Evaluation of kidney injury biomarkers in rat amniotic fluid after gestational exposure to cadmium

Abstract

Cadmium is a well-characterized nephrotoxic agent that is also capable of accumulating and diffusing across the placenta; however, only a few studies have addressed its effects over fetal kidneys and none of them has used a panel of sensitive and specific biomarkers for the detection of kidney injury. The goal of this study was to determine cadmium renal effects in rat fetuses by the quantification of early kidney injury biomarkers. Pregnant Wistar rats were exposed by inhalation to an isotonic saline solution or to CdCl2 solution (DDel =1.48 mg Cd kg(-1) day(-1) ) during gestational days (GD) 8-20. On GD 21, dams were euthanized and samples obtained. Kidney injury biomarkers were quantified in amniotic fluid samples and fetal kidneys were microscopically evaluated to search for histological alterations. Our results showed that cadmium exposure significantly raised albumin, osteopontin, vascular endothelial growth factor and tissue inhibitor of metalloproteinases-1 levels in amniotic fluid, whereas it decreased creatinine. Clusterin, calbindin and IFN-inducible protein 10 did not show any change. Accordingly, histological findings showed tubular damage and precipitations in the renal pelvis. In conclusion, gestational exposure to cadmium induces structural alterations in fetal renal tissue that can be detected by some kidney injury biomarkers in amniotic fluid samples. Copyright © 2016 John Wiley & Sons, Ltd.

Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models

“…In addition, the overexpression of receptors and transporters in the gut due to high nutrient demand [ 41 ] can promote Cd absorption too. Cadmium accumulates in the lung or gut depending on the route of exposure; then, it is distributed to the liver, kidneys, placenta, mammary glands, uterus and fetus [ 42 , 43 , 44 , 45 ] and it can be excreted into the milk [ 46 , 47 ].…”

“…For instance, it accumulated in the liver, brain and heart of Hartley guinea pig fetuses exposed to a dose of 0.05 mg Cd/m 3 , for 4 h a day from GD35 to 40 [ 80 ]. Also, the exposure to 17.4 mg Cd/m 3 for 2 h from GD8–20 significantly increased the levels of this metal in the kidney of Wistar rat fetuses [ 42 ]. Additionally, exposure to Cd acetate by a subcutaneous injection from 7 days prior to mating and until GD20 or PND21 also leads to hepatic Cd build up in rat fetuses and pups [ 111 ].…”

“…Cd can reach and accumulate in fetal kidney [ 34 , 42 , 96 ]; thus, it can cause structural alterations and damage just like in fully developed kidneys. Accordingly, Roman et al conducted a study that showed that a single intraperitoneal injection on GD10 with 5 mg CdCl 2 /kg induces significant alterations in proximal and distal tubules, as well as glomerular edema in the offspring [ 126 ].…”

“…More recently, our group found that inhalational exposure to Cd from GD8 to GD20 provoked tubular necrosis and degeneration, among other effects, in the kidneys of Wistar rat fetuses (GD21). Such alterations correlated with an increase in the levels of early kidney injury biomarkers in amniotic fluid samples that are composed of fetal urine [ 42 ]. Similarly, a previous study presented evidence that repeated doses of Cd increased β2-microglobulin excretion and lower activity of γ-glutamyl transferase, alkaline phosphatase and N-acetylglucosaminidase in the urine of 3-day old rat pups, which suggested a reduced number of nephrons or a delayed tubular maturation [ 115 ].…”

Renal injury in neonates: use of “omics” for developing precision medicine in neonatology

“…Assessment of amniotic fluid status is an established part of fetal testing mainly because it is produced by the chorion and the umbilical cord, with a significant contribution from fetal urine (8)(9)(10). The amniotic fluid composition is primarily regulated by the fetus and has been previously studied to detect certain biomarkers of kidney injury (11). Changes in the biochemistry of amniotic fluid throughout pregnancy may reflect fetal maturation.…”