SUBTOTAL NEPHRECTOMY ALTERS TUBULAR FUNCTION - EFFECT OF PHOSPHORUS RESTRICTION

Few studies have examined tubular function after subtotal nephrectomy (Nx) and conservative treatments. The effects of 70% and 80% Nx (assoc iated with dietary phosphate restriction in the latter case) on the ap ical brush border membrane (BBM) enzymes 5'-nucleotidase, gamma glutam yl-transferase and alkaline-phosphalase, and one BBM Na-phosphate cotr ansporter (NaPi-2) were studied in rats after a six week period. Chang es in activity and mRNA abundance of the BBM enzymes and in NaPi-2 pro tein and mRNA abundance were compared with changes in the distal marke rs of Na,K-ATPase activity and epidermal growth factor (EGF) productio n. The activity, but not the mRNA of BBM enzymes, was moderately reduc ed by the 70% Nx. Both the mRNA and activity of gamma glutamyl-transfe rase and alkaline-phosphatase were decreased in the 80% Nx, and the Na Pi-2 mRNA, protein and Na,K-ATPase activities were also reduced. These effects (except for 5'nucleotidase and Na,K-ATPase) were partly rever sed by phosphate restriction. Overproduction of EGF occurred after the 70% Nx, was blunted in the 80% Nx, and then partially restored by pho sphate restriction. Aggravation of tubular alteration was associated w ith enhanced renal hyperplasia (increased DNA mass), reduced GFR and h yperphosphatemia, and high PTH levels, but reduced cAMP excretion. Imp rovement following phosphate restriction was associated with reduced h yperplasia and lowering of phosphatemia and PTH levels. These data dem onstrate that Nx selectively affected BBM function through transcripti onal changes that were partially reversed by phosphate restriction. Re gulatory factors involved in these changes may include intracellular p hosphate content and growth factors, but not the PTH effects that are impaired in chronic renal failure.