Abstract and Introduction
Among renal diseases, over 100 conditions meet the epidemiological criteria to be defined as rare, including disorders in development, transport and metabolism. Clinical management of rare diseases is likely to be less investigated than that of common disorders and for this reason the scientific evidence to support clinical practice is limited. Furthermore, no specific and validated methods for designing, carrying out or analyzing clinical trials in small populations exist with important consequences for evidence-based medicine. In this paper we aim at discussing the inherent difficulty in finding evidence in rare renal diseases, providing some suggestions on how the quality of evidence and the guidance in these diseases can be improved.
In the USA, the National Institute of Health Office of Rare Diseases Research defines as 'rare' a disease that affects <200 000 people. In Europe, a disease is considered rare when the prevalence is lower than 5 per 10 000 persons. It has been estimated that, so far, between 5 000 and 8 000 rare diseases have been characterized, which collectively affect 6–8% of the European population. Clinical management of rare diseases is inherently bound to be less investigated than that of common disorders and for this reason these diseases are often without specific treatment (orphan diseases). Rare diseases exist, such as nephrogenic diabetes insipidus and Fabry's disease, where we have detailed pathophysiologic knowledge and also specific treatments. However these diseases are typically included among orphan diseases. The definition of orphan diseases has the broad scope of raising the attention of public and the scientific community on a growing series of rare diseases where knowledge on the pathophysiology and natural history is limited with little awareness among doctors and with no or very costly treatment. Approximately 80% of these conditions are genetic in nature. Progresses in genetics, from basic to clinical science, have opened unprecedented opportunities for the identification of faulty gene(s) responsible for these diseases thereby allowing the development of genetic tests and well-targeted treatments. Importantly, knowledge derived from the study of these disorders may also lead to a better understanding of normal biological processes as well as of other polygenic and acquired diseases. In this article, we discuss why the scientific evidence to support clinical practice is limited, what the consequences are for evidence-based medicine and how the quality of evidence and the guidance in these diseases can be improved.
Nephrol Dial Transplant. 2014;29(9):1628-1632. © 2014 Oxford University Press