The effectiveness of plasma infusion, saline injection, mannitol infusion and combined treatment with mannitol and saline in modifying the development of glycerol-induced hemoglobinuric acute renal failure was studied in the rat. All modes of therapy decreased the severity of azotemia considerably, and combined treatment with mannitol and saline almost totally prevented the development of azotemia. The intrarenal effects of prophylactic treatment on individual nephron function were studied by micropuncture techniques. Function of the best nephrons was comparable in all therapeutic groups, the degree of renal insufficiency in each group being a manifestation of the proportion of those nephrons which had only moderately diminished function. The effectiveness of each agent correlated with the prevention of severe renal ischemia shortly after glycerol injection. Their ability to modify GFR in dehydrated control rats did not correlate well with the degree of protection afforded after glycerol injection. Improvement in extracellular fluid volume was not the prime feature associated with protection from azotemia.

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The effect of unilateral papillectomy on renal function in the rat was compared with the effect of partial nephrectomy which produced a similar decrease in glomerular filtration rate (G.F.R.) in the presence of an intact papilla. Under hydropenic conditions the kidney with papillectomy had a higher urine flow rate, sodium excretion rate, fractional sodium excretion, and osmolar clearance, while urine osmolality was lower. After an acute saline load the differences in sodium and water excretion disappeared, and fractional excretion of sodium and water were significantly higher in both types of kidney damage than in the contralateral control kidney. Free water reabsorption was lower in the papillectomized kidney after saline loading. Thus removal of the papilla resulted in abnormalities in the renal handling of salt and water which varied with the state of hydration of the animal and which were distinct from the effects of a reduction in G.F.R. by partial nephrectomy. It was concluded that the site of nephron loss, whether mainly in the renal medulla or in the cortex, may be another factor, in addition to G.F.R. and tubular reabsorption, which influences sodium and water excretion by the moderately damaged kidney.

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