Defective Renal Autoregulation in the Chronic Bile Duct Ligation Model of Liver Failure

Overview

Journal Clin Exp Nephrol

Publisher Springer

Specialty Nephrology

Date 2018 Mar 9

PMID 29516300

Citations 1

Authors

Tomchika Maoka

Tetsuya Kawata

Takao Koike

Toshio Mochizuki

Jurgen Schnermann

Seiji Hashimoto

Affiliations

Soon will be listed here.

Abstract

Background: Cirrhosis of the liver is often associated with an impairment of renal function that is usually not associated with consistent structural abnormalities of the renal parenchyma, but is thought to be the functional consequence of arterial underfilling and reduced arterial blood pressure.

Method: We have used the cirrhosis model of chronic bile duct ligation (BDL) to assess the response of renal blood flow to a change of blood pressure. We have measured renal haemodynamics in BDL rats.

Result: Three weeks after BDL, rats showed elevated levels of total bilirubin, AST, and ALT as well as reduced arterial blood pressure. Creatinine clearance was significantly reduced, and plasma creatinine and urea nitrogen were elevated. Renal blood flow at baseline blood pressure was significantly lower in the BDL group than in the sham group. Clamp-induced reductions of renal perfusion pressure caused significantly greater changes of renal blood flow in BDL than control rats. The autoregulatory index over a comparable blood pressure range averaged 0.28 ± 0.35 in control rats and 1.26 ± 0.6 in BDL rats (p = 0.0004) indicating impairment of renal autoregulation in liver cirrhosis.

Conclusion: Tubuloglomerular feedback (TGF) responses were significantly attenuated in BDL rats, especially in the subnormal flow range. Impairment of renal blood flow autoregulation, to some extent mediated by reduced TGF-mediated vasodilatation, may contribute to the renal vascular constrictor state in liver cirrhosis by preventing the full dilatory response to the blood pressure reduction.

Citing Articles

Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin.

Hong S, Li S, Meng X, Li P, Wang X, Su M Acta Pharm Sin B. 2023; 13(1):227-245.

PMID: 36815051 PMC: 9939304. DOI: 10.1016/j.apsb.2022.06.010.

References

Koppel M, Coburn J, MIMS M, Goldstein H, Boyle J, RUBINI M . Transplantation of cadaveric kidneys from patients with hepatorenal syndrome. Evidence for the functionalnature of renal failure in advanced liver disease. N Engl J Med. 1969; 280(25):1367-71. DOI: 10.1056/NEJM196906192802501. View

Bradley S . Editorial: Hepatorenal and glomerulotubular imbalance. N Engl J Med. 1973; 289(22):1194-5. DOI: 10.1056/NEJM197311292892212. View

Kayali Z, Herring J, Baron P, Franco E, Ojogho O, Smith J . Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction. J Gastroenterol Hepatol. 2009; 24(6):1030-7. DOI: 10.1111/j.1440-1746.2008.05757.x. View

Veelken R, Hilgers K, Porst M, Krause H, Hartner A, Schmieder R . Effects of sympathetic nerves and angiotensin II on renal sodium and water handling in rats with common bile duct ligature. Am J Physiol Renal Physiol. 2005; 288(6):F1267-75. DOI: 10.1152/ajprenal.00069.2003. View

Rivera-Huizar S, Rincon-Sanchez A, Covarrubias-Pinedo A, Islas-Carbajal M, Gabriel-Ortiz G, Pedraza-Chaverri J . Renal dysfunction as a consequence of acute liver damage by bile duct ligation in cirrhotic rats. Exp Toxicol Pathol. 2006; 58(2-3):185-95. DOI: 10.1016/j.etp.2006.05.001. View

Takabatake T, Ohta H, Hara H, Ishida Y, Noda Y, Hattori N . Activation of tubuloglomerular feedback in rat nephrons by sera from rabbits with fulminant hepatic failure. Nephron. 1983; 35(2):136-9. DOI: 10.1159/000183062. View

WUNDERLICH P, Hermle M, Davis J, Mihatsch M, Brunner F, Thiel G . The role of tubuloglomerular feedback in acute impairment of renal function in obstructive jaundice. Clin Exp Dial Apheresis. 1983; 7(1-2):63-76. DOI: 10.3109/08860228309076040. View

Bernardi M, Trevisani F, Gasbarrini A, Gasbarrini G . Hepatorenal disorders: role of the renin-angiotensin-aldosterone system. Semin Liver Dis. 1994; 14(1):23-34. DOI: 10.1055/s-2007-1007295. View

Kramer L, Horl W . Hepatorenal syndrome. Semin Nephrol. 2002; 22(4):290-301. View

10.

Wu J, Yang T, Wang C, Liu Q, Yao J, Sun H . Laennec protects murine from concanavalin A-induced liver injury through inhibition of inflammatory reactions and hepatocyte apoptosis. Biol Pharm Bull. 2008; 31(11):2040-4. DOI: 10.1248/bpb.31.2040. View

11.

Bennett W, Keeffe E, MELNYK C, Mahler D, Rosch J, Porter G . Response to dopamine hydrochloride in the hepatorenal syndrome. Arch Intern Med. 1975; 135(7):964-71. View

12.

Wasser S, Tan C . Experimental models of hepatic fibrosis in the rat. Ann Acad Med Singap. 1999; 28(1):109-11. View

13.

Tunon M, Alvarez M, Culebras J, Gonzalez-Gallego J . An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure. World J Gastroenterol. 2009; 15(25):3086-98. PMC: 2705730. DOI: 10.3748/wjg.15.3086. View

14.

Vallon V, Richter K, Blantz R, Thomson S, Osswald H . Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J Am Soc Nephrol. 1999; 10(12):2569-76. DOI: 10.1681/ASN.V10122569. View

15.

Assimakopoulos S, Vagianos C . Bile duct ligation in rats: a reliable model of hepatorenal syndrome?. World J Gastroenterol. 2008; 15(1):121-3. PMC: 2653290. DOI: 10.3748/wjg.15.121. View

16.

Wunderlich P, Brunner F, Davis J, Haberle D, Tholen H, Thiel G . Feedback activation in rat nephrons by sera from patients with acute renal failure. Kidney Int. 1980; 17(4):497-506. DOI: 10.1038/ki.1980.58. View

17.

Yang K, Lin K, Wu S, Wang D . Uptake of Tc-99m MDP by renal cortex in a patient with advanced hepatic disease and oliguria. Clin Nucl Med. 1992; 17(2):143. DOI: 10.1097/00003072-199202000-00021. View

18.

Epstein M, Goligorsky M . Endothelin and nitric oxide in hepatorenal syndrome: a balance reset. J Nephrol. 1997; 10(3):120-35. View

19.

Hashimoto S, Kawata T, Schnermann J, Koike T . Chloride channel blockade attenuates the effect of angiotensin II on tubuloglomerular feedback in WKY but not spontaneously hypertensive rats. Kidney Blood Press Res. 2003; 27(1):35-42. DOI: 10.1159/000075621. View

20.

Tag C, Sauer-Lehnen S, Weiskirchen S, Borkham-Kamphorst E, Tolba R, Tacke F . Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis. J Vis Exp. 2015; (96). PMC: 4354634. DOI: 10.3791/52438. View