Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes.

Background: Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed.

Objectives: The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D.

Concordance With Screening and Treatment Guidelines for Chronic Kidney Disease in Type 2 Diabetes.

Importance: Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care.

Objective: To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D.

Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: Klotho deficiency may affect clinical outcomes in chronic kidney disease (CKD) through fibroblast growth factor-23 (FGF23)-dependent and -independent pathways. However, the association between circulating Klotho and clinical outcomes in CKD remains unresolved and was the focus of this study.

Study Design: Prospective observational study.

Plasma Serotonin and Cardiovascular Outcomes in Chronic Kidney Disease.

Background Platelet-poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney disease, the cardiovascular implications remain unknown. Methods and Results In 1114 participants from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we evaluated the association between plasma serotonin, categorized as undetectable, intermediate, and high (≥20 ng/mL) levels, and cross-sectional findings on echocardiography, including left ventricular hypertrophy, left ventricular ejection fraction, and pulmonary hypertension.

FGF23 and klotho at the intersection of kidney and cardiovascular disease.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). As CKD progresses, CKD-specific risk factors, such as disordered mineral homeostasis, amplify traditional cardiovascular risk factors. Fibroblast growth factor 23 (FGF23) regulates mineral homeostasis by activating complexes of FGF receptors and transmembrane klotho co-receptors.

Association of Chronic Renal Insufficiency with Inhospital Outcomes in Primary Heart Failure Hospitalizations (Insights from the National Inpatient Sample 2004 to 2018).

Chronic kidney disease (CKD) is a major co-morbidity in patients with heart failure (HF). There are limited contemporary data characterizing the clinical profile, inhospital outcomes, and resource use in patients hospitalized for HF with co-morbid CKD. We utilized a nationally representative population to address the knowledge gap.

Sildenafil and Kidney Function in Heart Failure with Preserved Ejection Fraction.

Key Points: Sildenafil induced an acute effect on eGFR without change in the overall eGFR slope after 24 weeks in a heart failure with preserved ejection fraction (HFpEF) cohort. -terminal pro–brain natriuretic peptide levels and baseline diuretic use were most strongly associated with eGFR decline in this HFpEF cohort. Long-term studies are required to determine sildenafil's influence on kidney function and outcomes in HFpEF.

Noninvasive Risk Score to Screen for Pulmonary Hypertension With Elevated Pulmonary Vascular Resistance in Diseases of Chronic Volume Overload.

Volume overload promotes pulmonary hypertension (PH) through pulmonary venous hypertension. However, PH with elevated pulmonary vascular resistance (hereafter PH-PVR) may develop in patients with diseases of volume overload, such as heart failure or chronic kidney disease (CKD). In such cases, volume management alone may be insufficient to slow PH progression.

Hypoxia signaling in renal pericytes-is it safe to activate?

While excitement has grown for the use of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors for treating renal anemia, multiple preclinical studies have shown the complex and cell-type-dependent roles of HIFs in kidney disease pathogenesis, including renal fibrosis. Pan et al. now clearly show that activating the HIF signaling in the Gli1-lineage myofibroblasts restores erythropoietin production while not adversely affecting matrix production, mitigating the concerns of exacerbated fibrosis by HIF prolyl hydroxylase inhibitors.

Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.

Background: Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.

Methods: The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide.

Coronavirus Disease 2019 and Hypertension: The Role of Angiotensin-Converting Enzyme 2 and the Renin-Angiotensin System.

Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of severe acute respiratory syndrome coronavirus 2, the virus responsible for COVID-19, into host cells.

Echocardiography to Screen for Pulmonary Hypertension in CKD.

Introduction: Pulmonary hypertension (PH) is a common yet incompletely understood complication of chronic kidney disease (CKD). Although transthoracic echocardiogram is commonly used to noninvasively estimate PH, it has not been validated in a CKD population. We investigated the utility of this diagnostic tool for CKD-associated PH in a large right heart catheterization (RHC) cohort.

Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphate Management for Patients Receiving Maintenance Hemodialysis.

Rationale & Objective: Hyperphosphatemia is a risk factor for poor clinical outcomes in patients with kidney failure receiving maintenance dialysis. Opinion-based clinical practice guidelines recommend the use of phosphate binders and dietary phosphate restriction to lower serum phosphate levels toward the normal range in patients receiving maintenance dialysis, but the benefits of these approaches and the optimal serum phosphate target have not been tested in randomized trials. It is also unknown if aggressive treatment that achieves unnecessarily low serum phosphate levels worsens outcomes.

Prescribing rates and characteristics of recipients of tenofovir-containing regimens before and after market entry of tenofovir alafenamide.

Tenofovir alafenamide (TAF) is a new formulation of tenofovir disoproxil fumarate (TDF) that was approved in 2015. While clinical trial evidence suggests that TAF has more favorable outcomes related to kidney injury and loss of bone mineral density, TAF also leads to higher lipid levels compared with TDF. To (a) determine prescribing rates of TDF and TAF among new recipients from 2014 to 2018 in a large academic health system and (b) compare baseline patient characteristics of those newly prescribed TDF versus TAF before and after the approval of TAF in November 2015.

Statins and atherosclerotic cardiovascular outcomes in patients on incident dialysis and with atherosclerotic heart disease.

Unlabelled: Statins failed to reduce cardiovascular (CV) events in trials of patients on dialysis. However, trial populations used criteria that often excluded those with atherosclerotic heart disease (ASHD), in whom statins have the greatest benefit, and included outcome composites with high rates of nonatherosclerotic CV events that may not be modified by statins. Here, we study whether statin use associates with lower atherosclerotic CV risk among patients with known ASHD on dialysis, including in those likely to receive a kidney transplant, a group excluded within trials but with lower competing mortality risks.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

Rationale & Objective: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes.

Study Design: Retrospective cohort study.

Drug Development in Kidney Disease: Proceedings From a Multistakeholder Conference.

Occasional bursts of discovery and innovation have appeared during the otherwise stagnant past several decades of drug development in nephrology. Among other recent drug discoveries, the unexpected kidney benefits observed with sodium/glucose cotransporter 2 inhibitors may herald a renaissance of drug development in kidney disease. This recent progress highlights the need to further promote and stimulate research and development of promising therapies that may ameliorate the morbidity and mortality associated with kidney disease.

Therapeutic options for chronic kidney disease-associated pulmonary hypertension.

Purpose Of Review: Pulmonary hypertension is a common and devastating complication of chronic kidney disease (CKD). Traditionally considered a consequence of volume overload, recent findings now expand this paradigm. These novel mechanisms herald new treatment options.

Controversies of renin-angiotensin system inhibition during the COVID-19 pandemic.

The current COVID-19 pandemic is associated with unprecedented morbidity and mortality. Early reports suggested an association between disease severity and hypertension but did not account for sources of confounding. However, the responsible virus — SARS-CoV-2 — gains entry to host cells via angiotensin-converting enzyme 2 (ACE2), highlighting the need to understand the relationship between the virus and the renin–angiotensin system (RAS) and how this might be affected by RAS inhibitors.