Ask the Experts - Use of Mannitol in Live-Donor Nephrectomy?
Is mannitol known to cause interstitial nephritis, and is there a dose limit for mannitol for renal protection in live-donor nephrectomy?

A. Mohan

To my knowledge there is no evidence that the use of mannitol results in interstitial nephritis. However, other diuretics, such as loop and thiazide diuretics, have been associated, rarely, with the development of an idiosyncratic interstitial nephritis. Interstitial nephritis can be attributed to other causes, including infection (10%); idiopathy (4%); and other drugs, such as antibiotics, analgesics, and NSAIDs (85%). Mannitol has, however, been associated with hydropic changes in the proximal tubular epithelium of kidneys. This usually results in little or no alteration in renal function. Large doses of mannitol may induce a form of hyperosmolar acute tubular necrosis similar to that seen with low-molecular-weight dextran, but this is rare.

The use of mannitol as a protective agent during renal transplantation stems from its ability to increase renal blood flow, thought to be the result of a release of intrarenal vasodilating prostaglandins and/or atrial natriuretic peptide. A second perceived benefit of mannitol is related to its role as an oxygen free-radical scavenger that may impart some protection to the kidney following reperfusion of the renal allograft. Finally, when administered early in the course of acute renal failure (ARF), mannitol tends to flush out cellular debris and prevent tubular cast formation. These actions may convert a patient from oliguric ARF to nonoliguric ARF and thus aid in the management of the patient. However, strong experimental data are lacking. van Valenberg and colleagues reported their experience in a randomized study of hydration with mannitol vs hydration without mannitol in cadaveric renal transplants. Their results demonstrated a significant reduction in postoperative acute tubular necrosis patients treated with mannitol. The commonly used dose for mannitol in renal protection is 250 mL of 20% mannitol. Our current range is 12.5 g to 25 g of mannitol. I am not aware of any study that examines a dose limit.