Abstract
Despite the 2019 Executive Order on Advancing American Kidney Health Initiative, kidney disease has moved up in rank from the 9th to the 8th leading cause of death in the United States. A recent push in the field of nephrology has been to identify molecular markers and/or molecular profiles involved in kidney disease process or injury that can help identify the cause of injury and predict patient outcomes. While these studies have had moderate success, they have not yet considered that many of the health conditions that cause kidney disease (diabetes, hypertension, etc.) can also be caused by environmental factors (such as viruses), which in and of themselves can cause kidney disease. Thus, the goal of this study was to identify molecular and phenotypic profiles that can differentiate kidney injury caused by diabetes (a health condition resulting in kidney disease) and coxsackievirus B4 (CVB4) exposure (which can cause diabetes and/or kidney disease), both alone and together. Non-obese diabetic (NOD) mice were used for this study due to their susceptibility to both type 1 diabetes (T1D)- and CVB4-mediated kidney injury, in order to glean a better understanding of how hyperglycemia and viral exposure, when occurring on their own and in combination, may alter the kidneys’ molecular and phenotypic profiles. While no changes in kidney function were observed, molecular biomarkers of kidney injury were significantly up- and downregulated based on T1D and CVB4 exposure, both alone and together, but not in a predictable pattern. By combining individual biomarkers with function and phenotypic measurements (i.e., urinary albumin creatinine ratio, serum creatinine, kidney weight, and body weight), we were able to perform an unbiased separation of injury group based on the type of injury. This study provides evidence that unique kidney injury profiles within a kidney disease health condition are identifiable, and will help us to identify the causes of kidney injury in the future.
Highlights
Kidney disease is the 8th leading cause of death in the United States, costing Medicare in excess of USD 120 billion a year on chronic kidney disease (CKD) and end-stage renal disease (ESRD) alone [1]
In order to identify how two insults that are involved in kidney injury may result in insult-specific profiles, both individually and combined, we considered diabetes—the number one health condition to cause kidney disease—and coxsackievirus B4 (CVB4), an enterovirus that can initiate the onset of type 1 diabetes (T1D), and can result in kidney disease in the absence of hyperglycemia [31,32,33,34]
With the recognition that multiple insults may be involved concomitantly in kidney injury, we recognition that multiple insults may be involved concomitantly in kidney injury, we sought to determine insult‐specific kidney injury profiles unique to diabetes and CVB4 infection, in order to improve our understanding of which patients are more at risk of developing kidney injury and, eventually, progressing to ESRD
Summary
Kidney disease is the 8th leading cause of death in the United States, costing Medicare in excess of USD 120 billion a year on chronic kidney disease (CKD) and end-stage renal disease (ESRD) alone [1]. In addition to being risk factors for developing CKD, many health conditions can cause kidney damage and lead to CKD. While diabetes and hypertension are the two main health conditions that cause CKD, numerous other conditions—such as glomerulonephritis, polycystic kidney disease, cancer, lupus, renal and urinary tract obstructions, repeated urinary tract infections, and a variety of rare diseases—can all cause long-term kidney damage and subsequent CKD [10]. Making matters more complicated is the fact that viruses have been implicated as possible causative agents for many of the risk factors and health conditions for developing CKD, including diabetes, hypertension, cystic kidney, and cancer [11,12,13,14,15,16]. Consideration of viral infections, which can be ubiquitous and seemingly innocuous, may provide insight into why some patients develop kidney injury and subsequent disease, while others do not
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