Urinary biomarker NGAL in renal dysfunction in cirrhosis: rational approach to decrease the high costs of the combined therapy with albumin and terlipressin for the SUS

• Grant number: 13/18214-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2014
• End date: January 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alberto Queiroz Farias
• Grantee: Alberto Queiroz Farias
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana de Lourdes Candolo Martinelli ; Flair José Carrilho

Abstract

Renal dysfunction has a high incidence among patients with cirrhosis, occurring in about 20% of in-hospital patients. The etiology is variable, including pre-renal azotemia, acute tubular necrosis (ATN) and hepatorrenal syndrome (HRS). HRS diagnosis is based on the raise of serum creatinine and the exclusion of other causes of renal dysfunction, which implicates volemic expansion with human albumin for two days to exclude pre-renal azotemia. Volemic expansion is expensive and delays the beginning of treatment. Serum creatinine measurement has a limited diagnostic accuracy, taking up to 48 hours to rise. Furthermore, serum creatinine cannot distinguish the etiology of renal dysfunction. For this reason, some patients with ATN are misdiagnosed as HRS cases, which is a consequence of current diagnostic criteria limitations. HRS treatment includes high cost medications (albumin and terlipressin), high incidence of adverse effects and limited efficacy (60% response rate). Neutrophil gelatinase-associated lipocalin (NGAL) measurement has been proposed as a more accurate renal biomarker in cirrhosis, because its urinary level vary according to the etiology of renal dysfunction. We hypothesized that urinary NGAL measurement would identify the subset of patients who would not respond to the therapy with albumin and terlipressin and therefore would not have any benefit from this high cost treatment. Objectives: The primary endpoint will be the establishment of the cut-off value of urinary NGAL clinically useful to predict no response to albumin and terlipressin treatment. Secondary endpoints will be: a) urinary NGAL cut-off to predict no response to initial albumin expansion; b) urinary NGAL accuracy to predict renal dysfunction; c) hemodynamic biomarkers (catecholamines and plasmatic renin activity) accuracy to predict no response to albumin and terlipressin treatment. Patients and methods: Two hundred patients with descompensated cirrhosis will be included, divided into two groups. Group 1 will be composed of patients with renal dysfunction (serum creatinine equal or greater than 1.5mg/dL), with or without bacterial infection. Group 2 will be composed of patients without renal dysfunction (serum creatinine below 1.5mg/dL) with bacterial infection. Inclusion criteria will be: a) diagnosis of cirrhosis; b) presence of ascites and/or hepatic hydrothorax; c) age greater than 18 years old; d) concordance to participate in the study; e) bacterial infection with or without renal dysfunction or absence of bacterial infection with renal dysfunction. Exclusion criteria will be: a) severe systemic comorbidities; b) shock; c) chronic kidney disease; d) intrinsic nephropathy; e) nephrotoxic drugs use; f) previous dialysis; g) liver transplantation. Blood and urine samples will be collected for urinary NGAL, serum catecholamines and renin plasmatic activity at the inclusion and, in those patients treated with albumin and terlipressin, new blood and urine samples will be collected. Patients of group 1 will receive standard treatment, with human albumin infusion for 2 days and, in no responders, albumin and terlipressin up to 14 days. Patients of group 2 who develop renal dysfunction will be treated as described for group 1. All patients will have clinical data collected until three months after hospital discharge. (AU)