Plasma Biomarkers of Kidney Health and Mortality in Diabetes and Chronic Kidney Disease in the REGARDS Study.

Key Points: In diabetes and CKD, creatinine- and cystatin C–based eGFR has a strong inverse correlation with plasma TNF receptor 1, TNF receptor 2, and soluble urokinase-type plasminogen activator receptor. Higher plasma soluble TNF receptors 1 and 2 and soluble urokinase-type plasminogen activator receptor were each individually associated with mortality, independent of baseline kidney measures.

Background: Several plasma biomarkers of kidney health have been associated with CKD progression in persons with diabetes, but their associations with mortality risk have been largely unexplored.

Peak Tricuspid Regurgitation Jet Velocity and Kidney Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

Introduction: Although venous congestion secondary to elevated pulmonary artery pressure (PAP) has been hypothesized to worsen kidney function, the association of peak tricuspid regurgitation jet velocity (pTRV), a surrogate of PAP, with kidney outcomes remains uncertain in heart failure (HF) with preserved ejection fraction (HFpEF).

Methods: This analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial analyzed participants with a left ventricular ejection fraction (LVEF) of ≥45% who had pTRV measured by echocardiography at baseline. For the cross-sectional analysis, the association of baseline pTRV with baseline estimated glomerular filtration rate (eGFR) was assessed using linear regression.

Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes.

Background: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear.

Methods And Results: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease : A Systematic Review and Retrospective Individual Participant-Level Meta-analysis of Clinical Trials.

Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear.

Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death.

Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023.

Association between Acute Declines in eGFR during Renin-Angiotensin System Inhibition and Risk of Adverse Outcomes.

Key Points: Renin-angiotensin system inhibition was favorable for risk of kidney failure (compared with 0% decline with use of placebo or other agents) up to declines in eGFR of 13% over a 3-month period. Relation between eGFR decline after renin-angiotensin system inhibitor initiation and risk of outcomes was stronger in the first 2 years of follow-up and waned over time.

Background: Declines in GFR occur commonly when renin-angiotensin system (RAS) inhibitors are started.

Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies.

Rationale & Objective: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.

Study Design: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).

Epidemiology and Management of Patients With Kidney Disease and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) comprises approximately one-half of all diagnoses of heart failure. There is significant overlap of this clinical syndrome with chronic kidney disease (CKD), with many shared comorbid conditions. The presence of CKD in patients with HFpEF is one of the most powerful risk factors for adverse clinical outcomes, including death and heart failure hospitalization.

The Gut Microbial Metabolite Trimethylamine N -oxide, Incident CKD, and Kidney Function Decline.

Key Points: In community-based US adults, higher plasma trimethylamine -oxide levels associated with higher risk of incident CKD and greater rate of kidney function decline. Findings from our study support future clinical trials to examine whether lowering plasma trimethylamine -oxide levels may prevent CKD development and progression.

Background: Trimethylamine -oxide (TMAO) is a gut microbiota–derived metabolite of dietary phosphatidylcholine and carnitine.

Changes in Cognitive Function After Kidney Transplantation: A Longitudinal Cohort Study.

Rationale & Objective: Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains.

Study Design: Prospective cohort study.

Mitochondrial genetic variation and risk of chronic kidney disease and acute kidney injury in UK Biobank participants.

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function.

Home Dialysis in Patients with Cardiovascular Diseases.

Kidney failure with replacement therapy and cardiovascular disease are frequently comorbid. In patients with kidney failure with replacement therapy, cardiovascular disease is a major contributor to morbidity and mortality. Conventional thrice-weekly in-center dialysis confers risk factors for cardiovascular disease, including acute hemodynamic fluctuations and rapid shifts in volume and solute concentration.

Plasma Biomarkers and Incident CKD Among Individuals Without Diabetes.

Rationale & Objective: Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established.

Study Design: Prospective observational cohort.

Development and Validation of Novel Free Vitamin D Equations: The Health Aging and Body Composition Study.

Vitamin D deficiency is prevalent in 25% of Americans. However, 25(OH)D may not be an accurate measure of vitamin D because the majority (85%-90%) of 25(OH)D is bound to vitamin D binding protein (VDBP), which varies by over 30% across individuals. Free 25(OH)D may be a better measure, but it is difficult to measure accurately and precisely.

Urinary Biomarkers of Kidney Tubule Health and Mortality in Persons with CKD and Diabetes Mellitus.

Key Points: Among adults with diabetes and CKD, biomarkers of kidney tubule health were associated with a greater risk of death, independent of eGFR, albuminuria, and additional risk factors. Higher urine levels of YKL-40 and KIM-1 were associated with a greater risk of death. For cause-specific death, UMOD was independently and inversely associated with the risk of cardiovascular death.

Association of Longitudinal B-Type Natriuretic Peptide Monitoring With Kidney Failure in Patients With CKD: A Cohort Study.

Rationale & Objective: Both hypervolemia and hypovolemia are associated with chronic kidney disease (CKD) progression. Although longitudinal monitoring of B-type natriuretic peptide (BNP) may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. This study assessed the association between BNP monitoring and the risk of incident kidney replacement therapy (KRT).

Acute Declines in Estimated GFR in Blood Pressure Target Trials and Risk of Adverse Outcomes.

Rationale & Objective: Acute decreases in glomerular filtration rate (GFR) occur commonly during intensive blood pressure (BP) lowering. Our objective was to determine the relationship between acute decreases in estimated GFR and patient outcomes.

Study Design: Retrospective observational study.

Association of Kidney Tubule Biomarkers With Cardiac Structure and Function in the Multiethnic Study of Atherosclerosis.

Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression.