Kidney changes in multiparous mice fed a nutrient-sufficient diet containing cadmium

Area of Science:

• Environmental Toxicology
• Reproductive Biology
• Mineral Metabolism

Background:

• Cadmium exposure is a public health concern, particularly regarding its effects on kidney and bone health.
• Reproductive cycles may influence cadmium accumulation and toxicity.
• The relationship between cadmium-induced renal dysfunction and bone disease requires further elucidation.

Purpose of the Study:

• To investigate the impact of repeated pregnancy and lactation cycles on cadmium accumulation in the kidneys of female mice.
• To assess the onset of cadmium-induced renal dysfunction and its relationship with bone mineral changes.
• To identify critical cadmium concentrations associated with altered kidney mineral homeostasis.

Main Methods:

• Female mice were fed diets with varying cadmium levels (0.25, 5, 50 ppm).
• Mice underwent 1 to 6 cycles of pregnancy/lactation (PL) or remained non-pregnant controls (NP).
• Kidney and urine cadmium, protein, amino acid, zinc, and copper levels were analyzed; bone mineral content was assessed.

Main Results:

• Kidney cadmium concentrations were 2-5 times higher in PL mice than NP controls across all dietary levels.
• At 50 ppm cadmium, kidney cadmium reached 115 µg/g in PL mice after 6 cycles, nearing the threshold for renal damage.
• No significant changes in urinary protein or amino acids indicated absence of typical cadmium-induced renal dysfunction, yet bone mineral loss was observed.

Conclusions:

• Repeated pregnancy and lactation exacerbate cadmium accumulation in mouse kidneys.
• Cadmium-induced bone mineral loss can occur independently of overt renal dysfunction characterized by proteinuria/aminoaciduria.
• These findings suggest that bone disease in Itai-Itai patients might initiate before the appearance of this specific type of kidney dysfunction.