To the Editor:
Mercury-associated membranous nephropathy (MN) is a rare but recognized entity, usually linked to chronic dermal or oral exposure through traditional medicines or cosmetics.1,2 Inhalational exposure, however, is extremely uncommon. We report a biopsy-proven case of NELL-1–positive MN following inhalational mercury exposure.
A 44-year-old man with psoriasis developed burning dysesthesias in his feet, inner restlessness, and increased urinary frequency after inhaling heated mercury mixed with animal bile daily for 2 weeks as an unconventional skin treatment. Laboratory evaluation revealed nephrotic-range proteinuria (urine protein-to-creatinine ratio: 5.6 g/g), hypoalbuminemia (3.29 g/dl), and hyperlipidemia, with preserved renal function. Blood pressure was 156/101 mm Hg, without hematuria or edema. Autoimmune serology was negative, and complement levels were normal. Neurological examination showed distal sensory loss and hyperreflexia; small fiber neuropathy was suspected, and pregabalin was initiated.
Renal biopsy demonstrated diffuse glomerular basement membrane thickening, subepithelial deposits, and spike formation. Immunofluorescence revealed granular IgG and C3 deposits; PLA2R was negative, but immunohistochemistry showed NELL-1 positivity (Figure 1). Electron microscopy confirmed stage 1 to 2 MN. Heavy metal testing detected elevated mercury levels (serum: 19.6 μg/l [normal: 0–10 μg/l]; urine: 86.7 μg/l [normal: 0–20 μg/l]). No other nephrotoxin exposure or secondary causes were identified.
Figure 1.
(a) Diffuse thickening of the glomerular basement membranes (hematoxylin and eosin stain; × 400). (b) Strong granular IgG deposits along the glomerular basement membranes (immunofluorescence microscopy; × 400). (c) No staining observed in glomeruli with anti-PLA2R antibody (× 400). (d) Diffuse granular staining of the glomerular basement membranes with anti-NELL1 antibody (× 400).
The patient was treated with i.v. and oral 2,3-dimercaptopropane-1-sulfonic acid (Dimaval), leading to a decline in mercury levels (to 4.5 μg/l within 2.5 months) and gradual improvement in neurological symptoms. At 6 months, proteinuria decreased to 0.8 g/g under renin–angiotensin system blockade and sodium-glucose cotransporter 2 inhibition, with normalization of serum albumin (Figure S1).
This case highlights 2 points. First, inhalational mercury exposure is an underrecognized but clinically significant cause of nephrotoxicity, emphasizing the need for careful environmental and occupational histories in MN evaluation. Second, NELL-1 positivity aligns with emerging evidence linking this antigen to toxin- or drug-induced MN.2,3 To our knowledge, this is the first reported case of NELL-1–positive MN following inhalational mercury exposure.4 These findings broaden the clinical and antigenic spectrum of mercury-associated MN and support routine antigen staining beyond PLA2R.
Disclosure
All the authors declared no competing interests.
Pateint Consent
Written informed consent was obtained from patient who participated in this study.
Footnotes
Figure S1. Changes in urinary protein-to-creatinine ratio (UPCR) and serum albumin over time following initiation of Dimaval (2,3-dimercaptopropane-1-sulfonic acid, DMPS).
Supplementary Material
Figure S1. Changes in urinary protein-to-creatinine ratio (UPCR) and serum albumin over time following initiation of Dimaval (2,3-dimercaptopropane-1-sulfonic acid, DMPS).
References
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Supplementary Materials
Figure S1. Changes in urinary protein-to-creatinine ratio (UPCR) and serum albumin over time following initiation of Dimaval (2,3-dimercaptopropane-1-sulfonic acid, DMPS).