Assessment of Renal Function in Adults Born Preterm: The HAPI-Kidney Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 157
- 试验地点
- 1
- 主要终点
- mGFR relative to kidney volume (scintigraphy), measurement 4
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
mGFR relative to kidney volume (scintigraphy), measurement 4
时间窗: 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.
mGFR relative to kidney volume (scintigraphy), measurement 1
时间窗: 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
时间窗: 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.
Whole-kidney GFR (MRI)
时间窗: 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.
mGFR relative to kidney volume (scintigraphy), measurement 3
时间窗: 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.
Rate of glomerular hyperfiltration
时间窗: 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.
次要结局
- Hydration levels, plasma electrolytes(15 minutes)
- Hydration levels, urine electrolytes(30 min)
- Hydration levels, urine osmolality(30 minutes)
- Biomarker of vasoregulatory mechanisms, kidney level, Copeptin(60 minutes)
- Biomarker of vasoregulatory mechanisms, kidney level, Apelin(60 minutes)
- Renal ultrasound and Doppler, Volume(10 minutes)
- Aerobic capacity and endurance test(6 minutes)
- Questionnaire # 2(10 minutes)
- Biomarker of vasoregulatory mechanisms, kidney level, Renin(60 minutes)
- Renal ultrasound and Doppler, urinary tract(10 minutes)
- Biomarker of vasoregulatory mechanisms, kidney level, Aldosterone(60 minutes)
- Estimated GFR(5 minutes)
- Muscle ultrasound(10 minutes)
- Muscle elastography(30 minutes)
- Muscular strength(15 minutes)
- Muscular endurance(15 minutes)
- Physical activity(7 days)
- Hydration levels, plasma osmolality(30 minutes)
- Cardiometabolic risk factors, plasma lipids(15 minutes)
- Cardiometabolic risk factors, waist-to-hip(10 minutes)
- SF-36(10 minutes)
- Renal ultrasound and Doppler, arterial resistive index(10 minutes)
- Liver echography(15 minutes)
- Cardiometabolic risk factors, glycated hemoglobin(15 minutes)
- Questionnaire #1(5 minutes)
- Hydration levels, plasma hematocrit(30 minutes)
- Questionnaire #3(2 hours)
- Diet, food frequency questionnaire(35 minutes)
- Diet, 24-hour meal interview(10 minutes)
- Blood pressure(10 minutes)
- Albuminuria(5 minutes)
- Renal ultrasound and Doppler, Echogenicity(10 minutes)
- Hydration levels, plasma total proteins(30 minutes)
- Cardiometabolic risk factors, BMI(15 minutes)
- WHO questionnaire(10 minutes)
- MAPA(24 hours)
研究者
Anne Monique NUYT,MD
Chair and Chief, Department of Pediatrics, Faculty of Medicine University of Montreal / CHU Sainte-Justine
St. Justine's Hospital