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Introduction: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients., Methods: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time., Results: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40-3.52) and 1.85 (95% CI 1.16-2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality., Conclusions: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Inflammation and oxidative stress play important roles in the pathogenesis and progression of chronic kidney disease (CKD) and in its complications, in particular cardiovascular disease, a major cause of death among patients undergoing dialysis treatment. We recently described that Glutaredoxin1 (Grx), an intracellular antioxidant, catalyzes oxidoreductase reactions also extracellularly, and that serum Grx levels correlate to disease severity in type 2 diabetes., Aim: In the current study we assess Grx as a potential clinical marker of oxidative stress in CKD., Methods: We examined Grx activity in 25 patients with different stages of chronic kidney failure, 19 control subjects, and 36 patients at initiation of dialysis and after 2 years of dialysis., Results: We found that Grx activity was significantly higher in CKD patients compared to control subjects, indicating an oxidized extracellular environment in CKD. Grx levels correlated to interleukin-6 and pentosidine, but not to age or GFR. In dialysis patients with Grx sampling before dialysis start and after 2 years of dialysis, Grx levels increased more in hemodialysis (HD) patients than in peritoneal dialysis patients, indicating an increased oxidative stress imbalance in HD patients. Patients who experienced a stroke or myocardial infarction at any time had a significantly higher increase in Grx during the 2 years of dialysis, compared to patients without stroke or myocardial infarction, indicating a possible association between high Grx levels and a cardiovascular event., Conclusion: Our pilot study indicates that Grx may be a useful marker for assessing the degree of oxidative stress in CKD, however this needs further investigation in a larger prospective patient cohort., (© 2018 S. Karger AG, Basel.)

Background/aims: Beta-trace protein (BTP) is a low-molecular-weight molecule, which may be used to assess residual renal function (RRF) in dialysis patients. Here we evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) on plasma BTP, and analyzed the inter- and intra-individual variability of plasma BTP over time in HD and peritoneal dialysis (PD) patients., Methods: In 12 prevalent HD patients, the effect of a single session of low-flux HD, high-flux HD and HDF on plasma BTP was studied. Blood samples were taken at baseline, after 120 and 240 minutes, and at the start of the next dialysis session. In 13 HD patients and 10 PD patients, inter- and intra-individual variability over three months was studied (monthly and weekly, respectively). Plasma BTP was measured using a nephelometric method., Results: No significant decrease in plasma BTP was seen following a session of low-flux HD. Both high-flux HD and HDF resulted in a significant decrease immediately after dialysis (22% and 61% median decrease, respectively). A significant reduction of the molecule persisted only in HDF and a significant decrease (-15%) was still found immediately before the start of the next dialysis session. In both HD and PD patients, the reproducibility over time was excellent with intra-class correlation coefficient of 0.96 (0.93-0.99) and 0.92 (0.86-0.99) respectively. In a small cohort of PD patients, fair agreement existed between mGFR (average of renal urea and creatinine clearance from a 24 hours urine collection) and the BTP-based GFR estimation., Conclusion: BTP is a stable marker and a promising tool for RRF estimations in PD and HD patients. In patients receiving HDF, plasma levels of BTP should be interpreted with caution., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined., Methods: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored., Results: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode., Conclusions: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients., (Copyright © 2013 S. Karger AG, Basel.)

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) has been demonstrated to be associated with cardiovascular disease (CVD) and mortality in end-stage renal disease patients. We hypothesized that common confounders, such as protein-energy wasting (PEW) and inflammation could modulate this relationship., Methods: NT-proBNP was measured in 222 prevalent hemodialysis (HD) patients (55.4% male, mean age 66 years, range 51-74) using commercial ELISA. Levels were related to clinical characteristics, biochemical markers and survival., Results: NT-proBNP levels were positively associated with IL-6 (rho = 0.37, p <0.001) and C-reactive protein (rho = 0.25, p <0.001), but negatively associated with serum IGF-1 (rho = -0.34, p < 0.001), handgrip strength (rho = -0.30, p <0.001) and body weight (rho = -0.20, p < 0.001). In multivariate analysis, an NT-proBNP level above the cutoff of the receiver-operating curve (9,761 pg/ml) was associated with PEW (odds ratio = 2.30, p = 0.008) even following adjustment for age, dialysis vintage, inflammation and the Davies score. As expected, NT-proBNP predicted clinical CVD (odds ratio = 1.90, p = 0.05) and all-cause mortality (Cox regression hazard ratio = 1.57, p = 0.03) also after adjustment for confounders. Patients with an NT-proBNP above the cutoff also exhibited a higher mortality (Kaplan-Meier chi(2) = 13.95, p < 0.001)., Conclusion: We demonstrate a novel association between NT-proBNP and PEW, which may be part of the explanation for the strong links between NT-proBNP and mortality in HD patients., ((c) 2008 S. Karger AG, Basel.)

Background: Peritoneal dialysis (PD) solutions contribute to peritoneal membrane damage. We investigated how conventional and biocompatible PD solutions with different glucose concentrations affect morphological and functional signs of peritoneal fibrosis as well as the TGF-beta1/Smad signaling pathway in a chronic PD rat model., Methods: Non-uremic male Wistar rats (n = 28) were dialyzed thrice daily for 28 days with 20 ml of a conventional solution (Dianeal 1.36%, D1, or 3.86%, D3) or a biocompatible solution (Physioneal 1.36%, P1, or 3.86%, P3). A peritoneal equilibration test was performed. Six rats without dialysis served as controls., Results: The use of conventional solutions, particularly D3, resulted in expansion of the submesothelial compact zone, loss of mesothelial cell layer integrity, hypercellularity, accumulation of collagen I, increased vessel numbers and increased TGF-beta1/Smad expression, but this did not significantly change fluid and solute peritoneal transport characteristics. In comparison with D1 and D3, the use of P1 and P3 was associated with less TGF-beta1/Smad expression and less expansion of the submesothelial cell layer., Conclusions: Our findings indicate that biocompatible solutions with less glucose may decrease the rate of peritoneal fibrosis. The TGF-beta1/Smad pathway is stimulated by PD solutions, representing a plausible pathophysiological mechanism., (Copyright 2008 S. Karger AG, Basel.)