Background C3 glomerulopathy (C3G) defines a group of rare complement-mediated kidney diseases with a shared underlying pathophysiology: dysregulation of complement in the fluid phase and glomerular microenvironment. Dysregulation can be driven by autoantibodies to C3 and C5 convertases. Study Design Case series Setting & Participants 168 C3G patients (dense deposit disease, 68; C3 glumerulonephritis, 100) selected from our C3G bio-bank. Outcomes Patient-purified IgGs were tested for C4 nephritic factors (C4Nefs). These autoantibodies recognize C4b2a, the C3 convertase of the classical pathway of complement. Measurements C4Nefs were detected using a modified hemolytic assay. Results C4Nefs were identified in 5 patients, 4 of whom had C3 glomerulonephritis. The C4Nefs were associated with dysregulation of C3 and C5 convertases and they appear to stabilize these convertases in a dose-dependent manner. The C4Nefs also appear to protect C4b2a from decay mediated by soluble CR1 and C4 binding protein (C4BP). The stabilizing activity of the autoantibodies was further demonstrated by using heat treatment to inactivate complement. C4Nefs were not detected in 150 patients with another complement-mediated kidney disease, atypical hemolytic uremic syndrome. They were also absent in 300 apparently healthy controls. Limitations In addition to C4Nefs, two patients had positive findings for other autoantibodies: one patient also had autoantibodies to factor H; the other patient also had autoantibodies to C3bBb (C3Nefs). Conclusions The finding of C4Nefs in a small percentage of C3G patients highlights the challenge in identifying autoantibodies that drive complement dysregulation and underscores the complexity of the autoantibody repertoire that can be identified in these patients.

SummaryBackground and objectives Data on physical activity are limited in children with CKD. The objectives of this study were to measure the level and correlates of physical activity in children and young adults with CKD and to determine the association of physical activity with physical performance and physical functioning.Design, setting, participants, & measurements Physical activity was measured for 7 days using pedometers; physical performance was measured by the 6-minute walk distance (6MWD) and physical functioning with the PedsQL 4.0.Results Study participants were 44 patients 7-20 years of age who had CKD stage 1-4 (n=12), had ESRD and were undergoing dialysis (n=7), or had undergone kidney transplantation (n=25). Participants were very sedentary; they walked 6218 (interquartile range, 3637, 9829) steps per day, considerably less than recommended. Physical activity did not differ among participants in the CKD stage 1-4, ESRD, and transplant groups. Females were less active than males (P,0.01), and physical activity was 44% lower among young adults (18-20 years) than younger participants (P,0.05). Physical activity was associated positively with maternal education and hemoglobin concentration and inversely with body mass index. Respective 6MWD in males and females was 2 and approximately 4 SDs below expected. Low levels of physical activity were associated with poor physical performance and physical functioning, after adjustment for age, sex, and body mass index.Conclusions In most participants with CKD, physical activity was considerably below recommended levels. Future studies are needed to determine whether increasing physical activity can improve physical performance and physical functioning.

Background Children and adolescents with chronic kidney disease (CKD) are inactive relative to their peers. Methods Forty-four children and adolescents aged 7-20 years with CKD, end-stage renal disease (ESRD) on dialysis or a kidney transplant participated in a12-week pedometer-based intervention to increase physical activity. Patients recorded daily step counts and reported them weekly. Pediatric Quality of Life Inventory (PedsQL) and six-minute walk (6MW) were administered at baseline and after 12 weeks. Results Age was 15.1±3.4 years; 27% had CKD, 16% were receiving dialysis, and 57% had received a kidney transplant. Mean daily step count did not change significantly (+48, 95% CI −48 to +145 steps/day per week). Transplant recipients and patients with CKD increased their activity by 100 steps/day (95% CI −14 to 208) and 73 steps/day (95% CI −115 to 262) each week, respectively, and patients on dialysis decreased by 133 steps/day (95% CI −325 to 58; p-value for interaction 0.03) in multivariable analysis. Change in physical activity was associated with change in 6MW distance (r=0.74, p<0.001) and change in physical functioning (r=0.53, p=0.001). Conclusions Youths with CKD did not significantly increase their activity over 12 weeks of a pedometer-based intervention. However, changes in physical activity were associated with changes in physical functioning and performance.