Novel crystallization inhibitors or good news for patients with nephrolithiasis

Recently, the team of Professor Gong Junbo of Tianjin University carried out international cooperation with the University of Houston and successfully discovered a new crystallization inhibitor. This inhibitor can effectively inhibit the growth of crystals that induce urate stone formation, which is expected to bring good news to patients with kidney stones. The research was supported by the National Natural Science Foundation of China, and the results were published in the international authoritative journal Nature Communications.

Kidney stones are common diseases of the urinary system, and the symptoms of early kidney stones are not obvious, but as the disease progresses, it can cause hematuria, renal colic, and in severe cases, it can damage kidney function, and even induce uremia. Kidney stones entering the ureter, urethra or bladder can form ureteral stones, urinary stones or bladder stones, which bring great pain to patients and seriously affect human life and health.

Kidney stones are crystalline coalescence formed by concentrated supersaturated precipitation of inorganic or organic salts in urine. Crystallization inhibitors are considered to be an important means of kidney stone prevention and control, and their principle is to inhibit crystal formation or even dissolve stones through “crystal-inhibitor interface interaction”, thereby blocking the stone formation process.

Traditional stone inhibitors are mostly derived from natural Chinese herbal medicines or fruit extracts, and these “natural inhibitor” molecules are different from stone components, and patients need to rely on drugs or health foods for a long time.

In the study, researchers discovered for the first time that urate ketone-enol covariants can be a highly effective “companion inhibitor”. This new inhibitor can produce “self-inhibition” crystallization at a specific concentration, which can control or even completely prevent crystal growth, providing a new idea for urate stone prevention and treatment – patients only need to control the uric acid concentration within a specific range, can inhibit urate crystal growth for a long time, and no longer need other foreign treatment drugs to inhibit the formation of kidney stones. Although the realization of this treatment pathway needs to be further developed, this discovery has broad research prospects and medical value.

How novel crystallization inhibitors work. Photo courtesy of Tianjin University

“Drug effectiveness is closely related to the rate at which they dissolve in humans. Through this study, we also found an important rule that when a tautomer is incorporated into a drug crystal as a defect, it has a significant impact on its dissolution rate. According to Tang Weiwei, the first author of the paper and a teacher at the School of Chemical Engineering of Tianjin University, this is not only an important progress made by the academic community in the pathological crystallization mechanism and regulation of kidney stones, but also provides scientific theoretical guidance for the quality control of high-end drug crystals and the development of industrial crystallization processes. (Source: China Science News, Jiao Defang, Chen Bin)

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