Kidney ageing: cellular mechanisms involved in renal concentrating ability

The ability to control body hydration is frequently impaired with age. This mainly results from changes in thirst and from loss of renal concentrating ability. The cellular mechanisms responsible for this functional renal fai lure have been extensively studied in different experimental models. Althou gh the loss of nephrons sometimes observed with age impairs the ability of the kidney to retain water, a similar defect was reported in animals free o f glomerulosclerosis, indicating that the reduction in the number of nephro ns was not the only cause. Because age-related polyuria has also been demon strated in rats with unchanged secretion of vasopressin, renal changes in w ater reabsorption was hypothesized Such alterations have been searched alon g the whole length of the nephron. Neither the single nephron filtration ra te nor proximal or early distal flow rates were modified in senescent anima ls where water reabsorption in the collecting duct was reduced. The affinit y and the density of the V-2 receptors were mainly constant in most experim ental models of ageing. In contrast, intracellular cAMP accumulation follow ing vasopressin stimulation was reduced in the oldest animals. The expressi on of aquaporins in luminal and basolateral membranes of the collecting duc t epithelial cells was altered. The amount of basolateral aquaporin 3 and 4 was respectively decreased by 50 per cent and unchanged in renal papilla. Tn addition, the expression of aquaporin 2, which is rate limiting for the osmotic permeability of the collecting duct, was reduced by 50 per cent in the outer medulla and by SO per cent in the inner medulla of the senescent animals. This drop in aquaporin 2 expression in the distal Dart of the neph ron could be the main cause for the fall in concentrating ability of the ki dney and the age related impaired control of hydration.