No abstract

In light of the recent pandemic, favipiravir (Avigan ®), a purine nucleic acid analog and antiviral agent approved for use in influenza in Japan, is being studied for the treatment of coronavirus disease 2019 (COVID-19). Increase in blood uric acid level is a frequent side effect of favipiravir. Here, we discussed the mechanism of blood uric acid elevation during favipiravir treatment. Favipiravir is metabolized to an inactive metabolite M1 by aldehyde oxidase and xanthine oxidase, and excreted into urine. In the kidney, uric acid handling is regulated by the balance of reabsorption and tubular secretion in the proximal tubules. Favipiravir and M1 act as moderate inhibitors of organic anion transporter 1 and 3 (OAT1 and OAT3), which are involved in uric acid excretion in the kidney. In addition, M1 enhances uric acid reuptake via urate transporter 1 (URAT1) in the renal proximal tubules. Thus, favipiravir is thought to decrease uric acid excretion into urine, resulting in elevation of uric acid levels in blood. Elevated uric acid levels were returned to normal after discontinuation of favipiravir, and favipiravir is not used for long periods of time for the treatment of viral infection. Thus, the effect on blood uric acid levels was subclinical in most studies. Nevertheless, the adverse effect of favipiravir might be clinically important in patients with a history of gout, hyperuricemia, kidney function impairment (in which blood concentration of M1 increases), and where there is concomitant use of other drugs affecting blood uric acid elevation.

Background: Elevated serum creatinine is associated with poor outcome in IgA nephropathy (IgAN). The efficacy and limitations of corticosteroids in advanced IgAN (Cr ≧1.5 mg/dl), however, remains controversial. Methods: We retrospectively investigated 70 patients with advanced IgAN (Cr ≧1.5 mg/dl) classified into three groups according to their treatment regimens, that is, steroid pulse with tonsillectomy, conventional steroid, and supportive therapy. We evaluated the three groups to elucidate predictors for the endpoints ESRF and doubled serum creatinine from baseline. Results: Steroid pulse with tonsillectomy, conventional steroid and supportive therapy were performed in 30, 25 and 15 patients, respectively. During the mean follow-up period of 70.3 (12–137) months, 41.4% of patients reached ESRF (13.3 vs. 56.0 vs. 73.3%, p < 0.001) and 45.7% doubled serum creatinine from baseline (16.7 vs. 64.0 vs. 73.3%, p < 0.001). The incidence of ESRF in the patients treated by steroid pulse with tonsillectomy was significantly lower than the incidences in the patients treated by conventional steroid and supportive therapy at a baseline creatinine level of 1.5–2 mg/dl, but no statistical difference was observed at a level of >2 mg/dl. The Kaplan-Meier estimated probability of renal survival without ESRF was 89.2, 74.1 and 72.2% at 5 years and 82.8, 51.0 and 45.1% at 8 years, respectively (p = 0.017). The predictors for ESRF, identified in a Cox proportional hazards model, were baseline serum creatinine (p < 0.001) and interstitial infiltrate (p = 0.003). Steroid pulse with tonsillectomy also had a protective effect on the risk of reaching ESRF (p = 0.013). By target cross-stratification, the patients with baseline creatinine of 1.5–2 mg/dl who underwent steroid pulse with tonsillectomy showed a better renal survival rate than the others (p < 0.001). Conclusion: Steroid pulse therapy combined with tonsillectomy may be more effective than conventional steroid therapy in patients with a baseline creatinine level of ≤2 mg/dl.

To examine the clinical significance of hypertensive nephropathy (HN) among non-diabetic chronic kidney disease (CKD) patients. The study comprised 2692 CKD patients recruited from 11 outpatient nephrology clinics; these included 1306 patients with primary renal disease (PRD), 458 patients with HN, 283 patients with diabetic nephropathy (DN) and 645 patients with other nephropathies (ONs). All patients fulfilled the criteria of CKD, with a persistent low estimated glomerular filtration rate (eGFR) o60 ml min À1 per 1.73 m 2 or proteinuria as determined by a urine dipstick test. The risk factors for cardiovascular disease (CVD), such as ischemic heart disease, congestive heart failure and stroke; all-cause mortality; and progression to end-stage renal failure (dialysis induction) were analyzed using a Cox proportional hazards model in each group. During a mean follow-up period of 22.6 months from recruitment, 100 patients were lost to follow-up and 192 patients began chronic dialysis therapy. A total of 115 CVD events occurred (stroke in 37 cases), and 44 patients died. Regarding CVD events and death, there were significant differences in the hazard ratios (HRs) for the groups of patients with different underlying renal diseases as determined by both univariate and multivariate analysis adjusted for confounding factors including estimated glomerular filtration rate: PRD, 1.0 (reference); HN, 3.33 (95% confidence interval, 1.82-6.09); DN, 5.93 (2.80-12.52); and ON, 2.22 (1.22-4.05). However, there were no differences in the hazard ratio for dialysis induction for the groups of patients with different underlying renal diseases. HN is associated with an increased risk of CVD events and death among non-diabetic CKD patients, which highlights the clinical significance of HN.