The DreamRCT is a great online project spearheaded by Jordan Weinstein at UKidney and Joel Topf at PBFluids. Nephrology bloggers from WhizBang, Nephron Power, Renal Fellow Network, PBFluids, UKidney, Ed El Sayed and Swapnil Hiremath are pitching their DreamRCT ideas. The goal is to attempt to get to the heart (or shall I say kidney) of fundamental questions we have been trying to answer in nephrology. No funding or IRB restrictions to hinder this project. A number of potential choices came to mind for my DreamRCT; a definitive trial of frequent vs. conventional dialysis, hypertension management in advanced CKD, treatment severe nephrotic syndrome in diabetes. However, I went for a BIG undertaking. I propose we create an international consortium for clinical trials in glomerular diseases.
While any one primary glomerular disease is rare, in the aggregate they make up a significant proportion of the dialysis population. According to the 2013 USRDS report, glomerulonephritis had a prevalence of 111/million population (compared to 550 for diabetes and 350 for hypertension). We need to shift more focus to this group of patients to prevent decline of kidney function and ESRD. The nephrology community holds several conferences a year dedicated to this topic and yet each one is filled with anecdote after small, underpowered trial. I am dismayed and frankly a bit embarrassed that when I see a newly diagnosed patient with membranous I recite old data collected from a few hundred patients.
The nephrology community does have several consortiums in existence. For example the Nephrotic Syndrome Study Network (NEPTUNE) from the NIH, Halpin foundation, Nephcure, and the UNC Glomerular Disease Collaborative Network (GDCN) NEPTUNE is enrolling patients in trials focused on Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN). The GDCN has been successful in recruiting patients for registries and trials focused on FSGS, MN, lupus nephritis and ANCA-associated vasculitis. Also, the Systemic Lupus International Collaborating Clinics (LSICC) group and the Amyloidosis Foundation have been successful as well.
We need to become more aggressive in the study of glomerular diseases. Novel biologics are being used in a variety of inflammatory and oncological diseases. However, these are not being studied in the nephrology community in a rigorous fashion. Instead we have case series after case series. We need to enroll more patients from a greater variety of settings. The goal of the iGDTN would be to deputize every private practice and academic medical center to enroll patients in both longitudinal cohorts for retrospective data as well as cutting edge biologic and traditional chemotherapy based phase 2 and 3 clinical trials. We can look to our pediatric hematology oncology colleagues for advice as they have been successful is creating the Childhood Cancer Research Network (CCRN).
For too long nephrologists have deflected criticism about the quality GN research by hiding behind the the rarity of the disease. In our connected age this is becoming threadbare. If the CCRN can be successful in recruiting cohorts of children with rare conditions then we can do the same thing in nephrology. I’m not an expert in how to make this happen. Nor am I an expert in the design of clinical trials. However, I do know that we need more randomized clinical trials in glomerular disease. If we are going to advance the field then we need to align our forces and start answering fundamental questions instead of relying on expert opinions based on case series, anecdotes, observational data and small single center/country randomized clinical trials. We have seen recent advances in well-done clinical trials aimed at lupus nephritis and ANCA-associated GN. Now lets push the envelope and make progress is FSGS, membranous, MPGN, minimal change disease and amyloidosis. KDIGO has already provided a terrific framework for the gaps in knowledge that needs to be filled. We have the opportunity as an international community to come together and establish a truly international network of clinical trials in glomerular diseases. Go to UKidney Starting Monday and vote for the iGDTN for your DreamRCT.
Dr. Matthew A. Sparks
eAJKD Advisory Board member