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Animal models may be helpful to gain insight into the long-term functional outcome of the hydronephrotic kidney. Inbred Brown-Norway rats frequently have kidneys with a delayed urine outflow. In 26 male rats 99mtechnetium-diethylenetriaminepentaacetic acid (Tc-DTPA) furosemide renography was performed to assess the presence and degree of obstruction, and the contribution of each kidney to the total glomerular filtration rate. The total glomerular filtration rate was measured as the plasma clearance of 51chromium-ethylenediaminetetraacetic acid. The measurements were first done at the age of 3 months, and repeated at ages 6, 10 and 15 months. From the renography curve we derived an obstruction score ranging from 0 (minimum) to 10 (maximum) based on the time to peak, the 99mTc-DTPA accumulation at 15 minutes and the furosemide response. Kidneys were classified as normal, obstructed or equivocal. At the first renography 21 kidneys were normal, 8 were equivocal and 23 were obstructed. The total obstruction score of the next 3 renographies indicated that 29 units were normal, 14 were equivocal and 9 were obstructed. Two groups of rats with unilateral hydronephrosis (hydronephrotic kidney-1 and hydronephrotic kidney-2) were selected based on the total obstruction score of all 4 renographies. These groups were compared with rats with 2 normal kidneys. The hydronephrotic kidney-1 rats had an obstruction score indicating equivocal obstruction, while the obstruction score of the hydronephrotic kidney-2 rats indicated obstruction. During the 15 months of followup the presence of a unilateral hydronephrotic kidney with an obstruction score indicating obstruction did not affect the contribution of the hydronephrotic kidney to the total glomerular filtration rate, or the total glomerular filtration rate. We conclude that the obstruction score of a hydronephrotic kidney in rats may change considerably with time. In cases in which renography suggested the permanent presence of ureteral obstruction the glomerular filtration rate remained stable. Thus, renal functional criteria did not indicate obstruction. In Brown-Norway rats a hydronephrotic kidney is able to maintain a normal glomerular filtration rate during at least 50% of the normal lfie span.

In order to obtain more information on the long-term changes in renal function of hydronephrotic kidneys, we have measured the glomerular filtration rate (GFR) in rats with a congenital or an experimental unilateral hydronephrotic kidney (HK). In Brown Norway rats, with congenital hydronephrosis, the presence of an HK affected neither the total GFR nor the contribution of that kidney to the total GFR, during a follow-up of 70 weeks. In Wistar rats with experimental unilateral hydronephrosis two groups could be distinguished on the basis of the contribution of the HK to the total GFR. In the first, the contribution of the HK to the total GFR was not different from that of controls. This contribution as well as the total GFR remained similar to that of controls during the follow-up. In the second group, the contribution of the HK to the total GFR was reduced to 25%. In these rats the total GFR was slightly less than that of controls. The contribution of the HK to the total GFR remained unchanged for the next 56 weeks. It is concluded that the long lasting presence of unilateral hydronephrosis in rats does not necessarily result in a progressive loss of renal function with time.

The renal handling of technetium-99m dimercaptosuccinic acid ([99mTc]DMSA) was studied in rats before and after treatment with Na-maleate (2 mmol/kg i.v.). In the control period, when measured 2 hr after the intravenous injection of [99mTc]DMSA, 39.9% of the injected dose was in the kidneys and 14.6% was in the bladder. After Na-maleate treatment, only 6.4% of the injected dose of [99mTc]DMSA was retained in the kidneys while 37.9% was found in the bladder. Subsequent studies revealed that Na-maleate produced a fall in the glomerular filtration rate, the effective renal plasma flow, and a generalized proximal tubular dysfunction. The latter was characterized by polyuria and an increased excretion of glucose, protein, albumin, calcium, and inorganic phosphate. It was concluded that proximal tubular dysfunction markedly alters the renal handling of [99mTc]DMSA. Whether this augmented urinary excretion is due to an inhibition of reabsorption or an enhanced cellular efflux of [99mTc]DMSA remains to be answered.

The renal handling of technetium-99m dimercaptosuccinic acid (99mTc DMSA) was studied in rats treated with high doses of nonradioactive DMSA to inhibit the renal uptake mechanism(s). A static scan was obtained 1 hour after the intravenous (iv) injection of 99mTc DMSA and the radioactivity in kidneys and bladder was calculated as a percentage of the injected amount. Total glomerular filtration rate (GFR) and effective renal plasma flow were also determined. Preloading with DMSA caused a fall in the renal accumulation of 99mTc DMSA together with a small increase in the amount excreted into the urinary bladder. Despite a stable GFR, the total amount of 99mTc DMSA handled by the kidneys (i.e., renal plus bladder activity) was reduced. These findings are compatible with the hypothesis that peritubular uptake and subsequent intracellular fixation are of importance in the renal accumulation of 99mTc DMSA. On the other hand, the radioactivity excreted into the urine probably stems from non-reabsorbed 99mTc DMSA initially filtered by the glomeruli.

Renal functional adaptation to additional nephrons was studied in rats in which a third kidney was transplanted isogeneically. Total renal function did not increase when an extra kidney was added. Quantitation of the contribution of each kidney, by means of a 99mTc-DTPA scan, showed that the glomerular filtration rate of the native kidneys had decreased to counterbalance the added function. The glomerular filtration rate of the transplanted kidneys as well as its number of glomeruli were 20% less than that of the intact native kidneys. The present findings once again illustrate the kidney's remarkable capacity for functional adaptation to a change in the total number of nephrons.