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

Prematurity; Extreme Clinical Trial

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

Status Recruiting

Clinical 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. 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Premature Birth
• Prematurity; Extreme

• NCT number: NCT04735315
• Study type: Observational
• Source: St. Justine's Hospital
• Contact: Anik Cloutier, M.Sc
• Phone: 514-345-4931
• Email: anik.cloutier2.hsj@ssss.gouv.qc.ca
• Status: Recruiting
• Start date: June 26, 2021
• Completion date: September 30, 2024