A collaborative study finds a dramatic association between asthma and nephrolithiasis in childhood.
Children with asthma are 4 times more likely to have kidney stones than those without asthma, and vice versa, according to a study published online in the medical journal PLoS One.1
“We evaluated children with kidney stones and children with asthma,” says co-investigator Serpil Erzurum, MD, chair of the Lerner Research Institute at the Cleveland Clinic, Cleveland, Ohio. “In either case, asthma and kidney stones are associated with each other.”
Data for the retrospective study were gleaned from the Cleveland Clinic’s electronic medical records of pediatric patients aged between 6 months and 18 years with a diagnostic code of either asthma or kidney stone, from 2000 to 2014. A total of 865 patients had a diagnosis of nephrolithiasis and 36,518 patients had a diagnosis of asthma.
The prevalence of kidney stone alone was 0.08% compared with 6.79% for asthma alone. However, the prevalence of kidney stones in children with asthma was 6-fold higher. “To the best of our knowledge, this is the first time such a connection has been described. It is important that pediatricians have this knowledge base when caring for children,” says Manoj Monga, MD, director of the Stevan B. Streem Center for Endourology and Stone Disease in the Glickman Urological and Kidney Institute at the Cleveland Clinic and senior investigator of the study.
A surprising association
The Cleveland Clinic doctors were inspired to undertake the evaluation for a number of reasons, including the understanding that in children with cystic fibrosis, there is an increased incidence of kidney stones, for unclear reasons.2 “We thought that asthma, being an inflammatory airway disease, might be another population that could have similar findings,” Erzurum says. “The airways and the tubules of the kidney have surprisingly similar functions.”
Inflammation is a common underlying process in asthma and kidney stones.3 Nevertheless, the researchers were surprised to find a dramatic association between the 2 diseases. “By eventually understanding the reason for this co-occurrence, we will better understand asthma and kidney stones,” Erzurum says. “Hopefully, this will open up some basic biology that we can understand about both disorders, resulting in new ideas for studying these 2 diseases.”
The investigators did not find any meaningful differences in patient characteristics or demographics, including age, sex, and body mass index (BMI). However, socioeconomic factors were not evaluated. There also was no difference in inhaled beta agonists, inhaled corticosteroids, or any antiasthmatic medication use among asthma patients, with or without a stone diagnosis. On the other hand, asthma-stone patients were more than twice as likely to be on a combination inhaled corticosteroid plus long-acting beta agonist than asthma patients without a stone (29.7% vs. 13.7%, respectively).
“Because this was a historical study looking at our database, we are limited in what we can conclude,” says Erzurum, holder of the Alfred Lerner Memorial Chair in Innovative Biomedical Research at the Cleveland Clinic. “It could be that some of this association is related to drugs or medications being taken by these children. But we did not find any evidence for that when we tried to compare by controlling for the drugs they were using for their asthma.”
Time to change protocols?
Asthma is a common diagnosis in children and kidney stones are also observed.4,5 “Both lead to discomfort,” Monga says. “Furthermore, parents miss work by staying home with their school-aged children.”
Based on the study, pediatricians should consider the co-occurrence of asthma and kidney stones.
Monga says it is too early for pediatricians to change their treatment protocols for treating asthma or kidney stones. Similarly, the results should not be overinterpreted. “If you are a child with asthma, you are likely to never have a kidney stone,” Monga says. “Kidney stones in childhood are still not that common. And if a child has kidney stones, there is nothing evidence based to consider this a process leading to asthma.”
Pediatricians are unlikely to be surprised by the study results, according to Erzurum. “In fact, long-time practicing pediatricians are likely to have seen asthma and kidney stones in their patients,” she says. “The study might be considered more of a confirmatory study of what pediatricians see in their daily practice.”
Collaboration is key
The Cleveland Clinic researchers are particularly proud of the study’s collaboration among various medical specialties, including urology and pulmonology. “Discovery occurs more rapidly by working together,” Erzurum says. The investigators hope to conduct a prospective follow-up trial.
“As a urologist, the fact that a significant proportion of the study’s pediatric population had both asthma and nephrolithiasis was of interest to me,” says Irene M. McAleer, MD, JD, MBA, a clinical professor of urology at the University of California, Irvine, and a pediatric urologist at Children’s Hospital of Orange County, Orange, California. “A pulmonary specialist may be more concerned that their patients with asthma may get kidney stones.”
McAleer says her own clinical experience of the connection between asthma and kidney stone has not been as remarkable as the study shows. “I tend to see more girls, particularly teenaged girls, more children with obesity, and more children with anatomic abnormalities that put them at risk for kidney or ureteral stones than noticing this association with asthma,” she says.
The study investigators’ speculation “that there may be some associated epithelial defect or condition that places this specific population at risk, like cystic fibrosis, is intriguing and sounds like a great idea for research for possible metabolic or molecular differences in these epithelial regions in these children, both for treatment and prevention of asthma and stone formation alike,” McAleer says.
McAleer found interesting the asthma treatment regimens. “Chronic steroid use, primarily oral administration, is associated with increase urolithiasis, due to increased mobilization of calcium from the bone and possible increased hypercalcuria,” she says. “It is uncertain that inhaled steroids would cause the same release of calcium.”
Additionally, the children that had 24-hour urine collections in the asthma and stone groups and stone-only group “did not have a markedly different urine calcium concentration, so it is difficult to see why these children at the Cleveland Clinic were more likely to have stones associated with their asthma,” McAleer says.
McAleer notes it is too early for pediatricians to be alarmed by any of the study’s findings. “I think that the association found here may be due to referral patterns to the Cleveland Clinic and their review of the data based on coding of the 2 conditions,” she says. “However, pediatricians should be aware that there may be a link between asthma and urolithiasis to help with a differential diagnosis for a child with abdominal or flank pain, with or without gross hematuria, as possibly having a kidney or ureteral stone, just as they are aware that children with cystic fibrosis are at higher risk for kidney or ureteral stone formation, due to their cystic fibrosis.”
Studying the cystic fibrosis population that has both significant pulmonary fibrosis and renal stone formation “may crack the presumed association that is softly associated in the general pediatric asthmatic population,” McAleer says.
Drs Erzurum, McAleer, and Monga report no relevant financial disclosures.
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3. Khan SR. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis. Transl Androl Urol. 2014;3(3):256-276.
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5. Routh JC, Graham DA, Nelson CP. Epidemiological trends in pediatric urolithiasis at United States freestanding pediatric hospitals. J Urol. 2010;184(3):1100-1104.