Opposing mechanisms in tubuloglomerular feedback
Article Outline
To the Editor:
We read with interest the article by Lorenz et al1 reporting the beneficial effect of early angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) therapy after transplantation. They found that ACE inhibitors and ARBs have induced faster recovery on allograft function, whereas delayed graft function was similar in treatment and control groups. The investigators state that decreased absorption of sodium and fluid due to severe injury of the proximal tubule causes more volume delivery to the distal tubule, which stimulates macula densa cells to release renin. “This mechanism, known as tubuloglomerular feedback, finally increases angiotensin II levels, which reduces the glomerular filtration rate (GFR).” Therefore, ACE inhibitors and ARBs can prevent angiotensin II–induced decreases in GFR.
Recent studies indicate that adenosine appears to mediate tubuloglomerular feedback. Hydrolysis of adenosine triphosphate produces adenosine, which diffuses from the macula densa to the preglomerular arteriole, where it elicits vasoconstriction. Several experimental reports confirmed the adenosine-mediated mechanism and blockade of the adenosine A1 receptor attenuated the decline in glomerular capillary pressure.2, 3 In macula densa, there seem to be 2 opposing events.4 The immediate tubuloglomerular feedback response (seconds) to high salt load of the distal tubule is vasoconstriction and a decrease in GFR, and in minutes, renin secretion decreases secondary to volume overload, which reduces angiotensin II production and increases the filtration rate, thereby assisting the urinary output. Therefore, the reported beneficial effect of ACE inhibitors and ARBs might not be related to the mechanism discussed in the article. These opposing mechanisms could have been mentioned.
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References
- . The effect of ACE inhibitor and angiotensin II blocker therapy on early posttransplant kidney graft function . Am J Kidney Dis . 2004;43:1065–1070
- . Adenosine and purinergic mediators of tubuloglomerular feedback . Curr Opin Nephrol Hypertens . 2002;11:81–86
- . Adenosine formed by 5′-nucleotidase mediates tubuloglomerular feedback . J Clin Invest . 2000;106:289–298
- . Glomerular ultrafiltration . In: Brenner BM editors. The Kidney . (ed 6). Philadelphia, PA: WB Saunders Company; 2000;p. 319–374
PII: S0272-6386(04)00959-X
doi:10.1053/j.ajkd.2004.06.024
© 2004 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved.
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- The effect of ACE inhibitor and angiotensin II blocker therapy on early posttransplant kidney graft function
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