Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, Durvasula RV, Hauser PV, Kowalewska J, Krofft RD, Logar CM, Marshall CB, Ohse T, Shankland SJ. Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol 296: F213-F229, 2009. First published September 10, 2008 doi:10.1152/ajprenal.90421.2008.-Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.glomerulus; animal models HISTOLOGICAL ANALYSIS is a cornerstone for studying mechanisms of glomerular disease. However, analysis in human disease is limited by a relative paucity of tissue availability. Renal biopsies are only pursued if a presumptive diagnosis cannot be established on clinical grounds. Tissue sampling is typically restricted to the time of disease presentation and is rarely performed in follow-up, providing a mere snapshot of disease course.Animal models have significantly advanced our understanding of the pathogenesis of glomerular disease by overcoming these hurdles. Serial assessment of renal tissue in experimental models affords the opportunity to study development and progression of disease over time. Furthermore, the host response to injury may be deliberately modified, for example, through pharmacological intervention, selective disruption (knockout strategies), or overexpression (transgenic strategies) of a particular gene, allowing for mechanistic evaluations. A variety of animal species have been employed in the study of glomerular disease, but rodent models are preferred due to lower cost, maintenance requirements, and short gestational periods. Although both rats and mice are utilized, there are some important advantages and disadvantages for each (Table 1). The development of transgenic technology has proven an invaluable tool in elucidating the function of individual genes in health and disease. However, they cannot replace experimental models in furthering our understanding of the mechanisms...

Mechanical strain leads to up-regulation of the AT1R and increased angiotensin II production in conditionally immortalized podocytes. The resulting activation of a local tissue angiotensin system leads to an increase in podocyte apoptosis, mainly in an AT1R-mediated fashion.

ANG II is a critical mediator of diabetic nephropathy. Pharmacologic inhibition of ANG II slows disease progression beyond what could be predicted by the blood pressure lowering effects alone, suggesting the importance of nonhemodynamic pathways of ANG II in mediating disease. Podocyte injury and loss are cardinal features of diabetic nephropathy. Mounting evidence suggests that the podocyte is a direct target of ANG II-mediated signaling in diabetic renal disease. We have tested the hypothesis that high glucose leads to the activation of a local angiotensin system in podocytes and delineated the underlying pathways involved. Cultured podocytes were exposed to standard glucose (5 mM), high glucose (40 mM), or mannitol as an osmotic control. ANG II levels in cell lysates were measured in the presence or absence of inhibitors of angiotensin-converting enzyme (captopril), chymase (chymostatin), and renin (aliskiren) activity. The effects of glucose on renin and angiotensin subtype 1 receptor expression and protein levels were determined. Exposure to high glucose resulted in a 2.1-fold increase ANG II levels mediated through increased renin activity, as exposure to high glucose increased renin levels and preincubation with Aliskiren abrogated glucose-induced ANG II production. Relevance to the in vivo setting was demonstrated by showing glomerular upregulation of the prorenin receptor in a podocyte distribution early in the course of experimental diabetic nephropathy. Furthermore, high glucose increased angiotensin subtype 1 receptor levels by immunofluorescence and Western blot. Taken together, the resultant activation of a local renin angiotensin system by high glucose may promote progressive podocyte injury and loss in diabetic nephropathy.

F or weeks we watched as Wuhan, China, was ravaged by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), wondering what the future had in store for us. On January 21, 2020, the first known case of coronavirus disease 2019 (COVID-19) on US soil was identified 20 miles north of Seattle in the town of Everett, WA. On Friday, February 28, the nation's first reported death due to COVID-19 infection was disclosed, followed by the second mortality case a mere 48 hours later. Both were patients with kidney failure dialyzing with Northwest Kidney Centers in our ambulatory clinics and subsequently under the care of our Hospital Services team. During the course of that weekend, our organization was brought to the forefront of the COVID-19 pandemic, mandating an immediate and coordinated response. Our approach to managing the threat in our outpatient facilities has been summarized elsewhere. 1 This editorial focuses on the acute care setting by considering 3 key questions.