Early Detection of Progressive Kidney Disease in Preterm Infants

Cardiovascular Diseases Clinical Trial

Official title:

Early Detection of Progressive Kidney Disease in Preterm Infants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02000895
• Other study ID #: 20100986
• Secondary ID: 66787R7011705KL2
• Status: Recruiting
• Start date: July 23, 2011
• Est. completion date: January 1, 2025

Study information

• Verified date: September 2023
• Source: University of Miami
• Contact: Marissa J DeFreitas, MD
• Phone: 305-585-6726
• Email: MDefreitas[@]med.miami.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Infants born preterm and of low birth weight are known to be at increased risk for early onset of cardiovascular and renal disease in adult life. This has been related to low nephron mass due to inadequate or early termination of glomerulogenesis in utero and during the perinatal period. Risks for subsequent development of hypertension and kidney disease include proteinuria, excessive weight gain during early life with insulin resistance and supplemental high calorie feedings. The long-term goal is for early diagnosis of those infants who are at risk for future development of hypertension and kidney disease so that the investigators might intervene to potentially avert progression to adult disease. The objective of this clinical trial is to acquire data on the natural history of neonatal kidney function and size in infants born preterm during the first 2 years of life. This will be done through the use of standard serum and urine markers as well as non-invasive ultrasound technology. The central hypothesis of this clinical trial is that a subgroup of patients born preterm and of low birth weight will demonstrate early markers of kidney injury including elevated serum cystatin C, proteinuria and low kidney size. This hypothesis has been formulated on the basis of preliminary data from our group studying this question retrospectively in older children born prematurely who have developed overt kidney disease. The rationale for the proposed research is to develop early serum and demographic markers of pre-clinical kidney disease so that early intervention can occur. The proposed clinical trial is innovative because it will investigate the risk factors for kidney dysfunction at a pre-clinical stage with the idea of gaining more knowledge regarding therapeutic interventions. In addition, the study will assess serum cystatin C as a surrogate test for glomerular filtration rate which could indicate worsening kidney function at an earlier stage than serum creatinine.

The proposed research is significant because it is expected to identify at-risk patients for future renal impairment and to prospectively monitor the persistence of proteinuria and its effect on kidney function in the short term.

Description:

Objectives and Hypotheses:

Infants born preterm and of low birth weight are known to be at increased risk for early onset of cardiovascular and renal disease in later life. This has been related to low nephron mass due to inadequate or early termination of glomerulogenesis in utero and during the perinatal period. Risks for subsequent development of hypertension and kidney disease include excessive weight gain during early life with insulin resistance and supplemental high calorie feedings.

Specific Aims The long-term goal is for early diagnosis of those infants who are at risk for future development of hypertension and kidney disease so that investigators might intervene to potentially avert progression to adult disease. The objective of this clinical trial is to acquire data on the natural history of neonatal kidney function and size in infants born preterm during the first year of life. This will be done through the use of standard serum and urine markers as well as non-invasive ultrasound technology. The central hypothesis of this clinical trial is that a subgroup of patients born preterm will demonstrate early markers of kidney injury including elevated serum cystatin C, proteinuria and hypertension. This hypothesis has been formulated on the basis of preliminary data from the group studying this question retrospectively in older children born prematurely who have developed overt kidney disease. The rationale for the proposed research is to develop early serum and demographic markers of pre-clinical kidney disease so that early intervention may occur.

Study Design. This is a single-center case-controlled prospective observational study with the rationale of evaluating parameters of renal function including proteinuria, microalbuminuria and cystatin C in preterm infants and associating this with kidney size and blood pressure during the first 10 years of life. Demographics including race, gender and growth will provide important perspectives relative to formula and/or breast feeding with/without high calorie supplements during the first year.

Part I of the Trial is enrollment from birth with collection of blood, urine and umbilical cords for histomorphometry.

Part II will be the "call-back" at 6 to 10 years of age for follow-up assessment of anthropometric and kidney growth, blood pressure and kidney function.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 10 Years

Eligibility

Inclusion Criteria:

Stable preterm infants <37 weeks' gestational age; Stable term infants >37 weeks' gestational age

Exclusion Criteria:

<24 weeks gestational age; <600 grams Any anomalies of the genital-urinary or gastrointestinal tract

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Locations

Country	Name	City	State
United States	University of Miami/ Holtz Children's Hospital	Miami	Florida

Sponsors (5)

Lead Sponsor	Collaborator
University of Miami	Micah Batchelor Foundation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), The Gerber Foundation

Country where clinical trial is conducted

United States, 

References & Publications (3)

Abitbol CL, Seeherunvong W, Galarza MG, Katsoufis C, Francoeur D, Defreitas M, Edwards-Richards A, Master Sankar Raj V, Chandar J, Duara S, Yasin S, Zilleruelo G. Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular — View Citation

DeFreitas MJ, Mathur D, Seeherunvong W, Cano T, Katsoufis CP, Duara S, Yasin S, Zilleruelo G, Rodriguez MM, Abitbol CL. Umbilical artery histomorphometry: a link between the intrauterine environment and kidney development. J Dev Orig Health Dis. 2017 Jun; — View Citation

DeFreitas MJ, Seeherunvong W, Katsoufis CP, RamachandraRao S, Duara S, Yasin S, Zilleruelo G, Rodriguez MM, Abitbol CL. Longitudinal patterns of urine biomarkers in infants across gestational ages. Pediatr Nephrol. 2016 Jul;31(7):1179-88. doi: 10.1007/s00 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in total kidney volume (TKV) from birth to 10 years	TKV will be measured by 2-D and 3-D renal ultrasound	Birth, 1 year, 2 years, 6 years, 10 years
Secondary	Development of Hypertension	Blood pressure measurements by sphygmomanometer	1 year, 2 years, 6 years, 10 years
Secondary	Vascular density	Capillary density/ rarefaction to be measured via capillaroscopy	1 year, 2 years, 6 years, 10 years
Secondary	Vascular stiffness	Vascular stiffness measured as pulse wave velocity by tonometry	1 year, 2 years, 6 years, 10 years
Secondary	Change in estimated glomerular filtration rate (eGFR) from birth to 2 years	Estimated GFR will be calculated from serum creatinine and Cystatin C	Birth, 1 year, 2 years, 6 years, 10 years