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The International Society of Nephrology has adopted a proactive approach to defining the current state of kidney care and unmet needs through a multifaceted Closing the Gaps initiative. As part of this initiative, the International Society of Nephrology convened a meeting of experts to develop an approach to tackle acute kidney injury and chronic kidney disease (CKD). This manuscript expands on the recently published International Society of Nephrology CKD Roadmap and reports on the discussions of the working group assigned to the task of reviewing the global impact of complication of CKD. The working group defined the following goals: Goal 1: Optimize the management of anemia and endocrine and metabolic abnormalities associated with CKD. The impact of these conditions at a global level is not well understood, particularly in regions where renal replacement therapy is not readily available. Some treatment regimens may be affordable in low- and middle-income countries and if implemented, could have an impact on the burden of suffering associated with CKD. Goal 2: Improve the prevention and management of cardiovascular complications linked to CKD. Most research on cardiovascular complications of CKD has focused on atherosclerotic diseases (myocardial infarction, ischemic stroke, and peripheral gangrene). There has been growing recognition that other forms of cardiovascular diseases, such as heart failure, valvular disease and arrhythmias, have a major impact on patient outcomes. Much less is known about the mechanisms and treatment of these non-atherosclerotic complications. Goal 3: Improve the diagnosis and management of symptoms associated with CKD. Symptom management is one of the greatest challenges in the management of CKD, with limited knowledge about the mechanisms associated with the development of these common problems and how best to characterize them into usable clinical phenotypes. Improved understanding of the complications of CKD may alleviate suffering and prolong life among millions of people worldwide both in developed countries and in regions where renal replacement therapy is not widely available.

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes.

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

The article examines the evaluation of the Kidney Failure Risk Equation (KFRE) in predicting the risk of kidney replacement therapy in patients with chronic kidney disease. The study finds that while the KFRE is effective in identifying patients with a low risk of requiring referral to a nephrologist, it has limitations in accurately predicting high-risk patients. The authors suggest exploring alternative methods to improve the accuracy of risk prediction. The study was funded by commercial partners, and the opinions expressed are those of the authors. [Extracted from the article]

BackgroundDiabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.Study designMeta-analysis of cohort studies.Setting & population8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.Selection criteria for studiesCohorts participating in the CKD Prognosis Consortium.PredictorsDiabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.OutcomeHospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.ResultsDuring a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.LimitationsAKI identified by diagnostic code.ConclusionsLower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

BackgroundAcute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).Study designCollaborative meta-analysis.Setting & population8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).Selection criteria for studiesAvailable eGFR, ACR, and 50 or more AKI events.PredictorsAge, sex, race, eGFR, urine ACR, and interactions.OutcomeHospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.Results16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.LimitationsOnly 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.ConclusionsReduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.

ContextFinancial and demographic pressures in US require an understanding of the most efficient distribution of physicians to maximize population-level health benefits. Prior work has assumed a constant negative relationship between physician supply and mortality outcomes throughout the US and has not addressed regional variation.MethodsIn this ecological analysis, geographically weighted regression was used to identify spatially varying relationships between local urologist density and prostate cancer mortality at the county level. Data from 1,492 counties in 30 eastern and southern states from 2006-2010 were analyzed.FindingsThe ordinary least squares (OLS) regression found that, on average, increasing urologist density by 1 urologist per 100,000 people resulted in an expected decrease in prostate cancer mortality of -0.499 deaths per 100,000 men (95% CI -0.709 to -0.289, p-value < 0.001), or a 1.5% decrease. Geographic weighted regression demonstrated that the addition of one urologist per 100,000 people in counties in the southern Mississippi River states of Arkansas, Mississippi, and Louisiana, as well as parts of Illinois, Indiana, and Wisconsin is associated with decrease of 0.411 to 0.916 in prostate cancer mortality per 100,000 men (1.6-3.6%). In contrast, the urologist density was not significantly associated with the prostate state mortality in the new England region.ConclusionsThe strength of association between urologist density and prostate cancer mortality varied regionally. Those areas with the highest potential for effects could be targeted for increasing the supply of urologists, as it associated with the largest predicted improvement in prostate cancer mortality.

Introduction Tobacco use among adolescents is an ongoing public health concern. Youth tobacco use has been associated with advertising, from both online sources and retail environments. Aims and Methods This study examined associations between exposure to tobacco advertisements from tobacco retail outlets (TROs), internet, and social media sources and ever tobacco use among adolescents. Data were obtained from youth, aged 11–17 years (N = 401) from Richmond, VA. Bayesian index and group index models were fitted to estimate indices of exposure to (1) social media use, (2) tobacco ads on social media, and (3) TRO store visits and their association with ever tobacco use. The most important components of the exposure indices were also determined based on the index component weights from the Bayesian index models. Results In Bayesian index models of single exposures, each exposure index was significantly associated with tobacco use. In the best-fitting model, social media tobacco ads (odds ratio [OR] = 2.2; 95% credible interval [CI]: 1.2, 4.5) and TRO store visits (OR = 1.6; 95% CI: 1.1, 2.3) were significantly associated with ever tobacco use, as was older age (OR = 1.4; 95% CI: 1.2, 1.8). Index component weights revealed Snapchat ad frequency as the most important platform in the social media index and convenience stores as the most important type of store in the TRO index. Conclusions Exposure to pro-tobacco advertisements on social media and visits to TROs are associated with adolescent ever tobacco use. Results provide support for policies that would restrict the promotion of tobacco products at TROs and on social media. Tobacco regulations and interventions targeting convenience stores and Snapchat may be warranted to reduce youth tobacco use. Implications Current evidence provide support for policies that would restrict the promotion of tobacco products at TROs and on social media. Findings suggest that regulations and interventions that specifically target advertisements in convenience stores and on Snapchat may be currently warranted to reduce youth tobacco use. [ABSTRACT FROM AUTHOR]

Background Sodium–glucose co-transporter 2 inhibitors (SGLT2is) are part of the standard of care for patients with chronic kidney disease (CKD), both with and without type 2 diabetes. Endothelin A (ETA) receptor antagonists have also been shown to slow progression of CKD. Differing mechanisms of action of SGLT2 and ETA receptor antagonists may enhance efficacy. We outline a study to evaluate the effect of combination zibotentan/dapagliflozin versus dapagliflozin alone on albuminuria and estimated glomerular filtration rate (eGFR). Methods We are conducting a double-blind, active-controlled, Phase 2b study to evaluate the efficacy and safety of ETA receptor antagonist zibotentan and SGLT2i dapagliflozin in a planned 415 adults with CKD (Zibotentan and Dapagliflozin for the Treatment of CKD; ZENITH-CKD). Participants are being randomized (1:2:2) to zibotentan 0.25 mg/dapagliflozin 10 mg once daily (QD), zibotentan 1.5 mg/dapagliflozin 10 mg QD and dapagliflozin 10 mg QD alone, for 12 weeks followed by a 2-week off-treatment wash-out period. The primary endpoint is the change in log-transformed urinary albumin-to-creatinine ratio (UACR) from baseline to Week 12. Other outcomes include change in blood pressure from baseline to Week 12 and change in eGFR the study. The incidence of adverse events will be monitored. Study protocol–defined events of special interest include changes in fluid-related measures (weight gain or B-type natriuretic peptide). Results A total of 447 patients were randomized and received treatment in placebo/dapagliflozin (n  = 177), zibotentan 0.25 mg/dapagliflozin (n  = 91) and zibotentan 1.5 mg/dapagliflozin (n  =  179). The mean age was 62.8 years, 30.9% were female and 68.2% were white. At baseline, the mean eGFR of the enrolled population was 46.7 mL/min/1.73 m2 and the geometric mean UACR was 538.3 mg/g. Conclusion This study evaluates the UACR-lowering efficacy and safety of zibotentan with dapagliflozin as a potential new treatment for CKD. The study will provide information about an effective and safe zibotentan dose to be further investigated in a Phase 3 clinical outcome trial. Clinical Trial Registration Number NCT04724837 [ABSTRACT FROM AUTHOR]