Advancing Treatments for Rare Renal Diseases: New Hopes and Opportunities to Address a High Unmet Need.

INTRODUCTION: The etiology of chronic kidney disease (CKD) is varied and complex. Diabetes and hypertension comprise 2/3 of cases and rare conditions, including inherited genetic diseases, comprise 1/3. We previously reported a 54% increase in clinical studies in CKD in the last 10 years. Hypothesizing a greater increase in rare renal disease studies, we undertook further analysis of metadata from Clinicaltrials.gov.

METHODS: CT.gov was searched for 49 conditions determined to be rare renal diseases posted between Jan-2003 and Dec-2022. Studies were divided into 2 time periods: P1 (2003-2012) and P2 (2013-2022) and analyzed by study type, phase, indication, primary endpoint, population, and funding.

RESULTS: Studies increased significantly in P2 versus P1 (123%, p < 0.001) with the greatest rise in observational studies (283%, p < 0.001). Interventional studies increased 93% ( p < 0.01), with the greatest rise in early phases (205%, p < 0.001). The most frequent indications were LN, ADPKD, and IgA nephropathy; all increased 77-166% in P2 ( p < 0.05 - p < 0.001). Proteinuria was the most frequent primary endpoint, which increased 63% ( p = 0.054). Studies with pediatric populations increased 78% ( p < 0.01). Most studies were nonindustry funded; however, industry-funded studies increased by 225% ( p < 0.001).

CONCLUSION: Clinical research in rare renal diseases has increased significantly in the last 10 years, particularly in glomerular diseases (GDs) and ADPKD. Proteinuria correlates with outcomes in GD, which explains the high percentage of studies with this primary endpoint. Rare renal diseases disproportionately affect children and the rise in studies with pediatric populations is encouraging. The rise in observational studies may signal an increased focus on understanding the natural course and pathophysiology of disease, which may lead to new potential therapeutic targets and future interventional studies. The increase in industry-funded studies suggests basic science is translating into industry-sponsored research.