Renal function and (NA+ + K+)-ATPase in chronic unilateral hydronephrosis in dogs

Recovery of various parameters of kidney function after varying periods of complete unilateral ureteral obstruction was studied in dogs under hydropenic conditions. Changes of PAH and inulin clearance appeared to be parallel. After one week of obstruction, renal clearances of PAH and inulin were decreased to seven per cent of values measured before the obstruction period, after two weeks to four per cent and after three or four weeks to two per cent. Within 10 to 28 days after release of obstruction by cutaneous ureterostomy, PAH and inulin clearance increased to 66 per cent after one week, to 50 per cent after two weeks, to 10 per cent after three weeks with no change after four weeks of obstruction. Na+ content in the hydronephrotic kidney differed from contralateral kidneys only in the inner medulla. The affinity for ouabain (dissociation constant, KD, normal = 3.85 X 10(-9) M; hydronephrotic = 3.05 X 10(-9) M; contralateral = 7.05 X 10(-9) M) was significantly higher only in the outer medulla of contralateral kidneys. Turnover number (normal = 3.6; hydronephrotic = 5.1; contralateral = 3.4 X 10(3) min.-1) in hydronephrotic or contralateral outer medulla was not significantly different from normal. Changes in kinetic constants (association rate constant, k+1, normal = 4.49 X 10(4) M-1 sec.-1; hydronephrotic = 4.13 X 10(4) M-1 sec.-1; contralateral = 5.97 X 10(4) M-1 sec.-1; dissociation rate constant, k-1, normal = 1.03 X 10(-4) sec.-1; hydronephrotic = 1.29 X 10(-4)sec.-1; contralateral = 1.39 X 10(-4) sec.-1) were considered to be too small to be relevant. Similar changes of KD, k+1 and k-1 were observed in the renal cortex. The osmotic concentrating capacity correlated well with (Na+ + K+)-ATPase activity (r = 0.85) and number of 3H-ouabain binding sites (r = 0.89) in renal outer medulla. The results indicate that recovery of osmotic concentrating capacity depends on the length of obstruction, and that a reduction of (Na+ + K+)-ATPase molecules in the thick ascending limb of the loop of Henle is a primary factor in the decrease in the concentrating capacity of chronic unilateral hydronephrotic kidneys.