A5045615753- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Lysosomal Storage Disorders Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Glycogen Storage Diseases and Myoclonus
- Biomedical Research and Pathophysiology
- Renal Transplantation Outcomes and Treatments
- Systemic Sclerosis and Related Diseases
- Dialysis and Renal Disease Management
- Renal and Vascular Pathologies
- Complement system in diseases
- Diabetes and associated disorders
- Systemic Lupus Erythematosus Research
- Cell Adhesion Molecules Research
- Trypanosoma species research and implications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Pediatric Urology and Nephrology Studies
- Cellular transport and secretion
- Organ Transplantation Techniques and Outcomes
- Vasculitis and related conditions
- Diabetes Treatment and Management
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Renal cell carcinoma treatment
- Organ Donation and Transplantation
University of Washington
2016-2025
Seattle University
2014-2023
Phoenix (United States)
2021
Columbia University
2019
University of Alberta
2019
University of Washington Medical Center
2012-2018
University of Minnesota
2002-2017
Vanderbilt University
2017
American Society of Nephrology
2016
National Kidney Foundation
2016
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation histopathological features in fatal cases disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed provide a clinicopathological report severe COVID-19 documenting changes evidence tissue tropism. In this case series, patients positive antemortem or post-mortem result...
The aim of this study was to investigate the structural characteristics podocytes and endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, five proteinuric), normal control subjects. Groups were not different for age. Type groups duration or age at onset. Podocyte foot process width (FPW), fraction glomerular basement membrane (GBM) surface intact nondetached processes (IFP), capillary luminal covered by...
Patients with Fabry disease (FD) are at a high risk for developing chronic kidney and cardiovascular disease. The availability of specific but costly therapy has elevated the profile this rare condition. This KDIGO conference addressed controversial areas in diagnosis, screening, management FD, included enzyme replacement nonspecific standard-of-care various manifestations FD. Despite marked advances patient care improved overall outlook, there is need to better understand pathogenesis...
Interstitial fibrosis/tubular atrophy (IF/TA) contributes to the loss of kidney allografts, and treatment or preventive options are lacking. We conducted a double-blind, randomized, placebo-controlled trial determine whether angiotensin II blockade prevents expansion cortical interstitial compartment, precursor fibrosis. randomly assigned 153 transplant recipients receive losartan, 100 mg (n=77), matching placebo (n=76) within 3 months transplantation, continuing for 5 years. The primary...
COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that selectively infects hPSC-CMs through receptor ACE2, whereas hPSC-SMCs there is minimal entry replication. After into cardiomyocytes, assembled...
Significance Statement In males with classic Fabry disease, the processes leading to frequent outcome of ESKD are poorly understood. Mutations in gene encoding α -galactosidase A leads globotriaosylceramide accumulation various cell types; podocytes, this progresses age. study 55 disease genotype and/or phenotype, authors found an increasing fraction podocyte cytoplasm occupied by globotriaosylceramide, which plateaued at around age 27 years. At same time, volume continued rise, apparently...
Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in reversal end-organ damage, like kidney injury and chronic disease, remains unclear. In this study, ultrastructural analysis serial human biopsies showed that long-term use ERT reduced Gb3 podocytes but did not reverse...
Significance Statement Although diabetic nephropathy is assessed clinically by measuring eGFR and albuminuria, structural kidney damage typically precedes these clinical manifestations. Previous studies have early change in type 1 diabetes but not 2. In a study of American Indian patients with 2 generally preserved function, the authors found changes structure over an average 9 years, as determined quantitative morphometric analysis biopsy specimens. They also that were more consistently...
Venglustat inhibits the enzymatic conversion of ceramide to glucosylceramide, reducing available substrate for synthesis more complex glycosphingolipids. It offers a potential new approach treatment patients with Fabry disease (α-Gal A deficiency), in whom progressive accumulation such glycosphingolipids, including globotriaosylceramide (GL-3), lysosomes wide range cell types often leads vital organ complications adulthood. An international, open-label, single-arm, Phase 2a uncontrolled...
Circulating proteins associated with transforming growth factor-β (TGF-β) signaling are implicated in the development of diabetic kidney disease (DKD). It remains to be comprehensively examined which these involved pathogenesis DKD and its progression end-stage (ESKD) humans. Using SOMAscan proteomic platform, we measured concentrations 25 TGF-β family four different cohorts composed total 754 Caucasian or Pima Indian individuals type 1 2 diabetes. Of circulating proteins, identified...
ABSTRACT. Atubular glomeruli (AG) have been described in several renal disorders. However, little attention has paid to AG diabetic nephropathy (DN). Preliminary studies suggested that tip lesions were frequently present type 1 (D) patients with proteinuria. The aim of this study was determine the frequency and their possible relationship DN. Renal biopsies from eight proteinuric D normal moderately reduced GFR (76 ± 26 ml/min per 1.73 m2) subjects studied by light (LM) electron microscopy...
Fibrillary GN has been defined as an immune complex-mediated with amyloid-like fibrils larger than amyloid which are IgG positive and Congo red negative. With discovery of DNAJB9 a highly sensitive specific marker for fibrillary GN, the specificity morphologic criteria establishing diagnosis come into question. We sought to (1) determine anatomic characteristics that best define (2) identify clinical pathologic features predict outcomes. retrospectively reviewed kidney biopsies from patients...
Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other cell types in patients. Podocyte injury occurs early age, and progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase patients correlate with clinical severity nephropathy. Urine specimens from 39 24 healthy subjects were evaluated for podocyturia. Most many had The number per gram creatinine...
Background SARS-CoV-2 is the cause of an ongoing pandemic with a projected 100,000 to 240,000 U.S. deaths. To date, documentation histopathologic features in fatal cases COVID-19 has been limited due small sample size and incomplete organ sampling. Methods Post-mortem examinations were performed on 12 Washington State during February-March 2020. Clinical laboratory data reviewed. Tissue examination all major organs was by light microscopy electron microscopy. The presence viral RNA sampled...
Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood.
Glomerulotubular junction abnormalities, frequent in proteinuric patients with type 1 diabetes, may contribute to the progressive GFR loss overt diabetic nephropathy. abnormalities were examined who have diabetes a wide range of albumin excretion rates (AER). Renal biopsies from five normoalbuminuric patients, microalbuminuric six and control subjects studied by light electron microscopy. Light microscopy specimens serially sectioned find classify glomerulotubular junctions. Glomerular...