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Elevation of intrarenal adenosine by maleic acid decreases GFR and renin release | JoVE Visualize

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Elevation of intrarenal adenosine by maleic acid decreases GFR and renin release

L J Arend, C I Thompson, M A Brandt

Kidney International|November 1, 1986

View abstract on PubMed

Summary

Maleic acid impairs kidney function, causing tubular reabsorption defects and reduced glomerular filtration rate (GFR). Elevated adenosine levels appear to mediate these harmful effects, particularly in sodium-depleted states.

Area of Science:

Nephrology
Renal Physiology
Biochemistry

Background:

Maleic acid induces Fanconi-like syndrome and decreases glomerular filtration rate (GFR).
The underlying mechanism involves altered nucleotide metabolism and decreased ATP levels.
Endogenous adenosine's role in maleic acid-induced renal dysfunction is unclear.

Purpose of the Study:

To investigate the role of elevated endogenous adenosine in mediating maleic acid's renal effects.
To compare the impact of maleic acid on renal function in sodium-depleted versus sodium-loaded dogs.
To assess the effect of the adenosine antagonist theophylline.

Main Methods:

Compared renal function in sodium-depleted and sodium-loaded dogs receiving maleic acid.
Measured renal venous plasma adenosine levels and urinary adenosine excretion.
Administered theophylline to evaluate its effect on maleic acid-induced changes.

Main Results:

Maleic acid significantly decreased GFR more in sodium-depleted dogs (55%) than sodium-loaded dogs (39%).
Renin release was significantly depressed in sodium-depleted dogs.
Renal venous adenosine concentration and urinary adenosine excretion increased significantly during maleic acid infusion.

Conclusions:

Elevated endogenous adenosine likely mediates maleic acid-induced renal dysfunction.
Sodium balance influences the severity of maleic acid's effects on GFR.
Adenosine antagonism may offer a therapeutic target for maleic acid nephrotoxicity.

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Elevation Of Intrarenal Adenosine By Maleic Acid Decreases Gfr And Renin Release