Co‐orchestration of acute kidney injury and non‐kidney organ failures in critically ill patients with cirrhosis

Maiwall, Rakhi; Pasupuleti, Samba Siva Rao; Chandel, Shivendra Singh; Narayan, Ashad; Jain, Priyanka; Mitra, Lalita Gouri; Kumar, Guresh; Moreau, Richard; Sarin, Shiv Kumar

doi:10.1111/liv.14809

Cited by 14 publications

(18 citation statements)

References 31 publications

(64 reference statements)

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“…Organ failures, especially AKI, form the diagnostic criteria for ACLF according to the European Association for the Study of the Liver (EASL) definition 1 . Furthermore, the presence of AKI determines the outcome of patients with ACLF 2 – 4 . The cause of AKI in ACLF is multi-factorial 3 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Kulkarni

Ravikumar

Tevethia

et al. 2022

Sci Rep

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Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF. We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying EASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, course of HRS-AKI and predictors of mortality. A total of 116 patients were included. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. TFS was 70.4% at day 30 and 57.8% at day 90. On multivariate stepwise Cox regression analysis terlipressin non-response (hazard ratio [HR], 3.49 [1.85–6.57]; P < 0.001) and MELD NA score (HR,1.12 [1.06–1.18]; P < 0.001) predicted mortality at day-90. Patients with ACLF who develop terlipressin related adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.

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Section: Introductionmentioning

confidence: 99%

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Kulkarni

Ravikumar

Tevethia

et al. 2022

Sci Rep

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“…Critically ill cirrhosis patients have a much higher incidence of AKI, which progresses to CKD 5 . Non‐resolution of AKI has been observed in almost 50% of these patients in the first week despite therapeutic interventions 6 . Patients with non‐resolution of AKI (either progression or persistence) in the first week have higher 28‐day mortality 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Non‐resolution of acute kidney injury in the first week portends the development of chronic kidney disease in critically ill patients with cirrhosis

Maiwall

Pasupuleti

Hidam

et al. 2023

Aliment Pharmacol Ther

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SummaryBackgroundRenal tubular epithelial cells (RTECs) cause maladaptive repair and perpetuate renal fibrosis.AimTo evaluate urinary neutrophil gelatinase‐associated lipocalin (NGAL) and RTEC as risk factors for non‐resolution of acute kidney injury (AKI–NR) at day seven and chronic kidney disease (CKD) in critically ill patients with cirrhosis.MethodsWe performed urinary NGAL and microscopy at enrolment and day 7 in all patients. We assessed 17 renal injury, endothelial injury and repair markers, genes for mitochondrial biogenesis by qRT–PCR in RTEC, and post‐mortem renal biopsies for understanding mechanisms of AKI non‐resolution (n = 30).ResultsWe enrolled 310 patients, aged 48.1 ± 11.6 years, 87% male, 90% alcoholic. Of these, 36% had RTEC at enrolment, and 53% had AKI–NR on day 7. On mean follow‐up of 136 days (range 43–365), 150 (48.3%) developed CKD. The presence of RTEC or granular casts, NGAL and AKI–NR were independent predictors of CKD development on competing risk analysis. Higher MCP‐1, renal endothelial injury, decrease in tubular repair markers and failure of mitochondrial biogenesis in RTEC were seen in patients with AKI–NR compared with AKI–R (p < 0.05). Renal biopsies showed infiltration with monocyte–macrophage, increased α‐SMA, and tubulointerstitial fibrosis.ConclusionAlmost two‐thirds of critically ill patients with cirrhosis have AKI, which resolves in only one‐half at day seven and predicts the development of CKD. Higher NGAL, RTEC, or granular casts were independent predictors of AKI–NR and CKD development. Enhanced tubular and endothelial injury, decreased repair, monocyte–macrophage infiltration and mitochondrial dysfunction in RTEC are associated with AKI non‐resolution and risk of renal fibrosis.

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“…There is some disagreement on the de nition/precipitants of ACLF across the continents. However, it is acknowledged that the presence of AKI does determine the outcome of patients with ACLF [2][3][4]. The cause of AKI in ACLF is multi-factorial [3,5].…”

Section: Introductionmentioning

confidence: 99%

Safety And Efficacy of Terlipressin In Acute-On-Chronic Liver Failure With Acute Kidney Injury – A Prospective Cohort Study

Kulkarni

T.R

Tevethia

et al. 2021

Preprint

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Background: Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF.Methods: We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying either EASL or APASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, and differential treatment response in EASL and APASL subgroups. Results: Of the 116 patients, 51 satisfied EASL criteria, and 65 satisfied APASL criteria. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. Response to terlipressin was higher in EASL (78.43%) than APASL subgroup (53.84%;P=0.006). Terlipressin non-response predicted mortality in EASL (aHR,6.35[1.15-35.13];P=0.03) and APASL subgroups (aHR,3.07[1.47-6.4];P=0.003).Conclusion: ACLF patients who develop terlipressin adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.

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Co‐orchestration of acute kidney injury and non‐kidney organ failures in critically ill patients with cirrhosis

Cited by 14 publications

References 31 publications

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Non‐resolution of acute kidney injury in the first week portends the development of chronic kidney disease in critically ill patients with cirrhosis

Safety And Efficacy of Terlipressin In Acute-On-Chronic Liver Failure With Acute Kidney Injury – A Prospective Cohort Study

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