Yogavijayan Kandasamy

Nephrin - a biomarker of early glomerular injury

Nephrin is a 180 KD trans-membrane protein expressed in glomerular podocytes. It was first identified in children with congenital nephrotic syndrome of the Finnish type (NPHS1). Nephrin forms an integral part of podocytes, which—together with endothelial cells and the basement—form the glomerular filtration barrier. Podocytopathies result in the detection of nephrin in the urine. We reviewed the literature to determine if urine nephrin measurements could become useful as a biomarker to detect early podocyte injury. Our search identified a total of 19 studies that have been published to date. The most common clinical conditions for which urine nephrin analyses were carried out included diabetic nephropathy, glomerulonephritis and pre-eclampsia. Nephrin measurement was carried out using commercially available ELISA kits, the messenger ribonucleic acid real-time polymerase chain Reaction, or electrophoresis. Nephrinuria showed positive correlation with proteinuria and severity of podocyte injury. In two studies, the level of nephrinuria declined in conjunction with clinical improvement in the patient following immunosuppressive treatment. Currently, there is no published data on the value of measuring urinary nephrin in pediatric patients.

Measuring cystatin C to determine renal function in neonates

Objectives: The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortality rate. The purpose of this review was to determine the feasibility of using serum cystatin C measurements to assist clinicians in making early and accurate diagnoses of acute kidney injury in neonates. Data Source: We searched for the following seven key words within the PubMed database and the Cochrane Database of Systematic Reviews: cystatin C, neonates, newborn, preterm, premature, kidney failure, and kidney injury. Study Selection: The selected studies included neonates within their study populations and were published in English. We reviewed literature published between January 1990 and May 2012. Data Extraction: Ten studies had conducted serum cystatin C measurements in neonates. Data Synthesis: The cystatin C level in neonates is not influenced by the maternal level and is highest at birth. In most studies, cystatin C levels on day 1 of life ranged between 1 and 2 mg/L, gradually declined during the first year and then remained relatively stable thereafter. Cystatin C levels did not differ between male and female infants, and no significant gestational age-dependent differences were found. Cystatin C levels were increased in cases of sepsis, acute kidney injury, and congenital renal abnormalities. Conclusions: Cystatin C has all of the theoretical properties needed to be an ideal marker of renal function. It can be used to determine baseline renal function on day 1 and is increasingly being used to determine renal function in sick neonates. In the majority of studies, the day 1 cystatin C level ranged between 1 and 2 mg/L, which gradually declined in the first year of life. However, the number of available studies evaluating cystatin C in sick neonates is currently limited, and there are also no studies linking cystatin C levels in sick babies with short-term and long-term outcomes.

Pain relief for premature infants during ophthalmology assessment.

BACKGROUND The ophthalmological examination of premature infants, which is essential for the detection of retinopathy of prematurity (ROP), can be painful and distressing for the infant. Various researchers have investigated the benefits of topical anesthesia, oral sucrose, and non pharmacological intervention for pain relief. The purpose of this study is to review the current state of knowledge on the effectiveness of these approaches. METHODS A literature search was performed with MEDLINE (January 1980 to January 2011) and the Cochrane Central Register of Controlled Trials, Issue 1 of 4 (January 2011), to determine the currently available evidence on methods of pain relief for premature infants undergoing ROP examination. RESULTS Most studies supported the use of topical proparacaine, which marginally decreased pain without any side effects. Oral sucrose did not significantly reduce pain scores during ROP examinations, and withholding feeding before the examination was not beneficial. Infants given pacifiers had lower pain scores than those without pacifiers, and infants who were nested experienced less distress during and after the procedure. Conflicting data existed on the benefits of different examination techniques, but the insertion of a lid speculum appeared to be the most uncomfortable aspect of the screening examination. CONCLUSIONS Topical anesthetics marginally reduce pain during eye examination in premature infants. Contrary to standard practice, it appears that patients are more comfortable if they are fed before the examination, and there is no benefit of oral sucrose. Nonpharmacological interventions, including sucking on a pacifier and nesting, may also be beneficial.

The effect of erythropoietin on the severity of retinopathy of prematurity

AimsExogenous human erythropoietin (EPO) artificially synthesised through recombinant DNA technology (rHuEPO) is currently used as a substitute for blood transfusion in preterm and low birth weight neonates. The objective of this study is to determine whether the use of rHuEPO is associated with an increased severity of retinopathy of prematurity (ROP) in preterm neonates.MethodThis retrospective review studies neonates who were admitted to a tertiary perinatal unit and screened for ROP during the 10-year period from January 2003 to December 2012.ResultsDuring the 10-year period, 688 preterm neonates underwent ROP screening, with 198 identified as having ROP. The incidence of stage 1 ROP was 51.5% (102/198), followed by 35.9% (71/198) for stage 2, and 12.6% (25/198) for stage 3 and greater. Plus disease was seen in 14 neonates (7.1%). Treatment (laser photocoagulation) was administered in 64% of neonates (16/25) with stage 3 of the disease and above because of progression to threshold ROP. Twenty-six (13%) of the neonates received rHuEPO treatment. There were no statistically significant differences in birth weight (910.4 vs 885 g; P=0.71), gestational age (26.5 vs 25.8 weeks; P=0.09), and duration of ventilation (512 vs 501.4 h; P=0.92) between neonates who did not receive rHuEPO compared with those who were treated with rHuEPO. Multivariate regression analysis showed that the use of EPO was associated with increased severity of ROP.ConclusionsEPO therapy appears to increase the risk of development and worsening of ROP.

The association between systemic vascular endothelial growth factor and retinopathy of prematurity in premature infants: a systematic review

Retinopathy of prematurity (ROP), a vasoproliferative disorder exclusive to premature infants is an important cause of childhood blindness. The number of premature infants surviving with this condition is expected to increase globally. Animal models of oxygen-induced retinopathy studies have shown vascular endothelial growth factor (VEGF) to be a key player in the pathogenesis of ROP. This has led to increased use of VEGF antagonist as an alternative treatment for ROP. The purpose of this systematic review is to determine the association between VEGF and ROP in human newborn. The literature review identified 12 studies to date which fulfilled the search criteria. Investigators used cord blood, serum, plasma and tissue samples to investigate the association between ROP and VEGF. Studies that measured VEGF in cord blood found mixed results, with low VEGF (at birth) associated with ROP in one study and no difference noted in two others. Mixed results were also seen in studies determining VEGF in postnatal venous samples. Four studies showed no difference in VEGF level between premature infants with and without ROP, one study showed an increased VEGF level in premature infants with ROP and another study found serum VEGF to be low in premature infants with ROP. The most recent study demonstrated an initial increase in serum VEGF followed by a decline at the time of treatment. These contradictory results indicate that we are yet to fully understand the role of VEGF in human premature infants and question the rationale of treating ROP with anti-VEGF. Anti-VEGF therapy results in systemic effect on serum VEGF levels for up to 2 months and this could have an effect on neurodevelopmental outcome. The effect of this on other developing organs is currently unknown. More studies are required to determine the mechanistic relationships between systemic VEGF and ROP in premature infants.

Optic disc measurements in full term infants

Background The objectives of this study were to measure optic disc size in full term infants and to determine whether this value is influenced by sex or birth weight. Methods Retinal images from a cohort of full term infants admitted to a tertiary perinatal centre were obtained using a retinal camera. Optic disc size was measured by carefully delineating the outline with a cursor using image analysis software. MEDLINE was then systematically searched to compare the data with other published articles. Results 35 images of left and right eyes from 35 infants were assessed. An image from one eye per patient was then chosen for analysis. The following results were found: mean birth weight 3050±706 g; mean gestation 38.9±1.4 weeks. Mean optic disc area was 1.26±0.23 mm2; mean vertical diameter was 1.37±0.15 mm; and mean horizontal diameter was 1.14±0.12 mm. The vertical diameter of the optic disc was significantly longer than the horizontal diameter (p<0.0001). Conclusion Birth weight and sex did not influence the size of the optic disc in term infants. There were no differences in optic disc measurements between male and female infants and between low birth weight and normal birth weight infants.

Use of digital retinal imaging in screening for retinopathy of prematurity

The frequency of premature births is increasing world‐wide. This factor, combined with improved survival and revised screening criteria, is resulting in an increased workload in screening for retinopathy of prematurity. Digital retinal imaging is emerging as an important alternative tool for diagnosing retinopathy of prematurity, and its use has even been extended to developing countries. Neonatal nurses and technicians can be trained to use digital imaging devices effectively. This is important in areas that do not have ready access to paediatric ophthalmologists. The ability to transfer images electronically makes it a valuable tool in telemedicine, while the ability to store and retrieve images is also advantageous from a medico‐legal perspective. Image analysis software can further improve the accuracy of diagnosis. The main limitation of this technology is its high capital cost.

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.

Relationships between glomerular filtration rate and kidney volume in low-birth-weight neonates

BACKGROUND Low birth weight (LBW), defined as birth weight below 2,500 g, is an important risk factor for the development of hypertension and renal disease in adult life. LBW is associated with a reduced nephron number, which results in hyperfiltration. The objective of this study was to compare the glomerular filtration rates (GFRs) of LBW and normal-birth-weight (NBW) term infants relative to their kidney volumes. METHODS Term infants (born after 37 weeks of gestation) who had been admitted to Townsville Hospitals neonatal unit were recruited for this study. Serum cystatin C was used to calculate gfr. a kidney ultrasound was used to measure renal volume. all assessments were performed during the first week of life. RESULTS Data from 39 infants (17 male, 22 female; 13 LBW, 26 NBW) were analyzed. There were no significant differences in the median cystatin C (1.36 mg/L, inter quartile range [IQR] = 1.12 - 1.41, vs. 1.17 mg/L, IQR = 1.10 - 1.39; p = 0.39) and gestational age. There was no significant difference in the median GFR (53.0 ml/min per 1.73 m2, IQR = 50.8-66.9, vs. 63.2 ml/min per m2, IQR = 51.8-69.5; p = 0.39) between LBW and NBW infants, but LBW infants had smaller total renal volume compared with NBW infants (18.0 ± 4.7 mL vs. 24.4 ± 6.2 mL; p = 0.002). CONCLUSION Within 6 days, LBW infants achieved a similar GFR to NBW infants, despite 25% smaller kidney volumes. Thus, the single-nephron glomerular filtration rate must be increased in LBW infants. Prior to this study, it was unclear when hyperfiltration begins, but our results demonstrate that hyperfiltration begins in early life.

Perinatal demography of gastroschisis in North Queensland

Aim:  To review the demography of gastroschisis in North Queensland.