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

NCT ID: NCT06595420

Last Updated: 2025-04-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

260 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-01-09

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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Cystic Fibrosis (CF) Chronic Kidney Disease(CKD) Acute Kidney Injury

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Outpatient CF Cohort

Not hospitalized CF group: Diagnosis of CF, age \>30 y, with ongoing care at one of the 3 CF Centers (Dartmouth, UAB, UVA).

No interventions assigned to this group

Inpatient CF Cohort

Hospitalized CF cohort: Diagnosis of CF, age \>7 y, being admitted for intravenous antibiotic treatment of pulmonary exacerbation.

No interventions assigned to this group

Healthy Controls

Healthy Volunteers without CF

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Outpatient CF Cohort

* Diagnoses of Cystic Fibrosis
* Age \> 30 years old
* Able to provide informed consent
2. 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
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 \<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
Minimum Eligible Age

7 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Virginia

OTHER

Sponsor Role lead

Responsible Party

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Agnieszka Swiatecka-Urban

Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

Dartmouth-Hitchcock Geisel School of Medicine at Dartmouth

Lebanon, New Hampshire, United States

Site Status NOT_YET_RECRUITING

University of Virginia Children's Hospital

Charlottesville, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Agnieszka Swiatecka-Urban, MD

Role: CONTACT

434-924-0946

Facility Contacts

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William T Harris, MD

Role: primary

205-638-9583

Sladjana Skopelja-Gardner, PhD

Role: primary

603-667-8259

Agnieszka Swiatecka-Urban, MD

Role: primary

434-924-0946

References

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Devuyst O, Burrow CR, Schwiebert EM, Guggino WB, Wilson PD. Developmental regulation of CFTR expression during human nephrogenesis. Am J Physiol. 1996 Sep;271(3 Pt 2):F723-35. doi: 10.1152/ajprenal.1996.271.3.F723.

Reference Type BACKGROUND
PMID: 8853436 (View on PubMed)

Southern KW. Acute renal failure in people with cystic fibrosis. Thorax. 2007 Jun;62(6):472-3. doi: 10.1136/thx.2006.072355.

Reference Type BACKGROUND
PMID: 17536029 (View on PubMed)

Al-Aloul M, Miller H, Alapati S, Stockton PA, Ledson MJ, Walshaw MJ. Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use. Pediatr Pulmonol. 2005 Jan;39(1):15-20. doi: 10.1002/ppul.20138.

Reference Type BACKGROUND
PMID: 15521084 (View on PubMed)

Bertenshaw C, Watson AR, Lewis S, Smyth A. Survey of acute renal failure in patients with cystic fibrosis in the UK. Thorax. 2007 Jun;62(6):541-5. doi: 10.1136/thx.2006.067595. Epub 2007 Jan 18.

Reference Type BACKGROUND
PMID: 17234661 (View on PubMed)

Quon BS, Mayer-Hamblett N, Aitken ML, Smyth AR, Goss CH. Risk factors for chronic kidney disease in adults with cystic fibrosis. Am J Respir Crit Care Med. 2011 Nov 15;184(10):1147-52. doi: 10.1164/rccm.201105-0932OC. Epub 2011 Jul 28.

Reference Type BACKGROUND
PMID: 21799076 (View on PubMed)

Stevanovic M, G.M. Primary Causes of ESRD in the US Cystic Fibrosis Population. JASN 33, 694

Reference Type BACKGROUND

Stevanovic, M.G.M.L. Characteristics of US Individuals with Cystic Fibrosis and ESRD. JASN 33, 694

Reference Type BACKGROUND

Lai S, Mazzaferro S, Mitterhofer AP, Bonci E, Marotta PG, Pelligra F, Murciano M, Celani C, Troiani P, Cimino G, Palange P. Renal involvement and metabolic alterations in adults patients affected by cystic fibrosis. J Transl Med. 2019 Nov 25;17(1):388. doi: 10.1186/s12967-019-02139-4.

Reference Type BACKGROUND
PMID: 31767021 (View on PubMed)

Berg KH, Ryom L, Faurholt-Jepsen D, Pressler T, Katzenstein TL. Prevalence and characteristics of chronic kidney disease among Danish adults with cystic fibrosis. J Cyst Fibros. 2018 Jul;17(4):478-483. doi: 10.1016/j.jcf.2017.11.001. Epub 2017 Dec 1.

Reference Type BACKGROUND
PMID: 29187303 (View on PubMed)

Alicandro G, Frova L, Di Fraia G, Colombo C. Cystic fibrosis mortality trend in Italy from 1970 to 2011. J Cyst Fibros. 2015 Mar;14(2):267-74. doi: 10.1016/j.jcf.2014.07.010. Epub 2014 Aug 20.

Reference Type BACKGROUND
PMID: 25151032 (View on PubMed)

Nazareth D, Walshaw M. A review of renal disease in cystic fibrosis. J Cyst Fibros. 2013 Jul;12(4):309-17. doi: 10.1016/j.jcf.2013.03.005. Epub 2013 Apr 22.

Reference Type BACKGROUND
PMID: 23618617 (View on PubMed)

van Duijl TT, Ruhaak LR, de Fijter JW, Cobbaert CM. Kidney Injury Biomarkers in an Academic Hospital Setting: Where Are We Now? Clin Biochem Rev. 2019 May;40(2):79-97. doi: 10.33176/AACB-18-00017.

Reference Type BACKGROUND
PMID: 31205376 (View on PubMed)

Kovesdy CP, Bleyer AJ, Molnar MZ, Ma JZ, Sim JJ, Cushman WC, Quarles LD, Kalantar-Zadeh K. Blood pressure and mortality in U.S. veterans with chronic kidney disease: a cohort study. Ann Intern Med. 2013 Aug 20;159(4):233-42. doi: 10.7326/0003-4819-159-4-201308200-00004.

Reference Type BACKGROUND
PMID: 24026256 (View on PubMed)

Breyer MD, Susztak K. The next generation of therapeutics for chronic kidney disease. Nat Rev Drug Discov. 2016 Aug;15(8):568-88. doi: 10.1038/nrd.2016.67. Epub 2016 May 27.

Reference Type BACKGROUND
PMID: 27230798 (View on PubMed)

Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022 Apr;12(1):7-11. doi: 10.1016/j.kisu.2021.11.003. Epub 2022 Mar 18.

Reference Type BACKGROUND
PMID: 35529086 (View on PubMed)

Other Identifiers

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005245A123

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HSR231650

Identifier Type: -

Identifier Source: org_study_id

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