septic shock , SBP leads to a pro-inflammatory cytokine storm that further impairs cardiovascular dysfunction . The ensuing worsening in effective volaemia can lead to acute kidney injury ( AKI ), with the phenotype of hepatorenal syndrome ( HRS ) or acute tubular necrosis ( ATN ), which occurs in about 30 % of cases and is a main cause of death . 8 Indeed , SBP-related in-hospital mortality rates can be as high as 20 %, despite the resolution of infection . 7 A prospective randomised study has shown the administration of a high dose of albumin ( 1.5g / kg at diagnosis and 1g / kg on day 3 ) in addition to antibiotic treatment decreases the incidence of renal failure ( from 30 % to 10 %) and improves in-hospital and three-month survival . 9 The capacity of albumin to improve the outcome of patients with SBP has been confirmed in a meta-analysis of randomised trials . 10
The amount of albumin to be administered in this setting and whether all patients have to be treated has not been fully defined . In fact , it would appear that patients at high risk of developing renal failure ( baseline bilirubin > 4mg / dl and / or creatinine > 1.0mg / dl ) benefit most from albumin administration , suggesting that it could be restricted to high-risk patients . However , two large subsequent retrospective studies showed that the incidence of poor outcome in low-risk patients not treated with albumin is not negligible . It has also been reported that a reduceddose regimen of albumin ( 1.0g / kg on day 1 and 0.5g / kg on day 3 ) is as effective as the standard regimen in preventing renal failure and reducing mortality . However , these results still need to be confirmed by further prospective studies in larger patient populations . Thus , to date , the European Association for the Study of the Liver recommends that all patients with SBP should receive intravenous albumin at the higher dosage in addition to antibiotics . 11
Diagnosis and treatment of hepatorenal syndrome HRS is a potentially reversible AKI that occurs
In several randomised trials , albumin was able to lower the incidence of PICD and showed its superiority when compared with other plasma expanders in patients with advanced cirrhosis , ascites and liver failure , associated with marked circulatory dysfunction . 8 HRS is the clinical manifestation of a severe intra-renal vasoconstriction . This results from impaired effective volaemia secondary to both arterial vasodilation and cardiac dysfunction ( cirrhotic cardiomyopathy ), which lead to a striking compensatory activation of vasoconstrictor systems such as the renin – angiotensin system , sympathetic nervous system , and arginine vasopressin . 12 Moreover , inflammation-induced kidney damage likely plays a relevant concomitant role . 6
The diagnosis of HRS requires the exclusion of other forms of AKI . 8 , 11 Ongoing diuretic treatment should be withdrawn . The differential diagnosis between HRS and pre-renal AKI is based on the failure to improve serum creatinine after two days of plasma volume expansion , which is preferentially performed with albumin administration ( recommended dose : 1g / kg of body weight per day , up to a maximum of 100g / day ). The presence of renal structural damage or urinary tract obstruction should be excluded by ultrasonography . Urinalysis abnormalities such as elevated urine sodium concentration , haematuria , proteinuria or presence of casts would suggest ATN . However , the differential diagnosis between HRS and ATN is not always easy , even with the assessment of urinary
13 , 14
biomarkers of renal tubular damage .
Once diagnosis is established , the most effective treatment of HRS includes the administration of vasoconstrictors ( mostly terlipressin ) in association with intravenous albumin ( 20-40g / day up to two weeks ). 11 This treatment improves renal function in about 40 % of cases and leads to the resolution of HRS in about one-third of cases . Survival is only improved in the short term , but this is unsurprising , as patients with HRS usually have a very advanced cirrhosis . Interestingly , the association of terlipressin plus albumin is more effective than terlipressin alone . 15
These favourable effects are amenable to an improvement of effective volaemia , which not only results from plasma volume expansion , but is also due to improvements in stroke work and peripheral vascular resistance , as shown by comparing the effect of albumin and hydroxyethyl starch . 16 These results suggest an effect of albumin on endothelial function , as plasma Von Willebrandrelated antigen only decreased in patients treated with albumin and serum nitrates and nitrites only increased in patients treated with hydroxyethyl starch . Furthermore , albumin infusion was also able to restore an impaired cardiac contractility in an experimental model of cirrhosis . 17
Prevention of paracentesis-induced circulatory dysfunction Large volume paracentesis ( LVP ) is the current treatment of choice for patients with tense and refractory ascites . 11 The removal of large volumes of ascitic fluid can be followed by paracentesisinduced circulatory dysfunction ( PICD ), defined as a significant increase (> 50 %) in plasma renin activity six days after LVP . PICD is a circulatory dysfunction characterised by an exacerbation of arteriolar vasodilation , reduction of effective blood volume , rapid re-accumulation of ascites , increased risk of HRS , water retention with dilution hyponatraemia and shortened survival . In several randomised trials , albumin was able to lower the incidence of PICD and showed its superiority when compared with other plasma expanders . On the basis of such evidence , both American and European guidelines
hospitalpharmacyeurope . com | 2019 | 17