A5079294410- Chronic Kidney Disease and Diabetes
- Renal Diseases and Glomerulopathies
- Dialysis and Renal Disease Management
- Genetic Associations and Epidemiology
- Ion Transport and Channel Regulation
- Liver Disease Diagnosis and Treatment
- Renal and related cancers
- Pancreatic function and diabetes
- Blood Pressure and Hypertension Studies
- Acute Kidney Injury Research
- Genetic and Kidney Cyst Diseases
- Renin-Angiotensin System Studies
- Biomedical Research and Pathophysiology
- Diabetes Treatment and Management
- Cell Adhesion Molecules Research
- Diabetes and associated disorders
- Metabolism and Genetic Disorders
- Vasculitis and related conditions
- Electrolyte and hormonal disorders
- Birth, Development, and Health
- Autoimmune Bullous Skin Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cardiovascular Function and Risk Factors
- Erythropoietin and Anemia Treatment
- Heart Failure Treatment and Management
University School
1997-2025
Case Western Reserve University
2015-2025
MetroHealth
2009-2024
University Hospitals of Cleveland
2022-2024
Indiana University School of Medicine
2024
National Institute of Diabetes and Digestive and Kidney Diseases
2022-2023
MetroHealth Medical Center
2009-2022
National Institutes of Health
2008-2022
University Medical Center
2014
Uniwersytecki Szpital Dziecięcy
2014
Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease African Americans, but whether APOL1-associated glomerular has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 American cases, 168 European and 939 control subjects. In recessive model, conferred seventeenfold higher odds (95% CI 11 to 26) focal segmental glomerulosclerosis (FSGS) twenty-nine-fold 13 68) HIV-associated nephropathy (HIVAN). FSGS associated two...
Diabetes is associated with altered cellular metabolism, but how metabolism contributes to the development of diabetic complications unknown. We used BKS db/db mouse model investigate changes in carbohydrate and lipid kidney cortex, peripheral nerve, retina. A systems approach using transcriptomics, metabolomics, metabolic flux analysis identified tissue-specific differences, increased glucose fatty acid kidney, a moderate increase retina, decrease nerve. In was enhanced protein acetylation...
purpose. Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity DR DN computed heritability estimates for were determined in a large, multiethnic sample families. The hypothesis was that (1) the correlates with presence individuals mellitus, (2) is under significant familial influence members multiplex methods. Family Investigation Nephropathy Diabetes (FIND) designed to evaluate genetic basis...
The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility diabetic nephropathy. A total 11 centers participated under a single collection protocol recruit large numbers sibling pairs concordant discordant for We report the findings from first-phase genetic analyses in 1,227 participants 378 pedigrees European-American, African-American, Mexican-American, American Indian descent recruited eight centers. Model-free linkage analyses, using...
Background and objectives Hyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures plasma lipids lipoproteins predict progression kidney disease Design, setting, participants, & measurements Prospective cohort adults (n=3939) CKD aged 21–74 years recruited between 2003 2008 followed for a median 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL (LDL-C), HDL (HDL-C), apoA-I ,...
Although diabetic kidney disease is the leading cause of ESKD in United States, identifying those patients who progress to difficult. Efforts are under way determine if plasma biomarkers can help identify these high-risk individuals.In our case-cohort study 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR <60 ml/min per 1.73 m2 at baseline, were randomly selected for subcohort; cases developed progressive (ESKD or 40% decline). Using a multiplex system, we...
Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across damaged glomerular filtration barrier subsequent reabsorption by downstream proximal tubule, causing lipoapoptosis. We sought identify apical tubule transporter that mediates NEFA uptake cytotoxicity. observed transporter-mediated fluorescently labeled in cultured cells microperfused rat tubules, with...
Apoptosis results in cell shrinkage and intracellular acidification, processes opposed by the ubiquitously expressed NHE1 Na(+)/H(+) exchanger. In addition to mediating transport, interacts with ezrin/radixin/moesin (ERM), which tethers cortical actin cytoskeleton regulate shape, adhesion, motility, resistance apoptosis. We hypothesize that apoptotic stress activates NHE1-dependent exchange, NHE1-ERM interaction is required for survival signaling. Apoptotic stimuli induced NHE1-regulated as...
Clinical states in which angiotensin II is increased are often associated with increases mineralocorticoids. To determine the effects of mineralocorticoids on action, we examined aldosterone receptor expression and function cultured rat vascular smooth muscle cells. Incubation resulted concentration- time-dependent number, without changes binding affinity. For example, incubation 1 microM for 40 hours 59% number. Increases receptors were dependent protein synthesis as evidenced by time...
IL-1–stimulated mesenchymal cells model molecular mechanisms of inflammation. Binding IL-1 to the type I receptor (IL-1R) clusters a multi-subunit signaling complex at focal adhesion complexes. Since Rho family GTPases coordinately organize actin cytoskeleton and regulate cell phenotype, we hypothesized that IL-1R contained these G proteins. stimulated stress fiber formation in serum-starved HeLa Rho-dependent manner rapidly activated nucleotide exchange on RhoA. Glutathione S-transferase...
Objective: To determine whether an elevated osmolal gap is specific for toxic alcohol ingestion. Design: Cross-sectional. Setting: Emergency room and medical surgical inpatient wards at a university-affiliated hospital. Patients: Twenty-three patients with lactic acidosis, 19 alcoholic ketoacidosis, 10 randomly selected controls. Measurements Main Results: Calculated measured serum osmolality was determined in all study participants. The increased acidosis (17.4 ± 5.4 mmol/kg) ketoacidosis...
<i>Background/Aims:</i> Currently available clinical indicators of kidney disease lack the sensitivity and/or specificity to identify early-stage diabetic nephropathy (DN). Quantitative diffusion magnetic resonance imaging (MRI), specifically tensor (DTI), has been used quantify pathophysiologic changes in other organs but not well studied diseases, including DN. The goal this pilot study was examine differences DTI parameters subjects versus healthy controls....
Human studies report conflicting results on the predictive power of serum lipids progression chronic kidney disease (CKD). We aimed to systematically identify that predict end-stage disease.From Chronic Renal Insufficiency Cohort, 79 patients with CKD stage 2 3 who progressed ESKD over 6 years follow up were selected and frequency-matched by age, sex, race, diabetes 121 non-progressors less than 25% decline in estimated glomerular filtration rate (eGFR) during up. The randomly divided into...
Background and objectives CKD is an important risk factor for cardiovascular disease (CVD) death. We investigated whether select urine kidney injury biomarkers were associated with higher of heart failure (HF), CVD, death in persons enrolled the Chronic Renal Insufficiency Cohort (CRIC) Study. Design, setting, participants, & measurements Urine molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, N -acetyl -β- d -glucosaminidase measured a...
Significance Statement Identifying novel biomarkers of kidney function decline in children may have clinical value and help elucidate the biologic mechanisms CKD progression. In CKiD prospective cohort study, authors evaluated 651 with measured plasma collected 5 months after enrollment. After multivariable adjustment, risk progression was significantly higher among concentrations a biomarker tubular injury (KIM-1) or either two inflammation (TNF receptor–1 [TNFR-1] TNFR-2) highest quartile...
Kidney disease is one of the most devastating complications diabetes, and tubular atrophy predicts diabetic kidney (DKD) progression to end-stage renal disease. We have proposed that fatty acids bound albumin contribute by inducing lipotoxicity, after filtration across damaged glomeruli, subsequent proximal tubule reabsorption a acid transport protein-2–dependent (FATP2-dependent) mechanism. To address this possibility, genetic (Leprdb/db eNOS–/–) induced (high-fat diet plus low-dose...