Mechanisms of Loop Diuretic Action and Resistance. Panel A, loop diuretics circulate bound to protein. As shown in Panel B, they are secreted into the tubule lumen by organic anion transporters (OAT1 and OAT2) at the basolateral membrane and by multidrug resistance–associated protein 4 (and others) at the apical membrane. As shown in Panel C, diuretics compete with chloride for binding to sodium–potassium–chloride cotransporter 2 (NKCC2), which is also present at the macula densa. Abnormalities at each step can mediate diuretic resistance. #Pathophysiology #Nephro #IM #LoopDiuretic #MechanismOfAction #Resistance #NEJM