Endotoxaemia differentially regulates the expression of renal Ca2+ transport proteins in mice

AbstractAimAlterations in parathyroid hormone (PTH) and/or vitamin D signalling are frequently reported in patients with sepsis. The consequences on renal and intestinal Ca2+ and Pi regulatory mechanisms are still unclear. We hypothesized that endotoxaemia alters the expression of important renal and intestinal Ca2+ and Pi transport proteins.MethodsMale C57BL/6 mice were treated with lipopolysaccharide (LPS; 3 mg/kg; i.p.). The mRNA and protein levels of renal and intestinal Ca2+ and Pi transport proteins were measured by RT‐qPCR, immunohistochemistry and western blot analysis.ResultsLipopolysaccharide‐induced hypocalcaemia and hyperphosphataemia was paralleled by a decrease in glomerular filtration rate and urinary excretion of Ca2+ and Pi. Endotoxaemia augmented plasma levels of PTH and affected the fibroblast growth factor 23 (FGF23)‐klotho‐vitamin D axis by increasing plasma levels of FGF23 and downregulation of renal klotho expression. Renal expression of CYP27b1 and plasma levels of 1,25‐dihydroxyvitamin D3 were increased in response to LPS. Endotoxaemia augmented the renal expression of TRPV5, TRPV6 and PiT1, whereas the renal expression of calbindin‐D28K, NCX1, NaPi‐2a and NaPi‐2c were decreased. Incubation of primary distal tubule cells with LPS increased TRPV6 mRNA levels. Furthermore, LPS decreased the intestinal expression of TRPV6, calbindin‐D9K and of NaPi‐2b.ConclusionOur findings indicate that endotoxaemia is associated with hypocalcaemia and hyperphosphataemia and a disturbed FGF23‐klotho‐vitamin D signaling. Further, LPS‐induced acute kidney injury was accompanied by an increased or decreased expression of specific renal and intestinal Ca2+ and Pi transporters respectively. It seems unlikely that LPS‐induced hypocalcaemia is due to renal loss of Ca2+.