Cystatin C: a more reliable biomarker of renal function in young infants? A longitudinal cohort study

Aim: We carried out a longitudinal cohort study to measure serial CysC (Cystatin C) in a cohort of neonates born preterm until the age of 2 years. We hypothesised that CysC levels are independent of body weight and would not vary with gestational age. Methods: This prospective cohort study was conducted from August 2014 until October 2016, and follow-up was completed in October 2018. Preterm infants at less than 28 weeks of gestation (extremely preterm infants) were recruited and followed up until the age of 24 months. Blood samples for measurement of CysC were collected at regular intervals. Results: We recruited 58 preterm neonates with mean gestation was 26.2 (1.5) weeks, and a mean birth weight was 917 (140) g. One-way analysis of variance (ANOVA) did not show any significant difference in CysC levels between 28, 32 and 37 weeks' gestation (P = .09) despite a significant increase in body weight (P < .001). The mean CysC level was higher in the neonatal period and subsequently plateaued by 24 months. Conclusion: Serum CysC level is independent of body weight and not influenced by postnatal age nor by gender

Vascular endothelial growth factor-A levels in term neonates

Vascular endothelial growth factor-A (VEGF-A) plays an integral role in physiological and pathophysiological angiogenesis and has increasingly been implicated in the development of retinopathy of prematurity (ROP) in preterm infants. Application of intravitreal anti-VEGF is frequently used to treat ROP with little consideration given to the role of VEGF-A in neonatal growth and development. Previous studies have demonstrated systemic anti-VEGF persistence, reduced peripheral VEGF levels following treatment, and possible diagnostic and prognostic uses for VEGF-A determination. This study seeks to determine a normal range for serum VEGF-A (sVEGF-A) in healthy,term infants. The sVEGF-A levels were obtained from 32 neonates born at term infants (16 males and 16 females) using an enzyme-linked immunosorbent assay. No significant correlations were found between sVEGF-A levels and time of sample collection, birth weight, or gender. The median sVEGF-A level was 976 (394–1635) pg/mL (95% confidence interval for median: 496–1,318 pg/mL). This preliminary study determines a normal range for the sVEGF-A level in healthy, term neonates. This normal range will provide a tool to assist in the diagnosis, prognosis, and monitoring of treatment of infants with ROP

Faculty Teaching Improvement: Opportunities Within a Graduate Student & Faculty Community of Practice

Improving higher-education teaching is a growing focus on American colleges. A program was developed to train current PhD students in effective pedagogy practices. The Community of Practice resulted in current teaching faculty pedagogical improvement

Intentional STEM Infusion (ISI) Approach for 4-H Non-STEM Project Volunteers: Finding STEM in Plain Sight

STEM literacy is identified as a necessary skill for participation in the future workforce. 4-H has responded to this need to develop STEM-ready youth by expanding access to project areas like Robotics. It has been acknowledged that recruiting and training STEM competent staff and volunteers is a limitation in expanding these types of programs. At the same time, 4-H youth are enrolled in many traditional non-STEM projects that are imbued with STEM concepts. 4-H volunteers with increased awareness of their role in fostering STEM education and STEM literacy can be a valuable resource in preparing 4-H youth with STEM-ready professional skills. 4-H professionals can train front-line volunteers to use an intentional STEM infusion approach within the experiential learning process. It is posited that volunteers will be better able to facilitate STEM learning in real-world contexts for a wide-range of 4-H youth by using this approach. The use of the ISI approach provides an opportunity for 4-H to develop more STEM-ready youth than by only serving those youths who are attracted to STEM-focused projects alone

Female preterm indigenous Australian infants have lower renal volumes than males: a predisposing factor for end-stage renal disease?

Aim: Indigenous Australians have an increased risk of developing chronic kidney disease (CKD). Indigenous women have a higher rate of CKD than men. In a cohort of Indigenous and non-Indigenous preterm neonates, we assessed total renal volume (TRV) (a proxy indicator for nephron number). We hypothesized that there would be no difference in renal volume between these two groups at term corrected (37 weeks gestation). Methods: Normally grown preterm neonates less than 32 weeks of gestation were recruited and at term corrected dates, the neonates underwent renal ultrasonography (TRV measurements), urine microalbumin-creatinine ratio and serum analysis for Cystatin C measurement for estimated glomerular filtration rate (eGFR) calculation. Results: One hundred and five neonates (38 Indigenous; 67 non-Indige-nous) were recruited. Indigenous neonates were significantly more prema-ture and of lower birth weight. At term corrected age, Indigenous neonates had a significantly smaller TRV (18.5 (4.2) vs 21.4 (5.1) cm3; P = 0.027) despite no significant difference in body weight. Despite having a smaller TRV, there was no significant difference in eGFR between Indigenous and Non-indigenous neonates (47.8 [43.2–50.4] vs 46.2 [42.6–53.3] ml/min per 1.73 m2; P = 0.986). These infants achieve similar eGFR through hyperfiltra-tion, which likely increases their future risk of CKD. There was no differ-ence in microalbumin-creatinine ratio. Female Indigenous neonates, however, had significantly smaller TRV compared with Indigenous male neonates (15.9 (3.6) vs 20.6 (3.6) cm3; P = 0.006), despite no difference in eGFR, birth weight, gestational age, and weight at term corrected. Conclusion: The difference in TRV is likely to be an important risk factor for the difference in morbidity and mortality from renal disease reported between male and female Indigenous adults

International Communications

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

Fetal renal parenchyma: evaluation of a novel ultrasound measurement to assess kidney development

Introduction: Abnormal fetal growth can adversely impact renal development and is associated with increased risks of developing hypertension and chronic kidney disease later in life. A non-invasive, sensitive method of assessing normal and abnormal fetal kidney development is required. We hypothesise that the fetal renal parenchymal thickness could be used to evaluate the development of the fetal kidneys and provide an indirect estimate of fetal nephron number. This study uses antenatal ultrasound to assess fetal renal parenchymal growth and blood flow to determine if these are affected by abnormal fetal growth. Methods: A longitudinal, observational study was conducted at the Townsville Hospital, Townsville, Australia between May 2017 to December 2018. Mixed risk women with an accurately dated, singleton pregnancy underwent a pregnancy ultrasound scan at least every four weeks between 16 and 40 weeks gestation. Renal parenchymal thickness and echogenicity, renal volume, fetal growth biometries, amniotic fluid measurements, renal artery Doppler and other fetal Dopplers were assessed in appropriately grown, fetal growth restriction or large for gestational age fetuses. Results: 155 participants were recruited, with 7 participants excluded due to fetal abnormalities. Mixed effects modelling was used so that variations between gestational ages within fetuses and between fetuses was considered. A reference graph was developed for normal fetal renal parenchymal growth. In growth restricted fetuses the renal parenchymal thickness was found to be significantly less when compared to the parenchymal thickness of appropriately grown fetuses. Conclusions: Measurement of the renal parenchymal thickness is an innovative method to evaluate the development of the fetal kidneys. This new chart of fetal renal parenchymal thickness may be useful for the diagnosis of nephropathologies and the identification of infants at risk of kidney disease. Fetal growth restriction was found to adversely affect the renal parenchymal growth. This suggests growth restricted fetuses are born with fewer nephrons and are therefore likely to be more susceptible to hypertension and early onset kidney disease later in life

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

Extension’s Response to the Change in Public Value: Considerations for Ensuring Financial Security for the Cooperative Extension System

Cooperative Extension is a partnership of county, state, and federal governments to fund the translation and community education of applied research from the land-grant university system. Cooperative Extension’s funding since the 1980s has experienced a few key trends such as federal budget stagnation as well as state and county cyclic funding cycles based on the states’ economic health. Accompanying the state-level budget cuts have been calls for Cooperative Extension to reinvent and improve communication about what it does. As budget stability has become a greater concern, ideas around value and return on investment have become more integrated into the messaging about why Cooperative Extension should be funded. These economic terms reflect the integration of neoliberalism’s frame. In a larger qualitative research study about how Cooperative Extension administrators recognize the need for change, funding emerged as a fundamental influence of organization adaptation. The public contract between citizen, legislature, and public-serving organizations has changed to, “What is the return on investment?” To respond to the shifting narrative, it was necessary to assess, measure, and communicate value. However, administrators also recognized relationships mattered to how the message was received by legislators and other funders

Maintaining normal blood pressure in a renovascular stenosis model of hypertension in adult Lewis rats: putative physiological modulation of the renin-angiotensin system

Prolonged unilateral renal artery stenosis using a Goldblatt Two-Kidney-One Clip (2K1C) technique is a validated scientific approach to inducing experimental hypertension in laboratory animals. This patho-physiological modulation is associated with the activation of the renin-angiotensin system with increased renin and angiotensin II release to initiate hypertension. This mode of experimental hypertension has been demonstrated for many rat strains including Sprague Dawley, Brown Norway and Wistar Kyoto but has not been fully characterized in syngeneic Lewis rats. The objective of this study was to develop and characterize a unilateral renal artery stenosis model of hypertension in adult male Lewis rats using a 2K1C method for hypertension studies in our laboratory. Thirty animals were randomly assigned to two groups to undergo sham or the 2K1C surgical procedure under isoflurane-induced anesthesia; approval was granted by our institutional animal ethics committee (A2404, n =15 per group). Hemodynamic parameters including heart rate; systolic and diastolic blood pressure were monitored weekly for 6 weeks, using a volume-pressure tail cuff and a CODA pressure computer. Plasma concentrations of critical biomarkers of the renin-angiotensin system were quantified using standard ELISA assays and renal histopathological changes were assessed microscopically. Unilateral renal arterial stenosis caused marked renal atrophy, glomerulosclerosis and interstitial fibrosis, but a compensatory renal hypertrophy was observed in contralateral kidneys. Interestingly, unilateral renal arterial stenosis failed to induce hypertension over the six week period. The resistance to develop hypertension in the 2K1C group was associated with a significant decrease in total plasma renin (P = 0.023), an increase in the ratio of plasma angiotensin (1-7) to total renin (P = 0.034) and a decrease in the ratio of angiotensin II to total renin (P = 0.013). There were no changes in plasma electrolytes, glucose, creatinine or urea. These data demonstrate that adult male Lewis rats may have physiologically modulated the activation of the renin-angiotensin system to maintain a homeostatic balance and resist hypertension following unilateral renal artery stenosis