Gianella FG, Prado VE, Poindexter JR, et al. - Given that serum bicarbonate level represents a relatively insensitive marker of acid-base status because of multiple compensating mechanisms, particularly in chronic kidney disease (CKD), and this impairs the ability to diagnose acid excess or monitor alkali therapy, so, it was investigated whether measuring the compensatory defense mechanism(s) would be more logical instead of measuring the defended parameter, which remains normal if the compensation is successful. For this purpose, a retrospective cross-sectional analysis was done with 1,733 stone formers along with a prospective cross-sectional analysis with 22 people with normal kidney function and 50 patients in different stages of CKD. Experts noted that serum bicarbonate was flat and did not reduce below the reference range until near CKD stage 5, but there was a progressive and significant decrease in citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective study, and spot urinary citrate-to-creatinine ratio in the prospective analysis) starting from CKD stage 2. Overall, experts concluded the utility of the urinary citrate-to-creatinine ratio (the defense mechanism) as a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) for evaluating acid-base status and for monitoring alkali therapy.