Polycystin-1 dysfunction impairs electrolyte and water handling in a renal precystic mouse model for ADPKD

The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp-Pkd1-/-) mice manifesting a pre-cystic phenotype. Serum and urinary electrolyte determinations indicated that iKsp-Pkd1-/- mice display reduced serum levels of magnesium (Mg2+), calcium (Ca2+), sodium (Na+) and phosphate (Pi) compared with control (Pkd1+/+) mice; and renal Mg2+, Ca2+ and Pi wasting. In agreement with these electrolyte disturbances, downregulation of key genes for electrolyte reabsorption in the thick ascending limb of Henle's loop (TAL, Cldn16, Kcnj1 and Slc12a1), distal convoluted tubule (DCT, Trpm6 and Slc12a...