Loop diuretic resistance (DR) is a major challenge in acute heart failure (HF) hindering adequate decongestion. DR is partly driven by distal convoluted tubule (DCT) remodelling and enhanced sodium reabsorption mediated by the thiazide-sensitive Na–Cl cotransporter (NCC) [1,2]. While sodium and calcium present net reabsorption in the DCT physiologically, a dissociation is observed in genetic tubulopathies affecting this segment: increased natriuresis and hypocalciuria in Gitelman syndrome (NCC loss of function) versus decreased natriuresis and hypercalciuria in Gordon syndrome (NCC hyperactivation).
