Effects of Imperatae Rhizoma and Lycium Barbarum Decoction in Treating Persistent Asymptomatic Isolated Hematuria in Children: An Exploratory Randomized, Open-label, Controlled Trial

摘要

Introduction: Asymptomatic isolated hematuria (AIH) is a common phenomenon in routine urinalysis of healthy children. Research suggests persistent AIH has a pathological role in kidney disease progression and may be an early sign of chronic kidney disease. The duration of AIH is associated with the prognosis of the kidney disease: the longer AIH lasts, the greater the risk of developing adverse renal complications (e.g. proteinuria, hypertension) or end stage renal disease will become. Despite frequent detection of AIH and its associated risk, there is currently no effective therapy, with few side effects, available for hematuria. Imperatae Rhizoma (IR) is one of the traditional Chinese medicine (TCM) herbs that have been used for hematuria in China. In clinical practice, it is often used in combination with other herbs in a form of decoction. According to the principle of TCM treatment for AIH, a simple TCM formula, in which IR was combined with Lycium Barbarum (LB), may be a potentially safe and effective treatment option for children with AIH.;Objectives: The study aims to evaluate the effects and safety of IR-LB decoction for treating children with persistent AIH.;Methods: This was an exploratory randomized, open-label, controlled clinical trial. A total of 121 children with AIH were recruited from a tertiary hospital and randomly assigned to the IR-LB treatment group (N=61) or control group (N=60). IR-LB treatment group was given IR-LB decoction (made from IR and LB herbs) for 3 months, and both the IR-LB and control groups were given the same healthy dietary recommendations as baseline intervention. Data collection was conducted at baseline, 3 months, and 6 months. The primary outcome was the change in urinary red blood cell counts (RBCs) per high power field (HPF) from baseline. Difference in relative urinary RBCs/HPF change between IR-LB and control groups was used as the primary measure of the effect of IR-LB decoction in controlling urine RBCs. Difference in absolute urinary RBCs/HPF change and difference in relative urinary RBCs/HPF change expressed as categorical variables between two groups were also analyzed to test the robustness of the main analyses. Secondary analyses included renal complications (proteinuria, hypertension, and impaired renal function), relapse of hematuria and adverse effects. 95% Confidence interval (CI) was constructed for all the estimates for the effect of IR-LB (efficacy) and statistical testing (eg. Mann-Whitney test and Chi-square test) was performed to identify statistically significant effects. Intention-to-treat analysis was applied.;Results: Participants in the IR-LB treatment group showed significantly greater relative reduction in urinary RBC/HPF from baseline compared to the control group at 3 months (-44.44% (95% CI: -76.97%, -4.36%) for IR-LB group vs. -9.38% (95% CI: -69.11%, 33.33%) for control, p=0.012) and 6 months (-52.38% (95%CI: -80.00%, 00.00%) vs. -6.25% (95%CI: -68.23%, 13.84%), p=0.029). The absolute reduction in urinary RBC/HPF in the IR-LB treatment group was also significantly greater than control group at 3 months (-6.00 (95%CI: -13.5, -1.00) vs. -1.00 (95%CI: -9.00, 2.00), p=0.021) and marginally significant reduction at 6 months (-5.00 (95%CI: -15.00, 0.00) vs. -0.50 (95%CI: -10.25, 1.00), p=0.051). Although the difference in the proportion of participants with complete remission between the two groups was not statistically significant at 3 months (34.4% vs. 21.6%, RR=1.59 (95% CI: 0.88, 2.87), p=0.118) and 6 months (34.4% vs. 23.3%, RR=1.48 (95% CI: 0.83, 2.62), p=0.178), the reduction in urinary RBC/HPF was evident and statistically significant when 50% relative reduction was used as the cutoff at 6 months (55.7% vs. 33.3%, RR=1.67 (95%CI: 1.10, 2.55), p=0.013). Participants in IR-LB treatment group did not show obvious liver or renal impairments or any other noticeable adverse effects.;Conclusions: Decoction of IR with LB may potentially be a safe and effective therapy for children with AIH. More clinical studies are required to demonstrate more firmly the effectiveness of IR-LB treatment, and identify the optimal dose and duration of IR treatment. This finding may also inspire more studies on the therapeutic mechanism of IR-LB treatment, the mechanism of hematuria and its association with renal disease prognosis.