Urine Ammonium Concentrations and Cardiovascular and Kidney Outcomes in Systolic Blood Pressure Intervention Trial Participants with CKD.

Key Points: Among nondiabetic individuals with hypertension and CKD, higher urine ammonium concentration is associated with higher risk of cardiovascular disease. Urine ammonium was not associated with all-cause mortality or CKD progression, AKI, or linear eGFR decline in the Systolic Blood Pressure Intervention Trial cohort.

Background: Impaired urine ammonium excretion is common in CKD and may identify risk of metabolic acidosis earlier than reductions in serum bicarbonate or pH and thus may have associations with cardiovascular disease (CVD) outcomes.

Proneurotensin/Neuromedin N and Risk of Incident CKD and Other Kidney Outcomes in Community-Living Individuals: The REGARDS Study.

Rationale & Objective: Plasma proneurotensin/neuromedin N (pro-NT/NMN) is a precursor of neurotensin, a tridecapeptide linked with type 2 diabetes mellitus and other comorbid conditions associated with kidney disease. Whether pro-NT/NMN is directly associated with incident chronic kidney disease (CKD), and whether that association differs by race, is uncertain. We evaluated whether pro-NT/NMN levels were associated with increased risk of kidney outcomes.

Association of Urinary Dickkopf-3 Levels with Cardiovascular Events and Kidney Disease Progression in Systolic Blood Pressure Intervention Trial.

Key Points: In unadjusted analyses, elevated urinary Dickkopf-3 levels were strongly associated with higher risks of cardiovascular disease, ESKD, AKI, and mortality. However, associations were substantially weakened after adjustment for eGFR and albuminuria, suggesting limited prognostic value.

Background: Urinary Dickkopf-3 (uDKK3) is a tubular epithelial-derived profibrotic protein secreted into the urine under tubular stress.

Plasma proenkephalin A and incident chronic kidney disease and albuminuria in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

Background: Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.

Tubule dysfunction and injury and future risk of sepsis-associated acute kidney injury.

Background: Novel biomarkers can quantify both kidney tubule function, including proximal tubule reabsorptive (urine α-1 microglobulin (uα1m)) and tubule protein synthesis capacities (urine uromodulin (uUMOD)), and tubular injury (urine neutrophil gelatinase-associated lipocalin (uNGAL)). In a blood pressure trial, we reported that lower reabsorptive and synthetic protein capacity at times of health predicted future risk of acute kidney injury (AKI), but most AKI was related to hemodynamic causes in this trial. Associations between tubular function and injury and future AKI related to other causes is unknown.

Urine Uromodulin, Kidney Tubulointerstitial Fibrosis, and Furosemide Response.

Background: Interstitial fibrosis and tubular atrophy (IFTA) are common findings on biopsy in chronic kidney disease (CKD) and are strongly predictive of kidney failure. IFTA is poorly correlated with estimated glomerular filtration rate (eGFR) and albuminuria, the most common measures of kidney function. Thus, IFTA is prognostically important, yet its presence and severity are invisible to the clinician except when kidney biopsies are obtained.

Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity.

Rationale & Objective: Cystatin C-based estimated glomerular filtration rate (eGFR) has stronger associations with adverse clinical outcomes than creatinine-based eGFR (eGFR). Obesity may be associated with higher cystatin C levels, independent of kidney function, but it is unknown whether obesity modifies associations of eGFR with kidney and cardiovascular outcomes.

Study Design: Cohort study.

Markers of Kidney Tubule Dysfunction and Major Adverse Kidney Events.

Background: Serum creatinine and albuminuria are primary markers of glomerular function and injury, respectively. Tubular secretion, acid-base homeostasis, protein reabsorption, among other tubular functions, are largely ignored. This mini-review aimed to discuss how two tubular functions, secretion, and acid-base homeostasis are associated with major adverse kidney events (MAKEs).

Risk Factors for Incident CKD in Black and White Americans: The REGARDS Study.

Rationale & Objective: Little information exists on the incidence of and risk factors for chronic kidney disease (CKD) in contemporary US cohorts and whether risk factors differ by race, sex, or region in the United States.

Study Design: Observational cohort study.

Setting & Participants: 4,198 Black and 7,799 White participants aged at least 45 years, recruited from 2003 through 2007 across the continental United States, with baseline estimated glomerular filtration rate (eGFR)>60mL/min/1.

Lipid accumulation product, visceral adiposity index and risk of chronic kidney disease.

Background: Lipid accumulation product (LAP) and visceral adiposity index (VAI) are novel, non-imaging markers of visceral adiposity that are calculated by using body mass index (BMI), waist circumference (WC) and serum lipid concentrations. We hypothesized that LAP and VAI are more strongly associated with adverse kidney outcomes than BMI and WC.

Methods: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we used multivariable logistic regression to evaluate associations of LAP, VAI, BMI and WC with incident chronic kidney disease (CKD), (incident eGFR < 60 ml/min/1.

Estimated Kidney Tubular Secretion and Kidney, Cardiovascular, and Mortality Outcomes in CKD: The Systolic Blood Pressure Intervention Trial.

Rational & Objective: Many drugs, metabolites, and toxins are cleared by the kidneys via tubular secretion. Whether novel endogenous measures of tubular secretion provide information about kidney, cardiovascular, and mortality risk is uncertain.

Study Design: Longitudinal subgroup analysis of clinical trial participants.

Renal Clearance of Fibroblast Growth Factor-23 (FGF23) and its Fragments in Humans.

Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 and C-terminal fragments) versus intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this finding. We measured cFGF23 and iFGF23 in the aorta and bilateral renal veins of 162 patients with essential hypertension undergoing renal angiography.

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Serious Adverse Events in SPRINT.

Background Assessing the risk of serious adverse events (SAEs) during hypertension treatment is important for understanding the benefit-harm trade-offs of lower blood pressure goals. It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide information about SAEs. Methods and Results In SPRINT (Systolic Blood Pressure Intervention Trial), hs-cTnT and NT-proBNP were measured at baseline in 8828 (94.

Complete Genome Sequence of a Novel Hafnia alvei Bacteriophage.

A bacteriophage that is able to infect Hafnia alvei and can also infect two other hosts, Klebsiella pneumoniae and Salmonella enterica, was isolated from wastewater. The complete genome sequence was determined by long-read PacBio sequencing. Based on sequence similarity, the bacteriophage is assigned to the viral genus within the family .

Kidney tubule health, mineral metabolism and adverse events in persons with CKD in SPRINT.

Background: Measures of kidney tubule health are risk markers for acute kidney injury (AKI) in persons with chronic kidney disease (CKD) during hypertension treatment, but their associations with other adverse events (AEs) are unknown.

Methods: Among 2377 Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD, we measured at baseline eight urine biomarkers of kidney tubule health and two serum biomarkers of mineral metabolism pathways that act on the kidney tubules. Cox proportional hazards models were used to evaluate biomarker associations with risk of a composite of pre-specified serious AEs (hypotension, syncope, electrolyte abnormalities, AKI, bradycardia and injurious falls) and outpatient AEs (hyperkalemia and hypokalemia).

Biomarkers of Kidney Tubule Health, CKD Progression, and Acute Kidney Injury in SPRINT (Systolic Blood Pressure Intervention Trial) Participants.

Rationale & Objective: The Systolic Blood Pressure Intervention Trial (SPRINT) compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal estimated glomerular filtration rate (eGFR) change and risk of acute kidney injury (AKI).

Study Design: Observational cohort nested in a clinical trial.

Intact and C-Terminal FGF23 Assays-Do Kidney Function, Inflammation, and Low Iron Influence Relationships With Outcomes?

Context: Higher fibroblast growth factor-23 (FGF23) concentrations are associated with heart failure and mortality in diverse populations, but the strengths of associations differ markedly depending up on which assay is used.

Objective: We sought to evaluate whether iron deficiency, inflammation, or kidney function account for differences in the strengths of associations between these 2 FGF23 assays with clinical outcomes.

Design: Case cohort study from the Cardiovascular Health Study.

Is Tubular Dysfunction a Risk Factor for AKI?

Tubular functions are critical for homeostasis maintenance. However, tubular function markers are not typically assessed in routine clinical care. Recent research by our group has revealed that tubular dysfunction at baseline is a risk factor for subsequent acute kidney injury (AKI), independent of estimated glomerular filtration rate and albuminuria.

A Simple Equation to Estimate Urinary Flow Rate Using Urine Creatinine.

Background: Accurate assessment of urine flow remains challenging in both inpatient and outpatient settings. We hypothesized we could derive an equation that would accurately estimate urine flow rate (eV) through derivation from other existing equations commonly used in nephrology clinical practice.

Methods: The eV equation was derived using the Cockcroft-Gault and the measured creatinine clearance (CrCl = UCrV/PCr) equations.