in the acetazolamide-treated mice with lithium-induced NDI. de Groot et al. 3 also found that acetazolamide treatment of mice with lithium-induced NDI reduces inulin clearance, reduces the cortical expression of the sodium/hydrogen exchanger 3, and reduces the increase in urinary prostaglandin E 2 observed in mice with lithium-induced NDI.de Groot et al. 3 concluded that the reduction in polyuria after acetazolamide treatment was partially caused by a tubular-glomerular feedback response and reduced GFR. In addition, de Groot et al. 3 concluded that the tubular-glomerular feedback response and/or a direct effect on collecting duct principal or intercalated cells may be responsible for the reduction in urinary prostaglandin E 2 levels in mice with lithium-induced NDI and treated with acetazolamide and that this contributes to the amelioration of the lithium-induced NDI. Thus, de Groot et al. 3 made the novel observation that acetazolamide, by inhibiting CA, attenuates lithium-induced NDI in mice similar to thiazide/amiloride but with fewer adverse side effects. This study establishes the basis for a future clinical trial to determine if acetazolamide would be effective in treating people with lithium-induced NDI with equal efficacy but fewer side effects than thiazide/amiloride.Together, these two papers in JASN provide important and novel insight into the pathogenesis and potential therapy for NDI. They also emphasize the importance of fundamental research in renal physiology for providing novel insights that can serve as the inspiration and foundation of future translational or clinical studies to advance the treatment of NDI specifically and renal disease in general.