Are certain patient populations (e.g., CKD, elderly, polypharmacy) at higher risk of kidney injury from ivermectin?
Executive summary
Ivermectin is mainly metabolized by the liver and excreted in feces, with less than 1% of unchanged drug found in urine, so routine dose adjustment for mild-to-moderate chronic kidney disease (CKD) is generally not required [1] [2]. However, clinical data are limited and a mix of animal toxicology, small human studies and rare case reports suggest certain groups — notably those with severe renal impairment, the very elderly, and patients with polypharmacy or immunologic vulnerability — warrant closer monitoring because indirect and rare direct kidney harms have been reported [3] [4] [5] [6].
1. Pharmacokinetic reality: why kidneys are usually less central
Pharmacology summaries and clinical reviews emphasize that ivermectin undergoes extensive hepatic metabolism and primary biliary/fecal elimination, with minimal renal excretion of unchanged drug (<1%), explaining why renal clearance is not the dominant determinant of ivermectin levels in most patients [1] [2].
2. Human studies: mostly reassuring but not definitive
Population and clinical studies have generally found only minor, transient glomerular or tubular changes after ivermectin treatment in infected cohorts, and authors judged those changes clinically insignificant in most cases, but these studies are limited in size and follow-up and therefore cannot exclude uncommon or delayed kidney injury [4] [7].
3. Animal and toxicology signals that raise caution
Preclinical work in rodents and some small clinical series show biochemical and histopathological kidney changes after repeated or high-dose ivermectin exposure — for example, rat studies demonstrating decreased antioxidant enzyme activity and impaired kidney function parameters after dosing — which provide biologic plausibility for nephrotoxicity under certain dosing or host conditions [3] [8].
4. CKD and dialysis: usual practice and caveats
Nephrology guidance for scabies outbreaks and reviews note that oral ivermectin typically does not require dose reduction in patients with CKD or on dialysis, and is often used in these populations, but authors also flag interactions (for example with warfarin) and advise monitoring because severe renal disease can alter drug distribution and protein binding in theory [9] [1].
5. Elderly and polypharmacy: indirect risk via comorbidity and interactions
Geriatric guidance and antimicrobial-safety reviews stress that elderly patients are more likely to have age-related liver, kidney, or cardiac dysfunction and to be taking multiple drugs, increasing the risk of adverse drug reactions and interactions even when a given agent is not primarily renally cleared; ivermectin’s hepatic metabolism via cytochrome P450 pathways means co‑medications could raise systemic levels or produce additive toxicity [6] [10] [2].
6. Rare immune-mediated or idiosyncratic renal injury has been reported
Case reports and conference abstracts document rare, severe kidney syndromes temporally linked to ivermectin, including a biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis associated with ANCA seropositivity in a patient after ivermectin exposure, underscoring that idiosyncratic immune-mediated injury — while uncommon — is possible [5].
7. Practical takeaways and uncertainties
Taken together, available evidence supports that frank, common nephrotoxicity from standard ivermectin dosing is not well documented and routine dose adjustment is often unnecessary, but patients with severe renal impairment, frailty or extensive polypharmacy carry higher practical risk because of altered pharmacokinetics, comorbid organ dysfunction, drug–drug interactions and the documented but rare serious immune-mediated events; clinical judgment and monitoring are therefore warranted, and the literature’s limitations (small studies, animal signals, case reports) leave residual uncertainty for high‑risk groups [1] [2] [3] [5] [6].