Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study).

BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. METHODS: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. CONCLUSIONS: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .

Study protocol: high-dose mizoribine with prednisolone therapy in short-term relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse (JSKDC05 trial).

BACKGROUND: Eighty percent of children with steroid-sensitive nephrotic syndrome (SSNS) relapse within 2 years and 40-50% patients show frequently-relapsing nephrotic syndrome (FRNS). Patients showing a relapse within 6 months after initial remission are at high risk of FRNS. Since frequent prednisolone treatment for FRNS induces severe prednisolone side effects, development of a treatment to prevent patients from shifting to FRNS is desirable. Mizoribine is an immunosuppressive drug with fewer side effects than prednisolone. Recent studies reported the efficacy of high-dose mizoribine in children with FRNS. METHODS/DESIGN: We conduct a multicenter, open, randomized controlled trial to investigate the efficacy and safety of standard prednisolone plus high-dose mizoribine therapy in children with SSNS showing a relapse within 6 months after an initial remission. Patients are allocated to either standard prednisolone alone treatment group, or standard prednisolone plus high-dose mizoribine group. For the former group, mizoribine is administered at a dose of 10 mg/kg/day once daily and continued for 2 years. The primary endpoint is the duration to frequent relapse. DISCUSSION: The results provide important data on use of high-dose mizoribine to prevent SSNS patients from shifting to FRNS. Since blood concentrations of mizoribine have not been investigated in detail until now, there is a possibility that mizoribine is underestimated in favor of other immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to prevention of relapse in children at high risk of FRNS, and to decreased total dose of prednisolone. TRIAL REGISTRATION: UMIN000005103 , (Prospectively registered 1st March 2011).

Accuracy of self-collected human papillomavirus samples from Japanese women with abnormal cervical cytology.

AIM: The aim of this study was to assess the accuracy of self-collected vaginal samples compared with physician-collected cervical samples for high-risk human papillomavirus (HPV) testing in Japanese women with abnormal cervical cytology. We also assessed the acceptability of self-collected HPV (sHPV) testing using a questionnaire. METHODS: Women aged 20-69 years (n = 136) attending Yokohama City University Hospital because of abnormal cervical cytology between April 2014 and January 2015 were enrolled in this study. Cervical samples for conventional cytology and physician-collected HPV (pHPV) testing were obtained before colposcopic examination. After this examination, patients were asked to provide a self-sampled vaginal specimen (sHPV) at home, some time between the following day and the next week and to complete a self-sampling acceptability questionnaire. RESULTS: The overall positive rates of HPV detection with pHPV and sHPV testing were 61.0% (83/136) and 40.4% (55/136), respectively (P < 0.001). sHPV testing had a lower sensitivity compared to pHPV for detection of cervical intraepithelial neoplasia (CIN)2 or worse (CIN2+: 59.4% vs 100%, P < 0.001; CIN3: 66.7% vs 100%, P = 0.248). There were no statistically significant differences in the sensitivity to detect CIN3 among pHPV testing, sHPV testing, and cytology. The self-collecting device had good acceptability. CONCLUSION: sHPV testing is a possible technique with which to improve poor cervical cancer screening uptake rates in Japan; however, the sensitivity to detect CIN2+ lesions must improve before it can be a substitute for conventional cytology or pHPV testing. Further large-scale acceptability studies involving non-responders are also needed before practical application.