Case Report: Mercury-induced renal autoimmunity – An insight into its pathogenesis

Introduction

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. They are characterized by basement membrane thickening and minimal or no cellular proliferation with immune deposits on the epithelial side of glomerular capillary walls.¹ The majority are idiopathic, and some can be due to autoimmune diseases, malignancies, and exposure to heavy metals like mercury. Mercury exposure has effects on various organ systems, including the immune system. Here, we would like to report a case with dual renal lesions on histopathology caused by the usage of mercury-containing skin cream.

Case

A 26-year-old male with nil comorbidities, driver by occupation, presented to our outpatient department with easy fatigability of 2 months duration. He had not been evaluated for the same prior. He was normotensive. Labs (Table 1).

He was admitted for renal biopsy and underwent the same. Post biopsy, he was discharged and came back to our OPD (outpatient department) with the biopsy reports almost a month later. Biopsy revealed features suggestive of a moderate degree of chronic interstitial nephritis and membranous glomerulonephritis (Figures 1 & 2). Immunofluorescence revealed glomerular tufts showing FOCAL and SEGMENTAL distributed finely granular deposits with IgG(3+), C3(1+), Kappa(2+), Lambda(2+) along the capillary walls and others were negative. PLA2R(phospholipase A2 receptor) - glomerular capillaries showed diffuse and globally distributed uniform granular staining along the capillary walls.

Figure 1. H&E stain severe interstitial inflammation composed of lymphocyte and eosinophils (300 dpi).

Figure 2. MAT stain 3 globally sclerosed glomeruli with tubulointersitium showing interstitial fibrosis and tubular atrophy with dense chronic inflammation (300 dpi).

Chest radiograph was normal, ultrasound of abdomen revealed normal-sized kidneys, and there was no history of NSAIDS or native medicine intake. On probing his history, he admitted that, due to his dark complexion, he had been using a skin-lightening cream [Beauty Cream] on his face and forearms for the previous eight months given by his friend, but stopped when he had developed symptoms of easy fatigability. The cream was sent for heavy metal analysis, and the mercury content was found to be 9308.6 mg/kg, which is approximately 7,500 times higher than that prescribed by the Minamata convention. We sent his 24-hour urine for mercury levels (though he had stopped using the cream for >3 months) for academic purposes, which was within normal limits. Serum PLA2R levels were not done due to financial constraints. He was treated with ACEi and other supportive care. He is better, and subsequent follow-up urine analysis showed proteinuria regression.

Discussion

Membranous Nephropathy is associated with a lot of morbidity and mortality, with 20–50% of may have progressive renal disease.² When it is associated with another renal lesion, as it happened in our patient, the progression of renal disease will be accelerated. Mercury may damage the kidney in several ways. It may cause tubular or glomerular damage based on whether the exposure is acute or chronic. Acute exposure causes tubular necrosis, and chronic exposure involves the glomerulus³; both the compartments are involved here. If the exposure doesn’t cease, then the tubular necrosis may lead to tubular atrophy and fibrosis, which is evident in the renal histology of our patient. There have been previously published reports of mercury poisoning caused by skin-lightening creams. For example, there were more than 200 cases of women poisoned by mercury after using one kind of skin-lightening cream produced by Mexico in 1995. Mercury poisoning was also reported in about 100 women in Hong Kong after the use of cosmetics made in Mainland China.⁴ The diagnosis mainly rests on the temporal association with history, detection of mercury in the sample, and if presented <3 Months, 24-hour urinary mercury levels may give a clue. The peculiarity of our case here is the presence of solid and uniform PLA2R staining along the capillary walls. This can be seen in mercury-induced MN due to the following reasons:

Previous case reports/reviews mentioned mercury-induced membranous nephropathy and minimal change disease. Here, we report dual renal lesions like chronic interstitial nephritis and membranous nephropathy that highlight the magnitude of mercury-induced renal toxicity caused by the application of this adulterated skin cream. Hence, we should be alert to the possibility of mercury toxicity in patients presenting with new-onset proteinuria and question their use of such mercury-containing products. In patients with mercury-induced MN, it is not mandatory to have a negative PLA2R staining.

Conclusion

Inflammatory indicators, autoantibodies, and renal disease are among the adverse effects of human exposure to mercury in its different forms. Due to the absence of appropriate diagnostic criteria and the modest number of small-scale epidemiological investigations, a definitive link with one or more diagnosable autoimmune illnesses could not be established. Our case with dual renal lesions, particularly with PLA2R-positive MN, strengthens the understanding of mercury-induced inflammation and renal autoimmunity.

Consent to participate

Written informed consent was given by the patient.

Consent to publish

Written consent from the patient was taken for publishing the case after de-identifying and anonymizing all the patient identifiers.