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NDT Advance Access originally published online on August 17, 2004
Nephrology Dialysis Transplantation 2004 19(10):2464-2471; doi:10.1093/ndt/gfh400
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Nephrol Dial Transplant Vol. 19 No. 10 © ERA-EDTA 2004; all rights reserved

Original Article

Beneficial effect of retinoic acid on the outcome of experimental acute renal failure

Alejandro Perez1, Marisela Ramirez-Ramos1, Consuelo Calleja1, Dolores Martin2, Maria C. Namorado2, Gerardo Sierra2, María E. Ramirez-Ramos1, Ramon Paniagua1, Yadira Sánchez2, Laura Arreola2 and Jose L. Reyes2

1 Departments of Nephrology and Pathology, Centro Medico La Raza, Instituto Mexicano del Seguro Social and 2 Physiology and Biophysics Department, Centro de Investigacion y de Estudios Avanzados, Mexico City, Mexico

Correspondence and reprint requests to: Jose L. Reyes, MD, PhD, Department of Physiology and Biophysics, Centro de Investigación y de Estudios Avanzados, Ave. Instituto Politecnico Nacional 2508, México, D.F. 07360. Email: jreyes{at}fisio.cinvestav.mx

Background. Retinoic acid (RA) exerts beneficial effects on vascular remodelling and experimental nephritis, and plays a role in kidney development. Pathological changes caused by acute renal failure (ARF) result in high mortality. We determined whether RA ameliorates ARF-induced pathology caused by potassium dichromate (PD).

Methods. Adult Wistar female rats (210–250 g) were randomly allocated to four groups: (i) an ARF group that received PD [15 mg/kg body weight (bw), single dose subcutaneously]; (ii) a group that received PD plus RA (1 mg/kg bw) beginning at 5 days before PD and that continued for 14 additional days; (iii) a group that received PD plus thyroxine (T4; 8 µg/100 g bw) with RA; and (iv) a group that received only the vehicle for PD (saline solution). We evaluated functional, biochemical and morphological characteristics of the kidneys.

Results. PD-induced alterations in serum creatinine, creatinine clearance (Ccr) and fractional excretion of sodium (FeNa) were less severe when rats received RA. PD increased lipoperoxidation and this alteration was partially blocked by RA. Animals undergoing ARF showed severe histological injury (brush border loss, acidophilia, oedema, pyknosis, karyorhexis, cell detachment and disruption of the basement membrane). These alterations were less severe in RA-treated rats, indicating a protective effect on functional and morphological alterations. Alterations in urinary sediment were reduced by RA. The simultaneous administration of T4 with RA did not produce additional protection.

Conclusion. RA exerted beneficial effects on the duration and severity of renal damage induced by PD in a model of renal failure resembling ARF in humans. The protective effect of RA may be mediated by diminished lipoperoxidative damage.

Keywords: acute renal failure; creatinine clearance; FeNa; potassium dichronate; retinoic acid; T4


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