Pathogenesis of acute renal failure: tubuloglomerular feedback in the HgCl/sub 2/ model

Journal Article · Tue Feb 01 00:00:00 EST 1977 · Am. J. Pathol.; (United States)

OSTI ID:7302882

McDowell, E M; Barnes, J; Sato, T; Flamenbaum, W; Nable, R B; Trump, B F

Despite numerous investigations on humans and animals dating to World War II, the pathogenesis of acute renal failure (ARF) remains obscure. the following hypothesis is being examined: The pathogenesis of ARF is very similar whether ischemic or toxic events are involved. Following initial interactions, usually reversible, involving the proximal tubule, Na/sup +/ resorption is diminished. This results in increased Na/sup +/ at macula densa resulting in feedback to renin-containing afferent arteriole (AA) with renin release, local production of angiotensin, and AA construction with decreased glomerular filtration rate (GFR). ARF was induced in rats by 4 mg/kg HgCl/sub 2/ subcutaneously. Within 15 minutes, changes involving brush border enzymes of pars convoluta (PC) occur, notably marked diminution of alkaline phosphatase. By 6 hours, increased Na/sup +/ excretion and decreased GFR occurs, accompanied by a progressive rise in the juxtaglomerular index which can be correlated with microdeterminations of renin in single dissected glomeruli using radioimmunoassay. Protection with dithiothreitol indicates that while an amelioration of ARF occurs, necrosis of pars recta persists. Some protection against enzymatic changes in PC was observed. The results indicate that following administration of HgCl/sub 2/ in a dose that causes ARF, very early reversible changes occur in PC followed by predicted changes in GFR and renin production. These results are compatible with the stated hypothesis and provide an explanation of why, in humans, tubular necrosis does not correlate with renal failure and indeed necrosis often does not exist at all.

• Research Organization: Univ. of Maryland, Baltimore
• OSTI ID: 7302882
• Journal Information: Am. J. Pathol.; (United States), Vol. 86:2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLOMERULI
KIDNEYS
PATHOLOGICAL CHANGES
MERCURY CHLORIDES
BLOOD
CELL CONSTITUENTS
ENZYMES
METABOLISM
NECROSIS
PATHOGENESIS
RADIOIMMUNOASSAY
RATS
RENIN
SODIUM IONS
TUBULES
VERTEBRATES
ANIMALS
ATOMIC IONS
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CHARGED PARTICLES
CHLORIDES
CHLORINE COMPOUNDS
DISEASES
HALIDES
HALOGEN COMPOUNDS
HYDROLASES
IONS
ISOTOPE APPLICATIONS
MAMMALS
MERCURY COMPOUNDS
MERCURY HALIDES
ORGANS
PEPTIDE HYDROLASES
RADIOASSAY
RODENTS
TRACER TECHNIQUES
550900* - Pathology