Introduction Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia of chronic kidney disease (CKD). This European, phase 3, randomized, open-label, active-controlled study investigated efficacy and safety of roxadustat in patients with end-stage kidney disease on dialysis for at least 4 months. Methods Patients were randomized to switch from an erythropoiesis-stimulating agent (ESA) (epoetin alfa or darbepoetin alfa) to roxadustat three times/week or to continue their previous ESA. Roxadustat and ESA doses were adjusted to maintain hemoglobin within 10.0–12.0 g/dL during the treatment period (day 1 up to 52–104 weeks). Primary endpoints were hemoglobin change from baseline (CFB) to the average of weeks 28–36 without rescue therapy and hemoglobin CFB to the average of weeks 28–52 regardless of rescue therapy. Treatment-emergent adverse events (TEAEs) were assessed descriptively. Results Of 1081 screened patients, 836 were randomized and received treatment (roxadustat, n = 415; ESA, n = 421). The least squares means (95% CI) of the treatment difference (roxadustat − ESA) for hemoglobin CFB to weeks 28–36 (without rescue therapy) and CFB to weeks 28–52 (regardless of rescue therapy) were 0.235 (0.132, 0.339) g/dL and 0.171 (0.082, 0.261) g/dL, respectively, demonstrating non-inferiority of roxadustat to ESA (non-inferiority margin of − 0.75 g/dL). The proportions of patients who achieved target hemoglobin without rescue therapy during weeks 28–36 were 84.2% (roxadustat) and 82.4% (ESA). Roxadustat was superior to ESA in decreasing LDL cholesterol from baseline to the average of weeks 12–28. Serious TEAEs occurred in 50.7% (roxadustat) and 45.0% (ESA) of patients. Common TEAEs in both treatment groups included hypertension, arteriovenous fistula thrombosis, headache, and diarrhea. Conclusion Roxadustat was non-inferior to ESAs in maintaining hemoglobin levels in this cohort of patients with anemia of CKD on dialysis for at least 4 months who were previously treated with ESAs. Observed TEAEs were consistent with previous studies.

Background/Aims: This cross-sectional study was designed to assess the relationship between vascular stiffness (VS) and bone-related proteins involved in the development of arteriosclerosis in patients on regular hemodialysis (HD). Methods: 68 consecutive patients in stable clinical condition who received regular HD in the FMC Dialysis Center, Pécs were included. VS parameters (carotid-femoral pulse wave velocity – PWV, aortic augmentation index - AIx) were determined by applanation tonometry (SphygmoCor, AtCor Medical, Sidney) and the routine latoratory test were completed with measurements of osteocalcin (OC), osteopontin (OP) and osteoprotegerin (OPG) by using commercially available ELISA kits. 35 heathcare workers served as controls. Results: In patients on regular HD PWV markedly increased and there was several-fold elevation in the interrelated bone-specific proteins (OC, OP, OPG). PWV was found to be independently associated only with OC (β:-0.25, p<0.029) and age (r=0.411,p<0.000), but risk factors for arterial calcification had significant impact on OC (systolic blood pressure, hsCRP, BMI), OPG (age, BMI) and OP (LDL-cholesterol). Conclusion: Except for OC, our results failed to document direct association of vascular lesion with OP and OPG, therefore their high circulating levels may be an epiphenomenon or they may have counter-regulatory role to attenuate the uremic calcification process.

Objective: In this observational study we addressed accelerated arteriosclerosis (AS) in patients with chronic renal failure (CRF) on hemodialysis (HD) by measuring vascular stiffness (VS) parameters and attempted to relate them to pro-inflammatory and protective factors.Patients: 96 consecutive patients receiving regular HD were included. 20 adult patients without major renal, cardiovascular or metabolic morbidities served as controls.Methods: AS parameters (carotid-femoral pulse wave velocity – PWV, aortic augmentation index – Aix) were measured by using applanation tonometry (SphygmoCor, AtCor Medical, Sidney). In addition to routine laboratory tests 25(OH) vitamin D₃ (vitamin D₃) and high-sensitivity C-reactive protein (hsCRP) were quantified by immunometric assay; whereas fetuin-A, α-Klotho, tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β₁) were determined by ELISA.Results: Pro-inflammatory biomarkers (hsCRP, TNF-α and TGF-β₁) were markedly elevated (P < 0.01), while anti-inflammatory factors (fetuin-A: P < 0.05, α-Klotho: P < 0.01, vitamin D₃: P < 0.01) significantly depressed in HD patients when compared to controls. PWV was significantly affected only by total cholesterol, fetuin-A and dialysis time. Multiple linear regression analyses revealed that several clinical and laboratory parameters were associated with pro- and anti-inflammatory biomarkers rather than VS. The impact of baseline clinical and biochemical variables on outcome measures were also analyzed after three-year follow-up, and it was demonstrated that low levels of vitamin D, α-Klotho protein and fetuin-A were related to adverse cardiovascular outcomes, whereas all-cause mortality was associated with elevated hsCRP and depressed vitamin D.Conclusions: Our results provide additional information on the pathomechanism of accelerated AS in patients with CRF, and documented direct influence of pro- and anti-inflammatory biomarkers on major outcome measures.

Cardiovascular (CV) morbidity and mortality are higher in chronic kidney disease (CKD) than in the general population. Reduced heart rate recovery (HRR) is an independent risk factor for CV disease. The aim of the study was to determine the prognostic role of HRR in a homogenous group of CKD patients. One hundred and twenty-five IgA nephropathy patients (82 male, 43 female, age 54.7 ± 13 years) with CKD stage 1–4 were investigated and followed for average 70 months. We performed a graded exercise treadmill stress test. HRR was derived from the difference of the peak heart rate and the heart rate at 1 min after exercise. Patients were divided into two groups by the mean HRR value (22.9 beats/min). The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularisation (CV) and end-stage renal disease, renal replacement therapy (renal). Patients with reduced HRR (< 23 bpm) had significantly more end point events (22/62 patients vs. 9/53 patients, p = 0.013) compared to the higher HRR (≥23 bpm). Of the secondary the endpoints (CV or renal separately) rate of the renal endpoint was significantly higher in the lower HRR group (p = 0.029), while there was no significant difference in the CV endpoint between the two HRR groups (p = 0.285). Independent predictors of survival were eGFR and diabetes mellitus by using Cox regression analysis. Kaplan-Meier curves showed significant differences in metabolic syndrome and non-metabolic syndrome when examined at the combined endpoints (cardiovascular and renal) or at each endpoint separately. The primary endpoint rate was increased significantly with the increased number of metabolic syndrome component (Met.sy. comp. 0 vs. Met. sy. comp. 2+, primary endpoints, p = 0.012). Our results showed that reduced HRR measured by treadmill exercise test has a predictive value for the prognosis of IgA nephropathy. The presence of metabolic syndrome may worsen the prognosis of IgA nephropathy.

Background: Patients with IgA nephropathy (IgAN), a chronic kidney disease (CKD), are significantly more likely to have cardiovascular (CV) mortality and morbidity than the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The purpose of this study was to determine how metabolic characteristics in a homogeneous population of CKD patients relate to prognosis. Methods: A total of 145 patients with CKD stages 1–4 diagnosed with IgA nephropathy (92 men and 53 women, aged 54.7 ± 13 years) were examined and monitored for a median of 190 months. All-cause mortality and any CV event, such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal), have been included in the composite endpoints (CV and renal). Results: Patients with MetS had significantly more primary endpoint events (23/65 patients vs. 15/60 patients, p < 0.001) compared to the non-MetS group. The MetS group had a statistically significant increase in both primary renal and CV endpoints (18/65 vs. 10/60, p = 0.001), and in CV endpoint events (7/65 vs. 6/60, p = 0.029) among the secondary endpoints (CV and renal separately). Based on Cox regression analysis, the main endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus. Independent predictors of secondary renal endpoints were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. When Kaplan–Meier curves were analyzed at the combined endpoints (CV and renal) or each endpoint independently, significant differences were seen between MetS and non-MetS. With more MetS components, the primary endpoint rate increased significantly (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusions: Our results show that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

Introduction: Data on the role of irisin in vascular calcification in patients with end-stage renal diseases on regular dialysis are inconsistent, and the underlying mechanisms are not clearly defined. The present study was designed to explore the association of serum irisin with vascular stiffness and with the impact of well-established risk factors. Methods: The clinical study enrolled 52 hemodialysis (HD) and 15 continuous ambulatory peritoneal dialysis (PD) patients with an age of >18 years receiving dialysis therapy for >3 months. Patients who had major pathologies affecting carbohydrate, lipid, and bone metabolism and those who had acute cardiovascular events were excluded. Thirty-seven healthy subjects matched for age and sex served as controls. Routine biochemical parameters were measured in fasting serum samples by standard methods. Serum irisin was determined using the commercial ELISA kit (BioVendor Laboratory Medicine Inc., Brno, Czech Republic). Arterial stiffness parameters – carotid-femoral pulse wave velocity (cf PWV) and augmentation index (Aix) – were measured using applanation tonometry (SphygmoCor System; AtCor Medical, Sydney, Australia). Body composition was assessed by segmental bioelectric impedance (InBody 2.0; Biospace Co. Ltd., Seoul, Korea). Results: It was demonstrated that serum irisin levels were markedly depressed (p < 0.05), while the cf PWV significantly increased (p < 0.05) in HD/PD patients as compared to controls. Serum irisin proved to be independent of serum insulin, glucose, and HOMA-IR. However, it was inversely related to HbA1c (β = −0.544, p = 0.035), iPTH (β = −0.260, p = 0.035), and alkaline phosphatase (r = −0.325, p = 0.007). Furthermore, significant negative relationships were found of irisin to serum triglyceride and indices of body fat mass. Retrospective analysis at a follow-up period of 40 months revealed a direct relationship of irisin to all-cause mortality (p = 0.039). Conclusions: Our study demonstrated that serum irisin levels are reduced in uremic patients on regular HD/PD but failed to establish significant associations of irisin deficiency with vascular stiffness. However, the significant negative relationship of irisin to HbA1c, iPTH, and alkaline phosphatase suggests that it improves insulin sensitivity, inhibits bone resorption, mitigates bone-vascular interaction, and protects vascular function.