Comparative study on the effects of cyclosporin a in renal cells in culture.

BACKGROUND: Although cyclosporin A (CSA) inhibits P-glycoprotein (ABCB1), the relationship between this inhibition and CSA-induced nephrotoxicity is not established. METHODS: Three renal cell lines were used to investigate the effects of CSA in cellular viability and accumulation of rhodamine 123 (Rho123): LLC-PK1, which does not express ABCB1 substantially; MDCK, expressing moderate amounts of this protein, and Ma104 cells, which express high amounts of ABCB1. RESULTS: The viability was significantly reduced in the three cell lines after treatment with CSA concentrations >10 microM. Ma104 was the more resistant and LLC-PK1 the more sensitive. CSA increased Rho123 accumulation in the three cell lines when incubated simultaneously, MDCK presenting the higher increase. However, different results were achieved when the periods of incubation with Rho123 and CSA were disconnected: a post-incubation with CSA was more effective in Ma104 cells, while MDCK and LLC-PK1 showed no difference between pre-, co- and post-incubation with CSA. CONCLUSIONS: Our results suggest that the effects of CSA may be divided into two groups: ABCB1-independent (direct injury), and ABCB1-dependent toxicity, due to modulation of its activity. This could result in increased accumulation of noxious ABCB1 substrates, contributing to CSA-induced nephrotoxicity. Furthermore, the mechanisms of ABCB1 modulation by CSA may be different for different cell lines.

Normal renal dimensions in a specific population.

INTRODUCTION: Renal dimensions (RD) are important for the diagnostic and the prognostic of nephropathies. MATERIALS AND METHODS: We selected 904 Brazilians subjects with normal excretory urographies, showing dense nephrogram at the 5th minute of the exam, serum creatinine < 1.3mg/dl, and absence of any disease that could modify RD. Length, width, and area of both kidneys were correlated with gender, age, height, and body weight. Five hundred and eighty one subjects were men (64.3%) and 323 were women (35.7%). Age ranged from 21 to 87 years old, body weight from 40 to 106kg (69.9+/-9.5 for men and 62.4+/-9.7 for women), and height from 1.37 to 1.94m (1.68+/-0.07 for men and 1.57+/-0.07 for women). RESULTS: There was an association (one-way Anova test) between length, width, and area, for each kidney and for both, with height (p<0.001), body weight (p<0.001), and gender (p<0.001). After adjustment for height (covariance analysis), both gender and body weight did not show influence on RD. Renal length and area reduced with aging (p<0.001), from the 7th decade compared to the others. Excluding these patients, height was the only variable to show association with RD, justifying data stratification by this variable. CONCLUSIONS: Renal length in this population showed that the normal patterns defined by other studies are inadequate for our population. Adjusting the data by height, gender, and body weight did not influence RD; however, the left kidney was bigger than the right kidney. Also, the influence of height was more pronounced below 1.66m.