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

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2004-10, Vol.19 (10), p.2464-2471
• Main Authors: Perez, Alejandro, Ramirez-Ramos, Marisela, Calleja, Consuelo, Martin, Dolores, Namorado, Maria C., Sierra, Gerardo, Ramirez-Ramos, María E., Paniagua, Ramon, Sánchez, Yadira, Arreola, Laura, Reyes, Jose L.
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - pathology; Acute Kidney Injury - physiopathology; Acute Kidney Injury - urine; acute renal failure; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Creatinine - metabolism; creatinine clearance; Diuresis - drug effects; Drug Combinations; Drug Synergism; Emergency and intensive care: renal failure. Dialysis management; Female; FeNa; Intensive care medicine; Lipid Peroxidation - drug effects; Medical sciences; Natriuresis - drug effects; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Potassium Dichromate; potassium dichronate; Rats; Rats, Wistar; Renal failure; retinoic acid; Severity of Illness Index; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Thyroxine - pharmacology; Tretinoin - pharmacology; Weight Loss - drug effects
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh400

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.