Nephronophthisis: should we target cysts or fibrosis?

Ciliopathy nephronophthisis (NPHP), a common cause of end-stage renal disease (ESRD) in children and young adults, is characterized by disintegration of the tubular basement membrane accompanied by irregular thickening and attenuation, interstitial fibrosis and tubular atrophy, and occasionally cortico-medullary cyst formation. Pharmacological approaches that delay the development of ESRD could potentially extend the window of therapeutic opportunity for this group of patients, generating time to find an appropriate donor or even for new treatments to mature. In this review we provide an overview of compounds that have been tested to ameliorate kidney cysts and/or fibrosis. We also revisit paclitaxel as a potential strategy to target fibrosis in NPHP. At low dosage this chemotherapy drug shows promising results in rodent models of renal fibrosis. Possible adverse events and safety of paclitaxel treatment in pediatric patients would need to be investigated, as would the efficacy, optimum dose, and administration schedule for the treatment of renal fibrosis in NPHP patients. Paclitaxel is an approved drug for human use with known pharmacokinetics, which could potentially be used in other ciliopathies through targeting the microtubule skeleton.