Transient increase in urine protein excretion during treatment with terlipressin and albumin for type-1 hepatorenal syndrome
Authors: Chiara Elia, Elsa Solà Vergés, Ezequiel Rodríguez, Pere Ginès
Journal: Journal of Hepatology (2014)

We recently had a patient admitted to our unit with cirrhosis and type-1 hepatorenal syndrome (HRS) who developed marked proteinuria during treatment with terlipressin and albumin. This led us to investigate whether pharmacological treatment of type-1 HRS could be associated with an increase in urine protein excretion. The effects of terlipressin and albumin on kidney function in patients with type-1 HRS have been investigated extensively [1Ginès P. Cárdenas A. Arroyo V. Rodés J. Management of cirrhosis and ascites.N Engl J Med. 2004; 350: 1646-1654Crossref PubMed Scopus (665) Google Scholar, 2Angeli P. Merkel C. Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis.J Hepatol. 2008; 48: S93-S103Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar], but to our knowledge there is no information on the potential effects of treatment on urine protein. We evaluated a series of 29 patients with type-1 HRS, treated at our institution. Patients were selected from a database of 75 patients with type-1 HRS, treated in our unit in the last 15 years. Clinical and laboratory data from all patients were recorded prospectively in this database at the time of treatment. For this analysis we selected 29 patients who had urine protein measurements available before treatment and at two time points during treatment. There were no significant differences regarding baseline liver and kidney function tests and the percentage of response to treatment between these 29 patients and the remaining 46 patients included in the database. Urine analyses were performed before treatment, at days 3–4, and at the end of treatment. The individual values of urine protein excretion in all patients evaluated are shown in Fig. 1 (left panel). Treatment with terlipressin and albumin was associated with a statistically significant increase in urine protein excretion that returned towards baseline values at the end of treatment (239 ± 151, 675 ± 961, and 380 ± 459 mg/24 h at baseline, days 3–4, and at the end of treatment, respectively; mean ± standard deviation, p = 0.001). Interestingly, in 4 of the 29 patients (14%) urine protein excretion increased above 1 g/day during treatment. To assess whether the magnitude of the increase in urine protein excretion was related to the response to treatment, we categorized patients into two groups according to urine protein excretion during treatment with terlipressin and albumin (patients with urine protein ⩾500 mg/24 h vs. patients with urine protein <500 mg/24 h). There were no significant differences between the two subsets of patients regarding baseline liver, kidney and circulatory function, dose of terlipressin used or length of therapy. In the overall series, the mean duration of therapy was 7 ± 4 days (7 ± 3 and 8 ± 45 days in patients with urine protein ⩾500 mg/24 h vs. patients with urine protein <500 mg/24 h, respectively; p = 0.7). Overall, 18 out of the 29 patients (62%) had complete response to treatment (serum creatinine <1.5 mg/dl at the end of treatment). The development of proteinuria was not related to an impaired response to treatment. In fact, three out of the 7 patients (43%) with urine protein excretion ⩾500 mg/24 h had a complete response to treatment compared to 15 out of the 22 patients (68%) with urine protein excretion <500 mg/24 h (p = 0.37). Moreover, 3 of the 4 patients with excretion greater than 1 g/day had a complete response to therapy. Urine protein excretion in responders to treatment with terlipressin and albumin was 268 ± 157, 756 ± 1178, and 436 ± 571 mg/24 h (at baseline, days 3–4, and end of treatment, respectively) compared to 191 ± 133, 543 ± 439, and 287 ± 138 mg/24 h in non-responders (p = n.s.). To assess to what extent the increase in urine protein excretion was related to treatment with terlipressin plus albumin or could be related to the administration of intravenous albumin alone we also investigated a historical control group of 12 patients with type-1 HRS, associated with bacterial infections that were treated with albumin alone, included in a previous study [[3]Guevara M. Terra C. Nazar A. Solà E. Fernandez J. Pavesi M. et al.Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study.J Hepatol. 2012; 57: 759-765Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. In this series of patients urianalysis was performed before treatment and at day 3. In patients with type-1 HRS, treated with albumin alone, there was no significant increase in urine protein excretion during treatment (108 ± 67 vs. 143 ± 118 at baseline and at day 3, respectively; p = n.s.). The individual values of urine protein excretion in patients treated with albumin alone are shown in Fig. 1 (right panel). The pathogenic mechanisms responsible for the increase in urine protein during treatment with terlipressin and albumin were not assessed in this study. This effect could be related to the increased renal perfusion pressure caused by terlipressin administration. It is also possible that terlipressin treatment may uncover some preexisting parenchymal nephropathy [[4]Trawalé J.M. Paradis V. Rautou P.E. Francoz C. Escolano S. Sallée M. et al.The spectrum of renal lesions in patients with cirrhosis: a clinicopathological study.Liver Int. 2010; 30: 725-732Crossref PubMed Scopus (140) Google Scholar]. In conclusion, regardless of the mechanism involved, our results indicate that treatment with terlipressin and albumin is associated with a transient increase in urine protein excretion that is significant in some patients. Based on our findings, the development of an increase in urine protein excretion during treatment of type-1 HRS should not modify the diagnosis and treatment of kidney failure. This information may be clinically useful for clinicians, caring for patients with acute complications of cirrhosis. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.