Calcium Handling by the Mammalian Kidney

The mammalian kidney plays a crucial role in the Ca2+ homeostasis of the body. To maintain a net Ca2+ balance, more than 98% of the filtered load of Ca2+ must be reabsorbed along the nephron. There are two potential pathways through which net Ca2+ reabsorption can occur. First, a paracellular and passive route that predominates in the proximal tubules and thick ascending limb of Henle's loop. Second, a transcellular, active transport that characterises Ca2+ reabsorption in the distal nephron. Transcellular Ca2+ transport involves passive influx across the luminal membrane, diffusion through the cytosol and active extrusion across the peritubular membrane. The rate of active Ca2+ reabsorption is controlled by the calciotropic hormones, i.e. parathyroid hormone, calcitonin and 1,25-dihydroxyvitamin D3. The application of new techniques in renal physiology has greatly increased our knowledge of the renal handling of Ca2+ and allowed the examination of Ca2+ transport processes at the cellular and subcellular level. This review focuses primarily on the mechanisms and regulation of transcellular Ca2+ transport. The distal nephron consists of at least four discrete segments and the contribution of each segment to active transcellular Ca2+ is discussed in detail.