1. To clarify why diuretic therapy raises plasma urea in patients with chronic renal failure, three groups of uraemic subjects were treated with frusemide for 6 days. 2. In group 1 ( n = 9), frusemide significantly decreased body weight and increased average plasma urea from 18.7 mmol/l to 28.8 mmol/l ( P <0.001). this rise in plasma urea was secondary to reduced urea excretion, which occurred in spite of an increase in urea filtration. 3. In group 2 ( n = 7), frusemide was associated with salt replacement, in order to prevent salt depletion; in these patients neither reduction in urea excretion nor increase in plasma urea occurred. 4. In group 3 ( n = 10), the marked diuretic-induced fall in urea clearance was found to be independent of enhanced proximal tubular re-absorption (measured in water diuresis). 5. These results show that the rise in plasma urea is due to increased tubular reabsorption of urea, presumably in the distal part of the nephron, secondary to extracellular fluid (ECF) volume depletion.

1. Urinary kallikrein, renal tissue kininogenase activity, and plasma kininogen were measured during the development of hypertension in rats, either with left renal artery clamped and contralateral kidney intact (Goldblatt 2-kidney) or removed (Goldblatt 1-kidney). Plasma urea, plasma volume and blood volume were also measured. 2. In Goldblatt 2-kidney rats, urinary kallikrein was not significantly different from that of sham-operated rats up to the 5th post-operative week even though at this time the Goldblatt 2-kidney animals were hypertensive. Urinary kallikrein started to decrease at week 8. Plasma kininogen was significantly elevated 5 and 10 weeks after surgery and returned to normal by week 15. No changes in renal tissue kininogenase activity were observed. Plasma urea and plasma and blood volumes were normal 5 weeks after, but significantly increased at 10 and 15 weeks after surgery. 3. In Goldblatt 1-kidney rats from the fifth week urinary kallikrein and renal kininogenase activity were significantly decreased compared with unilaterally nephrectomized rats, whereas plasma kininogen, plasma urea and plasma and blood volumes were significantly elevated. 4. These results show important differences in the kallikrein system between the Goldblatt 1-kidney and 2-kidney models of renovascular hypertension in rats.

1. The response to 60 min ischaemia was studied in male uninephrectomized 30-, 60-and 90-day-old rats in regard to changes of renal cytochrome oxidase activity and the effect on systemic arterial blood pressure. Mortality due to renal failure, changes in plasma urea concentration and in kidney morphology were used as indicators of the renal response. 2. Mortality was lowest in 30-day-old animals (13%) and highest in 60-day-old animals (77%). Renal cytochrome oxidase activity increased by 44% during the same period. The mortality decreased to 34% between the ages of 60 and 90 days without change in renal content of cytochrome oxidase; survival time after renal ischaemia was prolonged from 2 to 4 days. 3. Fifty days after renal ischaemia plasma urea concentration correlated positively with kidney weight. Both variables were increased in rats exposed to ischaemia at the ages of 60 and 90 days. The kidneys of these rats exhibited lesions. No relation was found between the degree of renal damage and blood pressure. 4. It is concluded that (a) the kidney of immature rats is more resistant to temporary ischaemia due to immaturity of renal oxidative metabolism, (b) the ability to survive ischaemic renal damage in less-resistant mature rats increases with age and (c) the postischaemic impairment of renal function does not influence systemic arterial blood pressure.