Mild hyperhomocysteinemia promotes renal hemodynamic dysfunction without histopathologic changes in adult rats

Ossani, Georgina P.; Fischer, Patricia A.; Caram, Silvia G.; Dominguez, Graciela N.; Monserrat, Alberto J.; Masnatta, Lucas D.
November 2004
Kidney International;Nov2004, Vol. 66 Issue 5, p1866
Academic Journal
Mild hyperhomocysteinemia promotes renal hemodynamic dysfunction without histopathologic changes in adult rats.Background.Hyperhomocysteinemia is able to promote glomerular damage and generate tubulointerstitial lesions. These findings were reported in rats with unilateral nephrectomy or in weanling rats with normal function, two experimental models that are exposed to other concomitant vascular risk factors. The aim of this work is to study whether mild hyperhomocisteinemia per se can induce renal histopathologic changes in adults rats with normal renal function at either 10 or 44 weeks of hyperhomocysteinemia.Methods.Two months old male Wistar rats (N= 52) were randomly allocated to either a normal control (N= 26) or hyperhomocysteinemic (N= 26) group. Control and hyperhomocysteinemic groups had free access to either tap water or homocysteine thiolactone 50 mg/kg/day, during 10 or 44 weeks. Plasma homocysteine levels were determined by a high-performance liquid chromatography (HPLC) method. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were calculated from inulin and sodium para-aminohippurate (PAH) clearance determinations. Structural renal changes were investigated in kidneys fixed by perfusion. Histopathologic and morphometric analysis were carried out by standard methods.Results.Plasma total homocysteine levels were 53% (10 weeks) and 56% (44 weeks) higher in hyperhomocysteinemic group compared to the control group. GFR and RPF were significantly lower in hyperhomocysteinemic than in control group. The histopathologic and morphometric studies did not show any differences between the control and hyperhomocysteinemic rats at 10 or 44 weeks.Conclusion.The present results show that mild hyperhomocysteinemia is able to induce renal functional and biochemical alterations in male adult rats that are not associated with renal histopathologic changes.


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