Studies using a new contrast agent have the potential to determine if infants born premature develop a full complement of nephrons.
A new magnetic resonance imaging contrast agent enables researchers to see the number and volume of blood-filtering nephrons in rodent kidneys and donated human adult kidneys, potentially offering a way to diagnose chronic renal disease far earlier than current methods.
The findings may be especially important for diagnosing and monitoring children born prematurely, says Jennifer Charlton, MD, a pediatric nephrologist involved in the research. Chronic renal disease results when a patient has too few nephrons to filter the blood and rid the body of extra water.
“You create all of your nephrons for all of your life by the time you’re born full-term, and most of those nephrons are formed in the last trimester of pregnancy,” says Dr. Charlton, who is also an assistant professor at the University of Virginia School of Medicine. “So if you’re born prematurely, do you complete this process normally? We don’t know.”
John David Spencer, MD, a nephrologist and principal investigator at the Center for Clinical and Translational Research at Nationwide Children’s Hospital, says, “This technique may be able to tell us how prematurity increases the risk for kidney disease, who will develop it and who won’t, and enables us to evaluate the development of kidney structure and function as patients grow up.”
“Early identification of at-risk patients,” says Dr. Spencer, who is not involved in the research, “will potentially allow them access to care or treatments that can limit the progression and/or prevent side effects of kidney disease.”
The commonly used test for waste products in the bloodstream tells how kidneys are functioning, but patients may lose half of their nephrons before changes are evident. And a biopsy from one region of the kidney may not provide the full picture of the organ.
Dr. Charlton and her colleagues seek images of all the glomeruli, the capillary networks that filter blood in each nephron, in real time. Kevin Bennett, PhD, associate chair of the Biology Department at the University of Hawaii at Manoa, developed the agent, cationized ferritin (CF).
Injected into the bloodstream of rodents and the renal artery of donated adult kidneys (from patients with varying levels of kidney and cardiovascular disease), CF particles bound to the glomeruli. Magnetic resonance images were used to determine nephron numbers, volume and distribution.
If the contrast agent proves unworkable in infants, Dr. Charlton says it may still be useful in testing the quality of donated kidneys prior to transplantation and monitoring the effects of toxic drugs on the kidneys. The agent could also show whether treatments increase or decrease nephron numbers or volume.
(A) CF-labeled glomeruli in a neonatal kidney detected using GRE-MRI. (B) Major vasculature identified and visualized in relationship to the cortex of the kidney. (C) Overlay of the vascular and cortical structures.
Beeman SC, Cullen-McEwen LA, Puelles VG, Zhang M, Wu T, Baldelomar EJ, Dowling J, Charlton JR, Forbes MS, Ng A, Wu QZ, Armitage JA, Egan GJ, Bertram JF, Bennett KM. MRI-based glomerular morphology and pathology in whole human kidneys. American Journal of Physiology Renal Physiology. 2014 Jun 1;306(11):F1381-F1390.
Photo Credit: Jennifer Charlton, MD (CF-labeled kidney); Adobe Stock