African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in .

Recently, a novel African ancestry specific Parkinson's disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (). This variant (rs3115534-G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups, but is almost absent in European and Asian ancestry populations.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Proteomic Assessment of the Risk of Secondary Cardiovascular Events among Individuals with CKD.

Key Points: Machine learning and large-scale proteomics led to a 16-protein secondary cardiovascular risk model in patients with CKD. Hepatic fibrosis and liver X receptor activation represented biologic pathways that link kidney disease and risk of secondary cardiovascular events. An understanding of the circulating proteins associated with secondary cardiovascular events may help to identify novel therapeutic targets.

Sex Differences in Hypertension and Its Management Throughout Life.

Background: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex.

Methods: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models.

Results: The prevalence of hypertension increased with age from 40% (ages, 43-46 years) to 93% (ages, 91-94 years).

Plasma proteomics of acute tubular injury.

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development.

Serum and Urine Metabolites and Kidney Function.

Key Points: We provide an atlas of cross-sectional and longitudinal serum and urine metabolite associations with eGFR and urine albumin-creatinine ratio in an older community-based cohort. Metabolic profiling in serum and urine provides distinct and complementary insights into disease.

Background: Metabolites represent a read-out of cellular processes underlying states of health and disease.

Plasma Proteins Associated with Chronic Histopathologic Lesions on Kidney Biopsy.

Key Points: Proteomic profiling identified 35 blood proteins associated with chronic histopathologic lesions in the kidney. Testican-2 was expressed in the glomerulus, released by the kidney into circulation, and inversely associated with glomerulosclerosis severity. NELL1 was expressed in tubular epithelial cells, released by the kidney into circulation, and inversely associated with interstitial fibrosis and tubular atrophy severity.

Association of Integrated Proteomic and Metabolomic Modules with Risk of Kidney Disease Progression.

Key Points: Integrated analysis of proteome and metabolome identifies modules associated with CKD progression and kidney failure. Ephrin transmembrane proteins and podocyte-expressed CRIM1 and NPNT emerged as central components and warrant experimental and clinical investigation.

Background: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes.

Eicosanoids and Related Metabolites Associated with ESKD in a Community-Based Cohort.

Key Points: High-throughput eicosanoid profiling can identify metabolites that may play a protective role in the development of kidney disease. In contrast to many other nonlipid metabolites, eicosanoid levels are minimally related with kidney filtration cross-sectionally.

Background: Eicosanoids are derivatives of polyunsaturated fatty acids and participate in the inflammatory response and the maintenance of endothelial function.

Associations of Baseline and Longitudinal Serum Uromodulin With Kidney Failure and Mortality: Results From the African American Study of Kidney Disease and Hypertension (AASK) Trial.

Rationale & Objective: Uromodulin (UMOD) is the most abundant protein found in urine and has emerged as a promising biomarker of tubule health. Circulating UMOD is also detectable, but at lower levels. We evaluated whether serum UMOD levels were associated with the risks of incident kidney failure with replacement therapy (KFRT) and mortality.

Transcriptome- and proteome-wide association studies nominate determinants of kidney function and damage.

Background: The pathophysiological causes of kidney disease are not fully understood. Here we show that the integration of genome-wide genetic, transcriptomic, and proteomic association studies can nominate causal determinants of kidney function and damage.

Results: Through transcriptome-wide association studies (TWAS) in kidney cortex, kidney tubule, liver, and whole blood and proteome-wide association studies (PWAS) in plasma, we assess for effects of 12,893 genes and 1342 proteins on kidney filtration (glomerular filtration rate (GFR) estimated by creatinine; GFR estimated by cystatin C; and blood urea nitrogen) and kidney damage (albuminuria).

Proteomic cardiovascular risk assessment in chronic kidney disease.

Aims: Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models.

Kidney Risk Variants and Proteomics.

Background And Objectives: The risk variants (G1 and G2) are associated with kidney disease among Black adults, but the clinical presentation is heterogeneous. In mouse models and cell systems, increased gene expression of G1 and G2 confers cytotoxicity. How risk variants relate to the circulating proteome warrants further investigation.