Providing Guidance in the Dark: Rare Renal Diseases and the Challenge to Improve the Quality of Evidence

Davide Bolignano; Evi V. Nagler; Wim Van Biesen; Carmine Zoccali


Nephrol Dial Transplant. 2014;29(9):1628-1632. 

In This Article

The Conundrum of Weak Evidence in Rare Renal Diseases

Observational studies represent a valid source of knowledge for addressing simple research questions in common as well as in rare diseases. Observational studies can provide key information on the epidemiology (e.g. incidence) and natural course of a given disease and suggest potential risk factors associated with different phenotypic manifestations of rare diseases. Because of sample size problems, cohort studies in rare diseases are tantalizing. Case–control studies in rare diseases are the only solution for diseases with a long latency period. However, this study design is weaker for assessing causal relationships than cohort studies and is more prone to bias.

The randomized controlled trial (RCT) is the golden standard for generating unbiased information on the benefits of an intervention. However, performing RCTs in most rare renal diseases is a most challenging undertaking. These conditions affect a few thousand or, sometimes, even fewer than one hundred patients on a world scale and therefore trials are often unrealistic. A RCT of sufficient power would need to recruit patients from very large areas over long periods, so that financial constraints are prohibitory for setting up this sort of trials. National or international registries, medical information platforms and regularly updated portals (see Table 2) may be useful to increase awareness and improve knowledge of rare conditions and to maximize recruitment of patients from multiple centres/countries thereby avoiding fragmentation of data collection. Furthermore, some rare renal diseases have also early manifestations in childhood. Although the need for RCTs in children is increasingly recognized in paediatric research and legislative measures have been taken by local governments to encourage RCTs in children, the enrollment of a large number of paediatric patients remains problematic. Finally, some rare kidney diseases are characterized by a very long course with variable phenotypic manifestation, making the follow-up and the correct definition of outcomes challenging.