Compensatory Hypertrophy Enhances Renal Uptake of Mercury
Approximately 15 % of the adult population in the United States has been diagnosed with some degree of chronic kidney disease (CKD). CKD is characterized by a progressive and permanent loss of functioning nephrons. Following this loss, the remaining functional nephrons undergo compensatory changes including increased renal blood flow, increased single nephron glomerular filtration rate (SNGFR), and cellular hypertrophy. We hypothesize that compensatory hypertrophy of proximal tubules leads to an increase in the uptake and accumulation of xenobiotics and toxicants, such as mercury (Hg). Mercury is a ubiquitous environmental toxicant to which humans are exposed through various routes. Patients with CKD may be more susceptible to Hg and thus, it is important to understand how Hg is handled in the kidneys of these patients. We hypothesize that hypertrophied proximal tubular cells take up more Hg and are also are more sensitive to the toxic effects of Hg. To test this hypothesis, we used New Zealand White rabbits and Wistar rats. Cellular uptake of Hg, as a conjugate of glutathione (GSH; GSH-Hg-GSH), was measured at the basolateral membrane of isolated non-perfused proximal tubules from control and nephrectomized rabbits. Differences in mercury uptake at the cellular level were measured in control and hypertrophied S2 segments of proximal tubules by measuring several biochemical parameters of GSH-Hg-GSH uptake. Expression of selected enzymes was assessed in unexposed control and hypertrophied tubules using quantitative Polymerase Chain Reaction (qPCR). Effects of Hg on the entire kidney were measured in kidneys from rats injected intravenously with HgCl2 (0.5 µmol/kg/2 ml). Specific laboratory techniques utilized were the Glutathione Colorimetric Detection Assay, TBARS (Thiobarbituric acid reactive substances) Assay, qPCR, and Western Blot. Collectively, our findings show that hypertrophied tubules take up and accumulate more Hg than normal tubules. Also, hypertrophied cells appear to be more sensitive to the toxic effects of Hg than normal cells. These data provide important information regarding the altered handling of mercuric ions in patients with renal insufficiency due to chronic kidney disease.
Matta, Kayla Elizabeth