kidney replacement therapy (KRT) initiation, mortality, hospitalization, cardiovascular events, infection events.Analytical approachAssociations with time-to-event outcomes were investigated using Cox proportional hazards models adjusted for potential confounders.ResultsThere were 4,410 patients from 91 clinics with a median age of 69 years and a median eGFR at patient questionnaire completion of 29 (21-38) mL/min/1.73 m2. The proportion of patients not at all, somewhat, moderately, very much, and extremely bothered by itchy skin was 49%, 27%, 13%, 7%, and 3%, respectively. Patients with more advanced stages of CKD, older age, and greater comorbidities reported to be more likely bothered by itchy skin. Among patients at least moderately bothered, 23% were prescribed at least 1 pharmacotherapy (35% in the United States, 19% in France, 4% in Brazil), including antihistamine (10%), gabapentin (6%), topical corticosteroids (4%), pregabalin (3%), or sedating antihistamine (3%). The HR (95% CI) for patients extremely (vs not at all) bothered was 1.74 (1.11-2.73) for all-cause mortality, 1.56 (1.11-2.18) for all-cause hospitalization, and 1.84 (1.22-2.75) for cardiovascular events. As CKD-aP severity increased, patients also had higher rates of infection events (P = 0.04); CKD-aP severity was not associated with KRT initiation (P = 0.20) or CKD progression (P = 0.87).LimitationsThe limitations were 25% nonresponse rate, recall bias, and residual confounding factors.ConclusionsThese results demonstrate a strong association between severe itch and clinical outcomes, providing the nephrology community new insights into the possible adverse consequences of CKD-aP in individuals with nondialysis CKD, and warrant further exploration.Plain-language summaryChronic kidney disease-associated pruritus (CKD-aP) is a common disturbing symptom of chronic kidney disease (CKD). This article analyzes longitudinal data from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) to describe prevalence of CKD-aP in 4,410 individuals with nondialysis CKD, and its association with clinical outcomes. We found that 51% of the surveyed population were bothered by pruritus. CKD-aP was more prevalent in those with more advanced stages of CKD, older age, and with more comorbid conditions. Compared to those not at all bothered by pruritus, those who were extremely bothered had a higher risk of all-cause mortality, hospitalizations, and cardiovascular events. Severity of CKD-aP was not associated with CKD progression or initiation of kidney replacement therapy.

Project description:BACKGROUND AND OBJECTIVES:Among patients on hemodialysis, pruritus has been associated with poorer mental and physical quality of life, sleep quality, depression, and mortality. We evaluated patients with nondialysis CKD to describe the prevalence of pruritus, identify associated factors, and investigate associations with patient-reported outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using cross-sectional data from patient questionnaires in the CKD Outcomes and Practice Patterns Study (CKDopps), we asked patients with CKD stages 3-5 (nondialysis) from the United States, Brazil, and France to identify how much they were bothered by pruritus. Response options ranged from "not at all" to "extremely." Log-Poisson regression, yielding prevalence ratios, was used to evaluate associations of moderate-to-extreme pruritus with patient characteristics, CKD stage, self-reported depression symptoms, and restless sleep. Mixed linear regression was used to examine associations between pruritus and physical and mental component summary scores, with lower scores indicating poorer quality of life. RESULTS:Of the 5658 CKDopps patients enrolled in the United States, Brazil, and France, 3780 (67%) answered the pruritus question. The prevalence of moderate-to-extreme pruritus was 24%, and more likely in older patients, women, and those with stage 5 CKD, lung disease, diabetes, and physician-diagnosed depression. In adjusted models, patients with moderate pruritus had physical and mental component summary scores 3.5 (95% confidence interval [95% CI], -4.6 to -2.3) and 2.3 (95% CI, -3.2 to -1.5) points lower, respectively, than patients without pruritus, and they also had a higher adjusted prevalence of patient-reported depression (prevalence ratio, 1.83; 95% CI, 1.58 to 2.11) and restless sleep (prevalence ratio, 1.69; 95% CI, 1.49 to 1.91) compared with patients without pruritus. These patient-reported outcomes were progressively worse with increasing severity of pruritus. CONCLUSIONS:Our findings demonstrate high prevalence of pruritus in nondialysis CKD, as well as strong associations of pruritus with poor health-related quality of life, self-reported depression symptoms, and self-reported poor sleep.

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Alteration of Skin Microbiome in CKD Patients Is Associated With Pruritus and Renal Function.

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