Prematurity; ExtremeNCT04735315
Assessment of Renal Function in Adults Born Preterm: The HAPI-Kidney Study
An observational study of Prematurity; Extreme, run by St. Justine's Hospital at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Prematurity; Extreme
- What is being tested?
- Preterm birth
- Type of treatment
- Injection or infusion
- How many people
- 157 participants
- Where
- 1 siteCanada
- Study dates
- 26 Jun 2021to 30 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Given that preterm birth is associated with reduced nephron endowment and higher glomerular area on renal histology suggesting compensatory glomerular hyperfiltration, we postulate that :
Hypothesis 1: mGFR relative to total kidney volume is higher in adults born preterm vs. to full-term controls.
Hypothesis 2: mGFR relative to kidney volume is associated with plasma renin activity, aldosterone, copeptin and apelin levels. Levels of these vasoactive factors may correlate to blood pressure values.
Hypothesis 3: Rates of decline in eGFR and increase in albuminuria is more important in the preterm vs. full-term group. Hypertension at baseline predicts faster decline in eGFR and increase in albuminuria. Decrease in eGFR and increase in albuminuria correlate with increasing blood pressure over time.
Hypothesis 4: Higher baseline copeptin levels and, reciprocally, lower baseline apelin levels are associated with faster decline in eGFR and increase in albuminuria.
Our overarching aim is to assess long-term glomerular function in adults born preterm ≤29 weeks' GA versus full-term controls.
- To assess the association between preterm birth and measured GFR, compared to estimated GFR, in young adulthood (18-40 years).
- To examine the association between mGFR and vasoactive humoral factors involved in kidney hemodynamics (plasma renin activity, aldosterone, copeptin, apelin) in relation to blood pressure in young adults born preterm versus full-term controls.
- To compare changes in eGFR and albuminuria over a 5-year period in relation to change in blood pressure in young adults born preterm versus full-term controls.
- To determine whether baseline levels of copeptin and apelin can predict changes in eGFR and albuminuria over a 5-year period in young adults born preterm versus full-term controls.
- Conditions
- Prematurity; Extreme
- Being tested
- Preterm birth
- Keywords
- Extremely preterm, Clinical study, Developmental origin of adult health and disease, Prematurity, Renal system, Cardiovascular system
- Medical subject headings
- Premature Birth, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Preterm birthOther
The study compares young adult subjects born premature (< 29 weeks) versus term > 37-41 weeks)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Preterm birth |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 30 minutes
Secondary outcomes (36)
Biomarker of vasoregulatory mechanisms, kidney level, Renin
Plasma renin activity is determined by measuring the mass of angiotensin-1 generated per volume of human plasma in one hour, using a PRA ELISA assay (IBL-America, MN, USA).
Measured: 60 minutes
Biomarker of vasoregulatory mechanisms, kidney level, Aldosterone
Plasma aldosterone is assessed using a high sensitivity ELISA assay (IBL-America), with a range of 7.75 - 1000 pg/ml and expected plasma aldosterone values of at least 40 pg/ml113.
Measured: 60 minutes
Biomarker of vasoregulatory mechanisms, kidney level, Copeptin
Plasma copeptin is assessed in the plasma using the BRAHMS KRYPTOR compact PLUS system available at London Health Sciences Centre, London, ON.
Measured: 60 minutes
Biomarker of vasoregulatory mechanisms, kidney level, Apelin
Plasma apelin-12 is assessed using an ELISA assay (Phoenix Pharmaceuticals, CA, USA).
Measured: 60 minutes
Blood pressure
Blood pressure (systolic and diastolic) is measured after seated rest for 5 min before blood sampling using an automated oscillometric device (Dinamap, GE Healthcare) according to the Canadian Hypertension Education Program. Blood pressure is measured in both arms and the average of 3 measures taken at 1-min intervals on the arm with highest readings is used. Participants also undergo 24-hour ambulatory blood pressure measurement (ABPM, Spacelabs Medical, Washington) on their non-dominant arm.
Measured: 10 minutes
Albuminuria
Albumin to creatinine ratio (ACR) is obtained from a spot urine collection.
Measured: 5 minutes
Estimated GFR
Estimated GFR is calculated using validated Full Age Spectrum (FAS) equation, with and without correction for height115 (with IDMS standardized creatinine), as this equation has been shown to be more accurate than the CKD-Epi equation in young adults.
Measured: 5 minutes
Renal ultrasound and Doppler, Volume
Morphologic studies of kidneys including size (volume)
Measured: 10 minutes
Renal ultrasound and Doppler, Echogenicity
Morphologic studies of kidneys including echogenicity (cortex and medulla)
Measured: 10 minutes
Renal ultrasound and Doppler, urinary tract
Morphologic studies of kidneys including urinary tract
Measured: 10 minutes
Renal ultrasound and Doppler, arterial resistive index
Morphologic studies of kidneys including arterial resistive index.
Measured: 10 minutes
Liver echography
Morphologic study of the liver using the echography machine, including the volume.
Measured: 15 minutes
Muscle ultrasound
Ultrasound imaging examinations of the musculoskeletal system, through the rectus femoris muscle. Images of the rectus femoris will be recorded while the participant is in a sitting position.
Measured: 10 minutes
Muscle elastography
For the elastography, the participant will stay still while the share wave is applied. Finally, ultrasound images of the rectus femoris will be recorded in three different states: 1) relaxed position, 2) maximal voluntary contraction and 3) sub-maximal voluntary contraction, using a dynamometer. A 30-second rest period will be implemented between contractions to minimize potential fatigue effects.
Measured: 30 minutes
Muscular strength
Measured in accordance with the standardized test protocol produced by the Canadian Society for Exercise Physiology (CSEP, 2013), using a dynamometer.
Measured: 15 minutes
Muscular endurance
Measured in accordance with the standardized test protocol produced by the Canadian Society for Exercise Physiology (CSEP, 2013), using a dynamometer.
Measured: 15 minutes
Physical activity
Measured using accelerometry for 7 seven consecutive days.
Measured: 7 days
Aerobic capacity and endurance test
Six-minute walking test (6MWT) assesses distance walked over 6 minutes.
Measured: 6 minutes
Questionnaire #1
Current medication, alcohol, drugs use 2)
Measured: 5 minutes
Hydration levels, plasma electrolytes
Plasma electrolytes measured by the Hospital clinical biochemistry.
Measured: 15 minutes
Hydration levels, plasma osmolality
Plasma osmolality measured by the Hospital clinical biochemistry.
Measured: 30 minutes
Hydration levels, urine electrolytes
Urine (spot) electrolytes measured by the Hospital clinical biochemistry.
Measured: 30 min
Hydration levels, urine osmolality
Urine (spot) osmolality measured by the Hospital clinical biochemistry.
Measured: 30 minutes
Hydration levels, plasma hematocrit
Plasma hematocrit measured by the Hospital clinical biochemistry.
Measured: 30 minutes
Hydration levels, plasma total proteins
Plasma total proteins measured by the Hospital clinical biochemistry.
Measured: 30 minutes
Cardiometabolic risk factors, glycated hemoglobin
Glycated hemoglobin in plasma measured by the Hospital clinical biochemistry.
Measured: 15 minutes
Cardiometabolic risk factors, plasma lipids
Plasma lipids measured by the Hospital clinical biochemistry.
Measured: 15 minutes
Cardiometabolic risk factors, BMI
BMI, calculated using the weight in kg and the height in meters.
Measured: 15 minutes
Cardiometabolic risk factors, waist-to-hip
Waist-to-hip ratio using the measurement of the hip and waist in centimeters
Measured: 10 minutes
Questionnaire # 2
Socio-economic status from the parents and the participant Occupation and education level (achieved or ongoing), parental education/income for students, primary earner status, personal income. Family history: Parental health history of cardiovascular, metabolic or renal diseases.
Measured: 10 minutes
Questionnaire #3
Obstetrical and neonatal history: (a) maternal: smoking, prepregnancy BMI, hypertension, diabetes, prenatal corticosteroids, chorioamnionitis Neonatal: GA (based on date of last period and/or obstetric ultrasound), birth weight and percentile as per Hadlock for preterm subjects (intrauterine growth curves) and Kramer (postnatal birth weight) for term controls, APGAR, major complications/conditions (mechanical ventilation, O2 and parenteral nutrition duration, umbilical arterial lines, sepsis, acute renal failure, necrotizing enterocolitis, bronchopulmonary dysplasia, ultrasound brain lesions, surgeries, medications (nephrotoxic antibiotics, steroids, indomethacin, diuretics), and length of hospital stay). Data are obtained from medical records.
Measured: 2 hours
SF-36
Quality of life and functional status
Measured: 10 minutes
WHO questionnaire
Quality of life and functional status
Measured: 10 minutes
Diet, food frequency questionnaire
Food frequency questionnaire
Measured: 35 minutes
Diet, 24-hour meal interview
24-hour meal interview
Measured: 10 minutes
MAPA
Monitoring device for 24 hours blood pressure measurement.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start26 Jun 2021
- Primary completion1 Mar 2024
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prematurity; ExtremeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Justine's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Centre hospitalier de l'Université de Montréal (CHUM), Canadian Institutes of Health Research (CIHR), European Georges Pompidou Hospital, Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal
- Responsible party
- Principal investigator, Anne Monique NUYT,MD, St. Justine's Hospital
- Investigators
- Anne Monique Nuyt, MD, Principal investigator, StJustine's HospitalThuy Mai Luu, MD, Principal investigator, StJustine's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04735315
- Sponsor's protocol ID
- HAPI-Kidneys
- Status last verified
- Jul 2025
- First submitted
- 14 Jan 2021
- Last updated
- 11 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Renal Function in Adults Born Preterm: The HAPI-Kidney Study
- ClinicalTrials.gov ID
- NCT04735315
- Acronym / sponsor ID
- HAPI-Kidneys
- Conditions
- Prematurity; Extreme
- Keywords
- Extremely preterm, Clinical study, Developmental origin of adult health and disease, Prematurity, Renal system, Cardiovascular system
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 157 participants (actual)
- Lead sponsor
- St. Justine's HospitalUniversity, hospital or other
- Collaborators
- Centre hospitalier de l'Université de Montréal (CHUM), Canadian Institutes of Health Research (CIHR), European Georges Pompidou Hospital, Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal
- Study start
- 26 Jun 2021 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 3 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Given that preterm birth is associated with reduced nephron endowment and higher glomerular area on renal histology suggesting compensatory glomerular hyperfiltration, we postulate that :
Hypothesis 1: mGFR relative to total kidney volume is higher in adults born preterm vs. to full-term controls.
Hypothesis 2: mGFR relative to kidney volume is associated with plasma renin activity, aldosterone, copeptin and apelin levels. Levels of these vasoactive factors may correlate to blood pressure values.
Hypothesis 3: Rates of decline in eGFR and increase in albuminuria is more important in the preterm vs. full-term group. Hypertension at baseline predicts faster decline in eGFR and increase in albuminuria. Decrease in eGFR and increase in albuminuria correlate with increasing blood pressure over time.
Hypothesis 4: Higher baseline copeptin levels and, reciprocally, lower baseline apelin levels are associated with faster decline in eGFR and increase in albuminuria.
Our overarching aim is to assess long-term glomerular function in adults born preterm ≤29 weeks' GA versus full-term controls.
- To assess the association between preterm birth and measured GFR, compared to estimated GFR, in young adulthood (18-40 years).
- To examine the association between mGFR and vasoactive humoral factors involved in kidney hemodynamics (plasma renin activity, aldosterone, copeptin, apelin) in relation to blood pressure in young adults born preterm versus full-term controls.
- To compare changes in eGFR and albuminuria over a 5-year period in relation to change in blood pressure in young adults born preterm versus full-term controls.
- To determine whether baseline levels of copeptin and apelin can predict changes in eGFR and albuminuria over a 5-year period in young adults born preterm versus full-term controls.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Born preterm | – | Other: Preterm birthInclusion : 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. |
| Born term | – | Other: Preterm birthInclusion : 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Preterm birthThe study compares young adult subjects born premature (< 29 weeks) versus term > 37-41 weeks) | Other | Born preterm, Born term |
Primary outcome
mGFR relative to kidney volume (scintigraphy), measurement 1
Time frame: 90 minutes
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.
mGFR relative to kidney volume (scintigraphy), measurement 2
Time frame: 120 minutes
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.
mGFR relative to kidney volume (scintigraphy), measurement 3
Time frame: 150 minutes
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.
mGFR relative to kidney volume (scintigraphy), measurement 4
Time frame: 180 minutes
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.
Whole-kidney GFR (MRI)
Time frame: 1 hour
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.
Rate of glomerular hyperfiltration
Time frame: 30 minutes
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.
36 secondary outcomes
Biomarker of vasoregulatory mechanisms, kidney level, Renin
Time frame: 60 minutes
Biomarker of vasoregulatory mechanisms, kidney level, Aldosterone
Time frame: 60 minutes
Biomarker of vasoregulatory mechanisms, kidney level, Copeptin
Time frame: 60 minutes
Biomarker of vasoregulatory mechanisms, kidney level, Apelin
Time frame: 60 minutes
Blood pressure
Time frame: 10 minutes
Albuminuria
Time frame: 5 minutes
Estimated GFR
Time frame: 5 minutes
Renal ultrasound and Doppler, Volume
Time frame: 10 minutes
Renal ultrasound and Doppler, Echogenicity
Time frame: 10 minutes
Renal ultrasound and Doppler, urinary tract
Time frame: 10 minutes
Renal ultrasound and Doppler, arterial resistive index
Time frame: 10 minutes
Liver echography
Time frame: 15 minutes
Muscle ultrasound
Time frame: 10 minutes
Muscle elastography
Time frame: 30 minutes
Muscular strength
Time frame: 15 minutes
Muscular endurance
Time frame: 15 minutes
Physical activity
Time frame: 7 days
Aerobic capacity and endurance test
Time frame: 6 minutes
Questionnaire #1
Time frame: 5 minutes
Hydration levels, plasma electrolytes
Time frame: 15 minutes
Hydration levels, plasma osmolality
Time frame: 30 minutes
Hydration levels, urine electrolytes
Time frame: 30 min
Hydration levels, urine osmolality
Time frame: 30 minutes
Hydration levels, plasma hematocrit
Time frame: 30 minutes
Hydration levels, plasma total proteins
Time frame: 30 minutes
Cardiometabolic risk factors, glycated hemoglobin
Time frame: 15 minutes
Cardiometabolic risk factors, plasma lipids
Time frame: 15 minutes
Cardiometabolic risk factors, BMI
Time frame: 15 minutes
Cardiometabolic risk factors, waist-to-hip
Time frame: 10 minutes
Questionnaire # 2
Time frame: 10 minutes
Questionnaire #3
Time frame: 2 hours
SF-36
Time frame: 10 minutes
WHO questionnaire
Time frame: 10 minutes
Diet, food frequency questionnaire
Time frame: 35 minutes
Diet, 24-hour meal interview
Time frame: 10 minutes
MAPA
Time frame: 24 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2025.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Monique Nuyt, MD principal investigator
StJustine's Hospital
Thuy Mai Luu, MD principal investigator
StJustine's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prematurity; Extreme, run by St. Justine's Hospital at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mGFR relative to kidney volume (scintigraphy), measurement 1 (time frame: 90 minutes). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2025.