Urine cadmium levels and albuminuria in a general population from Spain: A gene-environment interaction analysis

•The association between low-level exposure to nephrotoxic cadmium, with markers of kidney disease is not fully understood.•Abnormal albuminuria can reflect glomerular, tubular, or endothelial damage in the kidney.•Relatively low cadmium levels showed strong positive associations with albuminuria.•Identified statistical gene-cadmium interactions suggest that cadmium and albuminuria may share common biological pathways.•Certain genotypes may confer differential susceptibility to cadmium toxicity.

BackgroundThe interaction of cadmium with genes involved in oxidative stress, cadmium metabolism and transport pathways on albuminuria can provide biological insight on the relationship between cadmium and albuminuria at low exposure levels.ObjectivesWe tested the hypothesis that specific genotypes in candidate genes may confer increased susceptibility to cadmium exposure.MethodsCadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS) in urine from 1397 men and women aged 18-85 years participating in the Hortega Study, a representative sample of a general population from Spain. Urine albumin was measured by automated nephelometric immunochemistry. Abnormal albuminuria was defined as urine albumin greater than or equal to 30 mg/g.ResultsThe weighted prevalence of abnormal albuminuria was 6.3%. The median level of urine cadmium was 0.39 (IQR, 0.23-0.65) μg/g creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to the lowest tertile of urine cadmium were 1.62 (95% CI, 1.43-1.84) and 2.94 (95% CI, 2.58-3.35), respectively. The corresponding odds ratios of abnormal albuminuria were 1.58 (0.83, 3.02) and 4.54 (2.58, 8.00). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated including participants without hypertension, diabetes or chronic kidney disease. We observed Bonferroni-corrected statistically significant interactions between urine cadmium levels and polymorphisms in gene SLC30A7 and RAC1.ConclusionsIncreasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Genetic variation in oxidative stress and cadmium metabolism and transport genes may confer differential susceptibility to potential cadmium effects.