INTRODUCTION:Human induced pluripotent stem cell (iPSC)-derived kidney organoids have emerged as a valuable model for studying kidney development and disease. Phenotypically, these organoids resemble kidneys of gestational week 12. Embryonic kidneys have the capacity to reassemble after dissociation, which offers the possibility to study the effect of introducing additional cell types or gene expression modification through transfection of dissociated organoids before reassembly. We examined whether human iPSC-derived kidney organoids share the property of embryonic kidneys to reassemble after dissociation. This would open new research avenues with human kidney organoids. METHODS:Human iPSC-derived kidney organoids were dissociated into single cells by TrypLE Select and reaggregated by centrifugation. Organoids were collected 4 and 7 days after reaggregation and immunostaining was performed to assess structural organization. Restoration of endocrine activity was assessed by measurement of renin production. As a proof of principle, dissociated organoids were transfected with a GFP expressing plasmid, and expression was monitored in reaggregated organoids. RESULTS:Kidney organoids displayed the capacity to reassemble proximal and distal tubular structures, demonstrated by reappearance of Villin-1+ and E-cadherin+ structures. Podocalyxin (PODXL)+ glomerular structures reappeared sparsely after dissociation. Reassembled organoids responded to forskolin with renin secretion, albeit at a lower level than non-dissociated organoids. Dissociated organoids that were transfected with a GFP plasmid at the cell suspension stage showed robust GFP expression after reassembly. CONCLUSION:Human kidney organoids partially reassemble after dissociation. Dissociation and reassembly of kidney organoids offers a novel tool for kidney organoid research that allows the introduction of exogenous cell types or transfection of kidney organoid cells.
INTRODUCTION:Chronic kidney disease (CKD), particularly hypertension-associated CKD (HCKD), is a significant global health burden, with hypertension and diabetes as leading causes. Rising global temperatures and climate variability exacerbate HCKD risks by triggering mechanisms like dehydration, renal ischemia, and increased blood pressure. Using Global Burden of Disease (GBD) 2021 data and predictive models, this study examines trends in HCKD attributable to high and low temperatures. METHOD:This study utilizes GBD 2021 data, focusing on HCKD burden from temperature extremes. Age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years rates (ASDR) were analyzed using descriptive statistics and trend evaluations through estimated annual percentage change (EAPC). Forecasts employed the exponential smoothing (ES) and autoregressive integrated moving average (ARIMA) models. P <0.05 is considered statistically significant, with uncertainty intervals enhancing robustness. RESULT:In 2021, 5,013 (95% UI: -117-12,053) deaths and 117,175 (95% UI: 4,333-270,676) DALYs from HCKD attributable to high temperature were recorded worldwide, with increases in ASMR (EAPC: 3.43) and ASDR (EAPC: 3.18) since 1990. Low temperature caused 22,892 deaths and 420,310 DALYs, with slower ASMR and ASDR growth. Men consistently exhibited higher ASMR and ASDR than women. Mortality and burden peaked in the 95+ age group and varied across SDI regions, with the highest burdens in low-SDI areas. ARIMA and ES models project continued growth in HCKD burden due to temperature, though growth rates may decelerate by 2050. CONCLUSION:Males, the elderly, and people living in LMICs need to be particularly concerned about the threat of HCKD attributed to high and low temperatures.
BACKGROUND:Glaucoma is the leading cause of irreversible blindness worldwide, and chronic kidney disease (CKD) is associated with progression to end-stage renal disease, cardiovascular events, and increased mortality. Although both conditions share common vascular and metabolic risk factors, the long-term relationship between intraocular pressure (IOP) and CKD progression remains unclear. We investigated whether elevated IOP is associated with advanced CKD progression in a long-term observational cohort. METHODS:A total of 4,170 participants who visited a preventive medicine research center were followed for up to 20 years. Progression to an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² was defined as the primary endpoint. Hazard ratios (HRs) were estimated using competing risks regression with cumulative incidence function analyses. Multivariable analysis was performed using the Fine-Gray subdistribution hazard model. Propensity score matching was applied to validate the robustness of the results. RESULTS:Participants with baseline IOP ≥17.5 mmHg had a significantly higher risk than those with IOP <17.5 mmHg (HR 1.49; 95% CI: 1.08-2.05; p = 0.015) in multivariate analysis. The annual decline in eGFR associated with higher baseline IOP was -0.939 mL/min/year, based on ROC-derived risk stratification. Multivariable Fine-Gray analysis identified IOP ≥17.5 mmHg as an independent risk factor for advanced CKD, together with older age, obesity, diabetes, and proteinuria. These findings were consistent in the propensity score-matched cohort (HR 1.56; 95% CI: 1.01-2.39; p = 0.043). CONCLUSION:Elevated intraocular pressure is independently associated with progression to advanced CKD. Incorporating IOP into conventional risk assessment may improve identification of individuals at high risk for CKD progression.
OBJECTIVE:High-altitude hypoxia impairs frontal executive functions. This study examines whether serum creatinine (CR) mediates the relationship between altitude acclimatization (AAI) peripheral oxygen saturation (SpO2)/hematocrit (HCT) ratio and frontal neural oscillations. METHODS:In 190 adults at 3,650 m (Lhasa), we measured SpO2, hematocrit, CR, and resting-state frontal electroencephalography. Power spectral density was calculated across multiple frequency bands (1-80 Hz) and Z-standardized. Mediation analysis with bootstrap tested the indirect effect of AAI on each band via CR. RESULTS:AAI significantly negatively predicted CR (p < 0.001). CR significantly negatively predicted frontal Z-PSD in theta (4-7 Hz), alpha (8-13 Hz), and beta (14-30 Hz) bands (all p < 0.01), but not in other bands. The indirect effect via CR was significant for theta (p = 0.011, partial mediation), alpha (p = 0.031, full mediation), and beta (p = 0.020, full mediation). CONCLUSION:The kidney-brain axis mediates hypoxic neurocognitive adaptation with frequency-specific patterns. CR dynamics reflect acclimatization efficacy, suggesting a target for preserving frontal executive function at high altitude.
