Extrapulmonary manifestations in Cystic Fibrosis:

Cystic fibrosis (CF) is a genetic life-shortening multisystem disease resulting from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, causing the most devastating phenotypes in the airway and pancreas. Significant advances in treatment for CF lung disease, including the expanded use of high-efficiency modulator therapies (HEMT) such as Trikafta, have dramatically increased both quality of life and life expectancy for people with CF (PwCF). With these advances, long-term extrapulmonary manifestations are more frequently recognized.

As PwCF experience increased longevity due to advancements in treatments, there is a growing prevalence of aging-related and metabolic disorders, such as diabetes, which serve as independent risk factors for chronic kidney disease (CKD). Additionally, kidney stones are more commonly observed in the CF population. While HEMT have significantly reduced the morbidity and mortality associated with CF lung disease, leading to improved survival rates, there remains a limited understanding of the mechanisms, treatment, and prevention of kidney, urologic, and metabolic diseases in PwCF.

Newer data suggest that chronic kidney disease (CKD) is a new morbidity in the aging CF population. CKD carries a high risk of premature death from cardiovascular complications. Studies suggest that CFTR dysfunction increases kidneys’ vulnerability to injury caused by the downstream effects of CF. A recent study by Rosner et al. <DOI: 10.1016/j.jcf.2024.12.007> demonstrated an association between early kidney injury marker KIM-1 and neutrophils with diminished lung function and high P. aeruginous burden, suggesting that CF lung disease may contribute to kidney injury in PwCF.