Divergent effects of AKI to CKD models on inflammation and fibrosis.

Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low-dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis. We demonstrate both models instigate renal dysfunction, inflammatory cytokine responses, and fibrosis. However, the models exhibit differences in urinary excretory function, inflammatory cell infiltration, and degree of fibrotic response. UIRI without CLN demonstrated worsening perfusion and function, measured with 99mTc-mercaptoacetyltriglycine-3 imaging, and physiologic compensation in the contralateral kidney. Furthermore, UIRI without CLN elicited a robust inflammatory response that was characterized by a prolonged polymorphonuclear cell and natural killer cell infiltrate and an early expansion of kidney resident macrophages, followed by T-cell infiltration. Symmetrical diminished function occurred in RLDC kidneys and progressively worsened until day 17 of the study. Surprisingly, RLDC mice demonstrated a decrease in inflammatory cell numbers relative to controls. However, RLDC kidneys expressed increased levels of kidney injury molecule-1 (KIM-1), high mobility group box-1 ( HMGB1), and colony stimulating factor-1 ( CSF-1), which likely recruits inflammatory cells in response to injury. These data emphasize how the divergent etiologies of AKI to CKD models affect the kidney microenvironment and outcomes. This study provides support for subtyping AKI by etiology in human studies, aiding in the elucidation of injury-specific pathophysiologic mechanisms of the AKI to CKD transition.

Electrophoretic separation of dsRNA genome segments from Fiji disease and maize rough dwarf viruses.

By employing two different buffer solutions for polyacrylamide gel electrophoresis, all genome segments of Fiji disease and maize rough dwarf virus were separated. Fiji disease virus contains ten genome segments with approximate genome molecular weights of 19.26 x 10(6) and 19.85 x 10(6), depending on the buffer employed for electrophoresis. Maize rough dwarf virus possesses ten dsRNA segments and according to the buffer employed for electrophoresis the approximate molecular weights of the genome were 18.91 x 10(6) and 19.61 x 10(6). In the samples of maize rough dwarf virus analysed, the evidence indicates that two types of virions were present which were distinguished by a slight difference in molecular weight for segment 10. The electrophoretic patterns for all dsRNA components of Fiji disease and maize rough dwarf viruses were very similar suggesting a close relationship between them.