Renal Involvement in Down Syndrome: Developmental and Clinical Perspectives

With the increasing life expectancy of individuals with Down syndrome (DS), kidney disease has emerged as an important yet under-recognized contributor to long-term morbidity and mortality in this population. This narrative review summarizes current knowledge regarding the developmental, structural, histopathological, and clinical aspects of renal involvement in DS. A literature search was conducted, and studies addressing renal structure, function, development, or pathology in individuals with DS (clinical studies, autopsy studies, case reports, and experimental studies) were included. Available evidence indicates that renal involvement in DS extends beyond congenital anomalies to include altered nephrogenesis, acquired glomerulopathies, and progressive functional impairment. Histopathological studies of fetal kidneys suggest altered nephrogenesis and delayed renal maturation in DS, potentially resulting in reduced nephron endowment. However, the long-term functional consequences of these developmental findings remain uncertain. Reported acquired glomerular diseases are heterogeneous and include IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, ANCA-associated glomerulonephritis, and several rarer entities. Conventional renal biomarkers may underestimate kidney dysfunction in DS because of altered body composition and reduced muscle mass, while evidence regarding novel biomarkers such as NGAL and KIM-1 remains limited. Renal involvement in DS is multifactorial and likely reflects the interplay between disturbed nephrogenesis, developmental renal abnormalities, and acquired renal disease, resulting in increased renal vulnerability throughout life. Improved awareness, earlier nephrological surveillance, and validation of sensitive renal biomarkers may facilitate earlier detection of kidney injuries and improve long-term renal outcomes in individuals with DS.