Publications by authors named "Shlipak M"
Background: We have previously studied biomarkers of tubular health (EGF), injury (KIM-1), dysfunction (alpha-1 microglobulin), and inflammation (TNFR-1, TNFR-2, MCP-1, YKL-40, suPAR), and demonstrated that plasma KIM-1, TNFR-1, TNFR-2 and urine KIM-1, EGF, MCP-1, urine alpha-1 microglobulin are each independently associated with CKD progression in children. In this study, we used bootstrapped survival trees to identify a combination of biomarkers to predict CKD progression in children.
Methods: The CKiD Cohort Study prospectively enrolled children 6 months to 16 years old with an eGFR of 30-90 ml/min/1.
In October of 2023, the American Heart Association (AHA) published a scientific statement and advisory that defined a novel entity, the Cardiovascular-Kidney-Metabolic (CKM) Syndrome. The overall framework proposes that a substantial proportion of cardiovascular disease (CVD) burden is attributable to a syndrome that extends in stages from: Stage 1) obesity, Stage 2) metabolic/kidney risk factors for CVD (diabetes mellitus, chronic kidney disease (CKD), hypertension, and dyslipidemia), Stage 3) subclinical CVD, and finally Stage 4) clinical CVD. The report that describes the CKM paradigm documents the scientific justification for a syndrome, highlights the overlap in risk factors among individuals with obesity, diabetes, CKD, and CVD, and aligns the evidence and guideline statements that address screening, prevention, and management of these conditions.
View Article and Find Full Text PDFKey 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.
Article Synopsis
- Assessing glomerular filtration rate (GFR) is essential for kidney disease management, but current methods, particularly estimated GFR (eGFR), can have significant errors affecting patient care.
- Researchers propose using a panel of multiple filtration markers, alongside non-GFR determinants, to enhance the accuracy of these estimates, building on previous findings that cystatin C improves eGFR precision.
- Initial evaluations indicate that applying techniques like outlier identification and transfer learning can significantly improve eGFR accuracy, even in populations where traditional methods struggle.
Introduction: Urine epidermal growth factor (uEGF) has been found to be inversely associated with kidney function loss, whereas its associations with cardiovascular disease (CVD) and mortality have not been studied.
Methods: We measured baseline uEGF levels among 2346 Systolic Blood Pressure Intervention Trial (SPRINT) participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m.
Article Synopsis
- A study analyzed electronic health records of patients in the Veterans Health Administration to determine the impact of chronic kidney disease (CKD) on the discontinuation of sodium-glucose co-transporter-2 inhibitors (SGLT2i) after their initiation from 2017 to 2021.
- Among 222,772 patients, 32% stopped their SGLT2i within a median follow-up of 1.6 years, with the highest discontinuation rates occurring early in treatment; 41% of discontinuations happened within the first three months.
- There was a clear correlation between lower baseline eGFR and a higher risk of SGLT2i discontinuation, although this risk appeared to decrease over the years, indicating
Background: There are no shared decision-making frameworks for selecting blood pressure (BP) targets for individuals with hypertension. This study addressed whether results from the SPRINT (Systolic Blood Pressure Intervention Trial) could be tailored to individuals using predicted risks and simulated preferences.
Methods And Results: Among 8202 SPRINT participants, Cox models were developed and internally validated to predict each individual's absolute difference in risk from intensive versus standard BP lowering for cardiovascular events, cognitive impairment, death, and serious adverse events (AEs).
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.
Joint and Individual Mitochondrial DNA Variation and Cognitive Outcomes in Black and White Older Adults.
J Gerontol A Biol Sci Med Sci
September 2024
Article Synopsis
- This study investigates the role of inherited mitochondrial DNA variations in cognitive function among Black and White older adults, focusing on participants over 70 years old from two large aging studies.
- Researchers used a sequence kernel association test to analyze multiple mtDNA variants, finding significant links between specific genetic variants and cognitive test scores at baseline and their decline over time.
- The study highlights that certain mitochondrial variants in Complex I are associated with cognitive decline differently in Black and White participants, suggesting potential genetic factors influencing neurodegenerative disease risk across ethnicities.
Rationale & Objective: The diagnosis and prognostication of chronic kidney disease (CKD) largely rely on glomerular measures that may not reflect tubular damage. We investigated the associations of urine kidney tubule biomarkers with estimated glomerular filtration rate (eGFR) change among middle-aged adults, when chronic diseases typically emerge.
Study Design: An observational cohort study.
Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.
Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.
Background: Many patients with diabetic kidney disease (DKD) do not receive evidence-based, guideline-recommended treatment shown to reduce DKD progression and complications. Proactive electronic consultations (e-consults) are an emerging intervention strategy that could potentially allow nephrologists to provide timely and evidence-based guidance to primary care providers (PCPs) engaged in early DKD care.
Methods: The objective of this study was to explore perspectives about potential barriers and facilitators associated with a proactive e-consult program to improve DKD care delivery.
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]).
Rationale & Objective: The measurement of cystatin C has been recommended to enhance chronic kidney disease (CKD) detection and risk stratification in clinical practice. This study gathered insights into the perceptions and experiences of clinical staff regarding the use of cystatin C in CKD detection within the Veterans Health Administration (VHA) system.
Study Design: A qualitative approach was employed to explore barriers and facilitators of clinical staff regarding the use of cystatin C in CKD detection within the VHA system.
Rationale & Objective: Established therapeutic interventions effectively mitigate the risk and progression of chronic kidney disease (CKD). Countries and regions have a compelling need for organizational structures that enable early identification of people with CKD who can benefit from these proven interventions. We report the current global status of CKD detection programs.
View Article and Find Full Text PDFBackground: Heart failure (HF) is associated with poor outcomes in people with chronic kidney disease, yet it is unknown whether outcomes differ by HF subtype. This study aimed to examine associations of incident HF with preserved ejection fraction (HFpEF) versus HF with reduced ejection fraction (HFrEF) with progression to end-stage kidney disease (ESKD) and mortality.
Methods: We studied individuals with chronic kidney disease in the CRIC study (Chronic Renal Insufficiency Cohort) who were free of HF at cohort entry.
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.
Rationale & Objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values.
Study Design: Cohort study.
Article Synopsis
- - Nighttime blood pressure (BP) is more closely linked to heart disease risk than daytime BP, yet its relationship with early heart disease indicators is not well understood.
- - A study involving 897 participants found that higher nighttime BP was significantly associated with increased levels of heart-related biomarkers, specifically NT-proBNP and hs-cTnT, indicating potential heart issues.
- - While both nighttime and daytime BP were linked to higher hs-cTnT levels, only nighttime BP showed a strong connection to NT-proBNP levels, suggesting it may be a more important factor in assessing cardiovascular health.
Article Synopsis
- The KDIGO Clinical Practice Guideline for Chronic Kidney Disease (CKD) updates the 2012 guideline, reflecting a comprehensive review of new evidence and advancements in treatment but does not apply to dialysis patients or those with transplants.
- The guideline addresses evaluation, risk assessment, and management strategies to slow CKD progression, using a systematic approach to assess the quality and strength of recommendations.
- It includes practice points, infographics, and highlights future research needs, aiming to serve a wide audience and consider implications for healthcare policies and payment systems.*
Background: Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels.
Methods And Results: A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP.
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.