Complementary and Alternative Medicine Use and Glomerular Disease: A Contemporary Case Series

Rationale & Objective

Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India. Heavy metals are known ingredients in some of these formulations. We studied the spectrum of glomerular diseases in patients using CAM.

Study Design

Case series.

Setting & Participants

Patients with proteinuria or unexplained acute kidney injury, who underwent a kidney biopsy between May 2021 and September 2022, and who provided a history of recent CAM intake were included in the study. For patients enrolled prospectively, blood and urine samples were analyzed using mass spectrometry for the presence of mercury, lead, arsenic and cadmium. The CAM formulation, when available, was analyzed using inductively coupled plasma-optical emission spectroscopy.

Results

Twenty-eight patients were enrolled in the study, with a median duration of CAM intake of 4 months (interquartile range, 2-6 months). Heavy metal screening was performed in 17 patients, of whom 15 had elevated urine mercury levels, 10 had elevated blood mercury levels, and 1 had elevated blood and urine arsenic levels. Of the 6 CAM formulations that were analyzed, all had high levels of mercury. Kidney biopsy findings were membranous nephropathy (n = 19), minimal change disease (n = 8), and mesangial proliferative glomerulonephritis (n = 1). Of the 19 patients with membranous nephropathy, 14 were associated with neural epidermal growth factor-like protein 1 (NELL-1). With conservative management alone, 17 patients achieved complete remission.

Limitations

Not all patients underwent blood and urine mercury testing, and only 6 patients provided the CAM samples for analysis. Furthermore, occupational and residential exposure to mercury could not be excluded.

Conclusions

The most common kidney pathology noted in our study was membranous nephropathy, which was predominantly associated with neural epidermal growth factor-like protein 1. A significant proportion of the patients recovered completely after withdrawal of the offending agent and initiation of renin-angiotensin system blockade.

Plain Language Summary

Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India, and heavy metals are known ingredients in some of these formulations. We describe the clinical spectrum of kidney disease, among patients who had recently ingested CAM. All patients underwent a kidney biopsy, and the most common finding was an entity called “NELL-1-associated membranous nephropathy,” which is known to be associated with heavy metal toxicity and CAM intake. Of 17 patients screened for such heavy metals, 15 had greater-than-permissible levels of mercury. Furthermore, 6 patients provided the CAM formulations that they had consumed for analysis: all contained high levels of mercury. Most such patients recovered following withdrawal of the offending CAM agent.