Schematic representation of nephron sites contributing to loop diuretic resistance and the major classes of diuretic drug to correct these. CAIs, carbonic anhydrase inhibitors; CA, carbonic anhydrase; SGLT2i’s, sodium glucose linked transport 2 inhibitors; torsemide ER, torsemide extended release; NKCC2, sodium, potassium, 2 chloride transporter; NCC, sodium, chloride cotransporter; ENaC, epithelial sodium channel; V2 vasopressin type 2 receptor; MRA’s, mineralocorticosteroid receptor antagonists; RNaCl, reabsorption of sodium chloride; PT, proximal tubule; LH, Loop of Henle; DT, distal tubule; CD, collecting duct. Also shown is a summary from studies of patients with diuretic resistant heart failure that apportioned the contribution to diuretic resistance between proximal effects that limited diuretic and sodium delivery to the LH and distal effects of increased RNaCl in the DT and CD. After Rao, V et al, J Am Soc Nephrol 28:3414–3424, 2017, with permission.