Dataset Information

Emerging Role of Clinical Genetics in CKD.

ABSTRACT: Chronic kidney disease (CKD) afflicts 15% of adults in the United States, of whom 25% have a family history. Genetic testing is supportive in identifying and possibly confirming diagnoses of CKD, thereby guiding care. Advances in the clinical genetic evaluation include next-generation sequencing with targeted gene panels, whole exome sequencing, and whole genome sequencing. These platforms provide DNA sequence reads with excellent coverage throughout the genome and have identified novel genetic causes of CKD. New pathologic genetic variants identified in previously unrecognized biological pathways have elucidated disease mechanisms underlying CKD etiologies, potentially establishing prognosis and guiding treatment selection. Molecular diagnoses using genetic sequencing can detect rare, potentially treatable mutations, avoid misdiagnoses, guide selection of optimal therapy, and decrease the risk of unnecessary and potentially harmful interventions. Genetic testing has been widely adopted in pediatric nephrology; however, it is less frequently used to date in adult nephrology. Extension of clinical genetic approaches to adult patients may achieve similar benefits in diagnostic refinement and treatment selection. This review aimed to identify clinical CKD phenotypes that may benefit the most from genetic testing, outline the commonly available platforms, and provide examples of successful deployment of these approaches in CKD.

SUBMITTER: Devarajan P

PROVIDER: S-EPMC8971313 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Emerging Role of Clinical Genetics in CKD.

Devarajan Prasad P Chertow Glenn M GM Susztak Katalin K Levin Adeera A Agarwal Rajiv R Stenvinkel Peter P Chapman Arlene B AB Warady Bradley A BA

Kidney medicine 20220211 4

Chronic kidney disease (CKD) afflicts 15% of adults in the United States, of whom 25% have a family history. Genetic testing is supportive in identifying and possibly confirming diagnoses of CKD, thereby guiding care. Advances in the clinical genetic evaluation include next-generation sequencing with targeted gene panels, whole exome sequencing, and whole genome sequencing. These platforms provide DNA sequence reads with excellent coverage throughout the genome and have identified novel genetic ...[more]

PMID: 35372818

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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.

Dataset Information

Emerging Role of Clinical Genetics in CKD.

Publications

Emerging Role of Clinical Genetics in CKD.

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