Postnatal renal tubule development: roles of tubular flow and flux.

PURPOSE OF REVIEW: Postnatal renal tubule development is critical to adult kidney function. Several postnatal changes regulate the differentiation and proliferation of renal tubular cells. Here, we review the literature and our efforts on thick ascending limb (TAL) development in Bartter syndrome (BS). RECENT FINDINGS: Glomerular filtrate quickly increases after birth, imposing fluid shear stress and circumferential stretch on immature renal tubules. Recent studies showed that kidney organoids under flow (superfusion) have better development of tubular structures and the expression of cilia and solute transporters. These effects are likely mediated by mechanosensors, such as cilia and the piezo1 channel. Improved renal oxygenation and sodium pump-dependent active transport can stimulate mitochondrial respiration and biogenesis. The functional coupling between transport and mitochondria ensures ATP supply for energy-demanding reactions in tubular cells, including cell cycle progression and proliferation. We recently discovered that postnatal renal medulla maturation and TAL elongation are impaired in Clc-k2-deficient BS mice. Primary cultured Clc-k2-deficient TAL cells have G1-S transition and proliferation delay. These developmental defects could be part of the early pathogenesis of BS and worsen the phenotype. SUMMARY: Understanding how tubular flow and transepithelial ion fluxes regulate renal tubule development may improve the treatment of congenital renal tubulopathies.

Joint effect of BMI and metabolic status on mortality among adults: a population-based longitudinal study in United States.

We explored the joint effects of different metabolic obesity phenotypes on all-cause and disease-specific mortality risk among the American population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality outcome data were from mortality files linked to National Death Index record and follow-up information was up to December 31, 2019. 50,013 participants were finally included. Four metabolic obesity phenotypes were defined based on obesity and metabolic status: metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy non-obese (MHNO), and metabolically unhealthy non-obese (MUNO). Population-weighted Cox proportional hazards models were used to explore the all-cause and disease-specific mortality risk of metabolic obesity phenotypes. The all-cause mortality risk of MUO and MUNO was significantly higher than MHNO. MUNO was associated with a significantly increased risk of death from heart disease (HR: 1.40, 95% CI 1.16-1.70), hypertension (HR: 1.68, 95% CI 1.34-2.12), diabetes (HR: 2.29, 95% CI 1.67-3.15), and malignant neoplasms (HR:1.29, 95% CI 1.09-1.53). Metabolic unhealth significantly increased the risk of all-cause mortality, regardless of obesity status. Among individuals with metabolic unhealthy status, obesity significantly reduced the risk of all-cause mortality (HR: 0.91, 95% CI 0.85-0.98). Our study highlights the importance of identifying and characterizing metabolic obesity phenotypes in obese and metabolically abnormal patients, as well as healthy adults. Comprehensive evaluation of obesity and metabolic status is necessary to adopt appropriate interventions and treatment measures and maximize patient benefit.

Higher serum ferritins are associated with higher blood pressure: A cross-sectional study.

The aim of the study was to investigate the association between serum ferritin and hypertension among American adults from National Health and Nutrition Examination Survey (NHANES) 1999 to 2018. A total of 16,125 participants were included. Weighted logistic regression and subgroup analyses were performed to explore the association. We found that serum ferritin was closely correlated to hypertension. Individuals with high serum ferritin were more likely to have higher systolic or diastolic blood pressure (SBP, DBP) than those with lower serum ferritin. Restricted cubic spline showed a significant non-linear association between serum ferritin and SBP/DBP. Higher level of serum ferritin (Q3 74.1-147 µg/L and Q4 > 147 µg/L) was found to have positive association with high SBP [Q3 (OR: 1.246, 95% CI:1.020-1.523), Q4 (OR: 1.354, 95% CI:1.096-1.674)], and hypertension [Q3 (OR: 1.283, 95% CI:1.099-1.499), Q4 (OR: 1.424, 95% CI:1.197-1.63)] in the whole population. In people aged between 20 and 60, subjects with high serum ferritin were significantly associated with a higher risk of hypertension, but in those over 60, the relationship between serum ferritin level and hypertension is negative. A non-linear association between serum ferritin and SBP, as well as DBP, was discovered. There was age difference in association between serum ferritin and hypertension in American adults, and further researches were needed to understand the mechanisms behind the difference.