How frequently have immune‑mediated kidney injuries been attributed to ivermectin in case series and pharmacovigilance databases?
Executive summary
Reports of immune‑mediated kidney injury attributed to ivermectin are rare in the clinical literature but present as isolated case reports and scattered signals in pharmacovigilance datasets; systematic safety reviews conclude ivermectin retains an overall favorable safety profile while flagging renal events among other serious adverse drug reactions (sADRs) that merit continued monitoring [1] [2].
1. What the recorded cases actually show: isolated but severe presentations
The clearest clinical evidence linking ivermectin to immune‑mediated renal disease comes from individual case reports describing severe, immune‑pattern kidney injury—most notably an apparent drug‑associated ANCA (anti‑neutrophil cytoplasmic antibody) vasculitis with pauci‑immune necrotising crescentic glomerulonephritis after prolonged off‑label ivermectin use for COVID‑19 prophylaxis (case detailed in a report and conference abstract) where creatinine rose to 4.5 mg/dL and biopsy showed crescentic GN [3] [4].
2. What pharmacovigilance datasets say: signals without clear counts in published summaries
Large pharmacovigilance assessments have catalogued “renal disorders” among suspected sADRs associated with ivermectin, and vigiBase/other signal‑mining efforts have been used to describe geographical patterns of serious adverse events that include hepatic and renal disorders [1]. Published pharmacovigilance case series focused on COVID‑era misuse (FACT/ACMT) collected 40 ivermectin adverse‑event reports over 15 months but emphasized neurological toxicity; the FACT report does not present a headline count of immune‑mediated renal events in that series [2]. In short, databases contain renal‑event reports attributed to ivermectin, but publicly available summaries in these sources do not quantify a high incidence of immune‑mediated kidney disease.
3. The balance of evidence: rare occurrences vs background noise
Systematic pharmacovigilance work characterizes renal events as part of a broader, low‑frequency set of serious adverse reactions but explicitly states that these findings do not overturn ivermectin’s generally good safety record and instead call for routine vigilance [1]. Animal toxicology and experimental studies repeatedly show renal histologic and biochemical changes after high or chronic dosing—effects mediated by oxidative stress in rodents—which supports biological plausibility for renal injury but does not directly prove immune mediation in humans [5] [6] [7].
4. Confounders and alternative explanations that complicate attribution
Several factors weaken confident attribution of immune‑mediated kidney disease to ivermectin in case series and pharmacovigilance reports: off‑label and often self‑medicated use during COVID increased exposure and co‑exposures (veterinary formulations, polypharmacy) that can muddy causality [2] [4], endemic parasitic infections (e.g., onchocerciasis/Loa loa) produce Mazzotti‑type immune reactions that affect kidney markers after mass treatment (transient albuminuria/proximal tubular markers), and many pharmacovigilance reports lack full workups or biopsy confirmation [8] [1].
5. What can be concluded about frequency and clinical significance
Based on available published case reports and pharmacovigilance summaries, immune‑mediated kidney injuries attributed to ivermectin are uncommon—consisting largely of isolated case reports and dispersed adverse‑event reports rather than clusters or high disproportionality signals in public summaries—while pharmacovigilance studies continue to list renal disorders among suspected sADRs and urge ongoing monitoring [1] [2]. The literature supports plausibility (animal data, transient post‑treatment albuminuria in onchocerciasis) but not a demonstrable high frequency of immune‑mediated glomerulonephritis in humans tied to appropriate ivermectin use [5] [8].
6. How clinicians and regulators are likely to interpret this evidence
Regulatory and clinical readers of these sources will treat immune‑mediated renal injury after ivermectin as a rare but serious potential adverse outcome that requires careful case investigation—including exclusion of infectious, parenteral, or co‑exposure causes and, when present, biopsy confirmation—while recognizing that established pharmacovigilance reviews record such events without overturning ivermectin’s overall safety record [1] [2]. The practical implication is continued reporting, scrutiny of off‑label self‑medication patterns, and targeted investigation when immune features are suspected [4] [2].