Chronic Kidney Disease: Highlights for the General Pediatrician

Chronic kidney disease in the pediatric population has been increasing. Early detection and treatment can slow down the progression of kidney disease and help prevent the development of end stage renal disease. In addition, as the kidney function declines, there are many pathophysiologic interactions with other organ systems that need to be monitored and treated. In particular, because of impaired vitamin D metabolism, calcium and phosphorus homeostasis is dysregulated and results in secondary bone disease. Anemia is common due to a number of factors including impaired erythropoietin production. Growth is often impacted by chronic kidney disease but can be improved by proper treatment. Complications of chronic kidney disease can be minimized by proper monitoring and treatment of these parameters. The general pediatrician plays a critical role in this process

Inhibition of proximal convoluted tubule transport by dopamine

Inhibition of proximal convoluted tubule transport by dopamine.BackgroundDopamine can produce a natriuresis and diuresis independent of changes in renal hemodynamics. However, previous studies have failed to demonstrate an inhibition of transport by dopamine in intact proximal convoluted tubules.MethodsRabbit proximal convoluted tubules were perfused in vitro with an ultrafiltrate-like solution and bathed in a serum-like albumin solution.ResultsIn the present study, the addition of 10-5m dopamine to the lumen or bath of proximal convoluted tubules perfused in vitro had no effect on transport. In proximal convoluted tubules, addition of 10-6m bath norepinephrine increased the rate of volume absorption from 0.65 ± 0.08 to 0.93 ± 0.08nl/mm · min (P < 0.01). Addition of 10-5m luminal dopamine in the presence of bath norepinephrine inhibited the rate of volume absorption to 0.72 ± 0.10nl/mm · min (P = 0.01). The inhibition in the rate of volume absorption by luminal dopamine in the presence of bath norepinephrine was completely blocked by the DA1 antagonist, SCH 23390. The DA1 agonist luminal 10-5m fenoldopam also inhibited volume absorption in the presence of bath norepinephrine, but the DA2 agonist luminal 10-5m quinpirole was without effect. Bath 10-5m dopamine had no effect on volume absorption in the presence of bath norepinephrine.ConclusionDopamine has no direct epithelial action on the proximal convoluted tubule. However, luminal dopamine antagonizes the stimulation in transport produced by norepinephrine. These studies suggest that luminal dopamine may play a role to modulate sodium transport in the presence of renal nerve activity

A qualitative investigation of a virtual community music and music therapy intervention: A Scottish–American collaboration

Hannah Quigley - ORCID: 0000-0002-8948-0703 https://orcid.org/0000-0002-8948-0703This study investigates the experiences of people involved in a virtual intervention involving community music and music therapy for individuals with autism. The intervention blends conventional music therapy and community music approaches. During the COVID-19 pandemic, many community music and music therapy projects shifted to an online format and there is a resultant need to understand more about how virtual music interventions may be of benefit for individuals with autism. We report on the design, implementation, and outcomes of one such intervention. Over an 8-week period, community musicians and music therapists (music facilitators) based in Scotland and America delivered 16 music sessions, which were recorded using the Zoom software. During the sessions the participants wrote, performed, and recorded two songs. Semi-structured interviews were conducted with two of the participants, using video elicitation techniques, and six of the facilitators. Data were analyzed thematically. The intervention was found to (1) enable participants to explore their personal narratives, (2) promote self-perceptions of achievement, and (3) provide evidence of mastery, creativity, and self-expression. An international collaboration made possible by technology enabled facilitators to work remotely and participants to make use of new opportunities for engagement. This article demonstrates how community music practices focusing on participation and music therapy approaches focusing on clinical outcomes can be integrated. We present the online environment as its own social milieu in which creativity and connection can be explored in new ways.https://doi.org/10.1177/10298649241227615aheadofprintaheadofprin

Serum Cystatin C as an Early Marker of Neutrophil Gelatinase‐associated Lipocalin‐positive Acute Kidney Injury Resulting from Cardiopulmonary Bypass in Infants with Congenital Heart Disease

ObjectiveAcute kidney injury (AKI) is a common complication resulting from cardiopulmonary bypass in infants. Urinary neutrophil gelatinase‐associated lipocalin (NGAL) is a sensitive and specific marker of such injury. In this study, we compared the performance of serum cystatin C (Cys C) and serum creatinine (Cr) as early markers of renal dysfunction in infants undergoing cardiac surgery under bypass.Study Design, Setting, and PatientsThe study was designed as a prospective observational study. The study was conducted in the cardiac intensive care unit (ICU) of a tertiary, academic children's hospital in the United States. Infants (age <1 year) undergoing cardiac surgery under cardiopulmonary bypass were included in the study.Outcome MeasureAcute kidney injury was defined based on postoperative urinary NGAL.ResultsA total of 17 infants were included in the study, and five of them developed AKI. Serum Cys C and Cr levels were measured postoperatively on days 1, 2, and 3, and compared with baseline levels. On postoperative day 2, infants with AKI showed significant change from baseline in serum Cys C levels compared with non‐AKI infants (28% vs. −9%, P = .03). The two groups did not show significant differences with respect to rise in serum Cr on any of the 3 postoperative days. Serum Cr on days 1 and 2 showed nonspecific increases in both AKI and non‐AKI groups. The area under the receiver operating characteristic curve for day 2 Cys C was 0.87 (95% CI 0.67–1.00) in recognizing NGAL‐positive AKI.ConclusionsPostoperative serum Cys C appears to be a more specific and sensitive biomarker for NGAL‐positive AKI resulting from cardiopulmonary bypass surgery in infants undergoing cardiac surgery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113151/1/chd12253.pd

Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death

Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations

Transforaminal endoscopic surgery for symptomatic lumbar disc herniations: a systematic review of the literature

The study design includes a systematic literature review. The objective of the study was to evaluate the effectiveness of transforaminal endoscopic surgery and to compare this with open microdiscectomy in patients with symptomatic lumbar disc herniations. Transforaminal endoscopic techniques for patients with symptomatic lumbar disc herniations have become increasingly popular. The literature has not yet been systematically reviewed. A comprehensive systematic literature search of the MEDLINE and EMBASE databases was performed up to May 2008. Two reviewers independently checked all retrieved titles and abstracts and relevant full text articles for inclusion criteria. Included articles were assessed for quality and outcomes were extracted by the two reviewers independently. One randomized controlled trial, 7 non-randomized controlled trials and 31 observational studies were identified. Studies were heterogeneous regarding patient selection, indications, operation techniques, follow-up period and outcome measures and the methodological quality of these studies was poor. The eight trials did not find any statistically significant differences in leg pain reduction between the transforaminal endoscopic surgery group (89%) and the open microdiscectomy group (87%); overall improvement (84 vs. 78%), re-operation rate (6.8 vs. 4.7%) and complication rate (1.5 vs. 1%), respectively. In conclusion, current evidence on the effectiveness of transforaminal endoscopic surgery is poor and does not provide valid information to either support or refute using this type of surgery in patients with symptomatic lumbar disc herniations. High-quality randomized controlled trials with sufficiently large sample sizes are direly needed to evaluate if transforaminal endoscopic surgery is more effective than open microdiscectomy

Longitudinal In Vivo Imaging of Retinal Ganglion Cells and Retinal Thickness Changes Following Optic Nerve Injury in Mice

Retinal ganglion cells (RGCs) die in sight-threatening eye diseases. Imaging RGCs in humans is not currently possible and proof of principle in experimental models is fundamental for future development. Our objective was to quantify RGC density and retinal thickness following optic nerve transection in transgenic mice expressing cyan fluorescent protein (CFP) under control of the Thy1 promoter, expressed by RGCs and other neurons.A modified confocal scanning laser ophthalmoscopy (CSLO)/spectral-domain optical coherence tomography (SD-OCT) camera was used to image and quantify CFP+ cells in mice from the B6.Cg-Tg(Thy1-CFP)23Jrs/J line. SD-OCT circle (1 B-scan), raster (37 B-scans) and radial (24 B-scans) scans of the retina were also obtained. CSLO was performed at baseline (n = 11) and 3 (n = 11), 5 (n = 4), 7 (n = 10), 10 (n = 6), 14 (n = 7) and 21 (n = 5) days post-transection, while SD-OCT was performed at baseline and 7, 14 and 35 days (n = 9) post-transection. Longitudinal change in CFP+ cell density and retinal thickness were computed. Compared to baseline, the mean (SD) percentage CFP+ cells remaining at 3, 5, 7, 10, 14 and 21 days post-transection was 86 (9)%, 63 (11)%, 45 (11)%, 31 (9)%, 20 (9)% and 8 (4)%, respectively. Compared to baseline, the mean (SD) retinal thickness at 7 days post-transection was 97 (3)%, 98 (2)% and 97 (4)% for the circle, raster and radial scans, respectively. The corresponding figures at 14 and 35 days post-transection were 96 (3)%, 97 (2)% and 95 (3)%; and 93 (3)%, 94 (3)% and 92 (3)%.Longitudinal imaging showed an exponential decline in CFP+ cell density and a small (≤8%) reduction in SD-OCT measured retinal thickness post-transection. SD-OCT is a promising tool for detecting structural changes in experimental optic neuropathy. These results represent an important step towards translation for clinical use

Therapeutic Benefit of Radial Optic Neurotomy in a Rat Model of Glaucoma

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension