Approaches to Uremia

Meyer, Timothy W.; Hostetter, Thomas H.

doi:10.1681/asn.2013121264

Cited by 52 publications

(33 citation statements)

References 59 publications

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“…The permeability of the blood-brain barrier to small solutes such as sucrose and inulin is enhanced in the advanced stages of CKD and is associated with increased potassium transport and disturbed sodium transport 230 . The relationship between these dysfunctions and altered mental function in CKD remains elusive 231 .…”

Section: Neuropathology In Ckdmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.

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Section: Neuropathology In Ckdmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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“…Identification of these toxins is essential to develop therapies, both dialytic and non-dialytic, that can lower solute concentrations and hopefully improve survival of dialysis patients. 3 …”

Section: Introductionmentioning

confidence: 99%

Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are not associated with cardiovascular outcomes

Shafi

Sirich

Meyer

et al. 2017

Kidney International

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Cardiovascular disease, the leading cause of mortality in hemodialysis patients, is not fully explained by traditional risk factors. To help define non-traditional risk factors we determined the association of predialysis total p-cresol sulfate, indoxyl sulfate, phenylacetylglutamine and hippurate with cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273 participants of the HEMO Study. The results were adjusted for potential demographic, clinical, and laboratory confounders. The mean age of the patients was 58 years, 63% were Black and 42% were male. Overall, there was no association between the solutes and outcomes. However, in sub-group analyses, among patients with lower serum albumin (under 3.6 g/dL), a two-fold higher p-cresol sulfate was significantly associated with a 12% higher risk of cardiac death (hazard ratio 1.12; 95% confidence interval, 0.98–1.27) and 22% higher risk of sudden cardiac death (1.22, 1.06–1.41). Similar trends were also noted with indoxyl sulfate. Trial interventions did not modify the association between these solutes and outcomes. Routine clinical and lab data explained less than 22% of the variability in solute levels. Thus, in prevalent hemodialysis patients participating in a large U.S. hemodialysis trial, uremic solutes p-cresol sulfate, indoxyl sulfate, hippurate, and phenylacetylglutamine were not associated with cardiovascular outcomes. However, there were trends of toxicity among patients with lower serum albumin.

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“…Most dialysis patients suffer from treatment complications and toxicity caused by nondialyzable waste solutes [1]. Therefore, kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease (ESRD).…”

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confidence: 99%