Background Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated for treatment of anaemia of chronic kidney disease (CKD). Methods This randomised, open-label, active-controlled phase 3 study compared roxadustat versus darbepoetin alfa (DA) in non–dialysis-dependent (NDD) CKD patients with anaemia for ≤104 weeks. Doses were titrated to correct and maintain haemoglobin within 10.0–12.0 g/dL. The primary endpoint was haemoglobin response in the full analysis set (FAS), defined as haemoglobin ≥11.0 g/dL and haemoglobin change from baseline (CFB) ≥1.0 g/dL in patients with baseline haemoglobin >8.0 g/dL or CFB ≥2.0 g/dL in patients with baseline haemoglobin ≤8.0 g/dL during the first 24 weeks of treatment without rescue therapy (noninferiority margin, -15%). Key secondary endpoints included change in low-density lipoprotein (LDL), time to first intravenous iron use, change in mean arterial pressure (MAP), and time to hypertension occurrence. Adverse events were assessed. Results Of 616 randomised patients (roxadustat, 323; DA, 293), 424 completed treatment (roxadustat, 215; DA, 209). Haemoglobin response with roxadustat was noninferior to DA (roxadustat: 256/286, 89.5% vs. DA: 213/273, 78.0%, difference 11.51%, 95% confidence interval, 5.66-17.36%). Roxadustat maintained haemoglobin for up to 2 years. Roxadustat was noninferior to DA for change in MAP and time to occurrence of hypertension and superior for change in LDL and time to first intravenous iron use. Safety profiles were comparable between groups. Findings suggest that there was no difference between groups regarding the composite endpoints major adverse cardiovascular events (MACE) and MACE + (MACE: 0.81 [0.52, 1.25], P = 0.339; MACE+: 0.90 [0.61, 1.32], P = 0.583). Conclusion Roxadustat is a viable option to treat anaemia in NDD CKD patients maintaining haemoglobin levels for up to 104 weeks.

Background Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for the treatment of chronic kidney disease (CKD) anemia. Methods This phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with stage 3-5 CKD not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52-104 weeks. This study examined two primary efficacy endpoints: European Union (EMA) - hemoglobin (Hb) response, defined as Hb ≥ 11.0 g/dL that increased from baseline by ≥ 1.0 g/dL in patients with Hb > 8.0 g/dL or ≥ 2.0 g/dL in patients with baseline Hb ≤ 8.0 g/dL, without rescue therapy, during the first 24 weeks of treatment; United States (FDA) - change in Hb from baseline to the average Hb level during Weeks 28-52, regardless of rescue therapy. Secondary efficacy endpoints and safety were examined. Results A total of 594 patients were analyzed (roxadustat: 391; placebo: 203). Superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints: Hb response (odds ratio: 34.74 [95% CI: 20.48, 58.93]) and change in Hb from baseline (roxadustat - placebo: +1.692 [95% CI: 1.52, 1.86]; both P<0.001). Superiority of roxadustat was demonstrated for LDL cholesterol change from baseline, and time to first use of rescue medication (both P<0.001). The incidences of treatment-emergent adverse events were comparable between groups (roxadustat: 87.7%, placebo: 86.7%). Conclusions Roxadustat demonstrated superior efficacy versus placebo both in terms of Hb response rate and change in Hb from baseline. The safety profiles of roxadustat and placebo were comparable.

ObjectiveTo assess the prevalence of microalbuminuria and kidney dysfunction in low-income countries and in the USA.DesignCross-sectional study of screening programmes in five countries.SettingScreening programmes in Nepal, Bolivia, the USA (National Health and Nutrition Examination Survey (NHANES) 2005–2008) Bangladesh and Georgia.ParticipantsGeneral population in Nepal (n=20 811), Bolivia (n=3436) and in the USA (n=4299) and high-risk subjects in Bangladesh (n=1518) and Georgia (n=1549).Primary and secondary outcome measuresEstimated glomerular filtration rate (eGFR)<60ml/min/1.73 m2 and microalbuminuria (defined as urinary albumin creatinine ratio values of 30–300 mg/g) were the main outcome measures. The cardiovascular (CV) risk was also evaluated on the basis of demographic, clinical and blood data.ResultsThe prevalence of eGFR<60ml/min/1.73 m2 was 19%, 3.2% and 7% in Nepal, Bolivia and the USA, respectively. In Nepal, 7% of subjects were microalbuminuric compared to 8.6% in the USA. The prevalence of participants with predicted 10-year CV disease (CVD) risk ≥10% was 16.9%, 9.4% and 17% in Nepal, Bolivia and in the USA, respectively. In Bangladesh and Georgia, subjects with eGFR<60 ml/min/1.73 m2 were 8.6% and 4.9%, whereas those with microalbuminuria were 45.4% and 56.5%, respectively. Predicted 10-year CVD risk ≥10% was 25.4% and 25% in Bangladesh and Georgia, respectively.ConclusionsRenal abnormalities are common among low-income countries and in the USA. Prevention programmes, particularly focused on those with renal abnormalities, should be established worldwide to prevent CVD and progression to end-stage renal disease.

Background and Aims Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of anaemia in patients (pts) with chronic kidney disease (CKD). Efficacy and safety of roxadustat compared with darbepoetin alfa (DA) for the treatment of anaemia in CKD pts not on dialysis (NDD) was assessed in a randomised, open-label, active-controlled phase 3 study. Results from a protocol-specified interim analysis, performed after pts had either completed ≥36 weeks of treatment or had withdrawn from the study, are presented here. Method This study (CL-0610) enrolled pts with NDD CKD stages 3-5 and anaemia (haemoglobin [Hb] ≤10.5 g/dL) and randomised them to receive roxadustat or DA. Following prescribed initial doses (weight-based), dose adjustments were permitted, with the goal of correcting and maintaining Hb. The primary endpoint was Hb response, defined as Hb ≥11.0 g/dL and an Hb increase from baseline (BL) of ≥1.0 g/dL in pts with BL Hb &gt;8.0 g/dL, or an increase of ≥2.0 g/dL in pts with BL Hb ≤8.0 g/dL, during the first 24 weeks of treatment without rescue therapy. Key secondary endpoints included change in serum lipids, time to first IV iron use, change in mean arterial pressure (MAP), and occurrence of hypertension. Noninferiority of roxadustat to DA was declared if the lower bound of the two-sided 95% confidence interval (CI; roxadustat – DA) for change in Hb was &gt;-0.15. Adverse events (AEs) were assessed across the study and are presented as events/100 patient exposure years (PEY) unless otherwise specified. The full analysis set (FAS) included pts who received ≥1 dose of study drug and had ≥1 post-dose Hb assessment. The per protocol set (PPS) included FAS pts who did not meet exclusion criteria. The safety analysis set (SAF) included pts who received ≥1 dose of study drug. Results As of 15 June 2018, 616 pts were randomised to receive roxadustat (n=323) or DA (n=293); of these 616 pts, 395 pts (roxadustat, n=194; DA, n=201) were still receiving treatment and 89 pts had completed ≥2 years of treatment (roxadustat, n=55; DA, n=34). In the PPS, 89.5% (n=256) of roxadustat pts responded in the first 24 weeks compared with 78.0% (n=213) of DA pts, for a difference of 11.51% (95% CI: 5.66%, 17.36%), thereby establishing roxadustat’s noninferiority to DA. Noninferiority of roxadustat to DA was also demonstrated for MAP and time to occurrence of hypertension. In the FAS, superiority of roxadustat to DA was demonstrated for low-density lipoprotein (LDL) and time to first IV iron use. (Table) In the SAF, overall incidence of AEs was comparable between roxadustat and DA (85.8% and 84.6%, respectively). Conclusion This analysis demonstrates that roxadustat was noninferior to DA in correction of Hb levels during the first 24 weeks of treatment in pts with NDD CKD stages 3-5 and anaemia. Safety profiles were comparable between groups. Final analysis of this study’s data will be presented at the congress.

End-Stage Renal Disease (ESRD) represents one of the most challenging social and medical problems mainly due to substantial treatment-associated costs. The chronic nature of the disease needs expensive continuous care that majority of the patients cannot afford. Therefore, in many countries expenses associated with the ESRD treatment is paid by state government. These treatment options include: hemodialysis, peritoneal dialysis and kidney transplantation. Multiple studies have been conducted throughout the world to assess cost-effectiveness of these treatment modalities. The studies suggest that kidney transplantation not only reduces mortality and morbidity but improves a quality of life of ESRD patients. Furthermore, it is the most cost-effective treatment for the ESRD at least in high-income countries. The goal of our study was to determine whether above-mentioned is true for lower middle income countries, where the cost of the ESRD treatment is substantially lower. Despite the low dialysis costs, transplantation remains the cheapest form of renal replacement therapy RRT in lower income countries like Georgia. Our results reveal, that kidney transplantation is most expensive modality of Renal Replacement Therapy (RRT) at month 1, but count of costs reveals that after the 10 th month of treatment, the cumulative cost of transplantation is less than the cumulative cost of peritoneal dialysis and after the 23 rd month, cumulative cost of hemodialysis also surpasses the cumulative cost of transplantationrelated treatment and this cost comparison is in line with global data from upper-middle and high income countries. A. Tataradze et al. 438