Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1.

BACKGROUND: Hepatorenal syndrome type 1 (HRS1) is a functional, rapidly progressive, potentially reversible form of acute kidney injury occurring in patients with cirrhosis. Characterised by intense renal arterial vasoconstriction, it carries a very poor prognosis. There is a significant unmet need for a widely approved, safe and effective pharmacological treatment. AIM: To re-evaluate efficacy and safety of pharmacological treatments for HRS1, in the light of recently published randomised controlled trials (RCTs). METHODS: MEDLINE (OvidSP), EMBASE, PubMed and Cochrane registers were searched for RCTs reporting efficacy and adverse events related to pharmacological treatment of HRS1. Search terms included: 'hepatorenal syndrome', 'terlipressin', 'noradrenaline', 'octreotide', 'midodrine', 'vasopressin', 'dopamine', 'albumin' and synonyms. Comparison of vasoactive drugs vs. placebo/no treatment, and two active drugs were included. Meta-analysis was performed for HRS1 reversal, creatinine improvement, mortality and adverse events. RESULTS: Twelve RCTs enrolling 700 HRS1 patients were included. Treatment with terlipressin and albumin led to HRS1 reversal more frequently than albumin alone or placebo (RR: 2.54, 95% CI: 1.51-4.26). Noradrenaline was effective in reversing HRS1, but trials were small and nonblinded. Overall, there was mortality benefit with terlipressin (RR: 0.79, 95% CI: 0.63-1.01), but sensitivity analysis including only trials with low risk of selection bias weakened this relationship (RR: 0.87, 95% CI: 0.71-1.06). Notably, there was a significant risk of adverse events with terlipressin therapy (RR: 4.32, 95% CI: 0.75-24.86). CONCLUSIONS: Terlipressin treatment is superior to placebo for achieving HRS1 reversal, but mortality benefit is less clear. Terlipressin is associated with significant adverse events, but infusion regimens may be better tolerated. There is continued need for safe and effective treatment options for hepatorenal syndrome.

Chronic kidney disease prevalence and secular trends in a UK population: the impact of MDRD and CKD-EPI formulae.

INTRODUCTION: Most UK laboratories use the MDRD4 formula to estimate glomerular filtration rate (eGFR), but this may exaggerate chronic kidney disease (CKD) prevalence. In a large adult population, we examined the impact of the more accurate CKD-EPI formulae on prevalence estimates, and on secular trends in prevalence. METHODS: We extracted all serum creatinine (SCr) results for adults, processed in our laboratory during two 1-year periods (2004, 2009-10). To minimize the effect of acute illness, a patient's lowest SCr was used for each period. eGFR (traceable to isotope dilution mass spectrometry value) was calculated using the MDRD4 and CKD-EPI formulae. Prevalence estimates were compared, with sub-group analysis by age and sex. RESULTS: In 2004, 102 322 patients had SCr tested (35.4% of the adult population), rising to 123 121 (42.3%) in 2009-10. The proportion tested rose with age to 86% of 85- to 89-year olds. The prevalence of CKD stages 3-5 was lower with the CKD-EPI formulae than the MDRD4 formula. The CKD-EPI formulae reclassified 17 014 patients (5.8%) to milder stages of CKD, most commonly from eGFR 60-89 ml/min/1.73m(2) and CKD stage 3A, in women, and in those <70 years old. 5172 patients (1.8%), mostly elderly women, were reclassified to more severe stages of CKD. Between the two time periods, the prevalence of CKD stages 3-5 rose from 5.44% to 5.63% of the population using MDRD4, but was static at 4.94% with CKD-EPI. CONCLUSION: The CKD-EPI formulae, which are more accurate than the MDRD4 formula at higher GFR, reduced the estimated prevalence of CKD stages 3-5 by 0.5% in 2004 and 0.7% in 2009-10. The greatest reclassification was seen in CKD 3A, particularly amongst middle-aged females. The minor rise in CKD prevalence between 2004 and 2009-10 seen with the MDRD4 formula was not confirmed with the CKD-EPI formulae. The CKD-EPI formulae may reduce overdiagnosis of CKD, but further assessment in the elderly is required before widespread implementation.