Direct-acting Antivirals in Kidney Transplant Patients: Successful Hepatitis C Treatment and Short Term Reduction in Urinary Protein/Creatinine Ratios

Abstract

Background The role of Hepatitis C Virus (HCV) clearance in kidney graft survival is unknown. We examined short-term trends of protein/creatinine (P/C) ratios in HCV-infected kidney transplant recipients treated with direct-acting antivirals (DAAs). Methods This is a retrospective study of 19 kidney transplant patients with HCV infection treated with DAAs at the University of Alabama at Birmingham between January 2013 and June 2016. Markers of glomerular damage were assessed using average urinary protein/creatinine (P/C) ratios measured pretreatment and posttreatment. Treatment efficacy was defined as sustained virologic response at 12 weeks post-HCV treatment (SVR12). Results The median age of the 19 patients included was 59 years (Q1 = 58, Q3 = 64). Of these patients, 68% were African American, 32% were White and 63% were male. The median time between kidney transplant and initiation of DAA therapy was 2.25 years (Q1 = 0.79, Q3 = 3.79). Posttreatment P/C ratios (median = 0.127, Q1=0.090, Q3 = 0.220) were significantly lower (P = 0.01) than pretreatment ratios (median = 0.168, Q1 = 0.118, Q3 = 0.385). P/C ratios decreased in 14 of 19 patients (74%) with a median change of −0.072 (median percent change = −40%). Posttreatment estimated glomerular filtration rates (median = 58.9, Q1 = 48.9, Q3 = 72.3) were not significantly different (P = 0.82) than the pretreatment values (median = 57.0, Q1 = 48.8, Q3 = 67.8). All patients achieved SVR12. Conclusions In this preliminary study, there was a statistically significant decrease in P/C ratios associated with HCV clearance, suggesting a potential role for DAAs in improving kidney graft survival. Larger cohort studies will be needed to assess the clinical and long-term benefits of DAAs in this population.

Renal safety after one year of sofosbuvir‐based therapy for chronic hepatitis C: A Brazilian “real‐life” study

“…Similarly, Goetsch et al. identified a significant decrease in protein/Cr ratio after DAA treatment in a retrospective cohort of kidney transplant recipients, although few studies consider the assessment of urinary tubular biomarkers during HCV antiviral therapy . Taken together, these findings reinforce the necessity of further studies focusing on the assessment of renal function in chronic HCV patients with advanced kidney disease in a long‐term evaluation.…”

Hepatitis C virus infection in kidney transplantation‐changing paradigms with novel agents

“…The majority of patients received sofosbuvir regimens several months to years posttransplantation with an eGFR >30 mL/min/1.73 m 2 . To date, only 7 failures were reported in the retrospective data, with 2 of them being retreated with next generation DAA regimens and subsequently achieving SVR . These retrospective studies reported anemia in ∼11% of patients, largely attributed to the use of ribavirin.…”

“…Currently, some centers delay HCV treatment for approximately 6 months after transplantation to confirm stability of kidney function and calcineurin inhibitor dosing. This is done so because retrospective data has suggested that up to 1/3rd of patients have required dose adjustment of their immunosuppressive regimen to remain within therapeutic range . However, some studies have demonstrated a decline in proteinuria in kidney transplant patients following SVR, suggesting the potential for short and long‐term improvement in graft survival .…”

“…To date, only 7 failures were reported in the retrospective data, with 2 of them being retreated with next generation DAA regimens and subsequently achieving SVR. [29][30][31][32][33][35][36][37][38]40,48 These retrospective studies reported anemia in 11% of patients, largely attributed to the use of ribavirin.…”

“…In the studies reviewed above, acute allograft rejection was reported in 7 kidney transplant recipients. [27][28][29][30][31][32][33][34][35][36][37][38]40,[42][43][44][45][46][47][48] Approximately 36% of patients required calcineurin inhibitor dose adjustments during or shortly after DAA therapy; however, whether this is a direct effect of DAA is still unknown. [27][28][29][30][31][32][33][34][35][36][37][38]40,[42][43][44][45][46][47][48] Nevertheless, we recommend close monitoring of calcineurin inhibitor levels during and shortly after DAA therapy until further evidence is available.…”