An international study, involving more than 70 researchers including scientists from CNAG, has identified a genetic variant at the SUSD1 locus associated with the risk of renal impairment in patients with decompensated cirrhosis. The research, published in The Lancet Gastroenterology & Hepatology, analyzes genetic and clinical data from over 5,000 individuals of diverse ancestries.
Liver cirrhosis can lead to serious complications, including kidney injury, particularly in its most severe stage. While factors like age and the severity of liver disease are known, the contribution of genetic differences has remained unclear. This study sheds light on the biological mechanisms explaining kidney dysfunction in advanced cirrhosis.
The research, led by the Hôpital Universitaire de Bruxelles and the European Foundation for the Study of Chronic Liver Failure (EF CLIF), with contributions from CNAG and IDIBAPS–Hospital Clínic de Barcelona, involved nearly 5,000 patients. A genetic region around the SUSD1 gene was identified as consistently associated with serum creatinine, a key marker for assessing kidney function.
Researchers employed various techniques, including single-cell and spatial analyses, to explore how this genetic finding might affect SUSD1 gene activity. The analyses pointed to plasmacytoid dendritic cells, a type of immune cell, and type-I interferon as possible links between genetic variation and kidney injury.
“"Single-cell analyses allowed us to move from a genetic association to a plausible cellular mechanism. Across liver, blood and kidney, they consistently pointed to plasmacytoid dendritic cells as a major SUSD1-expressing population, with increased SUSD1 expression and type-I interferon activity in patients with renal impairment."
“"A key lesson from this study is that integrating genetic, single-cell, and spatial transcriptomic data provides a powerful framework for translating statistical associations into plausible biological mechanisms."
These findings open new avenues for potential therapeutic approaches and the identification of clinical biomarkers for assessing the risk of renal impairment in patients with decompensated cirrhosis.
