RNA therapeutics in kidney diseases: prospects and current status.

Abstract

In this narrative review, we summarize the current knowledge on RNA-based therapies used in rare and ultrarare disorders and congenital diseases in which the kidneys may be involved. In these therapies, RNA molecules are packaged into delivery vehicles to reach the desired target. We describe only drugs that have been approved or are under review for approval by the US Food and Drug Administration and/or the European Medicines Agency. We describe the potential therapeutic role of microRNA (miRNA) in Alport syndrome, polycystic kidney disease and renal cell carcinoma. Notably, large randomized clinical studies are required before these drugs can be introduced into clinical practice. The therapeutic effects of short interfering RNA molecules have been tested and evaluated in patients with various congenital or acquired diseases, such as primary hyperoxaluria, hereditary transthyretin amyloidosis, acute kidney injury after cardiovascular intervention or kidney transplantation (i.e. delayed graft function), and in individuals affected by hypercholesterolemia. In addition, synthetic antisense oligonucleotides have proven effective in patients with moderate or severe hypercholesterolemia who developed statin side effects, such as myalgia or rhabdomyolysis, and in individuals with amyloidosis. These new therapeutic approaches need to be validated through global clinical trials in which large patient samples can be enrolled. Nonetheless, some of these promising new approaches are currently undergoing evaluation for the treatment of common diseases, such as hypertension and diabetes, which are the main causes of chronic kidney disease.