Ursachen der chronischen Nierenschädigung in Patienten mit Lebererkrankungen – Pathophysiologie und Therapiemöglichkeiten

Florian Gunnar Scurt; Katrin Bose; Ali Canbay; Peter R Mertens; Christos Chatzikyrkou

doi:10.1055/a-1402-1502

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

Z Gastroenterol 2021; 59(06): 560-579
DOI: 10.1055/a-1402-1502

Übersicht

Ursachen der chronischen Nierenschädigung in Patienten mit Lebererkrankungen – Pathophysiologie und Therapiemöglichkeiten

Chronic kidney injury in patients with liver diseases – Reappraising pathophysiology and treatment options

Florian Gunnar Scurt

¹Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland

²Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany

,

Katrin Bose

²Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany

³Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland

,

Ali Canbay

⁴Ruhr-Universität Bochum, Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Deutschland

,

Peter R Mertens

¹Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland

²Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany

,

Christos Chatzikyrkou

¹Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland

²Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany

› Institutsangaben

Abstract

Zusammenfassung

Eine akute oder chronische Nierenschädigung bei gleichzeitig bestehender Lebererkrankung stellt ein häufiges Problem dar und geht im weiteren klinischen Verlauf mit zahlreichen Komplikationen sowie einer gesteigerten Dialysepflichtigkeit und Mortalität einher.

Die Prävalenz einer chronischen Niereninsuffizienz (CNI) bei Patienten mit Lebererkrankungen ist hoch, nicht zuletzt wegen parallel bestehender Komorbiditäten (z. B. metabolisches Syndrom, chronische Entzündungsprozesse, Hyperkoagulabilität, Hyperfibrinolyse, Diabetes mellitus, Dyslipidämie usw.). Doch nicht jede chronische Verschlechterung der Nierenretentionsparameter lässt sich auf ein hepatorenales Syndrom zurückführen. Neben diesem sind die häufigsten Ursachen der CNI bei bestehenden Lebererkrankungen die diabetische Nephropathie, die alkoholassoziierte IgA-Nephropathie, die mit Hepatitis C assoziierte membranoproliferative Glomerulonephritis und die mit Hepatitis B assoziierte membranöse Glomerulonephritis.

Koexistente Erkrankungen, ähnlich bzw. parallel ablaufende pathophysiologische Mechanismen und überlappende Erscheinungsbilder stellen hinsichtlich der Ursachenfindung und entsprechenden Behandlung der CNI im Rahmen einer existenten Lebererkrankung eine Herausforderung an den Kliniker dar. Diese Übersichtsarbeit skizziert sowohl häufige als auch seltene Entitäten, die zu einer chronischen Nierenschädigung in diesem speziellen Patientenkollektiv führen, und zeigt einen Überblick zu therapeutischen Möglichkeiten.

Abstract

Acute and chronic kidney disease concurs commonly with liver disease and is associated with a wide array of complications including dialysis dependency and increased mortality. Patients with liver disease or liver cirrhosis show a higher prevalence of chronic kidney disease. This is attributed to concomitant comorbidities, such as metabolic syndrome, chronic inflammation, hypercoagulability, hyperfibrinolysis, diabetes mellitus and dyslipidaemias. But chronic progressive kidney disease is not always due to hepatorenal syndrome. Beyond that, other diseases or disease entities should be considered. Among them are diabetic nephropathy, secondary IgA nephropathy, hepatitis C -associated membranoproliferative Glomerulonephritis (MPGN) and hepatitis B-associated membranous nephropathy.

Coexisting diseases, similar underlying pathophysiologic mechanisms, or simultaneously concurring pathophysiological processes and overlapping clinical manifestations, impede the etiologic diagnosis and corresponding treatment of chronic kidney disease in the setting of chronic liver disease. In this review, we focus on common and rare pathologies, which can lead to chronic kidney disease in this particular patient group and try to summarize the most recent therapeutic modalities.

Schlüsselwörter

Leberinsuffizienz - Leberzirrhose - Nierenschädigung - chronische Niereninsuffizienz - hepatorenales Syndrom - HRS - Hepatitis B - Hepatitis C - Diabetes mellitus - Pathophysiologie - Nierenbiopsie

Key words

liver insufficiency - liver cirrhosis - kidney injury - chronic renal insufficiency - hepatorenal syndrome - HRS - hepatitis B - hepatitis C - diabetes mellitus - pathophysiology - kidney biopsy

Volltext

Referenzen

Literatur
1 Slack A, Yeoman A, Wendon J. Renal Dysfunction in Chronic Liver Disease. New York, NY: Springer New York; 2010: 349-364
2 Targher G, Chonchol MB, Byrne CD. CKD and nonalcoholic fatty liver disease. Am J Kidney Dis 2014; 64: 638-652
3 Bonora E, Targher G. Increased risk of cardiovascular disease and chronic kidney disease in NAFLD. Nat Rev Gastroenterol Hepatol 2012; 9: 372-381
4 Lum EL, Homkrailas P, Bunnapradist S. Evaluation of Renal Disease in Patients With Cirrhosis. J Clin Gastroenterol 2020; 54: 314-321
5 Arase Y, Suzuki F, Kobayashi M. et al The development of chronic kidney disease in Japanese patients with non-alcoholic fatty liver disease. Intern Med 2011; 50: 1081-1087
6 Targher G, Mantovani A, Pichiri I. et al Nonalcoholic fatty liver disease is independently associated with an increased incidence of chronic kidney disease in patients with type 1 diabetes. Diabetes Care 2014; 37: 1729-1736
7 Wong F, Reddy KR, O'Leary JG. et al Impact of Chronic Kidney Disease on Outcomes in Cirrhosis. Liver Transpl 2019; 25: 870-880
8 Velez JCQ, Therapondos G, Juncos LA. Reappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis. Nat Rev Nephrol 2020; 16: 137-155
9 Mazzolini G, Sowa JP, Atorrasagasti C. et al Significance of Simple Steatosis: An Update on the Clinical and Molecular Evidence. Cells 2020; 9
10 Stefan N. [New aspects of nonalcoholic steatohepatitis]. Internist (Berl) 2019; 60: 128-132
11 Adams LA, Anstee QM, Tilg H. et al Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 2017; 66: 1138-1153
12 Tolman KG, Fonseca V, Dalpiaz A. et al Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care 2007; 30: 734-743
13 Wlazlo N, Beijers HJ, Schoon EJ. et al High prevalence of diabetes mellitus in patients with liver cirrhosis. Diabet Med 2010; 27: 1308-1311
14 Grancini V, Trombetta M, Lunati ME. et al Contribution of beta-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease. J Hepatol 2015; 63: 1484-1490
15 Targher G, Bertolini L, Rodella S. et al Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol 2010; 5: 2166-2171
16 Greco AV, Mingrone G, Mari A. et al Mechanisms of hyperinsulinaemia in Child's disease grade B liver cirrhosis investigated in free living conditions. Gut 2002; 51: 870-875
17 Shanik MH, Xu Y, Skrha J. et al Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse?. Diabetes Care 2008; 31 (Suppl. 02) S262-S268
18 Saitoh M. [Studies on histopathology of pancreas in portal hypertension]. Nihon Shokakibyo Gakkai Zasshi 1984; 81: 1444-1452
19 Gariani K, Philippe J, Jornayvaz FR. Non-alcoholic fatty liver disease and insulin resistance: from bench to bedside. Diabetes Metab 2013; 39: 16-26
20 Lecube A, Hernandez C, Genesca J. et al Proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis C patients: A case-control study. Diabetes Care 2006; 29: 1096-1101
21 Bose SK, Shrivastava S, Meyer K. et al Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance. J Virol 2012; 86: 6315-6322
22 Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368: 1696-1705
23 Balaban YH, Korkusuz P, Simsek H. et al Dipeptidyl peptidase IV (DDP IV) in NASH patients. Ann Hepatol 2007; 6: 242-250
24 Itou M, Kawaguchi T, Taniguchi E. et al Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol 2013; 19: 2298-2306
25 Yagmur E, Tacke F, Weiss C. et al Elevation of Nepsilon-(carboxymethyl)lysine-modified advanced glycation end products in chronic liver disease is an indicator of liver cirrhosis. Clin Biochem 2006; 39: 39-45
26 Sebekova K, Kupcova V, Schinzel R. et al Markedly elevated levels of plasma advanced glycation end products in patients with liver cirrhosis – amelioration by liver transplantation. J Hepatol 2002; 36: 66-71
27 Vlassara H, Uribarri J. Advanced glycation end products (AGE) and diabetes: cause, effect, or both?. Curr Diab Rep 2014; 14: 453
28 Christen V, Treves S, Duong FH. et al Activation of endoplasmic reticulum stress response by hepatitis viruses up-regulates protein phosphatase 2A. Hepatology 2007; 46: 558-565
29 Orsi E, Grancini V, Menini S. et al Hepatogenous diabetes: Is it time to separate it from type 2 diabetes?. Liver Int 2017; 37: 950-962
30 Rahier J, Loozen S, Goebbels RM. et al The haemochromatotic human pancreas: a quantitative immunohistochemical and ultrastructural study. Diabetologia 1987; 30: 5-12
31 Tang SC. Diabetic nephropathy: a global and growing threat. Hong Kong Med J 2010; 16: 244-245
32 Espinel E, Agraz I, Ibernon M. et al Renal Biopsy in Type 2 Diabetic Patients. J Clin Med 2015; 4: 998-1009
33 Krolewski AS. Progressive renal decline: the new paradigm of diabetic nephropathy in type 1 diabetes. Diabetes Care 2015; 38: 954-962
34 Imano E, Nishida T, Shibata M. et al Significance of oral glucose tolerance test for the diagnosis of diabetes mellitus in patients with liver cirrhosis. Intern Med 1999; 38: 918
35 Lahousen T, Hegenbarth K, Ille R. et al Determination of glycated hemoglobin in patients with advanced liver disease. World J Gastroenterol 2004; 10: 2284-2286
36 Nishida T, Tsuji S, Tsujii M. et al Oral glucose tolerance test predicts prognosis of patients with liver cirrhosis. Am J Gastroenterol 2006; 101: 70-75
37 Nishida T. Diagnosis and Clinical Implications of Diabetes in Liver Cirrhosis: A Focus on the Oral Glucose Tolerance Test. J Endocr Soc 2017; 1: 886-896
38 Ranjbar G, Mikhailidis DP, Sahebkar A. Effects of newer antidiabetic drugs on nonalcoholic fatty liver and steatohepatitis: Think out of the box!. Metabolism 2019; 101: 154001
39 Tacelli M, Celsa C, Magro B. et al Antidiabetic Drugs in NAFLD: The Accomplishment of Two Goals at Once?. Pharmaceuticals (Basel) 2018; 11
40 Peter PR, Lupsa BC. Personalized Management of Type 2 Diabetes. Curr Diab Rep 2019; 19: 115
41 Schubert M, Hansen S, Leefmann J. et al Repurposing Antidiabetic Drugs for Cardiovascular Disease. Front Physiol 2020; 11: 568632
42 Sumida Y, Yoneda M, Tokushige K. et al Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis. Int J Mol Sci 2020; 21
43 Grancini V, Resi V, Palmieri E. et al Management of diabetes mellitus in patients undergoing liver transplantation. Pharmacol Res 2019; 141: 556-573
44 Kumar R. Hepatogenous Diabetes: An Underestimated Problem of Liver Cirrhosis. Indian J Endocrinol Metab 2018; 22: 552-559
45 Heerspink HJL, Stefansson BV, Correa-Rotter R. et al Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020; 383: 1436-1446
46 McMurray JJV, Docherty KF, Jhund PS. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. Reply. N Engl J Med 2020; 382: 973
47 Packer M, Anker SD, Butler J. et al Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med 2020; 383: 1413-1424
48 Perkovic V, Jardine MJ, Neal B. et al Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med 2019; 380: 2295-2306
49 Wiviott SD, Raz I, Bonaca MP. et al Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380: 347-357
50 Bakris G, Oshima M, Mahaffey KW. et al Effects of Canagliflozin in Patients with Baseline eGFR <30 ml/min per 1.73 m(2): Subgroup Analysis of the Randomized CREDENCE Trial. Clin J Am Soc Nephrol 2020; 15: 1705-1714
51 Chalasani N, Younossi Z, Lavine JE. et al The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67: 328-357
52 Estes C, Anstee QM, Arias-Loste MT. et al Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol 2018; 69: 896-904
53 Musso G, Gambino R, Tabibian JH. et al Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med 2014; 11: e1001680
54 European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia 2016; 59: 1121-1140
55 Non-alcoholic Fatty Liver Disease Study G, Lonardo A, Bellentani S et al. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups. Dig Liver Dis 2015; 47: 997-1006
56 Younossi Z, Anstee QM, Marietti M. et al Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018; 15: 11-20
57 Kendrick J, Chonchol MB. Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nat Clin Pract Nephrol 2008; 4: 672-681
58 Kronenberg F. Emerging risk factors and markers of chronic kidney disease progression. Nat Rev Nephrol 2009; 5: 677-689
59 Targher G, Chonchol M, Miele L. et al Nonalcoholic fatty liver disease as a contributor to hypercoagulation and thrombophilia in the metabolic syndrome. Semin Thromb Hemost 2009; 35: 277-287
60 Targher G, Byrne CD. Diagnosis and management of nonalcoholic fatty liver disease and its hemostatic/thrombotic and vascular complications. Semin Thromb Hemost 2013; 39: 214-228
61 Byrne CD, Targher G. NAFLD as a driver of chronic kidney disease. J Hepatol 2020; 72: 785-801
62 Musso G, Cassader M, Cohney S. et al Emerging Liver-Kidney Interactions in Nonalcoholic Fatty Liver Disease. Trends Mol Med 2015; 21: 645-662
63 Lanaspa MA, Cicerchi C, Garcia G. et al Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver. PLoS One 2012; 7: e48801
64 Lanaspa MA, Sanchez-Lozada LG, Choi YJ. et al Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem 2012; 287: 40732-40744
65 Sanchez-Lozada LG, Andres-Hernando A, Garcia-Arroyo FE. et al Uric acid activates aldose reductase and the polyol pathway for endogenous fructose and fat production causing development of fatty liver in rats. J Biol Chem 2019; 294: 4272-4281
66 Anstee QM, Seth D, Day CP. Genetic Factors That Affect Risk of Alcoholic and Nonalcoholic Fatty Liver Disease. Gastroenterology 2016; 150: 1728-1744 e1727
67 Eslam M, Valenti L, Romeo S. Genetics and epigenetics of NAFLD and NASH: Clinical impact. J Hepatol 2018; 68: 268-279
68 Oniki K, Saruwatari J, Izuka T. et al Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects. PLoS One 2015; 10: e0132640
69 Musso G, Cassader M, Gambino R. PNPLA3 rs738409 and TM6SF2 rs58542926 gene variants affect renal disease and function in nonalcoholic fatty liver disease. Hepatology 2015; 62: 658-659
70 Mantovani A, Zusi C, Sani E. et al Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease. Diabetes Metab 2019; 45: 480-487
71 Sun DQ, Zheng KI, Xu G. et al PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels. Liver Int 2020; 40: 107-119
72 Targher G, Mantovani A, Alisi A. et al Relationship Between PNPLA3 rs738409 Polymorphism and Decreased Kidney Function in Children With NAFLD. Hepatology 2019; 70: 142-153
73 Marzuillo P, Di Sessa A, Guarino S. et al Nonalcoholic fatty liver disease and eGFR levels could be linked by the PNPLA3 I148M polymorphism in children with obesity. Pediatr Obes 2019; 14: e12539
74 Shen B, Lu LG. Efficacy and safety of drugs for nonalcoholic steatohepatitis. J Dig Dis 2021;
75 Vilar-Gomez E, Calzadilla-Bertot L, Friedman SL. et al Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2017; 45: 332-344
76 Saha MK, Julian BA, Novak J. et al Secondary IgA nephropathy. Kidney Int 2018; 94: 674-681
77 Seikrit C, Rauen T, Floege J. [Immunoglobulin A nephropathy]. Internist (Berl) 2019; 60: 432-439
78 Axelsen RA, Crawford DH, Endre ZH. et al Renal glomerular lesions in unselected patients with cirrhosis undergoing orthotopic liver transplantation. Pathology 1995; 27: 237-246
79 McGuire BM, Julian BA, Bynon Jr JS. et al Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation. Ann Intern Med 2006; 144: 735-741
80 Calmus Y, Conti F, Cluzel P. et al Prospective assessment of renal histopathological lesions in patients with end-stage liver disease: effects on long-term renal function after liver transplantation. J Hepatol 2012; 57: 572-576
81 Hommos MS, El-Zoghby ZM. Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study. Transplant Direct 2017; 3: e193
82 Suzuki H, Kiryluk K, Novak J. et al The pathophysiology of IgA nephropathy. J Am Soc Nephrol 2011; 22: 1795-1803
83 Tissandie E, Morelle W, Berthelot L. et al Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89-IgA and IgG-IgA complexes: common mechanisms for distinct diseases. Kidney Int 2011; 80: 1352-1363
84 Scurt FG, Bose K, Canbay A. et al [Paradigm shift in understanding Acute kidney injury in patients with chronic liver disease: From pathophysiology to defining disease entities]. Z Gastroenterol 2020; 58: 254-266
85 Francoz C, Durand F, Kahn JA. et al Hepatorenal Syndrome. Clin J Am Soc Nephrol 2019; 14: 774-781
86 Singhal J, Sharma J. IgA nephropathy secondary to liver disease. Pediatr Nephrol 2018; 33: 2393
87 Deviere J, Content J, Denys C. et al Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics. Gastroenterology 1992; 103: 1296-1301
88 Pouria S, Barratt J. Secondary IgA nephropathy. Semin Nephrol 2008; 28: 27-37
89 Rauen T, Eitner F, Fitzner C. et al Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med 2015; 373: 2225-2236
90 Liu LJ, Yang YZ, Shi SF. et al Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial. Am J Kidney Dis 2019; 74: 15-22
91 Floege J, Feehally J. Treatment of IgA nephropathy and Henoch-Schonlein nephritis. Nat Rev Nephrol 2013; 9: 320-327
92 Frisch G, Lin J, Rosenstock J. et al Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant 2005; 20: 2139-2145
93 Lafayette RA, Canetta PA, Rovin BH. et al A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. J Am Soc Nephrol 2017; 28: 1306-1313
94 Pozzi C, Andrulli S, Pani A. et al Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy. J Am Soc Nephrol 2010; 21: 1783-1790
95 Sarcina C, Tinelli C, Ferrario F. et al Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy. Clin J Am Soc Nephrol 2016; 11: 973-981
96 Lv J, Zhang H, Wong MG. et al Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA 2017; 318: 432-442
97 Pozzi C. Pro: STOP immunosuppression in IgA nephropathy?. Nephrol Dial Transplant 2016; 31: 1766-1770
98 Tesar V, Troyanov S, Bellur S. et al Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study. J Am Soc Nephrol 2015; 26: 2248-2258
99 Pozzi C, Andrulli S, Del Vecchio L. et al Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 2004; 15: 157-163
100 Manno C, Torres DD, Rossini M. et al Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant 2009; 24: 3694-3701
101 Smerud HK, Barany P, Lindstrom K. et al New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol Dial Transplant 2011; 26: 3237-3242
102 Fellstrom BC, Barratt J, Cook H. et al Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet 2017; 389: 2117-2127
103 Ismail G, Obrisca B, Jurubita R. et al Budesonide versus systemic corticosteroids in IgA Nephropathy: A retrospective, propensity-matched comparison. Medicine (Baltimore) 2020; 99: e21000
104 Vierling JM, Kerkar N, Czaja AJ. et al Immunosuppressive Treatment Regimens in Autoimmune Hepatitis: Systematic Reviews and Meta-Analyses Supporting AASLD Guidelines. Hepatology 2020;
105 Doycheva I, Watt KD, Gulamhusein AF. Autoimmune hepatitis: Current and future therapeutic options. Liver Int 2019; 39: 1002-1013
106 Sallustio F, Curci C, Di Leo V. et al A New Vision of IgA Nephropathy: The Missing Link. Int J Mol Sci 2019; 21
107 Bhimma R, Coovadia HM. Hepatitis B virus-associated nephropathy. Am J Nephrol 2004; 24: 198-211
108 Kupin WL. Viral-Associated GN: Hepatitis B and Other Viral Infections. Clin J Am Soc Nephrol 2017; 12: 1529-1533
109 Pipili CL, Papatheodoridis GV, Cholongitas EC. Treatment of hepatitis B in patients with chronic kidney disease. Kidney Int 2013; 84: 880-885
110 Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int 1990; 37: 663-676
111 Lai KN, Li PK, Lui SF. et al Membranous nephropathy related to hepatitis B virus in adults. N Engl J Med 1991; 324: 1457-1463
112 Li P, Wei RB, Tang L. et al Clinical and pathological analysis of hepatitis B virus-related membranous nephropathy and idiopathic membranous nephropathy. Clin Nephrol 2012; 78: 456-464
113 Fervenza FC, Sethi S, Specks U. Idiopathic membranous nephropathy: diagnosis and treatment. Clin J Am Soc Nephrol 2008; 3: 905-919
114 He XY, Fang LJ, Zhang YE. et al In situ hybridization of hepatitis B DNA in hepatitis B-associated glomerulonephritis. Pediatr Nephrol 1998; 12: 117-120
115 Xie Q, Li Y, Xue J. et al Renal phospholipase A2 receptor in hepatitis B virus-associated membranous nephropathy. Am J Nephrol 2015; 41: 345-353
116 Lin CY. Treatment of hepatitis B virus-associated membranous nephropathy with recombinant alpha-interferon. Kidney Int 1995; 47: 225-230
117 Yang Y, Ma YP, Chen DP. et al A Meta-Analysis of Antiviral Therapy for Hepatitis B Virus-Associated Membranous Nephropathy. PLoS One 2016; 11: e0160437
118 Mahajan V, D'Cruz S, Nada R. et al Successful Use of Entecavir in Hepatitis B-associated Membranous Nephropathy. J Trop Pediatr 2018; 64: 249-252
119 Jung WJ, Jang JY, Park WY. et al Effect of tenofovir on renal function in patients with chronic hepatitis B. Medicine (Baltimore) 2018; 97: e9756
120 De Clercq E. Role of tenofovir alafenamide (TAF) in the treatment and prophylaxis of HIV and HBV infections. Biochem Pharmacol 2018; 153: 2-11
121 Berchtold L, Zanetta G, Dahan K. et al Efficacy and Safety of Rituximab in Hepatitis B Virus-Associated PLA2R-Positive Membranous Nephropathy. Kidney Int Rep 2018; 3: 486-491
122 Buonomo AR, Viceconte G, Scotto R. et al Seronegative occult HBV reactivation complicated with fulminant acute liver failure after rituximab for chronic inflammatory demyelinating polyneuropathy. Infect Dis (Lond) 2020; 52: 216-218
123 Chang WY, Chiu YC, Chiu FW. et al High Risk of Clinical Relapse in Patients With Chronic Hepatitis B Virus Infection After Cessation of Prophylactic Antiviral Therapy for Rituximab-Containing Chemotherapy. J Infect Dis 2020; 222: 1345-1352
124 Venkataseshan VS, Lieberman K, Kim DU. et al Hepatitis-B-associated glomerulonephritis: pathology, pathogenesis, and clinical course. Medicine (Baltimore) 1990; 69: 200-216
125 Sharma A, Sharma K. Hepatotropic viral infection associated systemic vasculitides-hepatitis B virus associated polyarteritis nodosa and hepatitis C virus associated cryoglobulinemic vasculitis. J Clin Exp Hepatol 2013; 3: 204-212
126 Mucino-Bermejo MJ. Mechanisms of kidney dysfunction in the cirrhotic patient: Non-hepatorenal acute-on-chronic kidney damage considerations. Ann Hepatol 2020; 19: 145-152
127 Hughes LB, Bridges Jr SL. Polyarteritis nodosa and microscopic polyangiitis: etiologic and diagnostic considerations. Curr Rheumatol Rep 2002; 4: 75-82
128 Pagnoux C, Seror R, Henegar C. et al Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum 2010; 62: 616-626
129 Guillevin L, Mahr A, Callard P. et al Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore) 2005; 84: 313-322
130 Guillevin L, Mahr A, Cohen P. et al Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa. Arthritis Rheum 2004; 51: 482-487
131 de Luna G, Chauveau D, Aniort J. et al Plasma exchanges for the treatment of severe systemic necrotizing vasculitides in clinical daily practice: Data from the French Vasculitis Study Group. J Autoimmun 2015; 65: 49-55
132 Fernanda F, Serena C, Giustina R. et al Mycophenolate mofetil treatment in two children with severe polyarteritis nodosa refractory to immunosuppressant drugs. Rheumatol Int 2012; 32: 2215-2219
133 Castillo I, Martinez-Ara J, Olea T. et al High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies. Kidney Int 2014; 86: 619-624
134 Sabry AA, Sobh MA, Irving WL. et al A comprehensive study of the association between hepatitis C virus and glomerulopathy. Nephrol Dial Transplant 2002; 17: 239-245
135 Kupin WL. Viral-Associated GN: Hepatitis C and HIV. Clin J Am Soc Nephrol 2017; 12: 1337-1342
136 Barsoum RS, William EA, Khalil SS. Hepatitis C and kidney disease: A narrative review. J Adv Res 2017; 8: 113-130
137 Bunchorntavakul C, Mitrani R, Reddy KR. Advances in HCV and Cryoglobulinemic Vasculitis in the Era of DAAs: Are We at the End of the Road?. J Clin Exp Hepatol 2018; 8: 81-94
138 Terrier B, Carrat F, Krastinova E. et al Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey. Ann Rheum Dis 2013; 72: 374-380
139 Fogo AB, Lusco MA, Najafian B. et al AJKD Atlas of Renal Pathology: Cryoglobulinemic Glomerulonephritis. Am J Kidney Dis 2016; 67: e5-e7
140 Harle JR, Disdier P, Dussol B. et al Membranoproliferative glomerulonephritis and hepatitis C infection. Lancet 1993; 341: 904
141 Johnson RJ, Gretch DR, Yamabe H. et al Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med 1993; 328: 465-470
142 Gragnani L, Visentini M, Fognani E. et al Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia. Hepatology 2016; 64: 1473-1482
143 Saadoun D, Thibault V, Si Ahmed SN. et al Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVALDIC study. Ann Rheum Dis 2016; 75: 1777-1782
144 Sise ME, Bloom AK, Wisocky J. et al Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents. Hepatology 2016; 63: 408-417
145 Bonacci M, Lens S, Londono MC. et al Virologic, Clinical, and Immune Response Outcomes of Patients With Hepatitis C Virus-Associated Cryoglobulinemia Treated With Direct-Acting Antivirals. Clin Gastroenterol Hepatol 2017; 15: 575-583 e571
146 Obata F, Murakami T, Miyagi J. et al A case of rapid amelioration of hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis treated by interferon-free directly acting antivirals for HCV in the absence of immunosuppressant. CEN Case Rep 2017; 6: 55-60
147 Tsuge M, Hiramatsu A, Shinohara F. et al Improvement of renal dysfunction in a patient with hepatitis C virus-related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report. Hepatol Res 2016; 46: 944-948
148 Gane E, Lawitz E, Pugatch D. et al Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment. N Engl J Med 2017; 377: 1448-1455
149 Bruchfeld A, Roth D, Martin P. et al Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol 2017; 2: 585-594
150 Alric L, Ollivier-Hourmand I, Berard E. et al Grazoprevir plus elbasvir in HCV genotype-1 or -4 infected patients with stage 4/5 severe chronic kidney disease is safe and effective. Kidney Int 2018; 94: 206-213
151 Toyoda H, Kumada T, Tada T. et al Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. J Gastroenterol 2016; 51: 741-747
152 Kawakami Y, Imamura M, Ikeda H. et al Pharmacokinetics, efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: pilot study. J Viral Hepat 2016; 23: 850-856
153 De Vita S, Quartuccio L, Isola M. et al A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis Rheum 2012; 64: 843-853
154 Koratala A, Zeng X. Rituximab therapy for hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis. Clin Case Rep 2018; 6: 442-443
155 Montero N, Fava A, Rodriguez E. et al Treatment for hepatitis C virus-associated mixed cryoglobulinaemia. Cochrane Database Syst Rev 2018; 5: CD011403
156 Noble J, Jouve T, Malvezzi P. et al Renal complications of liver diseases. Expert Rev Gastroenterol Hepatol 2018; 12: 1135-1142
157 Mazzaro C, Dal Maso L, Quartuccio L. et al Long-term effects of the new direct antiviral agents (DAAs) therapy for HCV-related mixed cryoglobulinaemia without renal involvement: a multicentre open-label study. Clin Exp Rheumatol 2018; 36 (Suppl. 111) 107-114
158 Emery JS, Kuczynski M, La D. et al Efficacy and Safety of Direct Acting Antivirals for the Treatment of Mixed Cryoglobulinemia. Am J Gastroenterol 2017; 112: 1298-1308
159 Dammacco F, Lauletta G, Russi S. et al Clinical practice: hepatitis C virus infection, cryoglobulinemia and cryoglobulinemic vasculitis. Clin Exp Med 2019; 19: 1-21
160 Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol 2014; 20: 7544-7554
161 Appel GB. Immune-complex glomerulonephritis – deposits plus interest. N Engl J Med 1993; 328: 505-506
162 Sansonno D, Lauletta G, Montrone M. et al Hepatitis C virus RNA and core protein in kidney glomerular and tubular structures isolated with laser capture microdissection. Clin Exp Immunol 2005; 140: 498-506
163 Spatola L, Generali E, Angelini C. et al HCV-negative mixed cryoglobulinemia and kidney involvement: in-depth review on physiopathological and histological bases. Clin Exp Med 2018; 18: 465-471
164 Saadoun D, Terrier B, Semoun O. et al Hepatitis C virus-associated polyarteritis nodosa. Arthritis Care Res (Hoboken) 2011; 63: 427-435
165 Ramos-Casals M, Munoz S, Medina F. et al Systemic autoimmune diseases in patients with hepatitis C virus infection: characterization of 1020 cases (The HISPAMEC Registry). J Rheumatol 2009; 36: 1442-1448
166 Angeletti A, Cantarelli C, Cravedi P. HCV-Associated Nephropathies in the Era of Direct Acting Antiviral Agents. Front Med (Lausanne) 2019; 6: 20
167 Lai TS, Lee MH, Yang HI. et al Hepatitis C viral load, genotype, and increased risk of developing end-stage renal disease: REVEAL-HCV study. Hepatology 2017; 66: 784-793
168 Sabry A, A EA, Sheashaa H et al. HCV associated glomerulopathy in Egyptian patients: clinicopathological analysis. Virology 2005; 334: 10-16
169 Pol S, Parlati L, Jadoul M. Hepatitis C virus and the kidney. Nat Rev Nephrol 2019; 15: 73-86
170 Fabrizi F, Messa P. Treatment Choices for Hepatitis C in Patients with Kidney Disease. Clin J Am Soc Nephrol 2018; 13: 793-795
171 Perico N, Cattaneo D, Bikbov B. et al Hepatitis C infection and chronic renal diseases. Clin J Am Soc Nephrol 2009; 4: 207-220
172 European Association for theStudy of the Liver. Electronic address eee, Clinical Practice Guidelines Panel C, representative EGB et al. EASL recommendations on treatment of hepatitis C: Final update of the series. J Hepatol 2020; 73: 1170-1218
173 Sarrazin C, Zimmermann T, Berg T. et al [Prophylaxis, diagnosis and therapy of hepatitis-C-virus (HCV) infection: the German guidelines on the management of HCV infection – AWMF-Register-No.: 021/012]. Z Gastroenterol 2018; 56: 756-838
174 Jadoul M, Berenguer MC, Doss W. et al Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management. Kidney Int 2018; 94: 663-673
175 AASLD–IDSA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. In; 2017: HCV Guidelines
176 Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med 2009; 361: 1279-1290
177 Durand F, Graupera I, Gines P. et al Pathogenesis of Hepatorenal Syndrome: Implications for Therapy. Am J Kidney Dis 2016; 67: 318-328
178 Wong F. The evolving concept of acute kidney injury in patients with cirrhosis. Nat Rev Gastroenterol Hepatol 2015; 12: 711-719
179 Salerno F, Gerbes A, Gines P. et al Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut 2007; 56: 1310-1318
180 Gerbes AL, Labenz J, Appenrodt B. et al [Updated S2k-Guideline “Complications of liver cirrhosis”. German Society of Gastroenterology (DGVS)]. Z Gastroenterol 2019; 57: e168
181 Sort P, Navasa M, Arroyo V. et al Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. The New England journal of medicine 1999; 341: 403-409
182 Follo A, Llovet JM, Navasa M. et al Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. Hepatology 1994; 20: 1495-1501
183 Fasolato S, Angeli P, Dallagnese L. et al Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features. Hepatology 2007; 45: 223-229
184 Terra C, Guevara M, Torre A. et al Renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis: value of MELD score. Gastroenterology 2005; 129: 1944-1953
185 Gines A, Fernandez-Esparrach G, Monescillo A. et al Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology 1996; 111: 1002-1010
186 Angeli P, Fasolato S, Mazza E. et al Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial. Gut 2010; 59: 98-104
187 Akriviadis E, Botla R, Briggs W. et al Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119: 1637-1648
188 Leithead JA, Ferguson JW, Bates CM. et al The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure. Gut 2009; 58: 443-449
189 Lima C, Macedo E. Urinary Biochemistry in the Diagnosis of Acute Kidney Injury. Dis Markers 2018; 2018: 4907024
190 Davenport A, Argawal B, Wright G. et al Can non-invasive measurements aid clinical assessment of volume in patients with cirrhosis?. World J Hepatol 2013; 5: 433-438
191 Ostermann M, Joannidis M. Acute kidney injury 2016: diagnosis and diagnostic workup. Crit Care 2016; 20: 299
192 Francoz C, Nadim MK, Durand F. Kidney biomarkers in cirrhosis. J Hepatol 2016; 65: 809-824
193 Sinclair M, Gow PJ, Grossmann M. et al Review article: sarcopenia in cirrhosis – aetiology, implications and potential therapeutic interventions. Alimentary pharmacology & therapeutics 2016; 43: 765-777
194 Piano S, Rosi S, Maresio G. et al Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. Journal of hepatology 2013; 59: 482-489
195 Wong F, O'Leary JG, Reddy KR. et al New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection. Gastroenterology 2013; 145: 1280-1288 e1281
196 Belcher JM, Garcia-Tsao G, Sanyal AJ. et al Association of AKI with mortality and complications in hospitalized patients with cirrhosis. Hepatology 2013; 57: 753-762
197 Fagundes C, Barreto R, Guevara M. et al A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis. J Hepatol 2013; 59: 474-481
198 Tsien CD, Rabie R, Wong F. Acute kidney injury in decompensated cirrhosis. Gut 2013; 62: 131-137
199 de Carvalho JR, Villela-Nogueira CA, Luiz RR. et al Acute kidney injury network criteria as a predictor of hospital mortality in cirrhotic patients with ascites. Journal of clinical gastroenterology 2012; 46: e21-e26
200 Angeli P, Gines P, Wong F. et al Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Journal of hepatology 2015; 62: 968-974
201 Angeli P, Garcia-Tsao G, Nadim MK. et al News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document. J Hepatol 2019; 71: 811-822
202 [Anonym]. Summary of Recommendation Statements. Kidney international supplements 2012; 2: 8-12
203 Simonetto DA, Gines P, Kamath PS. Hepatorenal syndrome: pathophysiology, diagnosis, and management. BMJ 2020; 370: m2687
204 Badr KF, Ichikawa I. Prerenal failure: a deleterious shift from renal compensation to decompensation. N Engl J Med 1988; 319: 623-629
205 Sansoe G, Silvano S, Mengozzi G. et al Loss of tubuloglomerular feedback in decompensated liver cirrhosis: physiopathological implications. Dig Dis Sci 2005; 50: 955-963
206 Stadlbauer V, Wright GA, Banaji M. et al Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis. Gastroenterology 2008; 134: 111-119
207 Bonavia A, Vece G, Karamchandani K. Prerenal acute kidney injury-still a relevant term in modern clinical practice?. Nephrol Dial Transplant 2020;
208 Ala A, Walker AP, Ashkan K. et al Wilson's disease. Lancet 2007; 369: 397-408
209 Scheiber IF, Bruha R, Dusek P. Pathogenesis of Wilson disease. Handb Clin Neurol 2017; 142: 43-55
210 Tsuchiya M, Takaki R, Kobayashi F. et al Multiple pseudofractures due to Fanconi's syndrome associated with Wilson's disease. Rinsho Shinkeigaku 2017; 57: 527-530
211 Wang H, Zhou Z, Hu J. et al Renal impairment in different phenotypes of Wilson disease. Neurol Sci 2015; 36: 2111-2115
212 Efe C, Ozaslan E, Purnak T. et al Membranous glomerulonephritis associated with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a very rare condition. Eur J Gastroenterol Hepatol 2010; 22: 1149-1150
213 Fickert P, Krones E, Pollheimer MJ. et al Bile acids trigger cholemic nephropathy in common bile-duct-ligated mice. Hepatology 2013; 58: 2056-2069
214 van Slambrouck CM, Salem F, Meehan SM. et al Bile cast nephropathy is a common pathologic finding for kidney injury associated with severe liver dysfunction. Kidney Int 2013; 84: 192-197
215 Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology 2008; 48: 2064-2077
216 Russ KB, Stevens TM, Singal AK. Acute Kidney Injury in Patients with Cirrhosis. J Clin Transl Hepatol 2015; 3: 195-204
217 Hara N, Kawaguchi M, Takeda K. et al Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis. World J Gastroenterol 2014; 20: 16550-16558
218 Lei WH, Xin J, Shao CX. et al IgG4-related Kidney Disease Mimicking Malignant Ureter Tumor: Case Report and Literature Review. Medicine (Baltimore) 2016; 95: e2550
219 Esprit DH, Koratala A, Chornyy V. et al Obstructive Nephropathy Without Hydronephrosis: Suspicion Is the Key. Urology 2017; 101: e9-e10