Chronic kidney disease is a major and growing problem worldwide. The Centers for Disease Control and Prevention estimates that one in seven Americans, or about 35.5 million people, have CKD. One particularly damaging form is antibody-mediated glomerulonephritis (AGN), in which the immune system makes antibodies that attack the kidney’s glomeruli, causing inflammation, tissue injury and sometimes kidney failure.
New results reported in the Journal of Clinical Investigation Insight used a murine model to follow kidney inflammation. The study, led by Partha Biswas of the Renaissance School of Medicine at Stony Brook University, examined metabolically reprogrammed immune cells, with special attention to neutrophils. As Biswas notes, metabolic reprogramming has changed treatment strategies in cancer and autoimmune disease, but it had not been explored as a therapeutic avenue for neutrophils in AGN.
The researchers found that neutrophils in the nephritic kidney increase expression and function of Glucose Transporter 1 (Glut1). Glut1 moves glucose into kidney cells and aids glucose reabsorption, preventing glucose loss into urine. The team demonstrated that Glut1 activity in inflammatory cells is necessary for AGN to progress: this effect starts early and drives increased inflammation and tissue damage.
Selective disabling of Glut1 in neutrophils produced a dramatic reduction in tissue‑damaging effector functions throughout disease progression. Neutrophil‑specific Glut1 ablation reduced effector molecules at both early and late stages, while renal cytokine and chemokine production decreased only in the late stage. Treatment with a Glut1 inhibitor also improved kidney pathology in AGN mice. The authors conclude that a Glut1‑powered circuit in neutrophils is central to disease and highly targetable, and that neutrophil metabolic prevention may offer a promising therapeutic strategy. The research was supported in part by the National Institutes of Health and reported by Stony Brook University.
Difficult words
- glomerulonephritis — inflammation of the kidney's filtering units
- neutrophil — a white blood cell that fights infectionneutrophils
- reprogram — to change the normal function or activityreprogrammed, reprogramming
- glucose transporter 1 — a protein that moves glucose across cell membranesGlut1
- ablation — removal or destruction of tissue or function
- cytokine — a small protein used for immune cell signalling
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could targeting neutrophil metabolism change treatment options for people with AGN? Give reasons based on the article.
- What potential risks or side effects might come from blocking Glut1 in immune cells?
- The study used a murine model. How does using animal models affect confidence in applying these results to human patients?
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