Researchers have developed a method to design drugs that efficiently block rather than activate critical cell receptors which may help avoid adverse medication outcomes.
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Lithium is an interesting element that in trace amounts is essential for our physical and mental health and at therapeutic levels is a very effective treatment for bipolar disorder spectrum.
In some patients Lithium is the only effective treatment. Recently, it has also emerged as a potential treatment for Post Traumatic Stress Disorder and Traumatic Brain injury. But the downside of this very economic and beneficial drug is the renal adverse effects it causes at therapeutic concentrations after prolonged treatment. Of all patients taking Lithium, ~40 % report various degrees of acute increases in urine production ranging from moderate to very severe nephrogenic diabetes insipidus. Long-term Lithium treatment has more serious effects and can lead to chronic kidney disease, characterized by reduced glomerular filtration rate, interstitial nephritis, renal fibrosis, microcyst formation, and ultimately end-stage renal disease requiring hemodialysis or renal transplantation. Currently, we do not know who will develop these adverse effects and there is no early diagnostic test to determine when to terminate Lithium treatment. Our goal is to predict who will develop the long-term renal adverse effects and to discover an effective treatment to protect the kidney from these side effects.
- Lee KP*, Nair AV*, Grimm C, van Zeeland F, Heller S, Bindels RJ, Hoenderop JG.A helix-breaking mutation in the epithelial Ca(2+) channel TRPV5 leads to reduced Ca(2+)-dependent inactivation. Cell Calcium. 2010; 48(5): 275-87.
- van der Wijst J, Glaudemans B, Venselaar H, Nair AV, Forst AL, Hoenderop JG, Bindels RJ. Functional analysis of the Kv1.1 N255D mutation associated with autosomal dominant hypomagnesemia. J Biol Chem. 2010; 285(1): 171-8.
- Nair AV, Hocher B, Verkaart S, van Zeeland F, Pfab T, Slowinski T, Chen YP, Schlingmann KP, Schaller A, Gallati S, Bindels RJ, Konrad M, Hoenderop JG. Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy. Proc Natl Acad Sci U S A. 2012; 109(28): 11324-9.
- Leunissen EH, Nair AV, Büll C, Lefeber DJ, van Delft FL, Bindels RJ, Hoenderop JG. The epithelial calcium channel TRPV5 is regulated differentially by klotho and sialidase. J Biol Chem. 2013; 288(41): 29238-46
- Nomura N, Nunes P, Bouley R, Nair AV, Shaw S, Ueda E, Pathomthongtaweechai N, Lu HA, Brown D. High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration. Am J Physiol Cell Physiol. 2014; 307(7): C597-605.
- Nair AV, Keliher EJ, Core AB, Brown D, Weissleder R. Characterizing the interactions of organic nanoparticles with renal epithelial cells in vivo. ACS Nano. 2015; 9(4): 3641-53.
- Blanchard MG, Kittikulsuth W, Nair AV, de Baaij JH, Latta F, Genzen JR, Kohan DE, Bindels RJ, Hoenderop JG. Regulation of Mg2+ Reabsorption and Transient Receptor Potential Melastatin Type 6 Activity by cAMP Signaling. J Am Soc Nephrol. 2015 Jul 6
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About the Nephrology Division
The Division of Nephrology at Massachusetts General Hospital is a leading provider of services for patients with kidney disease, including diagnosis and management of kidney diseases and medical management of renal transplantation.