Kidney Function in People With Cystic Fibrosis in the Era of HEMT

The prevalence of chronic kidney disease is significantly increased in patients with cystic fibrosis (PwCF) with a major impact on morbidity and medication tolerance as people age. Although expressed in both the proximal and distal tubules, the specific contribution of CFTR dysfunction to renal disease remains uncertain. PwCF often are exposed to renal toxins such as frequent aminoglycosides, systemic inflammation, and activated leukocytes, but it is unknown if CFTR dysfunction predisposes to amplified tubular injury. Conventional measures of kidney function, such as serum creatinine, are insensitive to detecting early injury, limiting an opportunity to prevent CKD. This study will address the gaps in early detection and mechanisms of renal dysfunction in CF. The investigators will define the triggers and targetable mechanistic pathways of kidney injury in CF and discover novel strategies for renal protection. The central hypothesis of this study is that CFTR dysfunction alters renal development and increases the inflammatory and fibrogenic responses to nephrotoxic stimuli.

The study involves prospective evaluation of biospecimens (blood and urine) and clinical data. The study analyzes biospecimens in CF outpatients (n=110), CF inpatients (n=110), and healthy subjects (n=40). In the outpatient cohort, biospecimens will be collected at the time of each routine care visit every 3 months for 24 months. PwCF admitted for intravenous (IV) antibiotics will have biospecimens collected on admission and 2/week thereafter during the admission, and then after hospital discharge at each subsequent clinical encounter for 24 months.

These biospecimens will be analyzed for biomarkers, fibrogenic analysis, inflammatory signals, and extracellular vesicles. Clinical data will be examined from chart review and correlated with biospecimen result.

Inclusion criteria

• Outpatient CF Cohort

• Diagnoses of Cystic Fibrosis
• Age > 30 years old
• Able to provide informed consent
• Inpatient CF Cohort

• Diagnoses of Cystic Fibrosis
• Age > 7 years old
• Able to provide informed consent and assent (where applicable)
• 55 PwCF frequently hospitalized for a pulmonary exacerbation (>1 hospital admission in the prior 12 months)
• 55 PwCF sporadically hospitalized for a pulmonary exacerbation (no hospital admissions in the prior 12 months)
• Able to provide urine sample independently
• Healthy Controls

• Healthy, as per participant self-report
• Age between 30-50 years
• Able to provide informed consent

Exclusion criteria

• Outpatient CF Cohort

• History of any organ transplant
• History of immunodeficiency
• Previous or current cancer diagnoses
• Pregnant or breastfeeding
• On chronic dialysis
• Non-compliance (demonstrated by <2 visits during the 12 months before enrollment)
• Inpatient CF Cohort

• The initiation of intravenous antibiotic therapy after hospital admission before obtaining the first blood and urine sample
• History of any organ transplant
• History of immunodeficiency
• Previous or current cancer diagnoses
• Pregnant or breastfeeding
• On chronic dialysis
• Healthy Controls

• History or current kidney disease, organ transplantation, cancer, or any other chronic illness
• Current use of antibiotics
• Urinary symptoms or UTI (dysuria, frequency, urgency)
• Pregnant women
• Menstruating on the study visit day
• Blood relatives of PwCF