Largest Study of Glomerular Diseases Sheds Light on Pediatric Subtypes

Largest Study of Glomerular Diseases Sheds Light on Pediatric Subtypes 150 150 Cyndie Trapasso

In one of the first papers published from the largest study of glomerular diseases, researchers have found significant differences between patients who have IgA nephropathy and a subtype of the disease, IgA vasculitis, and between children and adults with these diagnoses.

The paper is from Cure Glomerulonephropathy (CureGN) — a longitudinal observational study of nearly 2,400 adults and children with one of four forms of glomerular disease: minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy and IgA nephropathy.

CureGN is important, researchers say, because the very large number of patients involved is providing data that have never been available before. Nationwide Children’s Hospital is a leading member of the pediatric component of the CureGN study – through the Pediatric Nephrology Research Consortium (PNRC), a research consortium that’s committed to the generation of new evidence to drive improvements in care for children with all forms of renal disease.

There are currently few effective therapies to treat these glomerular diseases, which can lead to progressive chronic kidney disease and in some cases the need for dialysis or kidney transplant. CureGN is studying commonalities and differences among each of the four glomerular diseases, and how they are treated and respond to various treatments over time, with the goal of developing more effective and more targeted treatments in the future.

CureGN has about a dozen papers in the publication process and members expect to publish several dozen more in the next few years.

In this particular study, published in Kidney International Reports, the researchers compared clinical aspects of IgAN to IgAV, between 382 adults and 285 children. The children were recruited from 33 sites within the PRNC, formerly called the Midwest Pediatric Nephrology Consortium, which is based at Nationwide Children’s Hospital and includes medical centers across the country.

The PNRC is one of the four Participating Clinical Centers that make up CureGN; the other three are largely adult centers.

“This is one of the early manuscripts to begin to harvest the data from about 2,350 patients,” says William E. Smoyer, MD, a nephrologist, vice president and director of the Center for Clinical and Translational Research at Nationwide Children’s, and a principal investigator in CureGN.  “With these new large amounts of data we are now able for the first time to look both across two populations with the same disease, as well as across the two disease subtypes specifically within the pediatric and adult populations.”

The researchers found that at biopsy, patients with IgAV were significantly younger, with an average age of 13 compared to 29.6 years for IgAN. Patients with IgAV were also more frequently white, 89.7% versus 78.9%, and had a higher estimated glomerular filtration rate (eGER) and lower serum albumin compared to IgAN patients.

Prior to or at enrollment in this study, 79.5% of adults and children with IgAV were treated with immunosuppressive therapy, compared to 54% of patients with IgAN. Among children, the 112 with IgAV were on average younger, had a shorter disease duration, and at biopsy had a lower serum albumin and higher degree of proteinuria compare to the 173 children with IgAN.

Compared to adults with the same disease subtypes, children with IgAN and those with IgAV each had significantly higher median eGER at the time of biopsy.

“Only because we had enough patients were we able to do this kind of analysis,” says Dr. Smoyer, who is also the Robert Kidder Chair in Clinical and Translational Research and a professor of Pediatrics at The Ohio State University College of Medicine.

Dr. Smoyer said this paper largely confirms what nephrologists have suspected about IgAN and IgAV, and helps lay important groundwork for more discoveries in the future.

“The machine has been built,” he says. “The infrastructure, the collection of patients, the collection of serial biological samples, and the collection of pathology images from these patients will be a tremendous resource for the entire world to study all four of these diseases into the future, in ways that we have never been able to before.”

Selewski DT, Ambruzs JM, Appel GB, Bomback AS, Matar RB, Cai Y, Cattran DC, Chishti AS, D’Agati VD, D’Alessandri-Silva CJ, Gbadegesin RA, Hogan JJ, Iragorri S, Jennette JC, Julian BA, Khalid M, Lafayette RA, Liapis H, Lugani F, Mansfield SA, Mason S, Nachman PH, Nast CC, Nester CM, Noone DG, Novak J, O’Shaughnessy MM, Reich HN, Rheault MN, Rizk DV, Saha MK, Sanghani NS, Sperati CJ, Sreedharan R, Srivastava T, Swiatecka-Urban A, Twombley K, Vasylyeva TL, Weaver DJ, Yin H, Zee J, Falk RJ, Gharavi AG, Gillespie BW, Gipson DS, Greenbaum LA, Holzman LB, Kretzler M, Robinson BM, Smoyer WE, Flessner M, Guay-Woodford LM, Kiryluk K; CureGN Consortium. Clinical characteristics and treatment patterns of children and adults with IgA nephropathy or IgA vasculitis: Findings from the CureGN study. Kidney International Reports. 2018 Aug 3;3(6):1373-1384.