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KidneyNewsAugust 2018 | Vol. 10, Number 8 Emerging Work on Boosting Nephron Number Could Aid Kidney Function Preservation in Preemies, Adults By Bridget M. Kuehn As the basic working units of the kidney, nephrons with emerging technologies to help clinicians count filter the blood, remove and eliminate urine, and help nephrons, may lead to new kidney-preserving strategies keep nutrients in the body. People have on average about for both preemies and individuals with other forms of 1 million nephrons per kidney, although the numbers kidney disease. may vary between individuals from 200,000 to about 2 million, said Marva Moxey-Mims, MD, chief of the Extending the clock division of nephrology at Children’s National Health Nephrons are under a lot of pressure, and it is normal System in Washington, DC. for some to die over the course of a life. But most people Because nephron formation typically stops by 36 have enough that they can lose some and still eliminate weeks of gestation, babies born earlier may not have a urine effectively. Those born early may not have enough full complement of nephrons, said Moxey-Mims. Some to spare. nephrons may still be formed after birth, she noted, but “One of the advantages of having so many is that you far fewer than if gestation continued. Life-saving treat- can lose some of them,” said Kevin Bennett, PhD, as- ments, such as certain antibiotics, also may damage the sociate professor of radiology at Washington University nephrons these premature infants have, she noted. in St. Louis. “We can keep very, very early birth babies alive, but Pioneering work by nephrologist Barry Brenner at a cost,” said Raphael Kopan, PhD, director of the showed that those born with fewer nephrons were more dvances in neonatal care are boosting survival division of developmental biology at Cincinnati Chil- likely to develop high blood pressure as adults, eventu- rates of those born prematurely, but these sur- dren’s. “The cost will be exacted when they are adults. ally leading to kidney failure, Bennett noted. A vivors may later face kidney complications. New They are at great risk for end stage renal disease.” Understanding why nephrogenesis ends so early in insights on how the kidney forms early in life and new Recent findings from a study by Kopan and his col- life and what lever turns it off might allow scientists to tools to help monitor kidney development may one day leagues suggest it may be possible to extend the pro- extend nephron production and boost the number of duction of nephrons early in life. These findings, along help improve their health. Continued on page 3 > Racial Disparities in Diabetes Complications Are Reduced by Delivering Inside Standardized Care Symptom Strategies By Tracy Hampton How can physicians better help ESRD patients manage their fatigue, ype 2 diabetes and associated chronic kidney dis- panic blacks than in non-Hispanic whites, and blacks have cramping, insomnia and depression? ease (CKD) disproportionately affect blacks. Yet an elevated risk of diabetes-related complications. In addi- when black and white individuals received compa- tion, after development of CKD, blacks with type 2 diabe- Reporting Infections T tes are more likely to progress to kidney failure. Local and state Healthcare Acquired rable diabetes care within the context of a clinical trial, black race was not associated with faster development or progres- It has been unclear whether these burdens may be ex- Infection programs are a good sion of CKD. The findings are published in the Clinical plained by biological factors that influence propensity to resource for nephrologists. Nephrologists Transforming Dialysis Journal of the American Society of Nephrology (CJASN). CKD and its severity or by differences in type 2 diabetes care. Safety helps the two build effective The prevalence of type 2 diabetes is higher in non-His- relationships. Continued on page 6 > Industry Spotlight FDA approves two new AV fistula devices Findings New model helps predict how long it will take a child with CKD to reach kidney failure August 2018 | ASN Kidney News | 3 Boosting Nephron Several groups are working on creating such tools. For example, Bennett and his colleagues are working Number on a kidney-safe contrast agent that would allow clini- Continued from page 1 cians to see individual nephrons in three dimensions in patients using magnetic resonance imaging (MRI). They’ve tested it in animals, as well as human organs not nephrons in premature infants. suitable for transplant, and are beginning the process of Kopan and his colleagues started with two distinct gaining U.S. Food and Drug Administration approval. ideas about how the process might work. One was that This technique could be useful for many kidney diseases. nephrogenesis could occur only during a set time period, “Pretty much every possible type of chronic kidney much like the story of Cinderella, Kopan explained. disease involves some type of nephron loss, and the ex- “When the clock struck 12, just like in the legend, Being able to use tent of that is really important to assess,” Bennett said. the whole process ended,” he said. It’s currently very difficult to assess the kidney health The other idea was that a special niche in the kidney imaging to count of those born prematurely, noted Jennifer Charlton, where nephron stem cells live disintegrates soon after MD, MS, professor in the department of pediatrics at birth, forcing all stem cells to differentiate, he said. nephrons would the University of Virginia in Charlottesville and Ben- To test these ideas, he and his colleagues studied nett’s collaborator. The size of the kidney is not a good young and old kidney stem cells in the laboratory. It help practitioners indicator of nephron numbers, and the kidney is so good turned out both ideas were wrong. So, they took a closer at compensating for low nephron numbers that prob- look at what was happening in the cells. provide better care lems often aren’t detected until they are severe, she said. “As often happens in science, it turned out something For example, the kidney health prospects of a child with even more exciting was going on, which we did not an- for [patients . just one kidney may vary greatly. ticipate,” Kopan said. “If that single kidney has 2.7 million nephrons in it, In a study they published in the Proceedings of the you’re fine,” she said. “You’re probably going to be good National Academy of Sciences, they manipulated genetic and] also could aid to go for the rest of your life. But if that kidney is less well switches in the nephron-producing stem cells of mice to endowed, and only has 500,000 nephrons in it, then you see how they affected nephrogenesis. If they completely the development of may be in trouble as you get to mid-adulthood.” eliminated the gene for the protein Mtor, which controls the metabolism and growth of cells, in mice, the animals drugs that are safer Matching kidney life with recipient life died within 2 days of birth and didn’t have normal kid- neys. for the kidney. Being able to use imaging to count nephrons would help Mice with just one copy of the gene for Mtor lived, practitioners provide better care for these patients. It but had smaller kidneys with fewer nephrons. If they also could aid the development of drugs that are safer completely eliminated the Mtor regulator Tsc1 gene, for the kidney by allowing researchers to monitor drugs’ which makes a protein called hamartin, the mice also ” effects on nephrons, Charlton said. It might also be used died within 2 days of birth, likely owing to kidney fail- to match donor kidneys with the best patients. For ex- ure. But mice with only one copy of the Tsc1 gene had ample, Charlton explained, a kidney from a 70-year-old about 25% more nephrons than expected because they brains, kidneys, and other organs. But Kopan is hope- with 2.7 million nephrons could be matched with a pa- produced nephrons through the 4th day of life, instead ful it will be possible to find alternative nephrogenesis- tient with a longer lifespan. of ending nephrogenesis by the second day, which is extending targets that don’t interfere with hamartin’s “Matching up nephron number with the recipient normal for mice, Kopan said. tumor suppression. He also thinks there may be other could reduce the [number] of organs that we need over “It suggested there could be a molecular handle strategies for extending nephrogenesis. a lifetime, because you’re matching up kidney life with with which we can manipulate how long the period of “Having found one, I’m absolutely certain there will be recipient life,” she said. “You wouldn’t have recipients nephron generation is in mice and then hopefully in more genetic pathways that can have the same effect,” Ko- dying with a graft that’s still functioning, or a recipient [humans],” Kopan said. pan said. “There might be several different pathways that needing two or three transplants, because they didn’t Moxey-Mims called the findings “exciting,” but cau- alone or synergistically will give you the desired effect.” have a good enough nephron endowment to begin with.” tioned much more work would be needed to translate He and his colleagues are currently looking at all the Moxey-Mims cautioned that these nephron-counting the findings into humans. These types of genetic ma- proteins that hamartin may be acting on. They are also tools aren’t yet ready for use in babies. If they do become nipulations would be difficult to do in humans because using large-scale genetic screening techniques to look for available, they might allow neonatologists to monitor of ethical and technical constraints.

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