title: Differential gender differences in ischemic and nephrotoxic acute renal failure.
abstract: OBJECTIVE
  Recent work has shown that female animals are more resistant to ischemic acute renal failure (ARF) than male animals. The mechanism underlying the gender difference is unclear. Moreover, whether the gender difference holds true for ARF induced by other insults is unknown. This study sought to determine the gender differences in ischemic and nephrotoxic ARF.
  
  
  METHODS
  Gender differences were tested in two experimental models of ARF. For ischemic ARF, bilateral clamping of renal pedicles was conducted in C57BL/6 and 129/Sv mice followed by reperfusion. For nephrotoxic ARF, cisplatin was administered to the animals. Renal function, tissue damage, animal survival, and renal cell apoptosis were examined.
  
  
  RESULTS
  Ischemic ARF was significantly ameliorated in female mice, as shown by lower serum creatinine and blood urea nitrogen (BUN). Female mice also showed better renal histology, less apoptosis and caspase activation, and a much better survival rate than male mice following ischemic insult. On the contrary, female mice were more sensitive to cisplatin-induced ARF. In these animals, BUN increased at day 1 following cisplatin injection, while in males BUN increases were not shown until day 3. Higher levels of serum creatinine were also recorded in female mice. Renal histology showed severer necrotic tubular damage in females, although apoptosis and caspase activation appeared similar in both genders. Consistently, male mice survived better than females in the nephrotoxic model.
  
  
  CONCLUSIONS
  While female mice were resistant to ischemic ARF, they appeared more sensitive to cisplatin-induced ARF. Investigation of the gender differences at the cellular and molecular levels might provide a new area for mechanistic study of ARF.
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wei
authors.forename: Mong-Heng
authors.initials: MH
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D002945:Cisplatin; D005260:Female; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015427:Reperfusion Injury / Q000401:mortality; D012727:Sex Characteristics; D016019:Survival Analysis
chemical_list: D002945:Cisplatin