Comment on "Association of peripheral NLRP3 inflammasome activation with prevalent and incident chronic kidney disease in patients with obstructive sleep apnea: a prospective study".

This correspondence comments on the study by Cai et al. examining circulating NLRP3 and prevalent and incident chronic kidney disease (CKD) in patients with obstructive sleep apnea (OSA). The inclusion of 648 participants, complementary cross-sectional and prospective analyses, and evaluation of estimated glomerular filtration rate (eGFR) and albuminuria are important strengths. Nevertheless, several methodological considerations affect interpretation. Prevalent CKD appears to have been classified using baseline eGFR or urinary albumin-to-creatinine ratio without consistent confirmation of chronicity. A single baseline NLRP3 measurement may not reflect long-term biological activity, while adjusted associations do not establish improved prediction beyond established risk factors. The possible causal roles of OSA severity, nocturnal hypoxemia, and inflammatory markers also merit explicit consideration. Building on these findings, future multicenter studies should confirm CKD with repeat renal measurements, assess serial NLRP3 reproducibility, prespecify causally informed models, and compare clinical prediction models with and without NLRP3 using discrimination, calibration, validation, and decision-curve analysis. These steps would help determine whether circulating NLRP3 offers meaningful incremental value for renal risk stratification in OSA.