The Preserving Kidney Function in Children with CKD (PRESERVE) Study: Rationale, design, and methods

RATIONALE & OBJECTIVE: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. STUDY DESIGN: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). SETTING & PARTICIPANTS: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to \u3c90 mL/min/1.73 m EXPOSURES: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. OUTCOMES: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of \u3c15 mL/min/1.73 m ANALYTICAL APPROACH: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. LIMITATIONS: Causal inference limited by observational analyses. CONCLUSIONS: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. PLAIN-LANGUAGE SUMMARY: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for \u3e19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management

Antibodies to C1q in systemic lupus erythematosus: Characteristics and relation to FcγRIIA alleles

Antibodies to C1q in systemic lupus erythematosus: Characteristics and relation to FcγRIIA alleles. Autoantibodies to the collagen-like region of the first complement component (C1qAB) are found in patients with systemic lupus erythematosus (SLE), particularly those with renal disease. In a cohort of 46 SLE patients with diffuse proliferative glomerulonephritis, we found declining C1qAB titers in 77% of treatment responders and in only 38% of treatment non-responders (P < 0.03). To further characterize this autoantibody, we tested 240 SLE patients for the presence of C1qAB. Positive titers were found in 44% of patients with renal disease and 18% of patients without renal disease (χ2 P < 0.0003). Analysis of IgG subclass revealed IgG2 C1qAB alone in 34%, IgG1 C1qAB alone in 20%, and both IgG1 and IgG2 in 46% of patients. Fewer than 10% of patients had measurable titers of IgG3 or IgG4 C1qAB. The pathogenic role of these IgG2-skewed C1qAB may relate to impaired immune complex clearance by the mononuclear phagocyte system: IgG2 antibodies are efficiently recognized by only one IgG receptor, the H131 allele of FcγRIIa (FcγRIIa-H131). In contrast, FcγRIIa-R131, which is characterized by minimal IgG2 binding, has recently been associated with lupus nephritis. In our C1qAB positive patients, the presence of FcγRIIA-R131 was associated with an increased risk for renal disease. Autoantibodies to C1q may have pathogenic significance in SLE patients with genetic defects in the ability to clear IgG2 containing immune complexes

Budesonide and Formoterol Reduce Early Innate Anti-Viral Immune Responses In Vitro

Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC) from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16) in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10−6 M) when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2′, 5′ oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits viral clearance in vivo remains to be determined

Improving Blood Pressure Screening in Neonatal Follow-up Clinic: A Quality Improvement Initiative.

Introduction: The American Academy of Pediatrics recommends blood pressure screening at every health care encounter in children younger than 3 years if they have a history of prematurity or other neonatal complications requiring intensive care because these children have an increased risk for hypertension. Methods: A multidisciplinary team conducted a quality improvement initiative to improve blood pressure screening at a single-center outpatient neonatal follow-up clinic. We developed a focused intervention program including a standardized blood pressure measurement protocol, staff training and education, and streamlined documentation. We conducted two Plan-Do-Study-Act cycles from November 2019 to January 2021. The outcome measure was the percentage of patients with a blood pressure measurement. Process measures included the percentage of medical assistants educated on the new protocol, percentage of patients 3 years, and younger old with the first blood pressure measurement taken from the right arm, and the percentage of patients 1 year and younger with 3 documented blood pressures. The balancing measure was staff satisfaction with time to obtain vital signs. We used statistical process control charts and Wilcoxon rank-sum test. Results: At baseline, only 15.3% of patients had documented blood pressure. During the 10-month intervention period, there were 954 patient visits. Overall, blood pressure measurement increased to 54.7% with study interventions. The balancing measure was not negatively impacted. Conclusions: After implementing a program of focused interventions, we substantially improved the frequency of blood pressure measurements and increased adherence to American Academy of Pediatrics screening guidelines. Improved blood pressure screening allows us to identify and evaluate at-risk infants after hospital discharge

When Dialysis Becomes Life : Pediatric Caregivers\u27 Lived Experiences Obtained From Patient-Reported Outcomes Measures

Introduction: Qualitative research reveals significant caregiver impact resulting from managing children requiring chronic dialysis but offers few quantitative measures of their lived experiences. Materials and Methods: This cross-sectional study included 25 caregivers of children on chronic peritoneal dialysis (PD) and hemodialysis (HD) enrolled from 2018 to 2019 at a large pediatric dialysis program in the U.S.Patient Reported Outcomes Measures Information System (PROMIS) measures and free text commentary were collected and analyzed to evaluate the self-reported impact and wellbeing of these caregivers. Results: Among all dialysis modalities, caregivers\u27 positive affect (43.4 ± 10) and general life satisfaction (45.1 ± 11.5) were significantly lower than the general adult population. Compared with HD caregivers, PD caregivers demonstrated significantly more fatigue and sleep disturbance and less positive affect and life satisfaction. Amongst HD caregivers, sleep disturbance, positive affect, and meaning/purpose differed significantly from the general population. Analyses of text commentary revealed that caregivers also expressed the feelings of loss, importance of knowing the impact of dialysis prior to initiation, need for a support group, and value of home nursing. Conclusions: Caregivers of children on chronic dialysis had significantly poorer self-rated health and wellbeing compared with the general adult population. This may be due in part to their feelings of social isolation. Our findings highlight opportunities to improve caregivers\u27 lived experiences