Relatively larger reductions in interstitial fluid compared with plasma volume, perhaps the result of combined natriuretic and osmotic diuretic effects of SGLT-2 inhibition, may have the potential to significantly improve organ congestion in people with fluid overload with less risk of causing arterial underperfusion or symptomatic dehydration [70], but studies directly measuring changes in interstitial and blood volume in people with CKD and people with HF are needed to test both the mathematical extrapolation and these hypotheses. This evidence concerns the gene SLC5A2 and hydrops fetalis.