Kidney growth following preterm birth: evaluation with renal parenchyma ultrasonography.

BACKGROUND: Preterm birth impairs nephrogenesis, leading to a reduced nephron endowment which is inextricably linked to hypertension and chronic kidney disease in adults. The aim of this study was to compare nephron endowment between preterm infants to that of intrauterine fetuses at the same gestational age (GA) using a novel indirect ultrasound measurement of the renal parenchymal thickness. We hypothesized that extrauterine and intrauterine renal parenchymal thickness would differ based on altered renal growth environments. METHODS: In this observational study, appropriately grown preterm infants (birth weight of between the 5th and 95th percentile) born <32 weeks, admitted to the neonatal department were eligible to participate. Renal parenchymal thickness of the infants was measured at 32- and 37-weeks postmenstrual age (PMA). These measurements were compared to the intrauterine renal parenchymal thickness of appropriately grown fetuses (control). RESULTS: At 32-weeks PMA, the preterm infants had a significantly thinner renal parenchyma compared to fetuses at 32-weeks GA suggesting they had less nephrons, however by 37-weeks there was no significant difference in renal parenchymal thickness. CONCLUSIONS: We propose that the differences in the extrauterine growth of the renal parenchyma in preterm infants may be due to a reduced number of nephrons and compensatory hyperfiltration. IMPACT: This article provides insight into the effects of prematurity on nephrogenesis by comparing extrauterine renal parenchymal growth of born preterm infants to the ideal intrauterine fetal growth. Renal parenchyma thickness measurement using ultrasonography is a novel non-invasive measurement of renal development for the determination of nephron endowment. Differences in the renal parenchymal thickness of the preterm infants may be due to a deficit in nephron number and compensatory hyperfiltration.

Fetal renal artery blood flow - Normal ranges.

INTRODUCTION: The study objectives were to develop standard charts for fetal renal artery blood flow to define normal ranges and to assess the reliability of the measurements. METHODS: This prospective, longitudinal study reviewed 72 low-risk singleton pregnancies who had serial ultrasound examinations. Pulse wave Doppler was used to obtain the resistivity and pulsatility indices of the fetal renal arteries. Standard charts of the fetal renal arteries were created using mixed effects modelling and the intra- and interobserver reliability for the renal blood flow measurements was analysed. RESULTS: Standard charts of the normal ranges of the renal artery resistive index (RI) and pulsatility index (PI) of the fetal renal arteries were created. The 3rd, 5th, 10th, 50th, 90th, 95th and 97th centiles were calculated. The intraclass correlation coefficient was acceptable for intraobserver reliability (RI = 0.66, PI = 0.88) and poor for interobserver reliability (RI = 0.11, PI = -0.56). CONCLUSIONS: These novel charts demonstrate the change of the fetal renal artery blood flow during pregnancy. These may be used in clinical practice to detect variations from these normal ranges and be useful in future studies of kidney function projection.

Can measurement of the foetal renal parenchymal thickness with ultrasound be used as an indirect measure of nephron number?

Chronic kidney disease continues to be under recognised and is associated with a significant global health burden and costs. An adverse intrauterine environment may result in a depleted nephron number and an increased risk of chronic kidney disease. Antenatal ultrasound was used to measure the foetal renal parenchymal thickness (RPT), as a novel method to estimate nephron number. Foetal renal artery blood flow was also assessed. This prospective, longitudinal study evaluated the foetal kidneys of 102 appropriately grown and 30 foetal growth-restricted foetuses between 20 and 37 weeks gestational age (GA) to provide vital knowledge on the influences foetal growth restriction has on the developing kidneys. The foetal RPT and renal artery blood flow were measured at least every 4 weeks using ultrasound. The RPT was found to be significantly thinner in growth-restricted foetuses compared to appropriately grown foetuses [likelihood ratio (LR) = 21.06, P ≤ 0.0001] and the difference increases with GA. In foetuses with the same head circumference, a growth-restricted foetus was more likely to have a thinner parenchyma than an appropriately grown foetus (LR = 8.9, P = 0.0028), supporting the principle that growth-restricted foetuses preferentially shunt blood towards the brain. No significant difference was seen in the renal arteries between appropriately grown and growth-restricted foetuses. Measurement of the RPT appears to be a more sensitive measure than current methods. It has the potential to identify infants with a possible reduced nephron endowment allowing for monitoring and interventions to be focused on individuals at a higher risk of developing future hypertension and chronic kidney disease.

The effect of diabetes during pregnancy on fetal renal parenchymal growth.

AIMS/HYPOTHESIS: Diabetes in pregnancy is thought to adversely affect the developing fetal kidneys. The rate of gestational diabetes is increasing globally with major consequences for future renal function. Very little is known about the impact of hyperglycaemia on the fetal renal parenchyma which contains the developing nephrons. The aim of this study was to measure the fetal renal parenchymal thickness and evaluate whether diabetes during pregnancy affects the growth of the fetal kidneys. METHODS: This prospective, observational study used serial ultrasound measurements to evaluate the fetal renal parenchymal growth of 55 pregnancies with diabetes compared to 72 control pregnancies. Mixed effects modelling was used to analyse the data. RESULTS: The renal parenchyma of fetuses from mothers with gestational diabetes was significantly thicker than those from the control group (LR Chisq = 4.8, df = 1, p = 0.029), however, the difference was proportional to the larger size of these fetuses. Fetuses of pregestational diabetics demonstrated no significant difference in renal parenchymal thickness compared to the control group even though they were also larger fetuses. Parenchymal growth slowed with increasing abdominal circumference in the pregestational diabetic group, suggesting an adverse effect on nephrogenesis, however this did not reach statistical significance. CONCLUSIONS/INTERPRETATION: Our study provides unique data on how diabetes during pregnancy influences fetal kidney growth. Appropriate management of diabetic pregnancies may mitigate some of the adverse effects on the fetal kidneys. Increasing degrees of hyperglycaemia, as seen sometimes in pregestational diabetes, may affect nephrogenesis; however larger studies are needed.

Surveillance Practice for Sonographic Detection of Intracranial Abnormalities in Premature Neonates: A Snapshot of Current Neonatal Cranial Ultrasound Practice in Australia.

There are no publications reporting on scan duration and Doppler use during neonatal cranial ultrasound scans. We investigated current practice of neonatal cranial ultrasound at four large tertiary neonatal intensive care units in Australia. Cranial scans were prospectively recorded between March 2015 and November 2016. Variables, including total number of scans, scan duration and frequency and duration of colour and spectral Doppler mode, were extracted. A total of 196 scans formed the final cohort. The median (range) number of scans for each neonate was 1 (1-12). The median (range) overall total scan duration was 309 (119-801) s. Colour mode with or without spectral Doppler mode was used in approximately half of the cohort (106/196, 54%). Our findings comport with our hypotheses. Operators performing neonatal cranial scans in Australia have low overall scan durations. Although the use of Doppler mode during neonatal cranial scans is not standard practice in all neonatal intensive care units, it is used widely irrespective of the degree of prematurity or the presence of brain pathology. Further efforts are required to incorporate recommendations on scan duration and the routine use of Doppler mode during neonatal cranial scans. This is especially imperative given that the most vulnerable neonates with the greater neural tissue sensitivity are likely to be scanned more often.

Fetal kidney charts of a novel measurement of the renal parenchymal thickness to evaluate fetal kidney growth and potential function.

OBJECTIVE: The objective of this study was to develop new standard growth charts for fetal renal parenchymal thickness, length, and volume to define normal ranges for use in clinical practice and to assess the reliability of these measurements. METHODS: This was a prospective, longitudinal study of 72 low-risk singleton pregnancies undergoing serial ultrasound examinations at least every four weeks. Multiple renal measurements were performed on both kidneys at each scan. The renal parenchymal thickness was measured in the mid-sagittal plane. Standard charts were developed and the intra and interobserver reliability for the renal measurements was analysed. RESULTS: Standard charts were developed for fetal renal parenchymal thickness, length, and volume. CONCLUSION: We present novel charts, which demonstrate the growth of the fetal renal parenchyma during pregnancy. They will be useful in clinical practice to identify any alterations from these normal ranges, which may be an important criterion for assisting prenatal diagnosis of renal pathologies and future studies in the prediction of kidney function.

Knowledge of Safety, Training, and Practice of Neonatal Cranial Ultrasound: A Survey of Operators.

OBJECTIVES: Ultrasound can lead to thermal and mechanical effects in interrogated tissues. This possibility suggests a potential risk during neonatal cranial ultrasound examinations. The aim of this study was to explore safety knowledge and training of neonatal cranial ultrasound among Australian operators who routinely perform these scans. METHODS: An online survey was administered on biosafety and training in neonatal cranial ultrasound, targeting all relevant professionals who can perform neonatal cranial ultrasound examinations in Australia: namely, radiologists, neonatologists, sonographers, and pediatricians. The survey was conducted between November 2013 and May 2014. RESULTS: A total of 282 responses were received. Twenty of 208 (10%) answered all ultrasound biosafety questions correctly, and 49 of 169 (29%) correctly defined the thermal index. Two-thirds (134 of 214 [63%]) of respondents failed to recognize that reducing the overall scanning time is the most effective method of reducing the total power exposure. Only 13% (31 of 237) indicated that a predetermined fixed period of training or that a specified minimum number of supervised scans was used during training. The reported number of supervised scans during training was highly variable. Almost half of the participants (82 of 181 [45%]) stated that they had received supervision for 10 to 50 scans (median, 20 scans). CONCLUSIONS: There is a need to educate operators on biosafety issues and approaches to minimize power outputs and reduce the overall duration of cranial ultrasound scans. Development of standardized training requirements may be warranted.

The renal parenchyma-evaluation of a novel ultrasound measurement to assess fetal renal development: protocol for an observational longitudinal study.

INTRODUCTION: Disorders of fetal growth, such as intrauterine growth restriction (IUGR) and large for gestational age (LGA), have been found to have a profound effect on the development of the fetal kidney. Abnormal kidney development is associated with hypertension and chronic kidney disease later in life. This study will use a novel ultrasound measurement to assess the renal parenchymal growth and kidney arterial blood flow in the fetus to evaluate the development of the fetal kidneys and provide an indirect estimate of nephron number. Measurements in normally grown, IUGR and LGA fetuses will be compared to determine if changes in renal parenchymal growth can be detected in utero. METHODS AND ANALYSIS: This longitudinal, prospective, observational study will be conducted over 12 months in the Ultrasound Department of the Townsville Hospital, Australia. The study will compare fetal renal parenchymal thickness (RPT) and renal artery Doppler flow between IUGR fetuses and appropriately grown fetuses, and LGA fetuses and appropriately grown fetuses between 16 and 40 weeks. The fetal RPT to renal volume ratio will also be compared, and correlations between RPT, renal parenchymal echogenicity, fetal Doppler indices and amniotic fluid levels will be analysed. ETHICS AND DISSEMINATION: This study was approved by the Townsville Health District Human Research Ethics Committee. The study results will form part of a thesis and will be published in peer-reviewed journals and disseminated at international conferences.

Evaluation of fetal kidney growth using ultrasound: A systematic review.

PURPOSE: To determine the role of ultrasound imaging in evaluating fetal kidney growth. METHODS: MEDLINE, CINAHL and EMBASE databases were electronically searched for studies between 1996 and January 2017 and limited to English language. Studies were included if they reported on an ultrasound technique to assess fetal kidney growth and they were not a case report or case series. There was independent selection of studies by two reviewers in consensus with one other reviewer. Data were extracted by one reviewer in consensus with two other reviewers. RESULTS: A total of 1785 articles were identified. The full text of 39 of these were assessed for eligibility for inclusion. Twenty-eight studies were then included in the review. Standard two dimensional (2D) fetal renal measurements are easy to perform, however, this review identified that most studies had some methodological limitations. The disadvantage with 2D and three dimensional (3D) fetal renal volumes are that they include the entire kidney and good reproducibility of 3D volumes has not yet been demonstrated. Currently there is limited research on fetal kidney growth in the setting of abnormal fetal growth. Research focussing directly on fetal kidney parenchyma and blood flow is scarce. CONCLUSIONS: Some nomograms of 2D and 3D fetal kidney size and volume have been developed. Kidney length is the most popular single fetal kidney measurement; however, it does not seem to be a good indicator of growth. In IUGR fetuses, kidney length remained similar to appropriately grown fetuses whereas AP and TS dimensions were significantly decreased. New ultrasound techniques focusing on the parenchyma of the kidney and perfusion to the kidney should be explored as they may provide more meaningful information on kidney development in the fetus and future kidney function.

Ultrasound Imaging of the Renal Parenchyma of Premature Neonates for the Assessment of Renal Growth and Glomerulomegaly.

Evidence is increasingly showing that prematurity results in chronic kidney disease. We hypothesized that we could use ultrasound imaging to measure and monitor the growth of the renal parenchyma in premature neonates. We conducted a prospective, case-control study to compare renal parenchymal growth between neonates born prematurely and term neonates. The study patients underwent ultrasound assessment at 32 wk postmenstrual age (PMA) and 37 wk PMA. Term neonates (gestation >37 completed wk) admitted to the neonatal unit with minor neonatal conditions were recruited into the control group. Complete data sets were available in 91 premature neonates and during the same period, 56 term neonates were recruited as the control. The median birth weight (preterm babies) was 930 g (780-1220 g), and the mean gestational age was 27.0 wk (2.1 wk). Total renal volume (TRV) increased from 14.6 (4.3) cm3 to 20.5 (5.3) cm3 from 32 to 37 wk PMA. During the same period, the total renal parenchyma (TRP) thickness increased from 1.6 (0.3) cm to 1.8 (0.3) cm. At 37 wk PMA, ex-premature neonates have a significantly smaller total renal volume (20.5 [5.3] versus 25.9 [6.4] cm3; p < 0.001) and total renal parenchyma thickness (1.8 [0.3] versus 2.0 [0.2] cm; p = 0.015) compared with term (control) neonates. However, premature neonates at 37 wk PMA have a larger TRP:TRV ratio compared with term neonates (0.09 [0.02] versus 0.0 8 [0.02] cm-2; p < 0.001). Reduced nephron endowment as a result of prematurity may cause the remaining nephrons to undergo compensatory glomerulomegaly and we postulate this is the reason for the observed differences. Ultrasound imaging of the renal parenchyma shows promise in assessing the effects of prematurity on the developing kidney.

Renal parenchymal thickness as a measure of renal growth in low-birth-weight infants versus normal-birth-weight infants.

Low birth weight (LBW, <2500 g) infants have a reduced number of glomeruli and nephrons and, therefore, smaller kidneys. The purpose of this pilot study was to determine whether renal parenchymal thickness might be a better indicator of renal growth. We carried out a pilot study over 12 mo to determine whether renal parenchymal thickness could be used to detect differences in renal growth between LBW and normal birth weight (NBW, 2500-4500 g) infants. Thirty-eight term infants (12 LBW and 26 NBW) underwent renal ultrasound. Parenchymal thickness, length, transverse diameter and antero-posterior diameter were measured. Mean renal parenchymal thickness was significantly lower in LBW infants than in NBW infants. Renal parenchymal thickness was closely correlated with an increase in renal volume (r = 0.76, p < 0.0001). Renal parenchymal thickness is a single measurement that could potentially be a more useful and accurate approach to monitoring renal growth in growth-restricted infants than renal volume.