GLP-1s Show No Link to AKI With Anticancer Therapy

SAN DIEGO – Patients receiving cancer treatment, while having an increased risk for acute kidney injury (AKI) linked to various cancer treatment regimens, show no higher risk in relation to exposure to glucagon-like peptide-1 (GLP-1) receptor agonist drugs, a large retrospective analysis shows.
“Contrary to our hypothesis, our data suggest that exposure to GLP-1s is not associated with an increased risk of AKI in patients receiving anticancer therapies,” first author Swetha Rani Kanduri, an assistant professor of medicine, Department of Nephrology, Ochsner Health, in New Orleans, Louisiana, told Medscape Medical News.
The findings were presented at the American Society of Nephrology (ASN) Kidney Week 2024 Annual Meeting.
Despite increasing evidence of renoprotective benefits of GLP-1 medications, along with their benefits in type 2 diabetes, obesity, and heart failure, some reports have emerged of GLP-1–related AKI. 
According to one inquiry of US Food and Drug Administration Adverse Event Reporting System (FAERS) data on GLP-1 receptor agonists and adverse events, 2375 total kidney-related adverse events were reported, with AKI the most common, representing 59% of cases, with 17 cases of proteinuria and one case of glomerulonephritis associated with semaglutide.
With the increased risk for AKI associated with receiving chemotherapy and other cancer treatments, Kanduri and her colleagues sought to determine whether an added effect occurred with GLP-1s, a particular concern due to the rapidly increasing numbers of patients using the medications.
To investigate, the authors conducted a retrospective review, identifying 14,783 patients treated with anticancer therapies over a 1-year period, from 2022 to 2023, at the Ochsner Medical Center. 
Cancer drugs that patients received included cytotoxic drugs such as alkylating agents, antimetabolites, targeted therapy (including anti-VEGF and tyrosine kinase inhibitors), hormonal therapy, and immunotherapy (including immune checkpoint inhibitors).
Patients’ mean age was 67; 64% were women, 24% had type 2 diabetes, 8% had congestive heart failure, and 13% had chronic kidney disease (CKD).
Overall, 9% (n = 1278) were treated with a GLP-1 drug during the study period.
Among those exposed to GLP-1s, 7.2% developed AKI within the first 90 days of initiation of anticancer therapies, compared with 6.4% of those with no GLP-1 exposure (n = 13,505).
In a univariate logistic regression analysis, exposure to GLP-1 was associated with an odds ratio of 1.14 for AKI, which was not statistically significant (P = .25).
A multivariate analysis adjusting for key risk factors further showed that AKI risk was significantly associated with congestive heart failure (odds ratio [OR], 2.387), CKD (OR, 4.922), type 2 diabetes (OR, 1.477), cytotoxic anticancer therapy (OR, 1.753), and targeted anticancer therapy (OR, 1.966; all P < .0001).
Of note, hormonal therapy was associated with a lower risk for AKI (OR,.645; P < .0001).
Again, GLP-1 use wasn’t significantly associated with a risk for AKI (OR, 1.138; P = .2568).
Kanduri noted the study’s limitations: The effect of the underlying cancer on GLP-1–related AKI risk is unknown, and the study accounted for only 1 year and didn’t account for GLP-1 exposure time.
She added that “hormonal therapy could be protective against AKI.”
Kanduri said the findings were somewhat of a surprise.
“Considering the vulnerability of patients with cancer to acquire AKI during administration of chemotherapy, we hypothesized that exposure to GLP-1 may further increase the risk of AKI in this clinical setting.”
Case Reports of AKI Following GLP-1 Exposure
Specific previous reports of GLP-1–associated adverse kidney events include a report of two cases of AKI associated with semaglutide treatment in a woman in her eighties and a man in his sixties.
In the first case, a kidney biopsy showed evidence of diabetic kidney disease with superimposed interstitial nephritis and acute tubular injury; and in the second, the patient had experienced substantial weight loss with semaglutide treatment, which the authors speculate may have contributed to the decline in kidney function. 
In both cases, a probable adverse drug reaction was suspected; AKI in both was associated with an increase in proteinuria. Of note, neither proteinuria nor kidney function improved in either patient despite drug cessation.
Another case describes GLP-1–associated acute interstitial nephritis requiring hemodialysis, Kanduri noted.
The case was said to be unique in that the patient, a man in his thirties who had a history of obesity, had no underlying CKD and normal baseline kidney function.
In terms of AKI associated with cancer therapy drugs, however, the new findings from the large cohort show no significant association.
“Given the cardiovascular and antidiabetic benefits of GLP-1 receptor agonists, we suggest that these agents can be safely continued during administration of anticancer therapy,” Kanduri said.
Kanduri had no disclosures to report. 
 
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