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Background and Objective: Chronic kidney disease (CKD) is a complex disorder, which results in several complications involving disturbance of mineral metabolism. Periodontal disease is an infectious disease that appears to be an important cause of systemic inflammation in CKD patients. Periodontal disease is characterized by clinical attachment loss (CAL) caused by alveolar bone resorption around teeth, which may lead to tooth loss. Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. Polymorphisms are the main source of genetic variation, and single nucleotide polymorphisms (SNPs) have been reported as major modulators of disease susceptibility. The aim of this study was to investigate the association of a polymorphism located at position -223 in the untranslated region of the OPG gene, previously known as -950, with susceptibility to CKD and periodontal disease. Material and Methods: A sample of 224 subjects without and with CKD (in hemodialysis) was divided into groups with and without periodontal disease. The OPG polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Results: No association was found between the studied OPG polymorphism and susceptibility to CKD or periodontal disease. Conclusion: It was concluded that polymorphism OPG-223 (C/T) was not associated with CKD and periodontal disease in a Brazilian population. Studies on other polymorphisms in this and other genes of the host response could help to clarify the involvement of bone metabolism mediators in the susceptibility to CKD and periodontal disease. [ABSTRACT FROM AUTHOR]

Objectives: Cardiac troponin T (cTnT) is a highly sensitive and specific marker of myocardial damage. It has been shown that elevated serum concentrations of cTnT in haemodialysis (HD) patients are associated with poor prognostic outcome. The aim of the present study was to investigate the predictive value of cTnT in samples from predialysis patients and to investigate associations between cTnT and inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6).Design: Cohort, follow-up study.Setting: Huddinge University Hospital, Sweden.Subjects: A total of 115 (62% males, 28% diabetic patients) end-stage renal disease (ESRD) patients (52 +/- 1 years), of which 29% had cardiovascular disease (CVD), were studied shortly before the onset of dialysis therapy. Sixty-four patients started peritoneal dialysis (PD) as renal replacement therapy, whilst 49 started HD during the follow-up.Main Outcome Measures: The cTnT was analysed with the third generation TnT assay on Elecsys 2010. The prognostic value was calculated for cTnT, IL-6, age, CVD, malnutrition, diabetes mellitus (DM) and gender. Survival analyses were made with Kaplan-Meier and Cox regression analyses, with all-cause mortality as the clinical end point (mean follow-up period 2.7 +/- 0.1 years).Results: Significant correlations were found between cTnT and CKMB (rho = 0.52, P < 0.0001), IL-6 (rho = 0.23, P < 0.05), CRP (rho = 0.30, P < 0.05), and serum albumin (rho = -0.31, P < 0.001), respectively. Diabetic patients had higher median serum cTnT level (0.09 microg L-1; range <0.01-0.51 vs. 0.04 microg L-1; range <0.01-0.67 microg L-1; P < 0.005) compared with nondiabetic patients. Likewise, patients with CVD had a significantly higher median level (0.08 microg L-1; range <0.01-0.67 microg L-1 vs. 0.04 microg L-1; range <0.01-0.61 microg L-1; P < 0.01) of cTnT compared with patients without CVD. Patients with cTnT > or =0.10 microg L-1 had a higher cumulative mortality rate than patients with cTnT < 0.10 microg L-1 (chi2 = 7.04; P < 0.01). Whilst age, CVD, malnutrition, DM, IL-6, cTnT and male gender were associated with poor outcome in the univariate analysis, only DM (P < 0.05) and cTnT (P < 0.05) were independently associated with mortality in a multivariate analysis.Conclusions: The present study demonstrates that serum concentrations of cTnT > or =0.10 microg L-1 is a significant predictor of mortality in patients starting dialysis. Moreover, the positive correlations between cTnT and IL-6, and CRP, respectively, suggest an association between inflammation and cTnT levels. Finally, the results of the present study suggest that cTnT is an independent predictor of mortality in ESRD patients starting dialysis. [ABSTRACT FROM AUTHOR]

Abstract Background Elevated serum leptin (S-leptin) levels have been reported in patients with end-stage renal disease (ESRD). Apart from the decreased glomerular filtration rate (GFR), body composition and inflammation may affect leptin levels in ESRD. Leptin circulates both free of and bound to soluble leptin receptors (sOB-R), which are the main determinants of leptin activity and have not been described in ESRD until now. Design To analyze the association between S-leptin, sOB-R, and inflammation and body composition, we studied 149 (62% males) normal weight (BMI 24·7 ± 0·4 kg m-2 ) ESRD patients (51 ± 1 years old) shortly before the start of dialysis (GFR 7·0 ± 0·2 mL min-1 ). sOB-R and plasma interleukin-6 (IL-6; n = 113) levels were evaluated using ELISA, S-leptin using RIA, and body composition was assessed by X-ray absorptiometry (n = 139). Forty-one healthy subjects age (51 ± 1 years), BMI (23·6 ± 0·5 kg m-2 ) and gender-matched (59% males) were used as controls. Results Median S-leptin was higher in the ESRD patients (10·0 ng mL-1 ) compared with the controls (3·9 ng mL-1 ) (P < 0·001). The median sOB-R did not differ significantly between the ESRD patients (44 U mL-1 ) and the controls (37 U mL-1 ). Thus, the sOB-R/S-leptin ratio was lower in the ESRD patients (9·5 ± 1·2 vs. 12·3 ± 1·8; P < 0·01) than the controls. A negative correlation was observed between S-leptin and sOB-R (Rho = -0·42; P < 0·0001) in the ESRD patients, a positive correlation was observed between lean body mass and the sOB-R/S-leptin ratio (Rho = 0·33, P = 0·0001) whereas fat mass was negatively correlated to both sOB-R (Rho = -0·26, P = 0·002), and the sOB-R/S-leptin ratio (Rho = -0·62, P < 0·0001). Positive correlations were observed between IL-6 and S-leptin... [ABSTRACT FROM AUTHOR]

Presents letters to the editor on state of chronic inflammation and hyperleptinemia in end-stage renal disease. Use of C-reactive protein as a biomarker for systemic inflammation; Relation between proinflammatory cytokines and leptins; Need of study to role of free leptin levels in anorexia in inflammatory condition.

The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP, and interleukin-6 (IL-6) in HD patients. The study included 118 HD patients (47% males, age 47 ± 13 years, 9% diabetics) who were treated by on standard HD for at least 6 months. The patients were divided in two groups, depending on the presence (HCV+) or absence (HCV–) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured, and the values were compared with 22 healthy controls. The median of hsCRP, IL-6, and the hsCRP/IL-6 ratio were: 3.5 vs. 2.1 mg/L, p < 0.05; 4.3 vs. 0.9 pg/mL, p < 0.0001; and 0.8 vs. 2.7 pg/mL, p < 0.0001 for patients and controls, respectively. Age, gender, S-Alb, IL-6, and hsCRP did not differ between the HCV+ and HCV– patients. However, HCV+ patients had higher ALT (29 ± 21 vs. 21 ± 25 UI/L) and had been a longer time on HD (6.1 ± 3.0 vs. 4.0 ± 2.0 years) (p < 0.0001), respectively. Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs. 0.9; p < 0.05) as compared to the HCV group. The finding that the hsCRP/IL-6 ratio was lower in HCV+ patients than in HCV– patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP may be required to define inflammation in HD patients. [ABSTRACT FROM AUTHOR]

Background: Contrast-associated acute kidney injury (CA-AKI) is frequent in patients with chronic kidney disease who are submitted to cardiac endovascular procedures using iodinated contrast. In hemoadsorption, cartridges containing styrene-divinylbenzene sorbent resin are applied to remove substances from the blood through an extracorporeal circuit. Importantly, iodinated contrast is also removed via adsorption. We aimed to determine the adsorptive kinetics of the iodinated contrast medium iohexol using a 1:3 scale model of the HA380 cartridge., Methods: An experimental in vitro study utilizing a closed-loop extracorporeal circuit with an interposed sorbent cartridge. A solution spiked with iohexol was recirculated for 60 min. Samples for the measurement of iohexol were drawn at 0, 5, 10, 15, 20, 30, 40, and 60 min. The experiment was carried out twice., Results: In experiments 1 and 2, the reduction ratio after 60 min was 53.0% and 53.1%, respectively. In experiment 1, iohexol clearance was 46.79 mL/min during the first 5 min and decayed to 3.57 mL/min during the last 20 min. In experiment 2, iohexol clearance was 46.72 mL/min and decayed to 3.87 mL/min during the last 20 min. The ratio of adsorbate/sorbent was 155 mg/g., Conclusion: A 1:3 scale model of the HA380 cartridge efficiently removes iodinated contrast in a clinical-scale in vitro circuit. These findings provide a rationale for hemoadsorption as an intervention in clinical trials to prevent or attenuate CA-AKI., (© 2025 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: People with kidney failure have a high risk of cardiovascular morbidity/death, including thromboembolic events. Factor XIa inhibitors are a new class of anticoagulants in development that may offer antithrombotic benefits with a lower risk of incremental bleeding events than traditional therapies. We investigated major adverse vascular events (MAVEs), a relevant composite outcome for testing novel antithrombotic agents, in a large cohort of patients on hemodialysis, to better understand the key requirements to adequately design a phase 3 trial., Methods and Results: We included 25 211 patients on hemodialysis for >90 days in phases 4 to 7 (2009-2021) of the DOPPS (Dialysis Outcomes and Practice Patterns Study). Atherosclerotic cardiovascular disease (ASCVD) was defined as history/presence of coronary, peripheral, or cerebrovascular disease. We estimated MAVE rates and cumulative incidence, overall and by ASCVD. Over half (52%) of the cohort met the ASCVD criteria. The MAVE hospitalization/death composite rate (per 100 patient-years) was 6.0 in the overall cohort and 8.7 in the ASCVD subset. Three-year cumulative incidence of MAVE was 13% in the overall cohort and 18% in the ASCVD subset. The estimated sample size to be randomized in a hypothetical trial in the ASCVD population was ≈7000 patients., Conclusions: Even in the enriched ASCVD group, the observed MAVE incidence combined with a high competing risk, regulatory requirements (α=0.01), and limited recruitment pool makes feasibility of a potential randomized trial targeting MAVE reduction challenging. These results highlight key considerations and challenges for developers of novel therapies targeting systemic thromboembolic events in patients on hemodialysis.

Oxidative stress (OS) is essential in uremia-associated comorbidities, including renal anemia. Complications experienced by hemodialysis (HD) patients, such as hypoxemia and uremic toxins accumulation, induce OS and premature death of red blood cells (RBC). We aimed to characterize reactive oxygen species (ROS) production and antioxidant pathways in HD-RBC and RBC from healthy controls (CON-RBC) and evaluate the role of uremia and hypoxia in these pathways. ROS production, xanthine oxidase (XO) and superoxide dismutase (SOD) activities, glutathione (GSH), and heme oxygenase-1 (HO-1) levels were measured using flow cytometry or spectrophotometry in CON-RBC and HD-RBC (pre- and post-HD), at baseline and after 24 h incubation with uremic serum (S-HD) and/or under hypoxic conditions (5% O 2 ). Ketoprofen was used to inhibit RBC uremic toxins uptake. HD-RBC showed higher ROS levels and lower XO activity than CON-RBC, particularly post-HD. GSH levels were lower, while SOD activity and HO-1 levels of HD-RBC were higher than control. Hypoxia per se triggered ROS production in CON-RBC and HD-RBC. S-HD, on top of hypoxia, increased ROS levels. Inhibition of uremic toxins uptake attenuated ROS of CON and HD-RBC under hypoxia and uremia. CON-RBC in uremia and hypoxia showed lower GSH levels than cells in normoxia and non-uremic conditions. Redox mechanisms of HD-RBC are altered and prone to oxidation. Uremic toxins and hypoxia play a role in unbalancing these systems. Hypoxia and uremia participate in the pathogenesis of OS in HD-RBC and might induce RBC death and thus compound anemia., (© 2022 John Wiley & Sons Ltd.)

Aims: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients., Methods: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m 2 at baseline, adjusted for comorbidities, laboratory data and drugs., Results: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38)., Conclusions: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure., (© 2020 British Pharmacological Society.)

Symptomatic intradialytic hypotension (IH) continues to be an important complication of hemodialysis treatment. It has been suggested that patients with left ventricular (LV) diastolic dysfunction may be more sensitive to the effects of reduced cardiac filling. Left atrial volume index (LAVi) reflects the chronicity of exposure to elevated LV filling pressures. The aim of this study was to identify the association between echocardiographic disease, in particular left atrium enlargement, and IH. Echocardiograms obtained in 172 patients undergoing hemodialysis in sinus rhythm and with no significant valvular or pericardial disease were analyzed. The independent association between LAVi and IH was assessed using multivariate logistic regression. IH was identified in 27 patients (16%). The patients who experienced the hypotensive episodes had a greater prevalence of previous heart failure (59% vs 22%, P < 0.001), systolic dysfunction (33% vs 14%, P = 0.003), and LAVi > 35 mL/m(2) (59% vs 32%, P = 0.008). No differences were noted for age, gender, body mass index, duration of dialysis, blood pressure, use of drugs, and proportions of arterial hypertension, diabetes, LV hypertrophy and diastolic dysfunction by Doppler. After multivariate analysis, only heart failure and LAVi > 35 mL/m(2) were seen to be independent predictors of IH. The finding of left atrium enlargement in patients undergoing hemodialysis may be useful in the clinical prediction of IH.

Article Title: Association between Left Atrium Enlargement and Intradialytic Hypotension: Role of Diastolic Dysfunction in the Hemodynamic Complications during Hemodialysis.

The aim of this study was to verify if dialysis solution volumes used in patients on continuous ambulatory peritoneal dialysis (CAPD) interfere with pulmonary function and if the pulmonary volumes interfere with the lymphatic absorption of the peritoneal cavity. We submitted 10 CAPD patients with a mean age of 48 +/- 18 years and on CAPD for 35 +/- 27 months to the following evaluations: first, measurement of the lymphatic absorption from the peritoneal cavity; second, measurement of the hydrostatic intraperitoneal pressure; and third, expirometry with the peritoneal cavity full of dialysis solution and empty. There were no differences between the expirometry results obtained with the peritoneal cavity full and empty of dialysis solution, and the results were in accordance with the prediction for this population. The values did not correlate with the peritoneal lymphatic absorption of the peritoneal cavity. The cumulative lymphatic absorption of the peritoneal cavity after 4 h dialysis solution permanence was 197 +/- 93 ml, and the hydrostatic intraperitoneal pressure was 13.9 +/- 2.8 column centimeters of water. Neither of these correlated with pulmonary volumes. In conclusion, CAPD did not interfere with the pulmonary function, nor did the pulmonary function influence the lymphatic absorption of the peritoneal cavity of these patients.