Knowledge Translation in Glomerulonephritis: Successes in Translational Research From the Bench to Bedside

Abstract

Purpose of review: Glomerulonephritis refers to a rare group of diseases characterized by glomerular inflammation, which collectively are a common cause of kidney failure. Until recently, there was a lack of high-quality clinical trials to inform the care of patients with glomerulonephritides. We identified examples of successful translational research spanning from basic science to clinical applications, and highlight gaps in implementation science.

Sources of information: The focus of our review was derived from discussions between health care professionals, researchers, and patient partners. We also performed literature searches pertaining to the treatment of glomerulonephritis in PubMed and Google Scholar.

Methods: Examples of successful knowledge translation were generated through review of new evidence in the past 5 years and by iterative discussions by the authors. We then conducted a narrative review of several themes related to knowledge translation in glomerulonephritis. This was complemented by an interview with a patient partner to provide an example of a patient's perspective living with glomerulonephritis.

Key findings: We summarized selected recent advances in glomerulonephritis and its knowledge translation in the following domains: (1) identification of auto-antibodies in membranous nephropathy and minimal change disease; (2) clinical trials of novel targeted therapies for IgA nephropathy and lupus nephritis, which have led to approval of new treatments; (3) developments in research networks and clinical trials in glomerulonephritis; (4) recognition of the importance in developing standardized patient reported outcome measures in clinical trials; and (5) barriers in knowledge translation including access to medication.

Limitations: A systematic search of the literature and formal assessment of quality of evidence were beyond the scope of this review.

Keywords: clinical trials; glomerulonephritis; knowledge translation; patient engagement.

Figure 1.

Pathogenesis of IgA nephropathy and targets of novel therapies. Note. The pathogenesis of IgA nephropathy involves pathogens and microbes from the gut microbiome interacting with the innate immune system, resulting in the release of BAFF and APRIL. This results in B cells activation and class switching to IgA-producing plasma cells, resulting in increased levels of galactose-deficient IgA1 (hit one). Anti-glycan antibodies which recognize galactose-deficient IgA1 form immune complexes and accumulate in the glomerular mesangium (hits 2 and 3). Hit 4, the deposition of immune complexes in the mesangium activates mesangial cells and triggers inflammatory and fibrotic responses via the complement system, resulting in an inflammatory response and glomerular injury. TRF-Budesonide is a gut-directed corticosteroid which is released locally in the Peyer’s patches where it is thought to suppress galactose-deficient IgA1 synthesis but avoids systemic adverse effects due to first-pass metabolism. Iptacopan is a small molecule inhibitor of factor B which prevents C3 convertase formation and thereby inhibits the alternative complement pathway. Narsoplimab is a MASP-2 inhibitor which inhibits the lectin pathway. TLR = Toll-like receptor; IgA = immunoglobulin A; BAFF = B-cell activating factor; APRIL = a proliferation-inducing ligand; TRF-budesonide = targeted-release formulation-budesonide.