Assessment of Renal Function in Adults Born Preterm: The HAPI-Kidney Study

NCT04735315 | Active Not Recruiting

• 1 other identifier: HAPI-Kidneys
• Study Type: observational
• Target: 157
• Locations: 1 country
• Sites: 1

Brief Summary

Every year in Canada, 1500 babies are born ≤29 weeks' gestational age (GA) and the majority survive to adulthood. Preterm birth occurs during a critical period of nephrogenesis. Antenatal and postnatal exposure to various insults may permanently disrupt normal kidney development. Indeed, preterm children have reduced nephron number and altered glomerular architecture, which may lead to glomerular hyperfiltration thus perpetuating renal damage. However, the long-term consequences of preterm birth on renal function remain under-studied. The existing reports on glomerular function have yielded contradictory results and were limited by use of imprecise estimates of glomerular filtration rate (GFR) or small sample size. Yet, a registry-based study has shown the increased risk of chronic kidney diseases (CKD) in individuals born preterm. In addition, individuals born preterm have higher blood pressure. As mechanisms for hypertension following preterm birth are being unravelled, the role of the kidneys, which is key in chronic hypertension, is to be determined. So far, we have shown a relationship between smaller kidney size and increased blood pressure. A better understanding of the early markers of kidney dysfunction following preterm birth will facilitate screening and intervention to halt progression to CKD as there are currently no long-term renal follow-up guidelines for individuals born preterm. This proposal builds on our previous works on long-term health outcomes of preterm birth and experimental model of prematurity-related conditions and renal development. We aim to assess glomerular function and renal vasoactive regulatory factors in relation to blood pressure using precise measures in a cohort of young adults born preterm ≤29 weeks versus full-term controls. We further take advantage of our previous assessment of this cohort (Health of Adults born Preterm Investigation (HAPI) - CIHR 2014-18) to evaluate changes in estimated GFR and albuminuria over a 5-year period.

Conditions

Prematurity; Extreme

Keywords

Extremely preterm; Clinical study; Developmental origin of adult health and disease; Prematurity; Renal system; Cardiovascular system

Outcome Measures

Primary Outcomes (6)

• mGFR relative to kidney volume (scintigraphy), measurement 1

  First, whole-kidney mGFR is measured from the plasma clearance of a radionuclide labeled tracer, 99mTc-DTPA, using the slope-intercept method and single-compartment simplification. A single bolus of 300 microcuries (11.1 mega-Becquerels) of 99mTc-DTPA is injected in one arm and plasma sampling for activity concentration (Hidex Automatic Gamma Counter) is performed in the other arm at 90, 120, 150 and 180 minutes. Calculation of mGFR is as follow: mGFR = (Q/Co) x (0.693/T1/2) where Q the injected dose and Co the extrapolated plasmatic activity at time 0.107 If needed, correction for the rapid component of the time activity curve is performed using the Brochner-Mortensen equation. Value of mGFR is then corrected to the patient's BSA, derived from measured weight and height using DuBois' formula, and expressed in mL/min/1.73 m2. Estimated effective dose of the procedure is 0.054 mSv.

  90 minutes

• mGFR relative to kidney volume (scintigraphy), measurement 2

  First, whole-kidney mGFR is measured from the plasma clearance of a radionuclide labeled tracer, 99mTc-DTPA, using the slope-intercept method and single-compartment simplification. A single bolus of 300 microcuries (11.1 mega-Becquerels) of 99mTc-DTPA is injected in one arm and plasma sampling for activity concentration (Hidex Automatic Gamma Counter) is performed in the other arm at 90, 120, 150 and 180 minutes. Calculation of mGFR is as follow: mGFR = (Q/Co) x (0.693/T1/2) where Q the injected dose and Co the extrapolated plasmatic activity at time 0.107 If needed, correction for the rapid component of the time activity curve is performed using the Brochner-Mortensen equation. Value of mGFR is then corrected to the patient's BSA, derived from measured weight and height using DuBois' formula, and expressed in mL/min/1.73 m2. Estimated effective dose of the procedure is 0.054 mSv.

  120 minutes

• mGFR relative to kidney volume (scintigraphy), measurement 3

  First, whole-kidney mGFR is measured from the plasma clearance of a radionuclide labeled tracer, 99mTc-DTPA, using the slope-intercept method and single-compartment simplification. A single bolus of 300 microcuries (11.1 mega-Becquerels) of 99mTc-DTPA is injected in one arm and plasma sampling for activity concentration (Hidex Automatic Gamma Counter) is performed in the other arm at 90, 120, 150 and 180 minutes. Calculation of mGFR is as follow: mGFR = (Q/Co) x (0.693/T1/2) where Q the injected dose and Co the extrapolated plasmatic activity at time 0.107 If needed, correction for the rapid component of the time activity curve is performed using the Brochner-Mortensen equation. Value of mGFR is then corrected to the patient's BSA, derived from measured weight and height using DuBois' formula, and expressed in mL/min/1.73 m2. Estimated effective dose of the procedure is 0.054 mSv.

  150 minutes

• mGFR relative to kidney volume (scintigraphy), measurement 4

  First, whole-kidney mGFR is measured from the plasma clearance of a radionuclide labeled tracer, 99mTc-DTPA, using the slope-intercept method and single-compartment simplification. A single bolus of 300 microcuries (11.1 mega-Becquerels) of 99mTc-DTPA is injected in one arm and plasma sampling for activity concentration (Hidex Automatic Gamma Counter) is performed in the other arm at 90, 120, 150 and 180 minutes. Calculation of mGFR is as follow: mGFR = (Q/Co) x (0.693/T1/2) where Q the injected dose and Co the extrapolated plasmatic activity at time 0.107 If needed, correction for the rapid component of the time activity curve is performed using the Brochner-Mortensen equation. Value of mGFR is then corrected to the patient's BSA, derived from measured weight and height using DuBois' formula, and expressed in mL/min/1.73 m2. Estimated effective dose of the procedure is 0.054 mSv.

  180 minutes

• Whole-kidney GFR (MRI)

  Whole-kidney GFR is a product of nephron number and single-nephron GFR. As a surrogate for single-nephron GFR, we are examining mGFR in relation to total kidney volume (i.e. mGFR per cm3 of kidney volume), which is reduced in adults born preterm and correlates to a certain extent to nephron number. Total kidney volume is measured by multi-parametric magnetic resonance imaging (MRI), which also allows for a comprehensive assessment of kidney structure and hemodynamics. No contrast is injected. Images are acquired using a Philips Ingenia 1.5T MRI system and a 16/32 channels dStream Torso coil (Philips). To quantify total kidney volume, localizer scans at end expiration are acquired using balanced turbo field echo and balanced fast field echo in three orthogonal planes. Volume is then calculated by manually tracing the kidney on the coronal images using Philips Intellispace Portal.

  1 hour

• Rate of glomerular hyperfiltration

  We also examine rate of glomerular hyperfiltration, which is typically described as ˃95th percentile of a reference population. The prevalence of single-nephron glomerular hyperfiltration is estimated by assessing the proportion of participants born preterm with a ratio of mGFR to total kidney volume ˃95th percentile calculated in participants born full-term.

  30 minutes

Secondary Outcomes (36)

• Biomarker of vasoregulatory mechanisms, kidney level, Renin

  60 minutes

• Biomarker of vasoregulatory mechanisms, kidney level, Aldosterone

  60 minutes

• Biomarker of vasoregulatory mechanisms, kidney level, Copeptin

  60 minutes

• Biomarker of vasoregulatory mechanisms, kidney level, Apelin

  60 minutes

• Blood pressure

  10 minutes

Study Arms (2)

Born preterm

Inclusion : Born preterm ≤29 weeks Aged 18-40 years Participants with type-2 diabetes Exclusion : Currently pregnant due to administration of radionucleotides and impact on GFR Severe neurosensory deficit preventing test completion History of characterized kidney disease independent of preterm birth, including type-1 diabetes, glomerulopathies (e.g. nephrotic syndrome, glomerulonephritis), polycystic kidney disease, polycystosis, severe uropathy (Grade 4 or 5 RVU, severe hydronephrosis (SFU IV and V), posterior valve history), history of nephrectomy, exposure to radiotherapy or chemotherapy - given that we are interested in isolating the effects of preterm birth and that prevalence of these conditions is not increased in individuals born preterm In case of contra-indication to MRI scanning (which should be rare in the young population studied), the participant will still be given the opportunity to complete the other examinations.

Other: Preterm birth

Born term

Inclusion : Born full-term at 37-41 weeks Birthweight ˃2500g Aged 18-40 years Participants with type-2 diabetes Exclusion : Currently pregnant due to administration of radionucleotides and impact on GFR Severe neurosensory deficit preventing test completion History of characterized kidney disease independent of preterm birth, including type-1 diabetes, glomerulopathies (e.g. nephrotic syndrome, glomerulonephritis), polycystic kidney disease, polycystosis, severe uropathy (Grade 4 or 5 RVU, severe hydronephrosis (SFU IV and V), posterior valve history), history of nephrectomy, exposure to radiotherapy or chemotherapy - given that we are interested in isolating the effects of preterm birth and that prevalence of these conditions is not increased in individuals born preterm In case of contra-indication to MRI scanning (which should be rare in the young population studied), the participant will still be given the opportunity to complete the other examinations.

Other: Preterm birth

Interventions

Preterm birth OTHER

The study compares young adult subjects born premature (\< 29 weeks) versus term \> 37-41 weeks)

Born preterm; Born term

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants are recruited from the HAPI study, which included 101 individuals born ≤29 weeks in the province of Quebec in 1987-97 (including 83 from CHU Ste-Justine (CHUSJ) who were similar to non-participant survivors for neonatal characteristics), and 105 individuals born full-term recruited among friends/siblings and through advertisement.

You may qualify if:

• Born preterm ≤29 weeks or full-term at 37-41 weeks;
• For full-term controls only, birthweight ˃2500g;
• Aged 18-40 years;
• Participants with type-2 diabetes can be included.

You may not qualify if:

• Currently pregnant due to administration of radionucleotides and impact on GRF,
• Severe neurosensory deficit preventing test completion,
• History of characterized kidney disease independent of preterm birth, including type-1 diabetes, glomerulopathies (e.g. nephrotic syndrome, glomerulonephritis), polycystic kidney disease, polycystosis, severe uropathy (Grade 4 or 5 RVU, severe hydronephrosis (SFU IV and V), posterior valve history), history of nephrectomy, exposure to radiotherapy or chemotherapy - given that we are interested in isolating the effects of preterm birth and that prevalence of these conditions is not increased in individuals born preterm,
• In case of contra-indication to MRI scanning (which should be rare in the young population studied), the participant will still be given the opportunity to complete the other examinations.

Sponsors & Collaborators

• St. Justine's Hospital: lead
• Centre hospitalier de l'Université de Montréal (CHUM): collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• European Georges Pompidou Hospital: collaborator
• Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal: collaborator

Study Sites (1)

StJustine's Hospital

Montreal, Quebec, H3T 1C5, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

The team collected the blood and urine of the participants. They kept whole blood and urine the the biobank. The group also isolated the plasma and serum to perform assays.

MeSH Terms

Conditions

Premature Birth; Disease

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Anne Monique Nuyt, MD

  StJustine's Hospital

  PRINCIPAL INVESTIGATOR

• Thuy Mai Luu, MD

  StJustine's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair and Chief, Department of Pediatrics, Faculty of Medicine University of Montreal / CHU Sainte-Justine

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: February 3, 2021
• Study Start: June 26, 2021
• Primary Completion: March 1, 2024
• Study Completion: December 30, 2025
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 1 year after all the results are published
• Access Criteria: Request of collaboration through data access will be examined by the PI's.

Locations

CA (1)