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      Contribution of ‘clinically negligible’ residual kidney function to clearance of uremic solutes

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          Abstract

          Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known. We aimed to assess whether levels of nonurea solutes differed among patients with ‘clinically negligible’ RKF compared with those with no RKF. The hemodialysis study excluded patients with urinary urea clearance >1.5 mL/min, below which RKF was considered to be ‘clinically negligible’. We measured eight nonurea solutes from 1280 patients participating in this study and calculated the relative difference in solute levels among patients with and without RKF based on measured urinary urea clearance. The mean age of the participants was 57 years and 57% were female. At baseline, 34% of the included participants had clinically negligible RKF (mean 0.7 ± 0.4 mL/min) and 66% had no RKF. Seven of the eight nonurea solute levels measured were significantly lower in patients with RKF than in those without RKF, ranging from −24% [95% confidence interval (CI) −31 to −16] for hippurate, −7% (−14 to −1) for trimethylamine- N -oxide and −4% (−6 to −1) for asymmetric dimethylarginine. The effect of RKF on plasma levels was comparable or more pronounced than that achieved with a 31% higher dialysis dose (sp K t /V urea 1.7 versus 1.3). Preserved RKF at 1-year follow-up was associated with a lower risk of cardiac death and first cardiovascular event. Even at very low levels, RKF is not ‘negligible’, as it continues to provide nonurea solute clearance. Management of patients with RKF should consider these differences.

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          Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2.

          A high delivered Kt/V(urea) (dKt/V(urea)) is advocated in the U.S. National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines on hemodialysis (HD) adequacy, irrespective of the presence of residual renal function. The contribution of treatment adequacy and residual renal function to patient survival was investigated. The Netherlands Cooperative Study on the Adequacy of Dialysis is a prospective multicenter study that includes incident ESRD patients older than 18 yr. The longitudinal data on residual renal function and dialysis adequacy of patients who were treated with HD 3 mo after the initiation of dialysis (n = 740) were analyzed. The mean renal Kt/V(urea) (rKt/V(urea)) at 3 mo was 0.7/wk (SD 0.6) and the dKt/V(urea) at 3 mo was 2.7/wk (SD 0.8). Both components of urea clearance were associated with a better survival (for each increase of 1/wk in rKt/V(urea), relative risk of death = 0.44 [P < 0.0001]; dKt/V(urea), relative risk of death = 0.76 [P < 0.01]). However, the effect of dKt/V(urea) on mortality was strongly dependent on the presence of rKt/V(urea), low values for dKt/V(urea) of <2.9/wk being associated with a significantly higher mortality in anuric patients only. Furthermore, an excess of ultrafiltration in relation to interdialytic weight gain was associated with an increase in mortality independent of dKt/V(urea). In conclusion, residual renal clearance seems to be an important predictor of survival in HD patients, and the dKt/V(urea) should be tuned appropriately to the presence of renal function. Further studies are required to substantiate the important role of fluid balance in HD adequacy.
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            Gut microbiome and kidney disease: a bidirectional relationship

            Recent technological advances and efforts, including powerful metagenomic and metatranscriptomic analyses, have led to a tremendous growth in our understanding of microbial communities. Changes in microbial abundance or composition of human microbial communities impact human health or disease state. However, explorations into the mechanisms underlying host–microbe interactions in health and disease are still in their infancy. Although changes in the gut microbiota have been described in patients with kidney disease, the relationships between pathogenesis, mechanisms of disease progression, and the gut microbiome are still evolving. Here, we review changes in the host–microbiome symbiotic relationship in an attempt to explore the bidirectional relationship in which alterations in the microbiome affect kidney disease progression and how kidney disease may disrupt a balanced microbiome. We also discuss potential targeted interventions that may help re-establish this symbiosis and propose more effective ways to deploy traditional treatments in patients with kidney disease.
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              Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

              Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.
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                Author and article information

                Journal
                Nephrology Dialysis Transplantation
                Oxford University Press (OUP)
                0931-0509
                1460-2385
                March 15 2019
                March 15 2019
                Affiliations
                [1 ]Department of Medicine, Division of Nephrology, University of Illinois at Chicago, Chicago, IL, USA
                [2 ]Department of Medicine, Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA
                [3 ]Department of Medicine, Palo Alto Veterans Affairs Health Care System, Stanford University, Palo Alto, CA, USA
                [4 ]Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
                [5 ]Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
                [6 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
                Article
                10.1093/ndt/gfz042
                7203561
                30879076
                4714c5d6-3dde-4357-9f84-7df8c6bcdfba
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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