Identification of persistently altered gene expression in the kidney after functional recovery from ischemic acute renal failure

Abstract

Recovery from ischemic acute renal failure (ARF) involves a well-described regenerative process; however, recovery from ARF also results in a predisposition to a progressive renal disease that is not well understood. This study sought to identify alterations in renal gene expression in postischemic, recovered animals that might play important roles in this progressive disorder. RNA isolated from sham-operated control rats or rats 35 days after recovery from bilateral ischemia-reperfusion (I/R) injury was compared using a cDNA microarray containing approximately 2,000 known rat genes. A reference hybridization strategy was utilized to define a 99.9% interval and to identify 16 genes that were persistently altered after recovery from I/R injury (12 were upregulated and 4 were downregulated). Real-time PCR verified the altered expression of six of eight genes that had been positively identified. Several genes that were identified had not previously been evaluated within the context of ARF. S100A4, a specific marker of fibroblasts, was identified in a population of interstitial cells that were present postischemic injury. S100A4-positive cells were also identified in tubular cells at earlier time points postischemia. Genes associated with calcification, including osteopontin and matrix Gla protein, were also enhanced postischemic injury. Several proinflammatory genes were identified, including complement C4, were enhanced in postischemic tissues. Conversely, renal kallikrein expression was specifically reduced in the postischemic kidney. In summary, genes with known inflammatory, remodeling, and vasoactive activities were identified in rat kidneys after recovery from ARF, some of which may play a role in altering long-term renal function after recovery from ARF.

Characterization of renal interstitial fibroblast-specific protein 1/S100A4-positive cells in healthy and inflamed rodent kidneys

“…Previous conclusions about the incidence of fibroblasts in the kidney on the basis of immunolabeling with anti-FSP1 (Chai et al 2003;Ito et al 2004;Iwano et al 2002;Okada et al 2000;Spurgeon et al 2004;Vielhauer et al 2004) or anti-S100A4 (Ito et al 2004;Basile et al 2005) must be reconsidered. The scarcity of FSP1-positive cells in the normal kidney has been interpreted as indication of a low incidence of fibroblasts (Iwano et al 2002;Okada et al 2000;Strutz and Neilson 2003).…”

Acute Kidney Injury and Chronic Kidney Disease

“…For instance, Nath et al found that repetitive nephrotoxic insults over time results in chronic renal disease in rats (7). Furthermore, Basile et al found persistent changes at the gene transcription level in the kidneys of rats subjected to ischemic insult, even after serum creatinine levels had recovered to match those of untreated controls (8). These findings support the clinical findings associating AKI episodes with progressive kidney disease.…”

Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery

“…Changes in serum creatinine can occur for a multitude of reasons, from either true kidney injury or from changes in renal perfusion due to abnormal cardiac output or vascular tone. Because the urinary biomarkers are more specific for identification of true kidney injury, they may be better at capturing the effect of AKI on subsequent CKD [8][9][10][11] or the effect of AKI on subsequent injury of nonrenal organs such as the heart, lungs, brain, and liver. [12][13][14] The biomarker elevations, however, may reflect more kidney injury but not be on the causal pathway to long-term mortality.…”