The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin.

Abstract

A B S T R A C T The role of high serum and tissue levels of unconjugated bilirubin in the pathogenesis of the impaired urinary concentrating ability was investigated in homozygous (fi) Gunn rats with the congenital absence of hepatic glucuronyl transferase. Continuous phototherapy with blue fluorescent lights at a wave length of 460 nm or oral cholestyramine feeding or both reduced serum levels of unconjugated bilirubin to levels consistently below 3.0 mg/100 ml for several weeks in both weanling and adult fi Gunn rats. The renal concentrating defect was already present in weanling jj Gunn rats by 21 days of age. In treated weanling jj animals, maximum concentrating ability and the concentration of urea and nonurea solutes in the papilla and medulla, determined after 24 h of fluid deprivation, were normal when compared to unaffected heterozygous (Jj) littermates. Solute-free water reabsorption which is reduced in jaundiced fi Gunn rats was restored to normal in treated weanling ji rats. The tissue concentration of unconjugated bilirubin was reduced throughout the papilla and inner and outer medulla in the treated jj rats in comparison with untreated jj littermates. The defect in urinary concentrating ability was only partially reversible and sometimes irreversible in adult ji rats, probably because of permanent renal parenchymal damage occurring secondary to massive crystalline deposits in the papilla and medulla.

Combined Treatment Strategies for Unconjugated Hyperbilirubinemia in Gunn Rats

“…Addition of PEG to phototherapy, orlistat, UDCA, or CaP did not affect plasma levels of urea, compared with controls, which pleaded against clinically relevant dehydration during PEG cotreatment. PEG ϩ orlistat treatment resulted in a mild increase in plasma Creat levels compared with the control group, although still within the reference range for Gunn rats (28). UDCA ϩ PEG-treated animals showed a 5% decrease in growth rate during the entire experiment, compared with a 2.5% increase in control animals (p Ͻ 0.01; Table 1).…”

Influence of distal ileum exclusion on hepatic and renal functions in presence of extrahepatic cholestasis

“…Functional changes of the kidney are linked to etiological agents or hemodynamic changes, characteristic of chronic liver disease, in which there is peripheral vasodilation, renal vasoconstriction and activation of the renin-angiotensin system [21][22][23][24] . There is also increased oxidative stress and increased production of free radicals 25,26 , as well as nephrotoxicity caused directly and indirectly by bile acids and bilirubin, especially in situations of renal ischemia 10,[27][28][29][30] . In this study, animals undergoing biliary-enteric anastomosis and ileal exclusion showed elevated levels of urea and creatinine.…”

Effect of sirolimus on renal injury induced by bile duct ligation in rats

“…Hyperbilirubinemia has been shown to potentially affect renal function. These are associated with a urinary concentration defect, decreased maximal free water clearance and increased fractional sodium excretion 16 . Besides this, a predominant observation is reversible renal vasoconstriction that can lead to hepatorenal syndrome and renal failure.…”

“…tubular brush border vesicles 16,18 , which also could represent one of the mechanisms for decreased fluid and sodium reabsorption in proximal and also in distal nephrons segment 18 . Rodrigo et al 19 suggested that the renal compromise of obstructive jaundice is characterized by changes in the tubular handling of electrolytes.…”