What Are the Clinical Implications of Crescentic Glomerulonephritis?

“We sometimes see crescents in renal biopsies, but we have never before been able to study enough children with these destructive lesions to really understand how important they are for predicting the clinical outcomes of patients,” says William E. Smoyer, MD, vice president and director for the Center for Clinical and Translational Research at the Abigail Wexner Research Institute at Nationwide Children’s Hospital and co-author of the publication. “This study presents the strongest evidence to date that the percentage of crescents on kidney biopsies is directly correlated with renal outcomes in children.”

The PNRC identified 305 children from 15 centers from the consortium’s Pediatric Glomerulonephritis with Crescents Registry.

“Because of the rarity of GN with crescents, particularly in children, cohorts of patients in past studies have been very limited,” says Dr. Smoyer, who is also a professor of Pediatrics at The Ohio State University College of Medicine. “In fact, the last multicenter study evaluating 50 children with GN with crescents was published 30 years ago by the Southwest Pediatric Nephrology Study Group. That’s why the PNRC’s multicenter collaborative approach to research is so important to helping us better understand this disease.”

In the PNRC’s cohort, the average age at biopsy was 11 years, and the percent crescents ranged from 3% to 100% (median 20%). The incidence of end stage kidney disease (EKSD) was 12% at one year and 16% at most recent follow-up, which was on average 3 years after biopsy.

“More than half of children with GN and crescents who eventually progress to EKSD do so within the first year after biopsy,” says Dr. Smoyer. “In our study, the median time to EKSD after biopsy was 100 days.”

Risk factors for ESKD included percent crescents, presence of fibrous crescents, estimated glomerular filtration rate and hypertension at biopsy. Notably, for each percent increase in glomerular crescents, the investigators found a 3% decrease in 1-year renal survival and a 2% decrease in renal survival at last follow-up.

“This study provides an important new evidence base for risk stratification for crescentic GN in future clinical trials,” says Dr. Smoyer. “Given recent increases in our understanding of GN pathophysiology and new therapeutic options, having an evidence-based baseline for renal survival in children with GN with crescents will notably enhance our ability to determine the potential benefits of future therapies.”

The PNRC’s Pediatric Glomerulonephritis with Crescents Registry offers more opportunities to answer questions related to this patient population as more sites and patients are enrolled, adds Dr. Smoyer.

Reference:

Maliakkal JG, Hicks MJ, Michael M, Selewski DT, Twombley K, Rheault MN, Seamon M, Misurac JM, Tran CL, Reyes L, Flynn JT, Onder AM, Constantinescu AR, Singh V, Pan C, Omoloja A, Wu Q, Smoyer WE, Hidalgo G, Wenderfer SE. Renal Survival in Children with Glomerulonephritis with Crescents: A Pediatric Nephrology Research Consortium Cohort Study. Journal of Clinical Medicine. 2020 Jul 26;9(8):2385.

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