Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial

Abstract

Background. There is no treatment for septic acute kidney injury (sAKI). The anti-inflammatory activity of prolonged-release pirfenidone (PR-PFD) could be beneficial in this clinical setting. Methods. This study was a double-blind randomized clinical trial in sAKI patients with nephrology consultation at the Civil Hospital of Guadalajara, in addition to the usual treatment of AKI associated with sepsis; patients were randomized to receive either PR-PFD at 1,200 mg/day (group A) or 600 mg/day (group B) or a matched placebo for 7 consecutive days. The primary objective was the decrease in serum creatinine (sCr) and increase in urinary volume (UV); the secondary objectives were changes in serum electrolytes, acid-base status, and mortality. Results. Between August 2016 and August 2017, 88 patients were randomized. The mean age was 54 (17 ± SD) years, and 47% were male. The main site of infection was the lung (39.8%), septic shock was present in 39.1% of the cases, and the mean SOFA score was 8.8 points. 28 patients received PFD 1,200 mg, 30 patients received PFD 600 mg, and 30 patients received placebo. During the study, sCr did not differ among the groups. The reversion rate of sCr, UV, and mortality was not different among the groups ( p = 0.70 , p = 0.47 , and p = 0.38 , respectively). Mild adverse events were not different among the groups. Conclusion. PR-PFD did not improve the clinical course of sAKI and seemed to be safe in terms of adverse events. This trial is registered with NCT02530359.

Probiotics in septic acute kidney injury, a double blind, randomized control trial

“…For decades, different therapeutic agents have been investigated for the management of AKI associated with sepsis with disappointing results; the use of agents such as statins [ 55 ], erythropoietin [ 56 ], steroids [ 57 ], alkaline phosphatase [ 58 ] and pirfenidone [ 17 ] is an important justified effort, and the search for a drug that consistently improves kidney function and potentially decreases the probability of dying continues.…”

“…The main cause of hospital-acquired AKI (HA-AKI) is sepsis, which accounts for 70% of cases in our community. Various efforts to identify specific treatments to attenuate sepsis-induced AKI, such as antifibrotics, anti-inflammatory agents and immunomodulators, have been unsuccessful [ 17 , 18 ]; therefore, the management of sepsis-induced AKI is currently limited to treating the main etiology [ 19 ] and, in severe cases, correcting its complications through kidney replacement therapies (KRTs) [ 20 ]. There is an urgent need to explore alternatives for the treatment of AKI [ 21 ].…”

Probiotics in septic acute kidney injury, a double blind, randomized control trial

“…For decades, different therapeutic agents have been investigated for the management of AKI associated with sepsis with disappointing results; examples such as statins (55), erythropoietin (56), steroids (57), alkaline phosphatase (58) and pirfenidone (17) are important justi ed efforts, and the search for a drug that consistently improves kidney function and potentially decreases the probability of dying continues.…”

“…The main cause of hospital acquired AKI (HA-AKI) is sepsis which accounts for 70% of cases in our community. Various efforts to nd speci c treatments to attenuate sepsis-induced AKI like anti brotics, anti ammatory and immunomodulators have been unsuccessful (17, 18) and therefore management of sepsis-induced AKI is currently limited to treating the main etiology (19) and in severe cases, correcting its complications through kidney replacement therapies (KRT) (20). There is an urgent need to explore alternatives for the treatment of AKI (21).Since AKI is a syndrome that generates intense systemic in ammation ( 22), attenuation of this phenomenon has been shown to improve renal function and parenchymal damage (23,24).…”

Acute Kidney Injury and Intestinal Dysbiosis

“…The dire need for a treatment for AKI has been suggested as a priority research area by expert consensus (15). To date, various therapeutic targets have failed to improve renal function and mortality in these patients (16)(17)(18)(19)(20)(21).…”