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Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet.

ABSTRACT: The effects of ketoanalogues (KA) supplementation on mortality and progression to dialysis in patients with pre-dialysis stage 5 chronic kidney disease (CKD) receiving a low-protein diet (LPD) remain ambiguous. From Taiwan's National Health Insurance Research Database during 1996-2011, 165 patients with pre-dialysis CKD on an LPD (0.6 g/kg/day) with KA supplementation were matched with 165 patients with pre-dialysis CKD on an LPD without KA supplementation. Of the 165 patients with advanced CKD receiving KA supplementation, 34 (20.6%) died, and 124 (75.2%) underwent long-term dialysis during the study period. There was no significant difference in mortality between the KA-user group and the KA-nonuser group (adjusted hazard ratio [HR], 1.41; 95% confidence interval [CI], 0.68-2.93; p = 0.355). KA supplementation significantly increased long-term dialysis risk (adjusted HR, 1.41; 95% CI, 1.04-1.90; p = 0.025) and combined outcome risk (defined as long-term dialysis and death; adjusted HR, 1.37; 95% CI, 1.02-1.83; p = 0.034). KA supplementation also increased long-term dialysis risk (adjusted HR, 1.49; 95% CI, 1.00-2.20; p = 0.048) in the subgroup of pre-dialysis patients with diabetes mellitus (DM), but not in those patients without DM. In conclusion, KA supplementation might increase long-term dialysis risk in patients with advanced CKD receiving an LPD, but it did not increase mortality.

SUBMITTER: Wang YC

PROVIDER: S-EPMC7551296 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet.

Wang Yi-Chun YC Juan Shu-Hui SH Chou Chu-Lin CL Hsieh Tsung-Cheng TC Wu Jung-Lun JL Fang Te-Chao TC

Nutrients 20200904 9

The effects of ketoanalogues (KA) supplementation on mortality and progression to dialysis in patients with pre-dialysis stage 5 chronic kidney disease (CKD) receiving a low-protein diet (LPD) remain ambiguous. From Taiwan's National Health Insurance Research Database during 1996-2011, 165 patients with pre-dialysis CKD on an LPD (0.6 g/kg/day) with KA supplementation were matched with 165 patients with pre-dialysis CKD on an LPD without KA supplementation. Of the 165 patients with advanced CKD ...[more]

PMID: 32899821

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Project description:Background and objectivesIn kidney transplant recipients, elevated circulating advanced glycation endproducts (AGEs) are the result of increased formation and decreased kidney clearance. AGEs trigger several intracellular mechanisms that ultimately yield excess cardiovascular disease. We hypothesized that, in stable kidney transplant recipients, circulating AGEs are associated with long-term risk of cardiovascular mortality, and that such a relationship is mediated by inflammatory, oxidative stress, and endothelial dysfunction biomarkers.Design, setting, participants, & measurementsProspective cohort study of stable kidney transplant recipients recruited between 2001 and 2003 in a university setting. We performed multivariable-adjusted Cox regression analyses to assess the association of AGEs (i.e., Nε -[Carboxymethyl]lysine (CML) and Nε -[Carboxyethyl]lysine (CEL), measured by tandem mass spectrometry) with cardiovascular mortality. Mediation analyses were performed according to Preacher and Hayes's procedure.ResultsWe included 555 kidney transplant recipients (age 51±12 years, 56% men). During a median follow-up of 6.9 years, 122 kidney transplant recipients died (52% deaths were due to cardiovascular causes). CML and CEL concentrations were directly associated with cardiovascular mortality (respectively, hazard ratio, 1.55; 95% confidence interval, 1.24 to 1.95; P<0.001; and hazard ratio, 1.53; 95% confidence interval 1.18 to 1.98; P=0.002), independent of age, diabetes, smoking status, body mass index, eGFR and proteinuria. Further adjustments, including cardiovascular history, did not materially change these findings. In mediation analyses, free thiol groups and soluble vascular cell adhesion molecule-1 consistently explained approximately 35% of the association of CML and CEL with cardiovascular mortality.ConclusionsIn stable kidney transplant recipients, circulating levels of AGEs are independently associated with long-term risk of cardiovascular mortality.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_17_CJN00540119.mp3.

Project description:IntroductionPrevalence of chronic kidney disease (CKD) amongst intensive care unit (ICU) admissions is rising. How mortality and risk of end-stage renal disease (ESRD) differs between those with and without CKD and with acute kidney injury (AKI) is unclear. Determining factors that increase the risk of ESRD is essential to optimise treatment, identify patients requiring nephrological surveillance and for quantification of dialysis provision.MethodThis cohort study used the Swedish intensive care register 2005-2011 consisting of 130,134 adult patients. Incomplete cases were excluded (26,771). Patients were classified (using diagnostic and intervention codes as well as admission creatinine values) into the following groups: ESRD, CKD, AKI, acute-on-chronic disease (AoC) or no renal dysfunction (control). Primary outcome was all-cause mortality. Secondary outcome was ESRD incidence.ResultsOf 103,363 patients 4,192 had pre-existing CKD; 1389 had ESRD; 5273 developed AKI and 998 CKD patients developed AoC. One-year mortality was greatest in AoC patients (54 %) followed by AKI (48.7 %), CKD (47.6 %) and ESRD (40.3 %) (P < 0.001). Five-year mortality was highest for the CKD and AoC groups (71.3 % and 68.2 %, respectively) followed by AKI (61.8 %) and ESRD (62.9 %) (P < 0.001). ESRD incidence was greatest in the AoC and CKD groups (adjusted incidence rate ratio (IRR) 259 (95 % confidence interval (CI) 156.9-429.1) and 96.4, (95 % CI 59.7-155.6) respectively) and elevated in AKI patients compared with controls (adjusted IRR 24 (95 % CI 3.9-42.0); P < 0.001). Risk factors independently associated with ESRD in 1-year survivors were, according to relative risk ratio, AoC (356; 95 % CI 69.9-1811), CKD (267; 95 % CI 55.1-1280), AKI (30; 95 % CI 5.98-154) and presence of elevated admission serum potassium (4.6; 95 % CI 1.30-16.40) (P < 0.001).ConclusionsPre-ICU renal disease significantly increases risk of death compared with controls. Subjects with AoC disease had extreme risk of developing ESRD. All patients with CKD who survive critical care should receive a nephrology referral.Trial registrationClinical trials registration numberNCT02424747 April 20th 2015.

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Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet.

Publications

Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet.

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