Xanthopterin-Induced Renal Dysfunction: A Reversible Model of Crystal Nephropathy
| Title: | Xanthopterin-Induced Renal Dysfunction: A Reversible Model of Crystal Nephropathy |
|---|---|
| Authors: | Garber, PhD, Sandra L.; Salmassi, MD, Jafar; Arruda, Jose A.L.; Dunea, George |
| Publisher: | Nephron |
| Date Published: | January 01, 1995 |
| Reference Number: | 81 |
Xanthopterin (XPT), an unconjugated pteridine compound, affects cell growth and differentiation. When injected into rats, XPT has caused changes that have been interpreted as renal growth and hypertrophy. In the present study, we investigated the effect of intraperitoneal administration of XPT on the renal function in the rat. XPT administration was associated with polyuria and a reversible form of nonoliguric acute renal failure (ARF), with renal function declining maximally after 2 days and returning to normal after 7 days. The polyuria was due, at least in part, to a concentrating defect that was vasopressin resistant. The ability of XPT to induce ARF was modulated by dietary salt intake, being enhanced by a low-sodium diet and prevented by a high sodium intake. Histologicalexamination of the kidneys showed intratubular crystal deposition and acute tubule necrosis, suggesting that XPT induces crystal nephropathy. There was an increase in wet and dry weights of the kidney and an increasedDNA/protein ratio, compatible with a hyperplastic response. Because the severity of other crystal nephropathies may be modulated by urine flow rate and pH, we studied the ability of water diuresis or alkaline diuresis to protect against XPT-induced ARF. Both water diuresis and HCO3 loading blunted the ability of XPT to decrease renal function. The change in renal function induced by XPT in the various groups was paralleled by corresponding changes in the levels of XPT-like substances in the kidney and by the amount of crystal deposition. Thus, XPT injection induces crystal nephropathy, the severity of which can be modulated by dietary salt intake, urine pH, and urine flow rate.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
XPT-induced kidney failure is made worse when accompanied by a low-sodium diet and it is prevented by a high-sodium diet. Its effects can also be modified by increasing the urine flow and making the urine more alkaline. Examination of kidney tissue showed XPT caused crystals to be deposited in the kidneys. This was considered a possible cause for the accompanying finding of severekidney tissue cell death. XPT increased kidney size and it increased kidney weight by causing the kidney to retain water. Use of XPT offers researchers a reproducible, easily induced and reversible model of acute kidney failure due to tissue death through deposition of crystals.