Subcutaneous CERA for the treatment of chronic renal anemia in predialysis patients

Background: We investigated the efficacy, safety and tolerability of once-monthly administration of C.E.R.A. in erythropoiesis stimulating agents (ESAs) naive predialysis patients with CKD for anemia treatmentStudy Design: Single arm, open label study.Methods: A total of 75 patients (mean (SD) age was 52.8 (16.4) years, 76.0% were female) were included in this study conducted between 12 August 2008 and 30 October 2009 in 9 centers across Turkey. The mean change in Hb concentration (g/dL) between baseline (week 0) and the efficacy evaluation period (EEP) was the primary efficacy parameter evaluated in three consecutive periods including a dose titration period (DTP; with initial 1.2 mu g/kg dose of C.E.R.A., subcutaneously, 28 weeks), EEP (8 weeks) and a long-term safety period (16 weeks).Results: Our analysis revealed an improvement in Hb levels from baseline value of 9.4 (0.4) g/dL to time adjusted average level of 11.4 (0.7) g/dL in EEP in the per protocol (PP) population and from 9.3 (0.5) g/dL to 11.1 (1.0) g/dL in intent-to-treat (ITT) population. Mean (SD) change in Hb levels from baseline to EEP was 2.0 (0.7) g/dl in the PP population (primary endpoint) and 1.7 (1.1) g/dL in the ITT population. The percentage of patients whose Hb concentrations remained within the target range of 10.0-12.0 g/dL throughout the EEP was 43.9% (95% CI: 28.5-60.3%) in the PP population and 38.7% (95% CI: 27.6% to 50.6%) in the ITP population. A total of 206 adverse events (AE) were reported in 77.0% of patients with hypertension (20%) as the most frequent AE.Conclusion: Once-monthly subcutaneous C.E.R.A. administration is effective and safe in the treatment of anemia in pre-dialysis patients with CKD, who are not currently treated with ESAs

Global nephrology workforce: gaps and opportunities toward a sustainable kidney care system

The health workforce is the cornerstone of any health care system. An adequately trained and sufficiently staffed workforce is essential to reach universal health coverage. In particular, a nephrology workforce is critical to meet the growing worldwide burden of kidney disease. Despite some attempts, the global nephrology workforce and training capacity remains widely unknown. This multinational cross-sectional survey was part of the Global Kidney Health Atlas project, a new initiative administered by the International Society of Nephrology (ISN). The objective of this study was to address the existing global nephrology workforce and training capacity. The questionnaire was administered online, and all data were analyzed and presented by ISN regions and World Bank country classification. Overall, 125 United Nations member states responded to the entire survey, with 121 countries responding to survey questions pertaining to the nephrology workforce. The global nephrologist density was 8.83 per million population (PMP); high-income countries reported a nephrologist density of 28.52 PMP compared with 0.31 PMP in low-income countries. Similarly, the global nephrologist trainee density was 1.87 PMP; high-income countries reported a 30 times greater nephrology trainee density than low-income countries (6.03 PMP vs. 0.18 PMP). Countries reported a shortage in all care providers in nephrology. A nephrology training program existed in 79% of countries, ranging from 97% in high-income countries to 41% in low-income countries. In countries with a training program, the majority (86%) of programs were 2 to 4 years, and the most common training structure (56%) was following general internal medicine. We found significant variation in the global density of nephrologists and nephrology trainees and shortages in all care providers in nephrology; the gap was more prominent in low-income countries, particularly in African and South Asian ISN regions. These findings point to significant gaps in the current nephrology workforce and opportunities for countries and regions to develop and maintain a sustainable workforce

On the Origin and Trigger of the Notothenioid Adaptive Radiation

Adaptive radiation is usually triggered by ecological opportunity, arising through (i) the colonization of a new habitat by its progenitor; (ii) the extinction of competitors; or (iii) the emergence of an evolutionary key innovation in the ancestral lineage. Support for the key innovation hypothesis is scarce, however, even in textbook examples of adaptive radiation. Antifreeze glycoproteins (AFGPs) have been proposed as putative key innovation for the adaptive radiation of notothenioid fishes in the ice-cold waters of Antarctica. A crucial prerequisite for this assumption is the concurrence of the notothenioid radiation with the onset of Antarctic sea ice conditions. Here, we use a fossil-calibrated multi-marker phylogeny of nothothenioid and related acanthomorph fishes to date AFGP emergence and the notothenioid radiation. All time-constraints are cross-validated to assess their reliability resulting in six powerful calibration points. We find that the notothenioid radiation began near the Oligocene-Miocene transition, which coincides with the increasing presence of Antarctic sea ice. Divergence dates of notothenioids are thus consistent with the key innovation hypothesis of AFGP. Early notothenioid divergences are furthermore congruent with vicariant speciation and the breakup of Gondwana

Status of care for end stage kidney disease in countries and regions worldwide:international cross sectional survey

ObjectiveTo determine the global capacity (availability, accessibility, quality, and affordability) to deliver kidney replacement therapy (dialysis and transplantation) and conservative kidney management.DesignInternational cross sectional survey.SettingInternational Society of Nephrology (ISN) survey of 182 countries from July to September 2018.ParticipantsKey stakeholders identified by ISN's national and regional leaders.Main outcome measuresMarkers of national capacity to deliver core components of kidney replacement therapy and conservative kidney management.ResultsResponses were received from 160 (87.9%) of 182 countries, comprising 97.8% (7338.5 million of 7501.3 million) of the world's population. A wide variation was found in capacity and structures for kidney replacement therapy and conservative kidney management-namely, funding mechanisms, health workforce, service delivery, and available technologies. Information on the prevalence of treated end stage kidney disease was available in 91 (42%) of 218 countries worldwide. Estimates varied more than 800-fold from 4 to 3392 per million population. Rwanda was the only low income country to report data on the prevalence of treated disease; 5 (<10%) of 53 African countries reported these data. Of 159 countries, 102 (64%) provided public funding for kidney replacement therapy. Sixty eight (43%) of 159 countries charged no fees at the point of care delivery and 34 (21%) made some charge. Haemodialysis was reported as available in 156 (100%) of 156 countries, peritoneal dialysis in 119 (76%) of 156 countries, and kidney transplantation in 114 (74%) of 155 countries. Dialysis and kidney transplantation were available to more than 50% of patients in only 108 (70%) and 45 (29%) of 154 countries that offered these services, respectively. Conservative kidney management was available in 124 (81%) of 154 countries. Worldwide, the median number of nephrologists was 9.96 per million population, which varied with income level.ConclusionsThese comprehensive data show the capacity of countries (including low income countries) to provide optimal care for patients with end stage kidney disease. They demonstrate substantial variability in the burden of such disease and capacity for kidney replacement therapy and conservative kidney management, which have implications for policy

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams