A case report published in the Journal of Veterinary Internal Medicine has described medication-based urolithiasis in two cats receiving GS-441524 for feline infectious peritonitis (FIP), with analysis showing that the removed uroliths were composed almost entirely of the antiviral compound.
Both cats developed clinically significant urinary tract disease while undergoing antiviral treatment. In each case, initial routine analysis was unable to identify the material within the uroliths. Further investigation found the calculi to be 98% consistent with GS-441524.
The authors believe these are the first reported cases of uroliths composed of an antiviral medication or its metabolites in cats.
The first cat was an eight-month-old female domestic short-haired cat being treated for presumptive FIP with neurological involvement. The owner had obtained GS-441524 through an online support group, and treatment had continued for approximately four months by the time the cat was referred with dehydration, weakness, lethargy and marked azotaemia.
Ultrasound revealed extensive urinary tract abnormalities, including renal and ureteral calculi, right hydronephrosis and multiple bladder stones. The obstruction progressed and bilateral subcutaneous ureteral bypass systems were placed, with cystotomy performed to remove the bladder stones.
The cat's azotaemia improved following surgery, but severe neurological and cardiovascular abnormalities persisted and the cat died following cardiopulmonary arrest nine days after admission.
The second case involved a two-year-old male domestic medium-haired cat with confirmed FIP. It received GS-441524, briefly received remdesivir and was subsequently treated with GS-441524 alongside the antiviral GC-376.
Needle-like unidentified crystals were already present on urinalysis around two weeks after the FIP diagnosis. Several weeks later, the cat developed a weak urine stream and urinary dribbling, followed by severe azotaemia, bilateral hydronephrosis and evidence of uroliths within the bladder and proximal urethra.
A cystotomy was performed and a temporary cystostomy tube placed. Although the cat initially improved, it deteriorated again after discharge and was euthanased.
Routine analysis initially classified the material from both cats as unidentified.
Investigators subsequently obtained a GS-441524 reference standard. Fourier transform infrared spectroscopy and X-ray powder diffraction showed the urolith from the first cat to be 98% consistent with GS-441524, while the second was also identified as 98% GS-441524 using infrared spectroscopy.
Further analyses, including liquid chromatography/mass spectrometry and nuclear magnetic resonance, supported the identification.
This makes the finding clinically notable. Medication-related uroliths are uncommon in veterinary patients, and the authors reported finding no previous descriptions of antiviral medications or their metabolites forming uroliths in cats.
The case report cannot establish how frequently this complication occurs or which cats are most at risk.
Both cats had crystalluria, lower urinary tract signs and documented or suspected urinary tract infections during their clinical course. Both also developed azotaemia.
The authors discuss several other factors that could potentially contribute to medication-based urolith formation, including high drug doses, longer treatment duration, urinary drug excretion, poor drug solubility, urinary stasis and pre-existing renal dysfunction. However, the contribution of any of these factors in the two cats remains uncertain.
There are important limitations when interpreting the cases. The cats were receiving unlicensed GS-441524 products obtained outside conventional veterinary supply routes, and the investigators could not establish the exact dose received by the first cat. The second cat had also received remdesivir and GC-376.
The study therefore does not show that urolithiasis is a predictable adverse effect of properly prescribed GS-441524 treatment, nor can two cases provide an estimate of its incidence.
The authors suggest considering urinary tract ultrasonography in cats receiving GS-441524, particularly those receiving higher doses. Because the uroliths in these cases were poorly visible or radiolucent on survey radiography, they suggest contrast radiography could be considered where ultrasonography is unavailable.
Monitoring renal function and urinalysis may also be appropriate, while cats that become azotaemic or develop lower urinary tract signs during treatment may warrant investigation for urolithiasis.
These proposals should be interpreted as clinical considerations arising from two cases rather than established screening guidelines. Larger retrospective or prospective studies will be needed to establish the incidence of GS-441524-associated urolithiasis, identify risk factors and determine whether routine screening or preventive measures are justified.
This report identifies a previously unreported potential complication of GS-441524 treatment: formation of urinary calculi composed predominantly of the antiviral itself.
It does not establish how common the problem is, and both cases had several potential contributing factors. But for a cat receiving GS-441524 that develops dysuria, haematuria, urinary obstruction or otherwise unexplained azotaemia, medication-associated urolithiasis may now be another differential worth keeping in mind.
Source: Allinder M, Tynan B, Martin C, et al. Uroliths composed of antiviral compound GS-441524 in 2 cats undergoing treatment for feline infectious peritonitis. Journal of Veterinary Internal Medicine. 2024;38(1):370–374.