The pathogenesis of albuminuria in cadmium nephropathy.

Background: Urinary cadmium excretion (E _Cd ) rises with renal tissue content of the metal. Whereas glomerulopathies are sometimes associated with massive albuminuria, tubular accumulation of Cd typically causes modest albuminuria. Since β ₂ -microglobulinuria (E _β2M ) is an established marker of proximal tubular dysfunction, we hypothesized that a comparison of albuminuria (E _alb ) to E _β2M in Cd-exposed subjects would provide evidence of similar mishandling of both proteins.
Methods: To depict excretion rates per functional nephron, E _Cd , E _alb , and E _β2M were normalized to creatinine clearance (C _cr ), a surrogate for the glomerular filtration rate (GFR). Estimation of GFR itself (eGFR) was accomplished with CKD-EPI formulas (2009). Linear and logistic regression analyses were performed to relate E _alb /C _cr , E _β2M /C _cr , and eGFR to several independent variables. Simple linear regressions of eGFR, E _alb /C _cr , and E _β2M /C _cr on E _Cd /C _cr were examined before and after adjustment of dependent variables for age. All regressions were performed after log-transformation of ratios and standardization of all variables. Increments in E _alb /C _cr and E _β2M /C _cr and decrements in eGFR were quantified through four quartiles of E _Cd /C _cr .
Results: As age or E _Cd /C _cr rose, E _alb /C _cr and E _β2M /C _cr also rose, and eGFR fell. In linear regressions, slopes relating E _alb /C _cr and E _β2M /C _cr to E _Cd /C _cr were similar. After adjustment of dependent variables for age, coefficients of determination (R ² ) for all regressions rose by a multiple, and slopes approached unity. E _alb /C _cr and E _β2M /C _cr were similarly associated with each other. Mean E _alb /C _cr and E _β2M /C _cr rose and mean eGFR fell in stepwise fashion through quartiles of E _Cd /C _cr . Whereas E _β2M /C _cr did not vary with blood pressure, E _alb /C _cr rose in association with hypertension in two of the four quartiles.
Conclusions: Our data indicate that Cd in renal tissue affected tubular reabsorption of albumin and β ₂ M similarly in a large cohort of exposed subjects. The results suggest that Cd reduced receptor-mediated endocytosis and subsequent lysosomal degradation of each protein by a shared mechanism.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Authors.)