Assessing health care disparities in US organ procurement organizations.

There is extensive system-wide evidence of disparities in access to organ transplantation in the US based on race, ethnicity, and socioeconomic status. However, little information is available regarding care disparities among US organ procurement organizations (OPOs). Commissioned by the US Centers for Medicare and Medicaid Services (CMS), we studied racial/ethnic disparities in organ donation and transplantation across and within OPOs.

The growth hormone/IGF-1 axis is a risk factor for long-term kidney allograft failure.

INTRODUCTIONMaladaptive hypertrophy, podocyte stress, and depletion contribute to kidney function decline. Although insulin-like growth factor 1 (IGF-1) plays a key role in early hypertrophic responses in the single kidney state, its impact on kidney transplant (KTx) outcomes remains uncertain. This report tests the hypothesis that early IGF-1 exposure reduces KTx survival.

Not all controls are made equal: Definition of human kidney reference samples by single cell gene expression profiles.

Unlabelled: Identifying kidney disease mechanisms often requires comparing samples from disease states with healthy reference tissues. However, the effect of variations in sample procurement, storage and donor baseline characteristics of reference samples has thus far not been evaluated. Three distinct kidney reference sample types were evaluated for integrity and injury biomarkers and in their ability to define differentially expressed genes (DEGs) when compared to three different diabetic kidney disease (DKD) states.

RESOLVE: Recurrence Posttransplant Observational Study in Focal Segmental Glomerulosclerosis and Minimal Change Disease.

Introduction: The morbidity of recurrent focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) after transplant is well recognized. Additional collaborative research is necessary to advance understanding of recurrence epidemiology, mechanisms, interventions, and outcomes, particularly in children.

Methods: RESOLVE is a multicenter, observational cohort study examining the posttransplant course of patients with FSGS and MCD across the lifespan.

Perioperative Acute Kidney Injury: Diagnosis, Prediction, Prevention, and Treatment.

In this review, the authors define acute kidney injury in the perioperative setting, describe the epidemiologic burden, discuss procedure-specific risk factors, detail principles of management, and highlight areas of ongoing controversy and research.

Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

BACKGROUNDIn type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.METHODSYoung adults with T1D (n = 30) and healthy controls (HCs) (n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA-Seq, and spatial metabolomics to assess this relationship.RESULTSParticipants with T1D had significantly higher glomerular basement membrane (GBM) thickness compared with HCs.

Identification of kidney cell types in scRNA-seq and snRNA-seq data using machine learning algorithms.

Introduction: Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) provide valuable insights into the cellular states of kidney cells. However, the annotation of cell types often requires extensive domain expertise and time-consuming manual curation, limiting scalability and generalizability. To facilitate this process, we tested the performance of five supervised classification methods for automatic cell type annotation.

COMPOSITE SCORES FOR TRANSPLANT CENTER EVALUATION: A NEW INDIVIDUALIZED EMPIRICAL NULL METHOD.

Risk-adjusted quality measures are used to evaluate healthcare providers with respect to national norms while controlling for factors beyond their control. Existing healthcare provider profiling approaches typically assume that the between-provider variation in these measures is entirely due to meaningful differences in quality of care. However, in practice, much of the between-provider variation will be due to trivial fluctuations in healthcare quality, or unobservable confounding risk factors.

Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy.

Objectives: To understand the early stages if Alport nephropathy, we characterize the structural, functional, and biophysical properties of glomerular capillaries and podocytes in mice, analyze kidney cortex transcriptional profiles at three time points, and investigate the effects of the ER stress mitigation by TUDCA on these parameters. We use human FSGS associated genes to identify molecular pathways rescued by TUDCA.

Findings: We define a disease progression timeline in mice.

APOL1 Kidney Risk Variants and Long-Term Kidney Function in Healthy Middle-Aged Black Individuals: The Atherosclerosis Risk in Communities (ARIC) Study.

Rationale & Objective: The effect of apolipoprotein L1( genotype on future risk of kidney disease among middle-aged individuals with good kidney function is not well established.

Study Design: Longitudinal cohort study.

Setting & Participants: In total, 5,886 healthy individuals (45-64 years old) enrolled in the Atherosclerosis Risk in Communities study with creatinine-based estimated glomerular filtration rate ≥ 80 mL/min who would be suitable kidney donors.

Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes.

Developing a Healthy Lifestyle Program for Recent Kidney Transplant Recipients.

Introduction: Many kidney transplant recipients experience weight gain in the first year after transplantation.

Research Question: The objective of this research study was to assess the desires of recent kidney transplant patients about the design features of a healthy lifestyle program to counter unnecessary weight gain.

Design: In this descriptive study, recent recipients at 2 transplant centers were invited to participate in an online survey.

An atlas of healthy and injured cell states and niches in the human kidney.

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations.

Defining the molecular correlate of arteriolar hyalinosis in kidney disease progression by integration of single cell transcriptomic analysis and pathology scoring.

Arteriolar hyalinosis in kidneys is an independent predictor of cardiovascular disease, the main cause of mortality in chronic kidney disease (CKD). The underlying molecular mechanisms of protein accumulation in the subendothelial space are not well understood. Using single cell transcriptomic data and whole slide images from kidney biopsies of patients with CKD and acute kidney injury in the Kidney Precision Medicine Project, the molecular signals associated with arteriolar hyalinosis were evaluated.

Genome-wide Association Study for AKI.

Key Points: Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.

Background: Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.

Cultured Renal Proximal Tubular Epithelial Cells Resemble a Stressed/Damaged Kidney While Supporting BK Virus Infection.

BK virus (BKV; human polyomavirus 1) infections are asymptomatic in most individuals, and the virus persists throughout life without harm. However, BKV is a threat to transplant patients and those with immunosuppressive disorders. Under these circumstances, the virus can replicate robustly in proximal tubule epithelial cells (PT).

SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth-onset type 2 diabetes.

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, and healthy controls (HCs). Participants with T2D were obese and had higher estimated glomerular filtration rates and mesangial and glomerular volumes than HCs.

A reference tissue atlas for the human kidney.

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 of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells.

Glomerular endothelial cell-podocyte stresses and crosstalk in structurally normal kidney transplants.

Increased podocyte detachment begins immediately after kidney transplantation and is associated with long-term allograft failure. We hypothesized that cell-specific transcriptional changes in podocytes and glomerular endothelial cells after transplantation would offer mechanistic insights into the podocyte detachment process. To test this, we evaluated cell-specific transcriptional profiles of glomerular endothelial cells and podocytes from 14 patients of their first-year surveillance biopsies with normal histology from low immune risk recipients with no post-transplant complications and compared these to biopsies of 20 healthy living donor controls.

Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney.

Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan.

Urine marker analysis identifies evidence for persistent glomerular podocyte injury across allograft lifespan.

Long-term kidney transplant (KT) survival has remained relatively stagnant. Protocol biopsy studies suggest that glomerulosclerosis is a significant contributor to long-term graft failure. We previously demonstrated that podocyte loss in the first year post-transplantation predicted long-term allograft survival.

Disseminated Intravascular Coagulation During Induction Treatment With Rabbit-Derived Antithymocyte Globulin For Kidney Transplant.

Rabbit antithymocyte globulin is a lymphocytedepleting agent commonly used as induction therapy in kidney transplants. Although its use is generally safe and well tolerated, serious side effects can occur. Here, we describe a case of a severe immune complex hypersensitivity reaction with disseminated intravascular coagulation in response to rabbit antithymocyte globulin infusion.