New therapeutic approaches to chronic kidney disease

The main research goal in patients with chronic kidney disease (CKD) is the development of new therapeutic approaches capable of slowing down the progression to end-stage renal disease. The aim of this work was to evaluate the effects of long-term administration of chaetomellic acid A (CAA), which selectively blocks H-Ras farnesylation, on chronic kidney lesions in 5/6 nephrectomized Wistar rats, an animal model of chronic renal disease. Materials and Methods: Sixty male Wistar rats were sham-operated (SO) or submitted to 5/6 nephrectomy (RMR). One week after surgery, surviving animals were distributed into four groups: SO–SO rats receiving no treatment (n = 13); SO+CAA–SO rats receiving CAA treatment (n = 13); RMR–RMR rats receiving no treatment (n = 14); RMR+CAA–RMR rats receiving CAA treatment (n = 13). CAA was administered intraperitoneally three times a week for 6 months. Renal fibrosis was evaluated by ultrasonography and histopathological analysis. All experimental procedures followed the European (European Directive 2010/63/EU) and National (Decree-Law 113/2013) legislation on the protection of the animals used for scientific purposes. Results: The kidneys of the RMR animals treated with CAA showed a significant decrease in medullary echogenicity (P <0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (P