Heat stroke (HS) is the most severe heat-related emergency, and its pathophysiology remains largely unknown, especially for exertional HS (EHS), which affects younger populations, athletes, and manual workers. Herein, we performed single-cell-transcriptomics, T cell receptor sequencing, and flow cytometry of PBMCs from 9 healthy control participants, 9 patients with heat exhaustion, and 9 patients with EHS to explore complex immunological responses associated with HS pathobiology. We showcased that granzyme-positive T cells and CD56 ^dim NK cells with high cytotoxicity features and IL-1B ⁺ NLRP3 ⁺ monocytes with high inflammation and pyroptosis scores were enriched in HS, while the CD161 ⁺ T cells with innate immune-like, low cytotoxicity, and clonal expansion features were reduced in HS. Importantly, elevated granzyme-positive T and NK cells might interact with monocytes to induce pyroptosis of hepatic and renal cells and target organ injuries, and blocking the NLRP3 inflammasome pathway prior to the induction could alleviate organ injury in HS. This study offers deeper insights into the pathogenesis of HS, supporting the development of optimal treatment strategies.

This study investigated the impact of 24-h urinary calcium excretion (UCaE) on renal function decline in hospitalized patients with and without chronic kidney disease (CKD). This study enrolled 3815 CKD patients in stages 1–4 and 1133 non-CKD patients admitted to the First Center of the Chinese PLA General Hospital between January 2014 and July 2022. The primary outcome for CKD patients was a composite of CKD progression, defined as a 40% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease. Annual eGFR change was the secondary outcome. For non-CKD patients, the primary outcome was an eGFR decline of ≥20% or CKD incidence, while annual eGFR change was the secondary outcome. The association between UCaE and kidney function decline was assessed using Cox proportional hazards and generalized linear models. Primary outcomes were observed in 813 CKD patients and 109 non-CKD patients over a median follow-up of 3.0 and 4.1 years, respectively. For CKD patients, every 1-mmol/d increase in UCaE was associated with a 15% decreased risk of CKD progression. The hazard ratio (HR) was 0.85, with a 95% confidence interval (CI) of 0.77–0.93. For non-CKD patients, the risk of renal function decline decreased by 11%. The multivariate models indicated that there was an annual decrease in eGFR in both CKD and non-CKD patients, with a reduction of 0.122 mL/min/1.73 m²/year (p < 0.001) and 0.046 mL/min/1.73 m²/year (p = 0.004), respectively, for every 1-mmol/d increase in UCaE. CKD experiences a decrease in 24-h UCaE as early as stage 1, with a significant decline in stage 4. CKD and non-CKD patients with lower UCaE levels are at an increased risk of renal decline, regardless of other variables.