Clinical trial NCT04735315: Assessment of Renal Function in Adults Born Preterm: The HAPI-Kidney Study
Official title: Assessment of Renal Function in Adults Born Preterm: The HAPI-Kidney Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Prematurity; Extreme
Keywords: Extremely preterm
Clinical study
Developmental origin of adult health and disease
Prematurity
Renal system
Cardiovascular system
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: Centre hospitalier de l'Université de Montréal (CHUM)
name: Canadian Institutes of Health Research (CIHR)
name: European Georges Pompidou Hospital
name: Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal
First posted: 2021-02-03
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

1. To assess the association between preterm birth and measured GFR, compared to estimated GFR, in young adulthood (18-40 years).
2. 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.
3. 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.
4. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: mGFR relative to kidney volume (scintigraphy), measurement 1
timeFrame: 90 minutes
measure: mGFR relative to kidney volume (scintigraphy), measurement 2
timeFrame: 120 minutes
measure: mGFR relative to kidney volume (scintigraphy), measurement 3
timeFrame: 150 minutes
measure: mGFR relative to kidney volume (scintigraphy), measurement 4
timeFrame: 180 minutes
measure: Whole-kidney GFR (MRI)
timeFrame: 1 hour
measure: Rate of glomerular hyperfiltration
timeFrame: 30 minutes
Secondary outcomes:
measure: Biomarker of vasoregulatory mechanisms, kidney level, Renin
timeFrame: 60 minutes
measure: Biomarker of vasoregulatory mechanisms, kidney level, Aldosterone
timeFrame: 60 minutes
measure: Biomarker of vasoregulatory mechanisms, kidney level, Copeptin
timeFrame: 60 minutes
measure: Biomarker of vasoregulatory mechanisms, kidney level, Apelin
timeFrame: 60 minutes
measure: Blood pressure
timeFrame: 10 minutes
measure: Albuminuria
timeFrame: 5 minutes
measure: Estimated GFR
timeFrame: 5 minutes
measure: Renal ultrasound and Doppler, Volume
timeFrame: 10 minutes
measure: Renal ultrasound and Doppler, Echogenicity
timeFrame: 10 minutes
measure: Renal ultrasound and Doppler, urinary tract
timeFrame: 10 minutes
measure: Renal ultrasound and Doppler, arterial resistive index
timeFrame: 10 minutes
measure: Liver echography
timeFrame: 15 minutes
measure: Muscle ultrasound
timeFrame: 10 minutes
measure: Muscle elastography
timeFrame: 30 minutes
measure: Muscular strength
timeFrame: 15 minutes
measure: Muscular endurance
timeFrame: 15 minutes
measure: Physical activity
timeFrame: 7 days
measure: Aerobic capacity and endurance test
timeFrame: 6 minutes
measure: Questionnaire #1
timeFrame: 5 minutes
measure: Hydration levels, plasma electrolytes
timeFrame: 15 minutes
measure: Hydration levels, plasma osmolality
timeFrame: 30 minutes
measure: Hydration levels, urine electrolytes
timeFrame: 30 min
measure: Hydration levels, urine osmolality
timeFrame: 30 minutes
measure: Hydration levels, plasma hematocrit
timeFrame: 30 minutes
measure: Hydration levels, plasma total proteins
timeFrame: 30 minutes
measure: Cardiometabolic risk factors, glycated hemoglobin
timeFrame: 15 minutes
measure: Cardiometabolic risk factors, plasma lipids
timeFrame: 15 minutes
measure: Cardiometabolic risk factors, BMI
timeFrame: 15 minutes
measure: Cardiometabolic risk factors, waist-to-hip
timeFrame: 10 minutes
measure: Questionnaire # 2
timeFrame: 10 minutes
measure: Questionnaire #3
timeFrame: 2 hours
measure: SF-36
timeFrame: 10 minutes
measure: WHO questionnaire
timeFrame: 10 minutes
measure: Diet, food frequency questionnaire
timeFrame: 35 minutes
measure: Diet, 24-hour meal interview
timeFrame: 10 minutes
measure: MAPA
timeFrame: 24 hours
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: StJustine's Hospital
state: Quebec
Study officials:
affiliation: StJustine's Hospital
name: Anne Monique Nuyt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: StJustine's Hospital
name: Thuy Mai Luu, MD
role: PRINCIPAL_INVESTIGATOR
References: