Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Autor:	Rosner GM; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA., Goswami HB; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA., Sessions K; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Mendyka LK; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Kerin B; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Vlasac I; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA., Mellinger D; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Gwilt L; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Hampton TH; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA., Graber M; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Ashare A; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.; Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Harris WT; AL, USA., Christensen B; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA., Stanton BA; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA., Swiatecka-Urban A; Department of Pediatrics, University of Virginia, VA, USA., Skopelja-Gardner S; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Sep 19. Date of Electronic Publication: 2024 Sep 19.
DOI:	10.1101/2023.11.10.23298378
Abstrakt:	Background: Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF. Methods: Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies. Results: PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronic Pseudomonas aeruginosa infection. Conclusions: Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and high Pseudomonas aeruginosa burden suggests that pulmonary disease may contribute to renal injury in CF. Competing Interests: Conflict of Interest Statement Authors declare no conflict of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu