What clinical studies or case reports document acute kidney injury after ivermectin use?
Executive summary
Animal toxicology and small clinical observations together paint a picture in which ivermectin can produce biochemical and histopathological signs of renal injury in experimental models and transient tubular/glomerular marker changes in treated patients, while documented human cases of true acute kidney injury (AKI) after ivermectin are exceptionally rare in the available reporting — one published conference case report suggests a severe ANCA-associated glomerulonephritis temporally linked to ivermectin use [1] [2] [3].
1. What the laboratory and animal literature shows about ivermectin nephrotoxicity
Multiple controlled animal studies report that ivermectin administration produces biochemical signs of renal impairment, oxidative stress and clear histopathological damage to glomeruli and tubules: Wistar rat experiments showed shrunken glomeruli, dilated tubules, epithelial cell vacuolation, increased matrix metalloproteinase‑9 (MMP9) activity and pro‑apoptotic markers after ivermectin exposure, effects that were mitigated by vitamin C in those studies [1] [4] [5]. Similar findings — elevated serum urea and creatinine and histologic kidney damage — have been reported in rabbits and other mammalian models after higher or repeated dosing [6] [7] [8]. These studies consistently propose oxidative stress, MMP9‑mediated cytoskeletal disruption and apoptosis as plausible mechanistic pathways for ivermectin‑related renal injury in animals [1] [5].
2. What clinical studies in humans have actually measured after ivermectin
A controlled clinical observation of patients treated for onchocerciasis documented a slight but statistically significant rise in urinary albumin and alpha1‑microglobulin five days after ivermectin treatment, and increased proteinuria in those with high microfilarial loads, yet the authors judged these changes minor and not clearly clinically relevant [2]. Beyond such short‑term marker changes in a specific parasitic disease context, the formal clinical literature provided in the reporting does not contain randomized trials or cohort studies showing routine AKI after standard ivermectin dosing in general populations [2] [9].
3. Case reports and signal detection: a notable human case of severe renal disease
The clearest human signal in the searched material is an abstract describing what the authors proposed as ivermectin‑associated ANCA vasculitis: a patient taking imported ivermectin developed abrupt renal failure with creatinine 4.5 mg/dL, hematuria, nephrotic‑range proteinuria and a kidney biopsy showing pauci‑immune necrotizing crescentic glomerulonephritis; c‑ANCA was positive and the timeline implicated prolonged ivermectin use (presented in the Journal of the American Society of Nephrology) [3]. The authors framed this as possibly the first reported case and urged clinicians to consider drug‑associated ANCA‑vasculitis, but the report is an isolated conference case and not a confirmed epidemiologic link [3].
4. Weighing the evidence: plausibility, frequency and limitations
Mechanistic plausibility exists from animal data (oxidative stress, MMP9, apoptosis) and small mammalian toxicology studies demonstrate dose‑dependent kidney damage [1] [5] [8]. Clinically, short‑term increases in urinary injury markers after ivermectin therapy have been documented in onchocerciasis patients but were characterized as minor [2]. Robust human evidence that ivermectin commonly causes AKI at therapeutic doses is lacking in the provided sources; the only strong human adverse‑event report is a single case abstract of severe glomerulonephritis temporally linked to ivermectin [3]. Pharmacokinetic summaries note ivermectin is largely hepatically metabolized with minimal renal excretion (<1%), an argument used to explain relative renal safety in many patients, while also acknowledging limited data in people with impaired renal function [9] [10].
5. Practical inference and research gaps
Taken together, the data support that ivermectin can cause nephrotoxic effects in animals and can produce transient tubular/glomerular marker changes in treated humans, and rare immune‑mediated severe renal injury has been reported as a case signal; however, there are no large clinical studies in the provided reporting that establish a clear causal incidence rate of AKI after standard ivermectin use, and the literature explicitly notes limited clinical data in renal‑impaired populations [1] [2] [9] [3]. Future pharmacovigilance, case series, and controlled studies in humans — especially examining dose, duration, co‑medications and host factors — are needed to quantify risk and mechanisms suggested by animal models [1] [5].