RSS-Feed abonnieren
DOI: 10.1055/s-0039-1698826
Cholemic Nephropathy Reloaded
Publikationsverlauf
Publikationsdatum:
18. Oktober 2019 (online)
![](https://www.thieme-connect.de/media/sld/202001/lookinside/thumbnails/10-1055-s-0039-1698826_1900049-1.jpg)
Abstract
Acute kidney injury (AKI) is a dreaded complication in patients with liver disease and jaundice, since it is associated with significant morbidity and mortality. Cholemic nephropathy (CN) is thought to represent a widely underestimated important cause of AKI in advanced liver diseases with jaundice. The umbrella term CN describes impaired renal function along with histomorphological changes consisting of intratubular cast formation and tubular epithelial cell injury directed primarily toward distal nephron segments. In cholestasis, biliary constituents may be excreted via the kidney and bilirubin or bile acids may trigger tubular injury and cast formation, but as we begin to understand the underlying pathophysiologic mechanisms, we become increasingly aware of the urgent need for clearly defined diagnostic criteria. In the following, we aim to summarize current knowledge of clinical and morphological characteristics of CN, discuss potential pathomechanisms, and raise key questions to stimulate evolution of a research strategy for CN.
-
References
- 1 Krones E, Pollheimer MJ, Rosenkranz AR, Fickert P. Cholemic nephropathy - historical notes and novel perspectives. Biochim Biophys Acta Mol Basis Dis 2018; 1864 (4 Pt B): 1356-1366
- 2 Dawson JL. Acute post-operative renal failure in obstructive jaundice. Ann R Coll Surg Engl 1968; 42 (03) 163-181
- 3 Armstrong CP, Dixon JM, Taylor TV, Davies GC. Surgical experience of deeply jaundiced patients with bile duct obstruction. Br J Surg 1984; 71 (03) 234-238
- 4 Ariza X, Graupera I, Coll M. , et al; CANONIC Investigators, EASL CLIF Consortium. Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis. J Hepatol 2016; 65 (01) 57-65
- 5 Arroyo V, Moreau R, Jalan R, Ginès P. ; EASL-CLIF Consortium CANONIC Study. Acute-on-chronic liver failure: a new syndrome that will re-classify cirrhosis. J Hepatol 2015; 62 (1, Suppl): S131-S143
- 6 Cardi E. The hepatorenal syndrome; a historical review. AMA Arch Surg 1956; 73 (02) 224-227
- 7 Quincke H, Hoppe-Seyler G, Oser L, Neusser E. Die Krankheiten der Leber/Die Erkrankungen des Pankreas/Die Erkrankungen der Nebennieren. In: Nothnagel H. , ed. Spezielle Pathologie und Therapie. Wien: A. Hölder; ; 1897–1899. Bd. 18 Tl. 1·3
- 8 van Slambrouck CM, Salem F, Meehan SM, Chang A. Bile cast nephropathy is a common pathologic finding for kidney injury associated with severe liver dysfunction. Kidney Int 2013; 84 (01) 192-197
- 9 Amin AA, Alabsawy EI, Jalan R, Davenport A. Epidemiology, pathophysiology, and management of hepatorenal syndrome. Semin Nephrol 2019; 39 (01) 17-30
- 10 Leclerc M, Lanot A, Béchade C, Le Naoures C, Comoz F, Lobbedez T. Bile salt nephropathy/cholemic nephrosis [in French]. Nephrol Ther 2016; 12 (06) 460-462
- 11 Flores A, Nustas R, Nguyen HL, Rahimi RS. Severe cholestasis and bile acid nephropathy from anabolic steroids successfully treated with plasmapheresis. ACG Case Rep J 2016; 3 (02) 133-135
- 12 Luciano RL, Castano E, Moeckel G, Perazella MA. Bile acid nephropathy in a bodybuilder abusing an anabolic androgenic steroid. Am J Kidney Dis 2014; 64 (03) 473-476
- 13 Fickert P, Krones E, Pollheimer MJ. , et al. Bile acids trigger cholemic nephropathy in common bile-duct-ligated mice. Hepatology 2013; 58 (06) 2056-2069
- 14 Krones E, Eller K, Pollheimer MJ. , et al. NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice. J Hepatol 2017; 67 (01) 110-119
- 15 Krones E, Wagner M, Eller K, Rosenkranz AR, Trauner M, Fickert P. Bile acid-induced cholemic nephropathy. Dig Dis 2015; 33 (03) 367-375
- 16 Adebayo D, Morabito V, Davenport A, Jalan R. Renal dysfunction in cirrhosis is not just a vasomotor nephropathy. Kidney Int 2015; 87 (03) 509-515
- 17 Gollan JL, Billing BH, Huang SN. Ultrastructural changes in the isolated rat kidney induced by conjugated bilirubin and bile acids. Br J Exp Pathol 1976; 57 (05) 571-581
- 18 Rivera-Huizar S, Rincón-Sánchez AR, Covarrubias-Pinedo A. , et al. Renal dysfunction as a consequence of acute liver damage by bile duct ligation in cirrhotic rats. Exp Toxicol Pathol 2006; 58 (2-3): 185-195
- 19 Elías MM, Comin EJ, Ochoa EJ, Rodríguez Garay EA. Evidence for a secretory component in the handling of unconjugated bilirubin by the isolated perfused rat kidney. Can J Physiol Pharmacol 1985; 63 (12) 1581-1585
- 20 Elías MM, Comin EJ, Grosman ME, Galeazzi SA, Rodríguez Garay EA. Possible mechanism of unconjugated bilirubin toxicity on renal tissue. Comp Biochem Physiol A Comp Physiol 1987; 87 (04) 1003-1007
- 21 Ozawa K, Yamada T, Tanaka J, Ukikusa M, Tobe T. The mechanism of suppression of renal function in patients and rabbits with jaundice. Surg Gynecol Obstet 1979; 149 (01) 54-60
- 22 Leung N, Croatt AJ, Haggard JJ, Grande JP, Nath KA. Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat. Kidney Int 2001; 60 (03) 1047-1057
- 23 Bolisetty S, Zarjou A, Agarwal A. Heme oxygenase 1 as a therapeutic target in acute kidney injury. Am J Kidney Dis 2017; 69 (04) 531-545
- 24 Adin CA, Croker BP, Agarwal A. Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney. Am J Physiol Renal Physiol 2005; 288 (04) F778-F784
- 25 Lanone S, Bloc S, Foresti R. , et al. Bilirubin decreases nos2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats. FASEB J 2005; 19 (13) 1890-1892
- 26 Oh SW, Lee ES, Kim S. , et al. Bilirubin attenuates the renal tubular injury by inhibition of oxidative stress and apoptosis. BMC Nephrol 2013; 14: 105
- 27 Deetman PE, Zelle DM, Homan van der Heide JJ, Navis GJ, Gans RO, Bakker SJ. Plasma bilirubin and late graft failure in renal transplant recipients. Transpl Int 2012; 25 (08) 876-881
- 28 Ryu S, Chang Y, Zhang Y. , et al. Higher serum direct bilirubin levels were associated with a lower risk of incident chronic kidney disease in middle aged Korean men. PLoS One 2014; 9 (02) e75178
- 29 Dawson PA, Lan T, Rao A. Bile acid transporters. J Lipid Res 2009; 50 (12) 2340-2357
- 30 Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci 2008; 65 (16) 2461-2483
- 31 Lee J, Azzaroli F, Wang L. , et al. Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat. Gastroenterology 2001; 121 (06) 1473-1484
- 32 Schlattjan JH, Winter C, Greven J. Regulation of renal tubular bile acid transport in the early phase of an obstructive cholestasis in the rat. Nephron, Physiol 2003; 95 (03) 49-56
- 33 Soroka CJ, Velazquez H, Mennone A, Ballatori N, Boyer JL. Ostα depletion protects liver from oral bile acid load. Am J Physiol Gastrointest Liver Physiol 2011; 301 (03) G574-G579
- 34 Soroka CJ, Mennone A, Hagey LR, Ballatori N, Boyer JL. Mouse organic solute transporter alpha deficiency enhances renal excretion of bile acids and attenuates cholestasis. Hepatology 2010; 51 (01) 181-190
- 35 Slitt AL, Allen K, Morrone J. , et al. Regulation of transporter expression in mouse liver, kidney, and intestine during extrahepatic cholestasis. Biochim Biophys Acta 2007; 1768 (03) 637-647
- 36 Kaler B, Karram T, Morgan WA, Bach PH, Yousef IM, Bomzon A. Are bile acids involved in the renal dysfunction of obstructive jaundice? An experimental study in bile duct ligated rats. Ren Fail 2004; 26 (05) 507-516
- 37 Hagey LR, Vidal N, Hofmann AF, Krasowski MD. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites. BMC Evol Biol 2010; 10: 133
- 38 Argmann CA, Houten SM, Champy MF, Auwerx J. Lipid and bile acid analysis. Curr Protoc Mol Biol 2006; Chapter 29: 2
- 39 Sathick IJ, Drosou ME, Leung N. Myeloma light chain cast nephropathy, a review. J Nephrol 2019; 32 (02) 189-198
- 40 Gnemmi V, Leleu X, Provot F, Moulonguet F, Buob D. Cast nephropathy and light-chain deposition disease in Waldenström macroglobulinemia. Am J Kidney Dis 2012; 60 (03) 487-491
- 41 Harrois A, Libert N, Duranteau J. Acute kidney injury in trauma patients. Curr Opin Crit Care 2017; 23 (06) 447-456
- 42 Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009; 361 (01) 62-72
- 43 Bräsen JH, Mederacke YS, Schmitz J. , et al. Cholemic nephropathy causes acute kidney injury and is accompanied by loss of aquaporin 2 in collecting ducts. Hepatology 2019; 69 (05) 2107-2119
- 44 Hofmann AF, Mysels KJ. Bile acid solubility and precipitation in vitro and in vivo: the role of conjugation, pH, and Ca2+ ions. J Lipid Res 1992; 33 (05) 617-626
- 45 Burnstine RC, Schmid R. Solubility of bilirubin in aqueous solutions. Proc Soc Exp Biol Med 1962; 109: 356-358
- 46 Nayak SL, Kumar M, Bihari C, Rastogi A. Bile cast nephropathy in patients with acute kidney injury due to hepatorenal syndrome: a postmortem kidney biopsy study. J Clin Transl Hepatol 2017; 5 (02) 92-100
- 47 Angeli P, Tonon M, Pilutti C, Morando F, Piano S. Sepsis-induced acute kidney injury in patients with cirrhosis. Hepatol Int 2016; 10 (01) 115-123
- 48 Piano S, Brocca A, Angeli P. Renal function in cirrhosis: a critical review of available tools. Semin Liver Dis 2018; 38 (03) 230-241
- 49 Arroyo V. Microalbuminuria, systemic inflammation, and multiorgan dysfunction in decompensated cirrhosis: evidence for a nonfunctional mechanism of hepatorenal syndrome. Hepatol Int 2017; 11 (03) 242-244
- 50 Okubo K, Kurosawa M, Kamiya M. , et al. Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury. Nat Med 2018; 24 (02) 232-238
- 51 Wong F. Acute kidney injury in liver cirrhosis: new definition and application. Clin Mol Hepatol 2016; 22 (04) 415-422
- 52 Ginès P, Solà E, Angeli P, Wong F, Nadim MK, Kamath PS. Hepatorenal syndrome. Nat Rev Dis Primers 2018; 4 (01) 23
- 53 Qamar I, Rehman S, Mehdi G, Maheshwari V, Ansari HA, Chauhan S. Utility of cytospin and cell block technology in evaluation of body fluids and urine samples: a comparative study. J Cytol 2018; 35 (02) 79-82
- 54 Bal C, Longkumer T, Patel C, Gupta SD, Acharya SK. Renal function and structure in subacute hepatic failure. J Gastroenterol Hepatol 2000; 15 (11) 1318-1324
- 55 Kiewe P, Korfel A, Loddenkemper C. , et al. Unusual sites of Hodgkin's lymphoma: CASE 3. Cholemic nephrosis in Hodgkin's lymphoma with liver involvement. J Clin Oncol 2004; 22 (20) 4230-4231
- 56 Betjes MG, Bajema I. The pathology of jaundice-related renal insufficiency: cholemic nephrosis revisited. J Nephrol 2006; 19 (02) 229-233
- 57 Uslu A, Taşli FA, Nart A. , et al. Human kidney histopathology in acute obstructive jaundice: a prospective study. Eur J Gastroenterol Hepatol 2010; 22 (12) 1458-1465
- 58 Bredewold OW, de Fijter JW, Rabelink T. A case of mononucleosis infectiosa presenting with cholemic nephrosis. NDT Plus 2011; 4 (03) 170-172
- 59 Rafat C, Burbach M, Brochériou I. , et al. Bilirubin-associated acute tubular necrosis in a kidney transplant recipient. Am J Kidney Dis 2013; 61 (05) 782-785
- 60 van der Wijngaart H, van Dam B, van den Berg JG, Krul-Poel YH, Klemt-Kropp M, Bax WA. A 73-year-old male with jaundice and acute kidney injury. Bile cast nephropathy. Neth J Med 2014; 72 (02) 95-99 , 99
- 61 Jain K, Gupta A, Singh HK, Nickeleit V, Kshirsagar AV. Bile cast nephropathy. Kidney Int 2015; 87 (02) 484
- 62 Sequeira A, Gu X. Bile cast nephropathy: an often forgotten diagnosis. Hemodial Int 2015; 19 (01) 132-135
- 63 Tabatabaee SM, Elahi R, Savaj S. Bile cast nephropathy due to cholestatic jaundice after using stanozolol in 2 amateur bodybuilders. Iran J Kidney Dis 2015; 9 (04) 331-334
- 64 Patel J, Walayat S, Kalva N, Palmer-Hill S, Dhillon S. Bile cast nephropathy: a case report and review of the literature. World J Gastroenterol 2016; 22 (27) 6328-6334
- 65 Sens F, Bacchetta J, Rabeyrin M, Juillard L. Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity. BMJ Case Rep 2016; 2016: 2016
- 66 Werner CR, Wagner V, Sipos B. , et al. Acute kidney injury in liver failure [in German]. Dtsch Med Wochenschr 2016; 141 (21) 1559
- 67 Alkhunaizi AM, ElTigani MA, Rabah RS, Nasr SH. Acute bile nephropathy secondary to anabolic steroids. Clin Nephrol 2016; 85 (02) 121-126
- 68 Alnasrallah B, Collins JF, Zwi LJ. Bile nephropathy in flucloxacillin-induced cholestatic liver dysfunction. Case Rep Nephrol 2016; 2016: 4162674
- 69 Mohapatra MK, Behera AK, Karua PC. , et al. Urinary bile casts in bile cast nephropathy secondary to severe falciparum malaria. Clin Kidney J 2016; 9 (04) 644-648
- 70 Aniort J, Poyet A, Kemeny JL, Philipponnet C, Heng AE. Bile cast nephropathy caused by obstructive cholestasis. Am J Kidney Dis 2017; 69 (01) 143-146