Sex differences in renal acid–base regulation

PURPOSE OF REVIEW: Sex-dependent differences are evident in most organs and contribute to variability in physiological function and disease susceptibility, which can consequently affect therapeutic responses. The kidney is no exception to this finding and recent data suggest that sexual dimorphism exists in the regulation of acid-base homeostasis. RECENT FINDINGS: While proteins involved in the renal regulation of acid-base homeostasis have been characterized over several decades, researchers have only recently begun investigating how biological sex affects these processes. Although males and females handle acid-base challenges similarly in many respects, there are critical, sex-specific differences in how several key kidney proteins respond to these challenges. This review highlights those distinct differences, focusing specifically on proteins including: NHE3, NBC1, NKCC2, pT58 NCC, Rhbg, Rhcg, H+-ATPase, and Na+/K+-ATPase. SUMMARY: Acid-base imbalances are among the most common and critical challenges in clinical medicine. Recent data reveal that female mice defend against systemic acid-base disruptions far more effectively than males, a resilience driven by distinct, sex-specific transport adaptations along the nephron. These findings underscore a critical gap in current care and the need for sex-specific therapeutic strategies in the clinical management of human acidosis and alkalosis.