Pre- and post-transplant renal complications in liver cirrhosis: Pathophysiology, risk factors, and management
Renal dysfunction is a major determinant of morbidity, mortality, transplant candidacy, and post-transplant outcomes in cirrhosis. Acute kidney injury (AKI) develops frequently during hospitalization and is driven by circulatory dysfunction, portal hypertension, infection, gastrointestinal bleeding, diuretic exposure, nephrotoxins, and hepatorenal syndrome (HRS). Chronic kidney disease is increasingly recognized in this population and often reflects recurrent AKI, viral or alcohol-related glomerular disease, metabolic dysfunction-associated steatotic liver disease, diabetes, hypertension, or persistent renal hypoperfusion. Diagnosis remains difficult because serum creatinine underestimates renal impairment in cirrhosis. Urinalysis, renal ultrasonography, medication review, volume assessment, and selected biomarkers such as urinary neutrophil gelatinase-associated lipocalin, cystatin C, and tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 may improve phenotyping, although biomarker-guided algorithms require further validation. Management before transplantation requires early discontinuation of nephrotoxins, careful volume resuscitation, albumin when indicated, timely treatment of infection, and vasoconstrictor therapy for HRS-AKI, with renal replacement therapy considered when standard indications arise. After liver transplantation, renal injury remains multifactorial and is influenced by pre-existing kidney disease, perioperative hemodynamic instability, ischemia-reperfusion injury, sepsis, and calcineurin inhibitor nephrotoxicity. Kidney-sparing immunosuppression, cardiovascular risk control, and structured follow-up are central to preserving renal function. Decisions regarding liver-alone transplantation, kidney-after-liver transplantation, or simultaneous liver-kidney transplantation should integrate the duration and reversibility of renal dysfunction, dialysis exposure, estimated glomerular filtration rate, and Organ Procurement and Transplantation Network Safety Net criteria. Accurate renal phenotyping across the pre- and post-transplant continuum is essential for improving survival and guiding transplant strategy.
- Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361(13):1279-90. doi: 10.1056/NEJMra0809139
- Nadim MK, Garcia-Tsao G, Hardin CC. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388(8):733– 745. doi: 10.1056/NEJMra2215289
- Gines A, Escorsell A, Ginès P, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993;105(1):229-36. doi: 10.1016/0016-5085(93)90031-7
- Patidar KR, Belcher JM, Regner KR, et al. Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US. J Hepatol. 2023;79(6):1408–1417. doi: 10.1016/j.jhep.2023.07.010
- Parke CY, Martin P, Bunnapradist S. Renal dysfunction in cirrhosis. Clin Liver Dis. 2015;5(6):150-153. doi: 10.1002/cld.485
- Kumar R, Priyadarshi RN, Anand U. Chronic renal dysfunction in cirrhosis: A new frontier in hepatology. World J Gastroenterol. 2021;27(11):990–1005. doi: 10.3748/wjg.v27.i11.990
- Wong F, Reddy KR, O’Leary JG, et al. Impact of chronic kidney disease on outcomes in cirrhosis. Liver Transpl. 2019;25(6):870-880. doi: 10.1002/lt.25454
- 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(6):1132-1139. doi: 10.1016/j.jhep.2019.12.020
- 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. J Hepatol. 2015;62(4):968–974. doi: 10.1016/j.jhep.2014.12.029
- Kellum JA, Lameire N, Ronco C, et al. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1–138. doi: 10.1038/kisup.2012.1
- Amathieu R, Al-Khafaji A, Sileanu FE, et al. Significance of oliguria in critically ill patients with chronic liver disease. Hepatology. 2017;66(5):1592–1600. doi: 10.1002/hep.29303
- Nadim MK, Kellum JA, Forni L, et al. Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol. 2024;81(1):163–183. doi: 10.1016/j.jhep.2024.03.031
- 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(6):1280-1288. doi: 10.1053/j.gastro.2013.08.051
- Siew ED, Ikizler TA, Matheny ME, et al. Estimating baseline kidney function in hospitalized patients with impaired kidney function. Clin J Am Soc Nephrol. 2012;7(5):712–719. doi: 10.2215/CJN.10821011
- Sawhney S, Bell S, Black C, et al. Harmonization of epidemiology of acute kidney injury and acute kidney disease produces comparable findings across four geographic populations. Kidney Int. 2022;101(6):1271–1281. doi: 10.1016/j.kint.2022.02.033
- Lameire NH, Levin A, Kellum JA, et al. Harmonizing acute and chronic kidney disease definition and classification: report of a kidney disease: improving global outcomes (KDIGO) consensus conference. Kidney Int. 2021;100(3):516–526. doi: 10.1016/j.kint.2021.06.028
- Martin PY, Ginès P, Schrier RW. Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. N Engl J Med. 1998;339(8):533–541. doi: 10.1056/NEJM199808203390807
- Ros J, Clària J, To-Figueras J, et al. Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology. 2002;122(1):85–93. doi: 10.1053/gast.2002.30305
- Møller S, Henriksen JH. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease. Heart. 2002;87(1):9–15. doi: 10.1136/heart.87.1.9
- Lhotta K. Beyond hepatorenal syndrome: glomerulonephritis in patients with liver disease. Semin Nephrol. 2002;22(4):302–308. doi: 10.1053/snep.2002.33671
- Sinn DH, Kang D, Jang HR, et al. Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: A cohort study. J Hepatol. 2017;67(6):1274-1280. doi: 10.1016/j.jhep.2017.08.024
- 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(7):e1001680. doi: 10.1371/journal.pmed.1001680
- Targher G, Chonchol MB, Byrne CD. CKD and nonalcoholic fatty liver disease. Am J Kidney Dis. 2014;64(4):638-652. doi: 10.1053/j.ajkd.2014.05.019
- Russ KB, Stevens TM, Singal AK. Acute kidney injury in patients with cirrhosis. J Clin Transl Hepatol. 2015;3(3):195– 204. doi: 10.14218/JCTH.2015.00015
- Moreau R, Durand F, Poynard T, et al. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology. 2002;122(4):923–930. doi: 10.1053/gast.2002.32364
- Russ KB, Kuo YF, Singal AK. Renal function and acute kidney injury among cirrhosis patients listed for liver transplantation: a prospective study. Am J Gastroenterol. 2014;109:S173. doi: 10.14309/00000434-201410002-00590
- Nadim MK, Durand F, Kellum JA, et al. Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol. 2016;64(3):717–735. doi: 10.1016/j.jhep.2015.10.019
- Angeli P, Bernardi M, Villanueva C, et al. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–460. doi: 10.1016/j.jhep.2018.03.024
- Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014–1048. doi: 10.1002/hep.31884
- Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247–2256. doi: 10.1056/NEJMoa040232
- Umgelter A, Reindl W, Wagner KS, et al. Effects of plasma expansion with albumin and paracentesis on haemodynamics and kidney function in critically ill cirrhotic patients with tense ascites and hepatorenal syndrome: a prospective uncontrolled trial. Crit Care. 2008;12(1):R4. doi: 10.1186/cc6765
- Facciorusso A, Chandar AK, Murad MH, et al. Comparative efficacy of pharmacological strategies for management of type 1 hepatorenal syndrome: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2017;2(2):94–102. doi: 10.1016/S2468-1253(16)30157-1
- Pitre T, Kiflen M, Helmeczi W, et al. The comparative effectiveness of vasoactive treatments for hepatorenal syndrome: a systematic review and network meta-analysis. Crit Care Med. 2022;50(10):1419–1429. doi: 10.1097/CCM.0000000000005595
- Best LM, Freeman SC, Sutton AJ, et al. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev. 2019;2019(11):CD013103. doi: 10.1002/14651858.CD013103.pub2
- Arora V, Maiwall R, Rajan V, et al. Terlipressin is superior to noradrenaline in the management of acute kidney injury in acute on chronic liver failure. Hepatology. 2020;71(2):600–610. doi: 10.1002/hep.30208
- Maddukuri G, Cai CX, Munigala S, et al. Targeting an early and substantial increase in mean arterial pressure is critical in the management of type 1 hepatorenal syndrome: a combined retrospective and pilot study. Dig Dis Sci. 2014;59(2):471–481. doi: 10.1007/s10620-013-2899-z
- Boyer TD, Sanyal AJ, Wong F, et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterology. 2016;150(7):1579–1589 e2. doi: 10.1053/j.gastro.2016.02.026
- Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021;384(9):818–828. doi: 10.1056/NEJMoa2008290
- Zarbock A, Küullmar M, Kindgen-Milles D, et al. Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial. JAMA. 2020;324(16):1629–1639. doi: 10.1001/jama.2020.18618
- Wong LP, Blackley MP, Andreoni KA, Chin H, Falk RJ, Klemmer PJ. Survival of liver transplant candidates with acute renal failure receiving renal replacement therapy. Kidney Int. 2005;68(1):362–370. doi: 10.1111/j.1523-1755.2005.00408.x
- Apsner R, Schwarzenhofer M, Derfler K, Zauner C, Ratheiser K, Kranz A. Impairment of citrate metabolism in acute hepatic failure. Wien Klin Wochenschr. 1997;109(4):123– 127.
- Kramer L, Bauer E, Joukhadar C, et al. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003;31(10):2450–2455. doi: 10.1097/01.CCM.0000084871.76568.E6
- Rajora N, De Gregorio L, Saxena R. Peritoneal dialysis use in patients with ascites: a review. Am J Kidney Dis. 2021;78(5):728–735. doi: 10.1053/j.ajkd.2021.04.010
- Bajo MA, Selgas R, Jimenez C, et al. CAPD for treatment of ESRD patients with ascites secondary to liver cirrhosis. Adv Perit Dial. 1994;10:73–76.
- Allegretti AS, Parada XV, Eneanya ND, et al. Prognosis of patients with cirrhosis and AKI who initiate RRT. Clin J Am Soc Nephrol. 2018;13(1):16–25. doi: 10.2215/CJN.03610417
- Rogal SS, Hansen L, Patel A, et al. AASLD Practice Guidance: palliative care and symptom-based management in decompensated cirrhosis. Hepatology. 2022;76(3):819–853. doi: 10.1002/hep.32378
- Pelusio C, Endres P, Neyra JA, Allegretti AS. Renal Replacement Therapy in Cirrhosis: A Contemporary Review. Adv Kidney Dis Health. 2024;31(2):133–138. doi: 10.1053/j.akdh.2024.01.003
- Allegretti AS, Ortiz G, Cui J, et al. Changes in kidney function after transjugular intrahepatic portosystemic shunts versus large-volume paracentesis in cirrhosis: a matched cohort analysis. Am J Kidney Dis. 2016;68(3):381-391. doi: 10.1053/j.ajkd.2016.02.041
- Charilaou P, Devani K, Petrosyan R, et al. Inpatient mortality benefit with transjugular intrahepatic portosystemic shunt for hospitalized hepatorenal syndrome patients. Dig Dis Sci. 2020;65(11):3378–3388. doi: 10.1007/s10620-020-06136-2
- Ponzo P, Campion D, Rizzo M, et al. Transjugular intrahepatic portosystemic shunt in cirrhotic patients with hepatorenal syndrome - chronic kidney disease: impact on renal function. Dig Liver Dis. 2022;54(8):1101–1108. doi: 10.1016/j.dld.2021.09.008
- Belcher JM, Sanyal AJ, Peixoto AJ, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014;60(2):622–632. doi: 10.1002/hep.26980
- Kanduri SR, Velez JCQ. Kidney Dysfunction in the Setting of Liver Failure: Core Curriculum 2024. Am J Kidney Dis. 2024;83(3):386-401. doi: 10.1053/j.ajkd.2023.08.013
- Gambino C, Piano S, Stenico M, et al. Diagnostic and prognostic performance of urinary neutrophil gelatinase-associated lipocalin in patients with cirrhosis and acute kidney injury. Hepatology. 2023;77(5):1630-1638. doi: 10.1002/hep.32799
- Schiefer J, Lichtenegger P, Berlakovich GA, et al. Urinary [TIMP-2] × [IGFBP-7] for predicting acute kidney injury in patients undergoing orthotopic liver transplantation. BMC Nephrol. 2019;20(1). doi: 10.1186/s12882-019-1456-1
- Lima C, Macedo E. Biomarkers in acute kidney injury and cirrhosis. J Transl Crit Care Med. 2024;6(2). doi: 10.1097/jtccm-d-23-00014
- Koyner JL, Zarbock A, Hoste EAJ. Update on perioperative acute kidney injury. Anesth Analg. 2018;127(5):1236–1245. doi: 10.1213/ANE.0000000000003741
- Asrani SK, Shankar N, da Graca B, et al. Role of novel kidney biomarkers in patients with cirrhosis and after liver transplantation. Liver Transpl. 2022;28(3):466–482. doi: 10.1002/lt.26344
- Liu J, Zhao Y, Li ZQ, Chen Q, Luo CQ, Su JX. Biomarkers for detecting and improving AKI after liver transplantation: from diagnosis to treatment. Transplant Rev. 2021;35(2):100602. doi: 10.1016/j.trre.2021.100602
- Jan MY, Patidar KR, Ghabril MS, Kubal CA. Optimization of Kidney Health in Liver Transplant Candidates: Pretransplant Considerations and Modalities. Transplantation. 2024;108(7):1542-1550. doi: 10.1097/TP.0000000000004851
- Jan MY, Patidar KR, Ghabril MS, Kubal CA. Optimization and Protection of Kidney Health in Liver Transplant Recipients: Intra- and Postoperative Approaches. Transplantation. 2025;109(6):938-944. doi: 10.1097/TP.0000000000005252
- Konkoľová M, Skladany L, Cellar M, et al. Acute kidney injury after liver transplantation. Acta Med Mart. 2024;24(2):66–74. doi: 10.2478/acm-2024-0009
- Ali H, Begum Ozturk N, Herdan NE, et al. Current status of simultaneous liver-kidney transplantation. Hepatol Forum. 2024;5(4):207-210. doi: 10.14744/hf.2023.2023.0071
63. Prudhomme T, Mesnard B, Branchereau J, et al. Simultaneous liver-kidney transplantation: future perspective. World J Urol. 2024;42(1):489. doi: 10.1007/s00345-024-05174-z
