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Establishing Efficacy of a Claudin-Based Treatment for Kidney Stones

Indra Gupta
The Research Institute of the McGill University Health Centre
Kidney Health Research Grant
2022 - 2024
$100,000
Urology, Water/Salt and Calcium Handling by the Kidney, Patient Care

Lay Abstract

Patients who suffer from recurrent kidney stones have a significant risk of kidney damage and some will progress to severe damage. Most kidney stones are composed of calcium that is removed from the blood by the filters of the kidneys and eliminated in the urine. If the filters do not eliminate calcium effectively, there may be a “buildup” of calcium in the urine, which leads to the formation of a kidney stone. To treat the buildup of calcium, patients are told to drink more water to dilute the calcium in the urine. They are also asked to reduce their salt consumption as a high salt diet promotes calcium buildup in the urine. There are also medications that can be given to patients to decrease the calcium in the urine. All of these treatments, however, have significant side-effects that limit a patient’s ability to commit to them over the long-term. Consequently, 50% of patients experience recurrent kidney stones, which puts them at high risk for permanent kidney damage. To identify new treatments, we are exploring the function of a family of proteins called the claudins that are expressed by the filters of the kidneys and affect the elimination of calcium in the urine. In this proposal, we will determine if patients with kidney stones have changes in their DNA that encodes claudin genes. We will then analyze the consequence of these DNA changes in claudin genes using cell lines to determine if they could affect the elimination of calcium in the urine. In our last objective, we will perform a pilot study to test a treatment for kidney stones. The leaf of the plant Bryophyllum pinnatum has been used as a traditional medicine to treat kidney stones and contains multiple compounds including one that can affect the function of claudins. We will treat patients with kidney stones with a tea made from the leaf of this plant and determine if it prevents the buildup of calcium in the urine. Our studies in patients will be complemented by experiments in which kidney cell lines and animal models are treated with the tea to determine if the tea exerts its beneficial effects by affecting the function of claudins. The experiments using cell lines and animal models will establish the mechanism of how the tea prevents calcium buildup in the urine.