A5069873786- Renal Transplantation Outcomes and Treatments
- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Organ Donation and Transplantation
- Diabetes Treatment and Management
- Organ Transplantation Techniques and Outcomes
- Renal and Vascular Pathologies
- Dialysis and Renal Disease Management
- Pancreatic function and diabetes
- Pregnancy and Medication Impact
- Polyomavirus and related diseases
- Genetic and Kidney Cyst Diseases
- Neurological Complications and Syndromes
- Diabetes and associated disorders
- Cannabis and Cannabinoid Research
- Birth, Development, and Health
- Health, Environment, Cognitive Aging
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Liver Disease and Transplantation
- Parvovirus B19 Infection Studies
- Blood donation and transfusion practices
- Machine Learning in Healthcare
- Bipolar Disorder and Treatment
University of Michigan
2016-2025
Michigan Medicine
2020-2024
Michigan United
2024
SleepMed
2023
University of Washington
2023
L V Prasad Eye Institute
2018-2021
Warde Medical Laboratory
2021
All India Institute of Medical Sciences Bhubaneswar
2020
Mahatma Gandhi Mission Medical College and Hospital
2016
University of Chicago
2002-2015
Abstract Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell single-nucleus assays (>400,000 nuclei or cells) spatial imaging technologies to a broad spectrum healthy reference kidneys (45 donors) diseased (48 patients). This has provided high-resolution cellular atlas 51 main types, which include rare previously undescribed...
To define cellular mechanisms underlying kidney function and failure, the KPMP analyzes biopsy tissue in a multicenter research network to build cell-level process maps of kidney. This study aimed establish single cell RNA sequencing strategy use transcriptional profiles from biopsies molecular subtypes glomerular diseases. Using multiple sources adult human reference samples, 22,268 passed quality control parameters. Unbiased clustering resulted 31 distinct clusters that were linked immune...
Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map cells, pathways, genes using unaffected regions nephrectomy tissues undiseased biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics proteomics, near-single-cell 3D CODEX imaging, spatial metabolomics to...
The molecular mechanisms of sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometric data were collected from research kidney biopsies donated by young persons with type 2 diabetes (T2D), aged 12 to 21 years, healthy controls (HCs). Participants T2D obese had higher estimated glomerular filtration rates mesangial volumes than HCs. Ten participants been prescribed SGLT2i (T2Di[+]) 6 not (T2Di[-]). Transcriptional...
COVID-19 morbidity and mortality are increased via unknown mechanisms in patients with diabetes kidney disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Because ACE2 is a susceptibility factor infection, we investigated how diabetic disease medications alter receptor expression kidneys. Single cell RNA profiling of biopsies from healthy living donors revealed primarily proximal tubular epithelial This cell-specific localization was confirmed by situ...
Abstract Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) spatial imaging technologies to a broad spectrum healthy reference (n = 42) kidneys. This has provided high resolution cellular atlas 100 that include rare novel populations. The multi-omic approach provides detailed transcriptomic...
Glomerular sclerotic lesions develop when the glomerular filtration surface area exceeds availability of podocyte foot process coverage, but mechanisms involved are incompletely characterized. We evaluated potential using a transgenic (podocin promoter-AA-4E-BP1) rat in which capacity for hypertrophy response to growth factor/nutrient signaling is impaired. FSGS resembling human developed spontaneously by 7 months age, and could be induced earlier accelerating kidney nephrectomy. Early...
Renal transplantation is a lifesaving intervention for end-stage renal disease. The demand outweighs the availability of organs; however, up to 20% recovered kidneys are discarded before transplantation. We aimed better characterize risk factors deceased donor kidney discard.We performed secondary analysis Organ Procurement and Transplantation Network database from 2000 2012 all solid organ donors. cohort was split into training (80%) validation (20%) subsets. stepwise logistic regression...
Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national registry pharmacy fill records, use at 6-12 12-24 mo after was evaluated for 22 453 patients transplanted 249 U.S. programs 2005-2010. Use triple comprising tacrolimus, mycophenolic acid or azathioprine,...
Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) after (post-DAA), stratified by donor (D) recipient (R) serostatus payer. Pre-DAA, 18% HCV+ LT recipients treated within 3 years without differences or Post-DAA, only...
The use of procurement biopsies in deceased donor kidney acceptance is controversial. We analyzed Scientific Registry Transplant Recipients data (n = 59 328 allografts, 2014-2018) to describe biopsy practices across US organ organizations (OPOs) and examine relationships with discards, using hierarchical modeling account for OPO factors. Median odds ratios (MORs) provide the median that allografts identical reported traits would be biopsied or discarded from 2 randomly drawn OPOs. Biopsies...
Evolving literature suggests that the epidemic of prescription opioid use affects transplant population. We examined a novel database wherein national U.S. registry records were linked to large pharmaceutical claims warehouse (2007-2015) characterize before and after kidney transplant, associations (adjusted hazard ratio, 95% LCLaHR95% UCL) with death graft loss. Among 75 430 eligible patients, 43.1% filled opioids in year transplant. Use was more common among recipients who women, white,...
Kidney transplantation has become more resource intensive as recipient complexity increased and average donor quality diminished over time. A national retrospective cohort study was performed to assess the impact of kidney characteristics on transplant center cost (exclusive organ acquisition) Medicare reimbursement. Data from registry, University HealthSystem Consortium hospital costs, payments for deceased (N = 53 862) living 36 715) transplants 2002 2013 were linked analyzed using...
Cannabis is categorized as an illicit drug in most US states, but legalization for medical indications increasing. Policies and guidance on cannabis use transplant patients remain controversial.We examined a database linking national kidney records (n = 52 689) with Medicare claims to identify diagnoses of dependence or abuse (CDOA) associations [adjusted hazard ratio (aHR) 95% upper lower confidence limits (CLs)] graft, patient, other clinical outcomes.CDOA was diagnosed only 0.5% 254) 0.3%...
Identifying kidney disease mechanisms often requires comparing samples from states with healthy reference tissues. However, the effect of variations in sample procurement, storage and donor baseline characteristics has thus far not been evaluated. Three distinct types were evaluated for integrity injury biomarkers their ability to define differentially expressed genes (DEGs) when compared three different diabetic (DKD) states. Unaffected parts tumor nephrectomies (TN), pre-transplant living...
The impact of pretransplant body mass index (BMI) on long-term allograft outcomes after kidney transplantation remains controversial. conventional approach using Kaplan-Meier method to calculate the cumulative risk death-censored failure may overestimate especially when competing risks are present.A retrospective cohort adult first-time transplant recipients was drawn from Organ Procurement and Transplantation Network database (2001 2009). Based World Health Organization obesity...
The infrequent use of ABO-incompatible (ABOi) kidney transplantation in the United States may reflect concern about costs necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor transplant recipients (2000 to March 2011), including 271 ABOi 62 A2-incompatible (A2i) recipients, were analyzed assess impact pretransplant, episode 3-year costs. marginal A2i versus ABO-compatible (ABOc) transplants quantified by multivariate linear regression adjustment recipient,...
Abstract While guidelines support metformin as a therapeutic option for diabetic patients with mild‐to‐moderate renal insufficiency, the frequency and outcomes of use in kidney transplant recipients are not well described. We integrated national U.S. registry data records from large pharmaceutical claims clearinghouse (2008‐2015). Associations (adjusted hazard ratio, 95% LCL aHR UCL ) diabetes regimens (with excluding metformin) first year post‐transplant patient graft survival over...
Kidney function decreases with age. A potential mechanistic explanation for kidney and allograft half-life has evolved through the realization that linear reduction in glomerular podocyte density could drive progressive glomerulosclerosis to impact both native half-lives.