Development of hepatorenal syndrome in bile duct ligated rats.
OBJECTIVE
To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology.


METHODS
Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats were placed in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue.


RESULTS
Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including significant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic fibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue.


CONCLUSIONS
Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.
Pereira
Regina M
RM
Departamento de Pediatria, Faculdade de Medicina, Endereco, Avenida Bernardo Monteiro, Minas Gerais 30150-281, Brazil.
dos Santos
Robson A S
RA
Oliveira
Eduardo A
EA
Leite
Virginia H R
VH
Dias
Filipi L C
FL
Rezende
Alysson S
AS
Costa
Lincoln P
LP
Barcelos
Luciola S
LS
Teixeira
Mauro M
MM
Simoes e Silva
Ana Cristina
AC
D000818:Animals; D001652:Bile Ducts / Q000601:surgery*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D006530:Hepatorenal Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006909:Hydroxyproline / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D003404:Creatinine; D006909:Hydroxyproline