Cystic fibrosis-related kidney disease-emerging morbidity and disease modifier

Cystic fibrosis (CF) is a 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. Pseudo-Barter syndrome, acute kidney injury (AKI) induced by medications or dehydration, amyloidosis, nephrolithiasis, and IgA and diabetic nephropathies have been previously reported in PwCF. Newer data suggest that chronic kidney disease (CKD) is a new morbidity in the aging CF population, affecting 19% of people over age 55. 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. Improving the mutant CFTR function by HEMT may help to tease apart the kidney responses resulting from extrinsic factors and those intrinsically related to the CFTR gene mutations. Additionally, given the novelty of HEMT approaches, the potential off-target effects of their long-term use are currently unknown. We review the evolving kidney complications in PwCF and propose the term CF-related kidney disease. We hope this review will increase awareness about the changing phenotype of kidney dysfunction in PwCF and help prevent morbidity related to this condition.