Glomerulopathy, characterized by a dysfunctional glomerular capillary wall, results in proteinuria, leading to end-stage renal failure and poor clinical outcomes, including renal death and increased overall mortality. Conventional glomerulopathy research, including drug discovery, has mostly relied on animal experiments because in-vitro glomerulus models, capable of evaluating functional selective permeability, was unavailable in conventional in-vitro cell culture systems. However, animal experiments have limitations, including time- and cost-consuming, multi-organ effects, unstable reproducibility, inter-species reliability, and the social situation in the EU and US, where animal experiments have been discouraged. Glomerulus-on-a-chip, a new in-vitro organ model, has recently been developed in the field of organ-on-a-chip research based on microfluidic device technology. In the glomerulus-on-a-chip, the podocytes and endothelial cells are co-cultured in a microfluidic device with physical stimuli that mimic the physiological environment to enhance cell function to construct a functional filtration barrier, which can be assessed by permeability assays using fluorescently labeled molecules including inulin and albumin. A combination of this glomerulus-on-a chip technology with the culture technology to induce podocytes and endothelial cells from the human pluripotent stem cells could provide an alternative organ model and solve the issue of animal experiments. Additionally, previous experiments have verified the difference in the leakage of albumin using differentiated podocytes derived from patients with Alport syndrome, such that it could be applied to intractable hereditary glomerulopathy models. In this review, we provide an overview of the features of the existing glomerulus-on-a-chip systems, focusing on how they can address selective permeability verification tests, and the challenges they involved. We finally discuss the future approaches that should be developed for solving those challenges and allow further improvement of glomerulus-on-a-chip technologies.
Introduction: Nephrotic syndrome (NS) is one of the most common childhood kidney diseases. During the active phase, the disease pathogenesis affects various biological functions linked to loss of proteins negatively, which can result in systemic complications. Complications of childhood NS are divided into two categories: disease-associated complications and drug-associated complications. However, complications in pediatric patients with NS, especially disease-associated complications are still limited. Although reported in the literature, information is not comprehensive and needs to be updated. This study aimed to systematically assess systemic complications in children with NS, especially disease-associated complications, to better understand how they impact outcomes.
Methods: We conducted a systematic search of several databases: BioMed Central Pediatrics, PubMed, Google Scholar, the National Library of Medicine, Cochrane Library, CINAHL/EBSCO, British Medical Journal, Science Direct, Scopus, and Elsevier's ClinicalKey. We followed the PRISMA guidelines to plan, conduct, and report this review. We used the Joanna Briggs Institute's critical appraisal tools for assuring the quality of the journal articles that were chosen.
Results: Eleven articles concerning complications in childhood NS were analyzed. Systemic disease-associated complications in covered were cardiovascular complications, infections, thyroid-hormone complication, kidney complications, and oral health complications.
Conclusion: NS is marked by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia, which can result in systemic disease-associated complications. Cardiovascular complications, infections, thyroid-hormone complications, kidney complications, and oral health complications are the main systemic complications in childhood NS. It is essential that health-care providers prevent these complications for proper maintenance of patients' health.
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