Dr. Brad Urquhart is a Professor in the Department of Physiology and Pharmacology at Western University's Schulich School of Medicine & Dentistry and serves as Associate Dean, Basic Medical Sciences Undergraduate Education. He completed his BSc, PhD, and postdoctoral training in pharmacology and toxicology at Schulich Medicine & Dentistry and Vanderbilt University Medical Center. His research focuses on understanding patient variability in medication response, with particular interest in kidney disease and drug toxicity. Dr. Urquhart is currently President of the Canadian Society of Pharmacology and Therapeutics and has received numerous honors including the Faculty Scholar Award, Young Alumni Award, Dean's Award of Excellence for Junior Faculty, and the Marilyn Robinson Award for Teaching Excellence.
A study of dialysis patients in Ontario, Canada, found that those starting low-dose methotrexate had a more than threefold higher risk of death or serious hospitalization compared to those starting hydroxychloroquine. Nearly 30 percent of patients taking methotrexate experienced severe complications such as sepsis, lung toxicity, or bone marrow suppression within 90 days. These findings suggest that methotrexate should be avoided in the dialysis population in favour of safer alternative medications.
Lim YJ, Thachil A, McMahon K, Tsuyuki RT, Rassekh SR, Mitchell LG, Devarajan P, Mammen C, Carleton BC, Cuvelier GDE, Lewis VA, Ross CJD, Zorzi AP, Baruchel S, Ramphal R, Bouffet E, Lemaire M, Blydt-Hansen TD, Urquhart BL, Applying Biomarkers to Minimize Long‐Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group
Researchers analyzed urine and blood samples from 86 children receiving cisplatin chemotherapy to identify early markers of kidney injury, which affects nearly half of pediatric patients treated with this drug. The study found that while overall metabolic differences were subtle, specific metabolites involved in the energy-producing NAD+ pathway were significantly higher in the urine of children who developed kidney injury shortly after treatment. These findings suggest that monitoring these specific metabolic changes could help identify at-risk children earlier than traditional blood tests and may point toward new ways to prevent kidney damage.
This review explores how mass spectrometry-based metabolomics can analyze small biological samples to improve the diagnosis and monitoring of various pediatric conditions, including inherited metabolic disorders and cancers. By integrating metabolic data with other genetic information, clinicians can provide more precise and preventive care tailored to a child's specific needs. While challenges remain in standardizing data across laboratories and establishing age-specific reference ranges, advances in artificial intelligence and testing technology are expected to enhance the role of this tool in personalized medicine.
This study explored how children's bodies process oral morphine and its active metabolites by measuring blood concentrations in healthy participants aged 5 to 17. Researchers found that the active metabolites of morphine remain in the system longer than the drug itself and identified a specific genetic variation that may influence how effectively the medication relieves pain. These findings help explain why different children may experience varying levels of pain relief or side effects when taking the same dose of morphine.
A study of older adults in Ontario found that taking the antibiotic clarithromycin while also using certain blood pressure medications, known as angiotensin receptor blockers, was associated with a higher risk of hospital visits for high potassium levels and acute kidney injury compared to taking azithromycin. This risk of high potassium was even greater for individuals with pre-existing reduced kidney function. These findings suggest a significant drug interaction occurs because clarithromycin interferes with the body's ability to transport and eliminate these blood pressure medications through the liver.
This study used a rat model to investigate how the progression of chronic kidney disease affects the liver's ability to break down medications. Researchers found that key liver enzymes responsible for drug metabolism were significantly reduced very early in the disease process, even before significant shifts in gut bacteria or the buildup of waste products in the blood occurred. These findings suggest that kidney disease may impair drug clearance much earlier than previously recognized, potentially impacting how medications should be dosed as kidney function declines.
Researchers in Ontario, Canada, studied older adults taking low-dose methotrexate to see if also taking the antibiotic trimethoprim-sulfamethoxazole increased the risk of death compared to taking a cephalosporin antibiotic. While the risk of death within 30 days was similar between the two groups, patients prescribed trimethoprim-sulfamethoxazole had a higher risk of being hospitalized for any cause or for persistent infections. These findings suggest that while the combination may not be more lethal in the short term, it is associated with a higher rate of serious illness requiring hospital care.
This review explores the field of pharmacometabolomics, which involves analyzing small molecules in blood or urine to predict how an individual will respond to specific medications. By identifying these metabolic markers, researchers can better understand drug metabolism and transport, potentially allowing for more precise dosing to improve treatment effectiveness and reduce harmful side effects. The authors highlight examples of this approach in treating major depressive disorder and managing cancer chemotherapy, while also discussing the current challenges in moving these techniques into routine clinical practice.
In older adults taking digoxin, starting a course of the antibiotic trimethoprim-sulfamethoxazole was associated with a nearly sixfold higher risk of hospitalization for digoxin toxicity compared to starting amoxicillin. While the absolute risk of this complication remained low at less than one percent, the interaction is clinically significant because digoxin has a narrow safety range. Physicians should consider using alternative antibiotics or reducing the digoxin dose when these medications must be used together.
Researchers tested the movement and breakdown of a new anti-inflammatory drug called SY-005 in patients hospitalized with severe COVID-19 and normal kidney function. The study found that the drug was cleared from the bloodstream within six hours of administration without building up in the body or affecting the blood's ability to clot. These findings help determine the appropriate dosing schedule for future clinical trials of this medication.
A study of older adults in Ontario, Canada, found that those with chronic kidney disease who started low-dose methotrexate had double the risk of serious adverse events, such as sepsis or lung and liver toxicity, compared to those starting hydroxychloroquine. This risk was even higher for individuals with more advanced kidney impairment, particularly those with an estimated glomerular filtration rate below 45. These findings suggest that the potential for severe complications should be carefully weighed against the benefits when prescribing methotrexate to patients with reduced kidney function.
This randomized trial investigated whether a highly absorbable form of curcumin could slow the progression of chronic kidney disease in adults with high levels of protein in their urine. Researchers found that taking 90 milligrams of micro-particle curcumin daily for six months did not significantly improve kidney function or reduce protein leakage compared to a placebo. These results suggest that this specific curcumin formulation does not provide measurable benefits for managing albuminuric chronic kidney disease over a short-term period.
Researchers used mouse models to identify 26 specific substances in the blood, urine, and kidneys that change early on after exposure to the chemotherapy drug cisplatin. These metabolic markers, which are linked to energy production in cells and the gut microbiome, could help identify kidney injury much sooner than current standard tests. This study provides a potential panel of markers to help monitor and understand how cisplatin damages the kidneys in clinical settings.
Researchers developed a new laboratory test to measure a molecule called TMAP in the blood and evaluated its potential as a marker for kidney function across several patient groups. The study found that TMAP levels were significantly higher in patients with chronic kidney disease and those receiving dialysis compared to healthy individuals, with levels rising as the kidney's filtering capacity declined. Because TMAP was also found in other species and even in maple tree sap, it appears to be part of a biological process that is widely conserved across nature.
Researchers studied patients with head and neck cancer to identify markers in the blood and urine that could predict or detect early kidney damage caused by the chemotherapy drug cisplatin. They found that specific metabolites related to energy production and mitochondrial health were significantly different in patients who developed kidney injury compared to those who did not. These findings suggest that testing for these specific substances before or shortly after treatment could help identify patients at high risk for this serious side effect.
This review explores why individuals with chronic kidney disease face a significantly higher risk of heart disease and stroke, focusing on the role of toxins that accumulate when kidney function declines. These substances, including those produced by gut bacteria and systemic metabolic processes, contribute to vascular damage beyond what is explained by traditional risk factors like high blood pressure. The authors suggest that reducing these toxins through specialized diets, intensive dialysis, kidney transplantation, or specific vitamin therapies may be necessary to improve cardiovascular outcomes in this population.
