Clinical trial NCT06595420: Kidney Function in People With Cystic Fibrosis in the Era of HEMT
Official title: Kidney Function in People With Cystic Fibrosis in the Era of HEMT
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis (CF)
Chronic Kidney Disease(CKD)
Acute Kidney Injury
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 260
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be derived from patients with CF with ongoing care at one of the 3 CF Centers (Dartmouth, UAB, UVA).

Brief summary: The purpose of this study is to find out what causes kidney disease in people with CF. The investigators will study biomarkers in the blood and urine that can either predict who is at risk or detect kidney damage early before it becomes permanent. The study will compare these markers in people with CF over time and during the treatment of lung flare-ups. It will also compare the blood and urine samples obtained from people without CF. The comparison aims to better understand the impact of cystic fibrosis and its treatment on the kidneys, as well as to develop improved methods for preventing, diagnosing, and treating kidney issues associated with CF.

Detailed description: 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 every 48 hrs 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.

Eligibility criteria: Inclusion Criteria:

1. Outpatient CF Cohort

   * Diagnoses of Cystic Fibrosis
   * Age \&amp;gt; 30 years old
   * Able to provide informed consent
2. Inpatient CF Cohort

   * Diagnoses of Cystic Fibrosis
   * Age \&amp;gt; 7 years old
   * Able to provide informed consent and assent (where applicable)
   * 55 PwCF frequently hospitalized for a pulmonary exacerbation (\&amp;gt;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
3. Healthy Controls

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

Exclusion Criteria:

1. 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 \&amp;lt;2 visits during the 12 months before enrollment)
2. 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
3. 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

Primary outcomes:
measure: Examine whether trajectories of eGFR (calculated from serum creatinine and cystatin C) correlate with urinary kidney injury signatures detected in different urine fractions, or urinary neutrophil levels/activation.
timeFrame: Enrollment and every 3 months for 24 months
measure: Correlation between recurrent hospitalizations and urinary kidney injury signature.
timeFrame: On admission before the initiation of intravenous antibiotic therapy, every 48 hrs during the hospitalization, after discharge at each subsequent routine CF care visit for 24 months.
measure: Relationship between recurrent hospitalization and change in slope of eGFR
timeFrame: On admission before the initiation of intravenous antibiotic therapy, every 48 hrs during the hospitalization, after discharge at each subsequent routine CF care visit for 24 months.
Secondary outcomes:
measure: The correlation between changes in the urinary protein biomarker panel, neutrophil activation, and extracellular vesicles over time and eGFR.
timeFrame: Enrollment and every 3 months for 24 months.
measure: Correlation between %FEV1 at admission or decline in %FEV1 and urinary kidney injury signature.
timeFrame: On admission before the initiation of intravenous antibiotic therapy, every 48 hrs during the hospitalization, after discharge at each subsequent routine CF care visit for 24 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Geisel School of Medicine at Dartmouth
state: New Hampshire
city: Charlottesville
country: United States
facility: University of Virginia Children&#39;s Hospital
state: Virginia
Study officials:
References:
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