Skip to main content
Top
Published in: Journal of Gastroenterology 1/2021

01-01-2021 | Acute Kidney Injury | Original Article—Liver, Pancreas, and Biliary Tract

Impact of acute kidney injury on prognosis and the effect of tolvaptan in patients with hepatic ascites

Authors: Yasunari Hiramine, Hirofumi Uto, Seiichi Mawatari, Shuji Kanmura, Yasushi Imamura, Takuya Hiwaki, Akiko Saishoji, Manei Oku, Koichi Tokushige, Shigeho Maenohara, Akio Ido

Published in: Journal of Gastroenterology | Issue 1/2021

Login to get access

Abstract

Background

In hepatic cirrhosis, ascites and acute kidney injury (AKI) portend poor prognosis. We examined the incidence and characteristics of AKI in patients with hepatic ascites and the impact of diuretics on AKI onset.

Methods

This study included 337 patients with hepatic ascites treated with oral diuretics during September 2013–June 2019. Incidence of AKI, cumulative survival by AKI status, and prognostic factors were investigated.
Patients were divided into those treated with tolvaptan (TLV) [TLV group (n = 244)] and those not treated with TLV [control group (n = 93)]. After propensity score matching, the incidence of AKI and changes in renal function and doses of diuretics were compared.

Results

The incidence of AKI overall was 35% (n = 118). Patients with AKI had a significantly worse survival than those without AKI (P = 0.001), indicating that AKI is an independent prognostic factor for hepatic ascites (P = 0.025).
After adjustment for background factors in the two groups (n = 77 each), the TLV group had a significantly lower incidence of AKI (27.6% vs. 44.7%, P = 0.028). While renal function worsened with higher natriuretic agent doses in the control group, no significant change was observed in the TLV group, suggesting that TLV is an independent prognostic factor for AKI onset.

Conclusions

Our study suggests that concomitant AKI significantly worsens survival in Japanese patients with hepatic ascites, and TLV and natriuretic agent combination therapy might lead to an excellent synergistic therapeutic effect of hepatic ascites and inhibition of AKI onset.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987;7:122–8.PubMed Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987;7:122–8.PubMed
2.
go back to reference European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397–417. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397–417.
3.
go back to reference Arroyo V, Gines P. Mechanism of sodium retention and ascites formation in cirrhosis. J Hepatol. 1993;17:24–8. Arroyo V, Gines P. Mechanism of sodium retention and ascites formation in cirrhosis. J Hepatol. 1993;17:24–8.
4.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical practice guideline for acute kidney injury. Kidney Int. 2012;2:1–138. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical practice guideline for acute kidney injury. Kidney Int. 2012;2:1–138.
5.
go back to reference Kellum JA, Ronco C, Bellomo R. Acute kidney disease and the community. Lancet. 2016;387:1974–6.PubMed Kellum JA, Ronco C, Bellomo R. Acute kidney disease and the community. Lancet. 2016;387:1974–6.PubMed
6.
go back to reference Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48:2064–77.PubMed Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48:2064–77.PubMed
7.
go back to reference Belcher JM, Sanyal AJ, Peixoto AJ, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014;60:622–32.PubMedPubMedCentral Belcher JM, Sanyal AJ, Peixoto AJ, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014;60:622–32.PubMedPubMedCentral
8.
go back to reference 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;59:474–81.PubMed 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;59:474–81.PubMed
9.
go back to reference Piano S, Rosi S, Maresio G, et al. Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. J Hepatol. 2013;59:482–9.PubMed Piano S, Rosi S, Maresio G, et al. Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. J Hepatol. 2013;59:482–9.PubMed
10.
go back to reference Tsien CD, Rabie R, Wong F. Acute kidney injury in decompensated cirrhosis. Gut. 2013;62:131–7.PubMed Tsien CD, Rabie R, Wong F. Acute kidney injury in decompensated cirrhosis. Gut. 2013;62:131–7.PubMed
11.
go back to reference 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. Gut. 2015;64:531–7.PubMed 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. Gut. 2015;64:531–7.PubMed
12.
go back to reference European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–60. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–60.
13.
go back to reference Bassegoda O, Huelin P, Ariza X, et al. Development of chronic kidney disease after acute kidney injury in patients with cirrhosis is common and impairs clinical outcomes. J Hepatol. 2020;72:1132–9.PubMed Bassegoda O, Huelin P, Ariza X, et al. Development of chronic kidney disease after acute kidney injury in patients with cirrhosis is common and impairs clinical outcomes. J Hepatol. 2020;72:1132–9.PubMed
14.
go back to reference Cullaro G, Park M. “Normal” creatinine levels predict persistent kidney injury and waitlist mortality in outpatients with cirrhosis. Hepatology. 2018;68:1953–60.PubMedPubMedCentral Cullaro G, Park M. “Normal” creatinine levels predict persistent kidney injury and waitlist mortality in outpatients with cirrhosis. Hepatology. 2018;68:1953–60.PubMedPubMedCentral
15.
go back to reference Huelin P, Solà E, Elia C, et al. Neutrophil gelatinase-associated lipocalin for assessment of acute kidney injury in cirrhosis: a prospective study. Hepatology. 2019;70:319–33.PubMed Huelin P, Solà E, Elia C, et al. Neutrophil gelatinase-associated lipocalin for assessment of acute kidney injury in cirrhosis: a prospective study. Hepatology. 2019;70:319–33.PubMed
16.
go back to reference Laffi G, La Villa G, Carloni V, et al. Loop diuretic therapy in liver cirrhosis with ascites. J Cardiovasc Pharmacol. 1993;22(Suppl 3):S51–S5858.PubMed Laffi G, La Villa G, Carloni V, et al. Loop diuretic therapy in liver cirrhosis with ascites. J Cardiovasc Pharmacol. 1993;22(Suppl 3):S51–S5858.PubMed
17.
go back to reference Costello-Boerrigter LC, Smith WB, Boerrigter G, et al. Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol. 2006;290:F273–F278278.PubMed Costello-Boerrigter LC, Smith WB, Boerrigter G, et al. Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol. 2006;290:F273–F278278.PubMed
18.
go back to reference Imamura T, Kinugawa K, Fujino T, et al. Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure. Circ J. 2014;78:2240–9.PubMed Imamura T, Kinugawa K, Fujino T, et al. Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure. Circ J. 2014;78:2240–9.PubMed
19.
go back to reference Sakaida I, Kawazoe S, Kajimura K, et al. Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Hepatol Res. 2014;44:73–82.PubMed Sakaida I, Kawazoe S, Kajimura K, et al. Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Hepatol Res. 2014;44:73–82.PubMed
20.
go back to reference Sakaida I, Nakajima K, Okita K, et al. Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis? A post hoc analysis of previous clinical trials in Japan. J Gastroenterol. 2015;50:1047–53.PubMedPubMedCentral Sakaida I, Nakajima K, Okita K, et al. Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis? A post hoc analysis of previous clinical trials in Japan. J Gastroenterol. 2015;50:1047–53.PubMedPubMedCentral
21.
go back to reference Fukui H, Saito H, Ueno Y, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51:629–50.PubMed Fukui H, Saito H, Ueno Y, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51:629–50.PubMed
22.
go back to reference Iwamoto T, Maeda M, Saeki I, Hidaka I, Tajima K, Ishikawa T, et al. Analysis of tolvaptan non-responders and outcomes of tolvaptan treatment of ascites. J Gastroenterol Hepatol. 2019;34:1231–5.PubMed Iwamoto T, Maeda M, Saeki I, Hidaka I, Tajima K, Ishikawa T, et al. Analysis of tolvaptan non-responders and outcomes of tolvaptan treatment of ascites. J Gastroenterol Hepatol. 2019;34:1231–5.PubMed
23.
go back to reference Sakaida I, Terai S, Kurosaki M, Okada M, Hirano T, Fukuta Y. Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study). J Gastroenterol. 2020;55:800–10.PubMedPubMedCentral Sakaida I, Terai S, Kurosaki M, Okada M, Hirano T, Fukuta Y. Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study). J Gastroenterol. 2020;55:800–10.PubMedPubMedCentral
24.
go back to reference Hiramine Y, Uojima H, Nakanishi H, Hiramatsu A, Iwamoto T, Kimura M, et al. Response criteria of tolvaptan for the treatment of hepatic edema. J Gastroenterol. 2018;53:258–68.PubMed Hiramine Y, Uojima H, Nakanishi H, Hiramatsu A, Iwamoto T, Kimura M, et al. Response criteria of tolvaptan for the treatment of hepatic edema. J Gastroenterol. 2018;53:258–68.PubMed
25.
go back to reference Hiramine Y, Uto H, Mawatari S, et al. Effect of tolvaptan on the prognosis of patients with hepatic ascites. Hepatol Res. 2019;49:765–77.PubMed Hiramine Y, Uto H, Mawatari S, et al. Effect of tolvaptan on the prognosis of patients with hepatic ascites. Hepatol Res. 2019;49:765–77.PubMed
26.
go back to reference Wong F, O'Leary JG, Reddy KR, et al. Acute kidney injury in cirrhosis: baseline serum creatinine predicts patient outcomes. Am J Gastroenterol. 2017;112:1103–10.PubMed Wong F, O'Leary JG, Reddy KR, et al. Acute kidney injury in cirrhosis: baseline serum creatinine predicts patient outcomes. Am J Gastroenterol. 2017;112:1103–10.PubMed
27.
go back to reference Umemura T, Joshita S, Shibata S, et al. Renal impairment is associated with increased risk of mortality in patients with cirrhosis: a retrospective cohort study. Medicine (Baltimore). 2019;98:e14475. Umemura T, Joshita S, Shibata S, et al. Renal impairment is associated with increased risk of mortality in patients with cirrhosis: a retrospective cohort study. Medicine (Baltimore). 2019;98:e14475.
28.
go back to reference Ginès P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361:1279–90.PubMed Ginès P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361:1279–90.PubMed
29.
go back to reference Boyer TD, Warnock DG. Use of diuretics in the treatment of cirrhotic ascites. Gastroenterology. 1983;84(5 Pt 1):1051–5.PubMed Boyer TD, Warnock DG. Use of diuretics in the treatment of cirrhotic ascites. Gastroenterology. 1983;84(5 Pt 1):1051–5.PubMed
30.
go back to reference Kanzaki G, Puelles VG, Cullen-McEwen LA, et al. New insights on glomerular hyperfiltration: a Japanese autopsy study. JCI Insight. 2017;2:94334.PubMed Kanzaki G, Puelles VG, Cullen-McEwen LA, et al. New insights on glomerular hyperfiltration: a Japanese autopsy study. JCI Insight. 2017;2:94334.PubMed
31.
go back to reference Arroyo V, Ginès P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Internat Ascites Club Hepatol. 1996;23:164–76. Arroyo V, Ginès P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Internat Ascites Club Hepatol. 1996;23:164–76.
32.
go back to reference Okabe T, Yakushiji T, Kido T, et al. The association between high-dose loop diuretic use at discharge and cardiovascular mortality in patients with heart failure. ESC Heart Fail. 2018;5:87–94.PubMed Okabe T, Yakushiji T, Kido T, et al. The association between high-dose loop diuretic use at discharge and cardiovascular mortality in patients with heart failure. ESC Heart Fail. 2018;5:87–94.PubMed
33.
go back to reference Atsukawa M, Tsubota A, Takaguchi K, et al. Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema. J Gastroenterol Hepatol. 2020;35:1229–377.PubMed Atsukawa M, Tsubota A, Takaguchi K, et al. Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema. J Gastroenterol Hepatol. 2020;35:1229–377.PubMed
34.
go back to reference Mehta RL, Pascual MT, Soroko S, et al. PICARD Study Group Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA. 2002;288:2547–53. Mehta RL, Pascual MT, Soroko S, et al. PICARD Study Group Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA. 2002;288:2547–53.
35.
go back to reference Kapelios CJ, Kaldara E, Ntalianis A, et al. High furosemide dose has detrimental effects on survival of patients with stable heart failure. Hellenic J Cardiol. 2015;56:154–9.PubMed Kapelios CJ, Kaldara E, Ntalianis A, et al. High furosemide dose has detrimental effects on survival of patients with stable heart failure. Hellenic J Cardiol. 2015;56:154–9.PubMed
36.
go back to reference Vaz NF, da Cunha VNR, Cunha-Silva M, et al. Evolution of diagnostic criteria for acute kidney injury in patients with decompensated cirrhosis: a prospective study in a tertiary university hospital. Clin Res Hepatol Gastroenterol. 2019;16:2210–7401. Vaz NF, da Cunha VNR, Cunha-Silva M, et al. Evolution of diagnostic criteria for acute kidney injury in patients with decompensated cirrhosis: a prospective study in a tertiary university hospital. Clin Res Hepatol Gastroenterol. 2019;16:2210–7401.
37.
go back to reference Prowle JR, Echeverri JE, Ligabo EV, et al. Fluid balance and acute kidney injury. Nat Rev Nephrol. 2010;6:107–15.PubMed Prowle JR, Echeverri JE, Ligabo EV, et al. Fluid balance and acute kidney injury. Nat Rev Nephrol. 2010;6:107–15.PubMed
38.
go back to reference Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797–805.PubMedPubMedCentral Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797–805.PubMedPubMedCentral
39.
go back to reference Mori T, Ohsaki Y, Oba-Yabana I, et al. Diuretic usage for protection against end-organ damage in liver cirrhosis and heart failure. Hepatol Res. 2017;47:11–22.PubMed Mori T, Ohsaki Y, Oba-Yabana I, et al. Diuretic usage for protection against end-organ damage in liver cirrhosis and heart failure. Hepatol Res. 2017;47:11–22.PubMed
40.
go back to reference Sersté T, Gustot T, Rautou PE, et al. Severe hyponatremia is a better predictor of mortality than MELDNa in patients with cirrhosis and refractory ascites. J Hepatol. 2012;57:274–80.PubMed Sersté T, Gustot T, Rautou PE, et al. Severe hyponatremia is a better predictor of mortality than MELDNa in patients with cirrhosis and refractory ascites. J Hepatol. 2012;57:274–80.PubMed
41.
go back to reference Angeli P, Wong F, Watson H, et al. Hyponatremia in cirrhosis: Results of a patient population survey. Hepatology. 2006;44:1535–42.PubMed Angeli P, Wong F, Watson H, et al. Hyponatremia in cirrhosis: Results of a patient population survey. Hepatology. 2006;44:1535–42.PubMed
42.
go back to reference Uojima H, Hidaka H, Nakayama T, et al. Efficacy of combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients: a randomized study. World J Gastroenterol. 2017;23:8062–72.PubMedPubMedCentral Uojima H, Hidaka H, Nakayama T, et al. Efficacy of combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients: a randomized study. World J Gastroenterol. 2017;23:8062–72.PubMedPubMedCentral
43.
go back to reference Namba M, Hiramatsu A, Aikata H, et al. Management of refractory ascites attenuates muscle mass reduction and improves survival in patients with decompensated cirrhosis. J Gastroenterol. 2020;55:217–26.PubMed Namba M, Hiramatsu A, Aikata H, et al. Management of refractory ascites attenuates muscle mass reduction and improves survival in patients with decompensated cirrhosis. J Gastroenterol. 2020;55:217–26.PubMed
44.
go back to reference Mindikoglu AL, Hernaez R, Liu Y, et al. Renal trajectory patterns are associated with post-discharge mortality in patients with cirrhosis and acute kidney injury. Clin Gastroenterol Hepatol. 2020;18:1858–66.PubMed Mindikoglu AL, Hernaez R, Liu Y, et al. Renal trajectory patterns are associated with post-discharge mortality in patients with cirrhosis and acute kidney injury. Clin Gastroenterol Hepatol. 2020;18:1858–66.PubMed
45.
go back to reference Chawla LS, Eggers PW, Star RA, et al. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014;371(1):58–66. Chawla LS, Eggers PW, Star RA, et al. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014;371(1):58–66.
46.
go back to reference Komiyama Y, Kurosaki M, Nakanishi H, Takahashi Y, Itakura J, Yasui Y, et al. Prediction of diuretic response to tolvaptan by a simple, readily available spot urine Na/K ratio. PLoS ONE. 2017;12:e0174649.PubMedPubMedCentral Komiyama Y, Kurosaki M, Nakanishi H, Takahashi Y, Itakura J, Yasui Y, et al. Prediction of diuretic response to tolvaptan by a simple, readily available spot urine Na/K ratio. PLoS ONE. 2017;12:e0174649.PubMedPubMedCentral
47.
go back to reference Kudo M, Kitano M, Sakurai T, et al. General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the liver cancer study group of Japan. Dig Dis. 2015;33:765–70.PubMed Kudo M, Kitano M, Sakurai T, et al. General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the liver cancer study group of Japan. Dig Dis. 2015;33:765–70.PubMed
Metadata
Title
Impact of acute kidney injury on prognosis and the effect of tolvaptan in patients with hepatic ascites
Authors
Yasunari Hiramine
Hirofumi Uto
Seiichi Mawatari
Shuji Kanmura
Yasushi Imamura
Takuya Hiwaki
Akiko Saishoji
Manei Oku
Koichi Tokushige
Shigeho Maenohara
Akio Ido
Publication date
01-01-2021
Publisher
Springer Singapore
Published in
Journal of Gastroenterology / Issue 1/2021
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-020-01727-2

Other articles of this Issue 1/2021

Journal of Gastroenterology 1/2021 Go to the issue