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

Background The etiology of chronic kidney disease (CKD) is varied and complex, with diabetes mellitus and hypertension responsible for the 2/3 of cases and rare conditions, including inherited genetic diseases such as autosomal dominant polycystic kidney disease (ADPKD) and glomerulonephritis (GN), comprising 1/3. We previously reported a 54% increase in clinical studies in CKD in the last 10 years. Summary CT.gov was searched for 39 conditions determined to be rare renal diseases posted between 01-Jan-2003 and 31-Dec-2022. Of 876 records returned, 50 were excluded. 826 in the analysis were divided into 2 time periods: P1(2003-2012) and P2 (2013-2022) and analyzed by study type, phase, primary indication, primary endpoint, population and funding. Studies increased 123% in P2 with the greatest rise in observational studies (283%). Interventional studies increased 93%, with the greatest rise in early phases (205%). The most frequent indications were lupus nephritis (22%), ADPKD (16%) and IgA nephropathy (IGAN) (15%); all increased 77-166% in P2. Proteinuria, measured by 24-hour urine protein (24hUP) excretion or urine protein-creatinine ratio (UPCR), was the most frequent primary endpoint in both periods. Most studies were in adult-only populations (P1 60%; P2 68%); however, there was a 78% increase in studies with pediatric populations in P2. Most studies were non-industry funded (P1 64%; P2 57%); however, the number of industry funded studies increased by 225% in P2. Key Messages Our data provides evidence of a marked rise in clinical research in rare renal diseases in the last 10 years, particularly in GN and ADPKD. Proteinuria correlates with outcomes in GN, which explains the high percentage of studies with this as a primary endpoint. Rare renal diseases disproportionately affect children and the rise in the number of studies with pediatric populations is encouraging. The rise in observational studies signals an increased focus on understanding the natural course and pathophysiology of disease, which may lead to new potential therapeutic targets and future interventional studies.