Introduction:
Mercury has long been prohibited for use in skin-lightening agents, but such products are still widely available in many parts of the world.Objective: To evaluate the characteristics of subjects with
nephrotic syndrome caused by exposures to skin-lightening products containing
mercury and the impact of treatments with chelation agents and/or
steroids on the time to achieve remission of
proteinuria and normal urine
mercury concentrations.Methods: We searched Medline and Embase (1971-31 March 2019), Google Scholar (2001-March 2019) and WanFang Data (1999-March 2019), using
mercury,
mercury poisoning,
cosmetics, skin-lightening and
nephrotic syndrome as search terms. Affected subjects must have had nephrotic range
proteinuria and a renal biopsy performed. The searches revealed 46 citations, but 32 were excluded because of a doubtful history, incomplete data collection, more than one source of
mercury exposures, non-nephrotic
proteinuria, treatments by
herbal medicines and duplicate articles. The 14 remaining reports describing 30 cases formed the basis of this review.Incidence and geographical origins: There was an obvious increase in the number of reports with more complete information from Asia (n = 13) and Europe (n = 1) during 2002-2006 (n = 3) and 2010-2017 (n = 11), involving 3 subjects in 2002-2006 and 27 subjects in 2010-2017.Characteristics of subjects: All 30 subjects were Asian females, mostly aged 18-52 years (median 34 years).
Nephrotic syndrome occurred 1-60 months (median 5 months) after exposures to
mercury. The
proteinuria was heavy (urinary
protein excretion 3.2-20.7 g/day, median 5.7 g/day). Other features of
mercury toxicity were generally absent. Blood
mercury concentrations were normal in 6 subjects and 1.1-10.9 times (median 3.5 times) the upper limit of normal in 14 subjects. Urine
mercury concentrations were much higher in 24 subjects, at 1.2-94.6 times (median 9.8 times) the upper limit of normal. Renal biopsy typically revealed
minimal change disease (67%) or
membranous nephropathy (23%).Etiological importance of
mercury: Several clinical observations strongly support the etiological importance of
mercury, including a positive relationship between body
mercury burden (24-h urine
mercury excretion) and severity of
proteinuria, the parallel (often proportional) reductions in body
mercury burden and
proteinuria after cessation of exposures and initiation of
chelation therapy and the risk of persistent
proteinuria in subjects not treated with
chelating agents.Natural history and impact of specific treatments: Spontaneous recovery (within 1.5 months) of
mercury-induced
nephrotic syndrome was rare.Twenty-three subjects were treated with
chelating agents (n = 7) or
chelating agents plus
steroids (n = 16). There was relatively clear information on the time to remission of
proteinuria (urine
protein <150 mg/day) in nine subjects following
chelation therapy (n = 5) or
chelation therapy plus
steroids (n = 4) (median 2 months, range 1-9 months). In comparison, the time to remission was longer in three subjects not treated with
chelation therapy (≥12 months). There were fewer reports with relatively clear information on the time to achieve normal urine
mercury concentrations (<35 nmol/day, <50 nmol/L or <5.0 nmol/mmol
creatinine). In four subjects with treatment by
chelating agents (n = 1) or
chelating agents plus
steroids (n = 3), this took 9-16 months (mean ∼11 months). The adjunctive role of
steroids in
mercury-induced
nephrotic syndrome was unclear.Conclusions: Repeated exposures to inorganic
mercury in skin-lightening cosmetic products typically cause
minimal change disease or
membranous nephropathy, resulting in
nephrotic syndrome. Apart from cessation of product use,
chelation therapy is clearly indicated, in view of the etiological importance of
mercury and the presence of increased body burden with target organ damage. The optimal dosages and treatment strategies for
unithiol (2,3-dimercapto-1-propanesulfonic acid) and
succimer (
dimercaptosuccinic acid) have yet to be determined.