Dataset Information

Sex differences in solute and water handling in the human kidney: Modeling and functional implications.

ABSTRACT: The kidneys maintain homeostasis by controlling the amount of water and electrolytes in the blood. That function is accomplished by the nephrons, which transform glomerular filtrate into urine by a transport process mediated by membrane transporters. We postulate that the distribution of renal transporters along the nephron is markedly different between men and women, as recently shown in rodents. We hypothesize that the larger abundance of a renal Na⁺ transport in the proximal tubules in females may also better prepare them for the fluid retention adaptations required during pregnancy and lactation. Also, kidneys play a key role in blood pressure regulation, and a popular class of anti-hypertensive medications and angiotensin converting enzymes (ACE) inhibitors have been reported to be less effective in women. Model simulations suggest that the blunted natriuretic and diuretic effects of ACE inhibition in women can be attributed, in part, to their higher distal baseline transport capacity.

SUBMITTER: Hu R

PROVIDER: S-EPMC8209279 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Sex differences in solute and water handling in the human kidney: Modeling and functional implications.

Hu Rui R McDonough Alicia A AA Layton Anita T AT

iScience 20210529 6

The kidneys maintain homeostasis by controlling the amount of water and electrolytes in the blood. That function is accomplished by the nephrons, which transform glomerular filtrate into urine by a transport process mediated by membrane transporters. We postulate that the distribution of renal transporters along the nephron is markedly different between men and women, as recently shown in rodents. We hypothesize that the larger abundance of a renal Na<sup>+</sup> transport in the proximal tubule ...[more]

PMID: 34169242

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Project description:Background: Osteoarthritis (OA) primarily affects mechanical load-bearing joints. The knee joint is the most impacted by OA. Knee OA (KOA) occurs in almost all demographic groups, but the prevalence and severity are disproportionately higher in females. The molecular mechanism underlying the pathogenesis and progression of KOA is unknown. The molecular basis of biological sex matters of KOA is not fully understood. Mechanical stimulation plays a vital role in modulating OA-related responses of load-bearing tissues. Mechanical unloading by simulated microgravity (SMG) induced OA-like gene expression in engineered cartilage, while mechanical loading by cyclic hydrostatic pressure (CHP), on the other hand, exerted a pro-chondrogenic effect. This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences. Methods: Tissue-engineered menisci were made from female and male meniscus fibrochondrocytes (MFCs) under static conditions of normal gravity in chondrogenic media and subjected to SMG and CHP culture. Constructs were assayed via histology, immunofluorescence, GAG/DNA assays, RNA sequencing, and testing of mechanical properties. Results: The mRNA expression of ACAN and COL2A1, was upregulated by CHP but downregulated by SMG. COL10A1, a marker for chondrocyte hypertrophy, was downregulated by CHP compared to SMG. Furthermore, CHP increased GAG/DNA levels and wet weight in both female and male donors, but only significantly in females. From the transcriptomics, CHP and SMG significantly modulated genes related to the ossification, regulation of ossification, extracellular matrix, and angiogenesis Gene Ontology (GO) terms. A clear difference in fold-change magnitude and direction was seen between the two treatments for many of the genes. Furthermore, differences in fold-change magnitudes were seen between male and female donors within each treatment. SMG and CHP also significantly modulated genes in OA-related KEGG pathways, such as mineral absorption, Wnt signalling pathway, and HIF-1 signalling pathway. Conclusion: Engineered menisci responded to CHP and SMG in a sex-dependent manner. SMG may induce an OA-like profile, while CHP promotes chondrogenesis. The combination of SMG and CHP could serve as a model to study the early molecular events of KOA and potential drug-targetable pathways.

Project description:Aging is associated with altered water, electrolyte, and glucose handling. Alternative beverages to those containing carbohydrate (CHO) should be considered for older adults. We hypothesized that reduced sodium (CNa+) and/or water (CH2O) clearance would underlie greater beverage retention in older compared with young adults, secondary to reduced glomerular filtration rate (GFR). We further hypothesized that amino acid (AA)- and CHO-based beverages would promote retention better than water. Over five visits, 12 young (23 ± 3 yr; 7 men, 5 women) and 12 older (67 ± 6 yr; 5 men, 7 women) subjects consumed 1 liter of distilled water or beverages with 6% CHO, 0.46 g/l Na+ [Gatorade (GAT)]; 2.5% CHO, 0.74 g/l Na+ [Pedialyte (PED)]; 5 AA, 1.04 g/l Na+ [enterade (ENT)-5]; or 8 AA, 1.38 g/l Na+ (ENT-8) over 30 min. Blood and urine were collected every hour for 4 h after ingestion; retention, CH2O, and CNa+ were calculated at 2 and 4 h. Additional calculations adjusted CH2O and CNa+ for estimated GFR (eGFR). Water yielded the lowest retention in both groups ( P ≤ 0.02). Retention was higher in older vs. young adults except for ENT-8 at 4 h ( P = 0.73). CH2O was higher for older vs. young adults for GAT at 2 h ( P < 0.01) and GAT and PED at 4 h ( P < 0.01) after ingestion but was otherwise similar between groups. CNa+ was lower in older vs. young adults except for ENT-8 ( P ≥ 0.19). Adjusting for eGFR resulted in higher CH2O for all beverages in older vs. young adults ( P < 0.05) but did not influence CNa+. Older adults may better retain beverages with less Na+ than young adults because of reduced CNa+. AA- and CHO-based electrolyte-rich beverages may similarly promote beverage retention. NEW & NOTEWORTHY Commercially available amino acid (AA)-containing beverages may provide an alternative to traditional carbohydrate (CHO)-containing beverages, particularly for older adults with attenuated water, electrolyte, and glucose handling. We compared beverage retention and free water and sodium clearance between young and older adults after ingestion of water, two CHO-based beverages, and two AA-based beverages. Our data suggest that older adults better retain beverages with less sodium compared with young adults and that AA-based and CHO-based electrolyte-containing beverages similarly promote retention.

Dataset Information

Sex differences in solute and water handling in the human kidney: Modeling and functional implications.

Publications

Sex differences in solute and water handling in the human kidney: Modeling and functional implications.

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