Henoch-Schonlein purpura (HSP) is one of the most common forms of vasculitis in children, with an incidence of around 6-24 cases per 100,000 per year and with 90% of cases presenting before age ten. While many cases are self-limited, 30-50% of patients with HSP will develop renal involvement with about 20% having a nephritic or nephrotic syndrome, and 1-3% of patients progressing to end stage renal disease.
Currently there is a lack of evidence to guide treatment decisions for patients with HSP nephritis (HSPN), and therefore there is wide variation in treatment practices. Many small, uncontrolled, retrospective studies have attempted to describe various treatment regimens and their outcomes, but a large, multi-center, prospective trial has not been attempted. Current treatment recommendations are based on case series, retrospective analyses, and extrapolation of studies in patients with IgA nephropathy.
Thus, a prospective, multicenter clinical trial is needed to examine the outcomes in children with HSPN treated with different agents and protocols (e.g. ACE inhibition, corticosteroids, and other immunosuppressive agents). With the results of such a study, specific evidence-based guidelines could be created to guide the management of children with HSPN.Prior to initiation of such a trial, we need to better understand current treatment practice of HSPN. PEDSnet is the ideal platform to address our questions about treatment of HSP nephritis.Benefits of Using Learning Health System CorePediatric nephrology is a small field, and therefore multi-institutional research networks and learning health systems are essential for research, especially when working with rare diseases like HSPN. PEDSnet will allow us to access clinical data from a large number of patients treated at tertiary care centers. We will be able to analyze clinical and demographic data at presentation, indications for treatment, prescribing patterns at the various sites, and clinical and laboratory outcomes.
Central Hypothesis and Specific Aims:
We hypothesize that wide practice variation exists in the treatment of children with HSPN. Aim 1: To evaluate clinical and laboratory factors at initial presentation which can predict the course of patients with HSP nephritis, including duration of proteinuria and development of chronic kidney disease/end stage renal disease. Aim 2: To evaluate the association of various treatment regimens (e.g. ACE inhibitors, oral/IV steroids, other immunosuppressive agents, and conservative management without pharmaceutical agents) with outcomes such as time to remission of proteinuria and change in GFR in children with HSP nephritis.
We plan to retrospectively review all patients with HSP nephritis seen at the eight PEDSnet hospitals. We will collect demographic and laboratory data from the time of initial presentation, renal biopsy findings, prescription history (ACE inhibitors, oral steroids, IV steroids, other immunosuppressive agents), and outcome data (duration of proteinuria, change in GFR, progression to ESRD, etc.). We will perform statistical analyses to compare outcomes of patients receiving various combinations of therapies, with the goal to identify two or more potential treatments/treatment combinations associated with improved outcomes which can then be further analyzed in a prospective study.
Implications for Potential Findings and Future Applications:
The findings from this pilot study will allow us to retrospectively analyze outcomes in patients who received various treatment combinations. We plan to use these preliminary data to help guide a prospective study to compare different treatment regimens. Our goal is to use support from the PCEN Core to help design a pragmatic trial to compare the clinical efficacy of two or more agents for the treatment of HSPN, as informed by the findings of our pilot study.