Following on the heels of studies showing a potentially beneficial effect for vasopressin receptor antagonists and rapamycin in the treatment of renal cystic disorders, an article in this month's JASN by Gattone et al suggests another class of commonly-used nephrology-related drug which may be of use: calcimimetics (such as cinacalcet, or sensipar).The logic is as follows: The growth of cysts in PKD is thought to be driven by low intracellular calcium levels and elevated cAMP levels. The calcium sensing receptor (upon which cinacalcet acts) is activated by binding to serum ionized calcium, and results in a G-protein-mediated decrease in cAMP levels & increase in intracellular calcium concentration. The investigators therefore suggested that cinacalcet might be an effective way to reduce cyst growth in late PKD.
To test their hypothesis, they took a rat model of PKD (Cy/+) and treated them either with placebo or with the calcimimetic R-568, which is similar in function to cinacalcet. Interestingly, rats in the treatment group showed less advanced cyst formation and fibrosis at later time points, suggesting that their hypothesis may be correct. This study is somewhat unique in that it looks at fairly advanced stages of cystic kidney disease, whereas other animal studies have focused on a more prophylactic approach to cyst growth.
Cautious optimism for ADPKD patients--if I were a young guy with the PKD1 or PKD2 gene, I would seriously consider enrollment in one of the ongoing trials.
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