A Retrospective Pharmacovigilance Disproportionality Analysis of Possible Nephrotoxicity and Natural Products Using Data from the FDA Adverse Event Reporting System

Abstract

Background:

Dietary and herbal supplements are widely utilized around the world. These products can cause adverse effects, including nephrotoxicity, through pharmacologically active ingredients, contaminants, or drug–herb interactions, even though they may be perceived as safe. While nephrotoxicity is well documented for certain pharmaceuticals, there are limited studies regarding safety concerns of nephrotoxicity associated with natural products.

Objective:

To identify signals for possible nephrotoxicity involving natural products using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods:

A retrospective analysis of FAERS data (2004–2021) was conducted using the medical dictionary for regulatory activities (MedDRA) terminology to identify possible signals of nephrotoxicity with natural products. Disproportionality analysis was completed by calculating the reporting odds ratio (ROR) for signal detection. Significant signals (ROR ≥ 2.0 with 95% CI lower bound ≥ 1.0) with a case count greater than one were then supplemented by a literature review for clinical and preclinical evidence.

Results:

The analysis identified 231 nephrotoxic event–natural product pairs, representing disproportionate reporting signals for 63 natural products. Three significant signals were detected from a total of 15 cases, including ginger (n = 11) with an ROR (95% CI) of 6.21 (3.85–10), butcher’s broom (n = 2) with an ROR (95% CI) of 7.99 (2.56–24.94), and valerian (n = 2) with an ROR (95% CI) of 2.03 (1.09–3.78).

Conclusion:

While definitive associations between natural products and nephrotoxicity could not be established using a disproportionality analysis, the presence of significant signals for ginger, butcher’s broom, and valerian with respect to kidney-related adverse events highlights the need for further investigations and monitoring by clinicians.