The Role of the Concentration Mechanism in the Development of Acute Renal Failure: Micropuncture Studies Using Diabetes Insipidus Rats

Abstract

The role of the concentrating mechanism in the potentiation of acute renal failure by dehydration has been studied using rats with complete diabetes insipidus. These rats were shown to be continually dehydrated even when allowed free access to water. Despite massive volumes of highly dilute urine at the time that hemoglobinuria was induced by glycerol injection, these animals developed acute renal insufficiency whose severity was intermediate between that of non-dehydrated and severely dehydrated normal rats treated similarly. Micropuncture experiments showed the appearance of the kidney in vivo and the functional abnormalities of the three types of rats to be qualitatively identical. It appears that dehydration’s effect on hemoglobinuric acute renal failure is independent of the concentrating mechanism and correlates well with plasma volume depletion. It is suggested that factors other than ADH titre, high urine concentration and low flow rate are the prime determinants of the effect of dehydration on hemoglobinuric acute renal failure in the rat.

Glomerular hemodynamics in established glycerol-induced acute renal failure in the rat.

“…The kidneys of these animals showed essentially the same changes found earlier in rats whose fluid deficit had not been systematically restored (e.g., 5,[16][17][18]. Two populations of nephrons existed side by side, one fluid-filled and the other totally collapsed.…”

“…Renal failure thus reflected both the number of totally nonfunctioning nephrons and the degree to which filtration was impaired in the remainder. The finding of one superficial nephron that is filtering briskly surrounded by others that form virtually no filtrate, noted previously in this form of ARF (5,(16)(17)(18)(19), suggests a local basis for filtration failure.…”

“…A new and extremely potent adenosine receptor blocker, BW A 1433U, did appear to totally protect glomerular filtration in initial experiments (37) (38), but biologically effective active or passive immunization against renin (39) and angiotensin (40), and treatment with angiotensin-converting enzyme (unpublished data) have all been of no discernible value. This form of renal failure is not mitigated in Brattleboro rats with complete central diabetes insipidus (41), making the antidiuretic hor-. mone an unlikely suspect.…”

“…As in the human syndrome, this ARF model yields near total renal failure (5,(16)(17)(18) from which the rats recover spontaneously after some 5-7 d (19). The pathogenetic features and natural history of this model have been well characterized in previous studies (e.g., 5,[16][17][18][19], but the mechanisms immediately responsible for the apparent filtration deficit thus far have not been examined. The present report describes the glomerular dynamic abnormalities responsible for failed filtration in this murine ARF model.…”

Micropuncture studies of the recovery phase of myohemoglobinuric acute renal failure in the rat

“…Previous micropuncture studies of the development stage and of the period of sustained renal insufficiency in glycerol induced myohemoglobinuric renal failure in the rat have shown almost complete cessation of glomerular filtration (1)(2)(3). Because of this, the majority of surface nephrons were collapsed and, although there was no evidence for passive backflow of filtrate, the tubular epithelial integrity of the most severely affected nephrons could not be assessed directly.…”