Integrated Analysis of Zinc, Copper, and Magnesium Homeostasis in Pediatric Idiopathic Nephrotic Syndrome: A Prospective Cohort Study with Serial Clinical Evaluation

Background: Idiopathic nephrotic syndrome (NS) in children is characterized by urinary protein loss and potential disruptions in trace element homeostasis. The dynamic changes in zinc, copper, and magnesium levels in relation to disease activity remain incompletely defined. Objective: This study aimed to evaluate serum zinc, copper, and magnesium and urinary copper and magnesium alterations in homeostasis in pediatric nephrotic syndrome and to examine their associations with disease stage, proteinuria, disease duration, renal function, and corticosteroid response. Materials and Methods: This is a prospective cohort study involving 108 participants, including 74 pediatric patients with idiopathic nephrotic syndrome and 34 healthy controls, comprising 164 clinical and biological assessments. Serum and urinary concentrations of Zn, Cu, and Mg were analyzed, alongside clearance parameters and the fractional excretion of magnesium. Statistical analysis included non-parametric tests, Spearman correlations, ROC analysis, and multivariable logistic regression. Results: Serum zinc levels were significantly lower during active disease phases and normalized during remission (p < 0.001); however, these differences in serum zinc concentration with stages of the NS disappeared after adjustment for serum protein levels (p = 0.424), suggesting a transport deficit secondary to hypoproteinemia. Although serum zinc concentrations were also significantly reduced in patients with concomitant infection, adjustment for serum protein levels attenuated this association, and the zinc-to-protein ratio did not differ significantly according to infection status (p = 0.08). Urinary copper levels and clearance were elevated during active disease and positively correlated with proteinuria (rho = 0.35–0.38; p < 0.001); the Cu/Zn ratio varied significantly across disease stages (p < 0.001) and was associated with both disease activity and a tendency toward corticosteroid resistance. Magnesium demonstrated a pattern of tubular conservation during active phases, with elevated fractional excretion values during remission (p < 0.001) and inverse correlations with proteinuria. Disease duration, but not relapse burden, was positively correlated with serum zinc and fractional magnesium excretion and inversely correlated with serum magnesium. In the multivariable analysis, serum proteins emerged as the sole independent predictor of disease activity, while age and the Cu/Zn ratio were associated with corticosteroid resistance. Conclusions: Pediatric nephrotic syndrome induces significant alterations in zinc, copper, and magnesium homeostasis, dependent on glomerular permeability and plasma protein status. Zinc changes with stages of NS likely reflect a secondary transport defect. In contrast, zinc changes with infection likely occurred because of a shift of zinc to the intracellular compartment. Urinary copper serves as a marker of glomerular permeability and magnesium highlights tubular adaptation. The Cu/Zn ratio and magnesium handling parameters may prove clinically useful in monitoring disease activity and treatment response.