Frequently measured clinical markers can predict end-stage renal disease in children with obstructive uropathy, according to a new study published in Pediatric Nephrology.
The article was produced through a collaborative effort by researchers at Nationwide Children’s Hospital, Yale University, the University of Pennsylvania, the Children’s Hospital of Philadelphia, and The Ohio State University.
Obstructive uropathy is a “blanket diagnosis,” explains Daryl McLeod, MD, a member of the Section of Urology at Nationwide Children’s and first author of the manuscript; the term encompasses several complications that can occur during fetal development or after birth that impede urine flow from the bladder, which can ultimately injure the kidneys.
“A lot of damage has already occurred to the kidneys and urinary tract before we are able to intervene,” says Dr. McLeod. “We need to come up with a better way to identify which kids are going to have a worse course than others because a large number of these kids, up to 40 or 50 percent, end up requiring renal replacement therapy in the form of dialysis or kidney transplant.”
“This study looks at a large prospective cohort of children with obstructive uropathy and identifies distinguishing features in their urine testing and serum chemistries that predict future need for renal replacement therapy. Studies like ours are needed to help risk stratify these kids,” says Brian Becknell, MD, PhD, a member of the Division of Nephrology at Nationwide Children’s and senior author on the study.
The researchers took advantage of the prospectively collected, longitudinal dataset called CKiD, Chronic Kidney Disease in Children, which contains over 900 cases of children with mild to moderate chronic kidney disease. They performed a retrospective review of the data and aimed to characterize renal decline in children with obstructive uropathy and to potentially associate seven clinical markers with those children who progressed to end-stage renal disease and those who did not.
After matching children who received renal replacement therapy (renal transplant or dialysis) with children who did not, 27 cases and 41 controls (1:3) were included in the analysis. Follow-up duration was 4.9 and 6.8 years in cases and controls, respectively. The median age at outcome (failure of renal replacement therapy) was 10 and 16 years in cases and controls, respectively.
Glomerular filtration rate, urine protein/Cr, urine microalbumin/Cr, and serum hemoglobin were significantly different at baseline when the study began and changed over time in cases compared with controls, providing both initial and progressive predictive value.
Serum CO2 was significantly different between cases and controls at baseline but not over time. No differences were observed in serum phosphate and serum albumin at baseline but significant differences arose over time. Therefore, all markers demonstrated some predictive value either at baseline, over time, or both.
“This study had a lot of heterogeneity with regards to diagnosis,” says Dr. Becknell, who is also an assistant professor at The Ohio State University College of Medicine. “These kids might have had an obstruction, but we have no idea of the level of that obstruction or the manner in which that was managed. That's a really big deal. What we need is more uniform diagnostic groups of children to see how well these vital markers really perform. Then, we can ask how well do they perform five years out, ten years out, and fifteen years out; because in certain instances, children may require renal replacement therapy as adolescents instead of in the first several years of life.”
This study also demonstrates the importance of collaboration, explains Dr. McLeod. “When you have a disease process like this that affects multiple organ systems, including the urinary tract and the kidneys, it’s important to bring in the expertise and different thought processes from people that are trained differently. I think that is one of the greatest takeaways of this paper.”
McLeod DJ, Ching CB, Sebastião YV, Greenberg JH, Furth SL, McHugh KM, Becknell B.. Common clinical markers predict end-stage renal disease in children with obstructive uropathy. Pediatric Nephrology. 2019 March; 34(3):443-448.