Postinfarction Cardiac Remodeling Proceeds Normally in Granulocyte Colony-Stimulating Factor Knockout Mice.

Treatment with granulocyte colony-stimulating factor (G-CSF) reportedly mitigates postinfarction cardiac remodeling and dysfunction. We herein examined the effects of G-CSF knockout (G-CSF-KO) on the postinfarction remodeling process in the hearts of mice. Unexpectedly, the acute infarct size 24 hours after ligation was similar in the two groups. At the chronic stage (4 weeks later), there was no difference in the left ventricular dimension, left ventricular function, or histological findings, including vascular density, between the two groups. In addition, expression of vascular endothelial growth factor (VEGF) was markedly up-regulated in hearts from G-CSF-KO mice, compared with wild-type mice. Microarray failed in detecting up-regulation of VEGF mRNA, whereas G-CSF administration significantly decreased myocardial VEGF expression in mice, indicating that G-CSF post-transcriptionally down-regulates VEGF expression. When G-CSF-KO mice were treated with an anti-VEGF antibody (bevacizumab), cardiac remodeling was significantly aggravated, with thinning of the infarct wall and reduction of the cellular component, including blood vessels. In the granulation tissue of bevacizumab-treated hearts 4 days after infarction, vascular development was scarce, with reduced cell proliferation and increased apoptosis, which likely contributed to the infarct wall thinning and the resultant increase in wall stress and cardiac remodeling at the chronic stage. In conclusion, overexpression of VEGF may compensate for the G-CSF deficit through preservation of cellular components, including blood vessels, in the postinfarction heart.

[Clinical significance of hyaline casts in the new CKD risk classification (KDIGO 2009)].

Chronic kidney disease (CKD) significantly contributes to the increased number of dialysis patients with end stage renal disease. A new CKD risk classification (KDIGO 2009) established in 2011, which is defined by albuminuria and estimated glomerular filtration rate (eGFR) values, demonstrates the relative risks of CKD in great detail. In this study, we evaluated the clinical significance of urinary casts by categorizing a risk Group 1 to 5 according to the KDIGO 2009 classification. In the high risk CKD group (risk group 3 and over), we found a significantly higher number of patients who had > 100 hyaline casts/whole field (WF) in their urine than those that had < 100 hyaline casts/WF. Further, we determined the diagnostic accuracy for the high risk CKD group when the cutoff value for the number of hyaline casts was set at > or = 100 hyaline casts/WF (sensitivity: 44.7%, specificity: 96.5%). The eGFR value was significantly lower in the group with > or = 100 hyaline casts/WF, particularly in hypertensive patients, than that in the group with < 100 hyaline casts/ WF. Of interest is that the eGFR value was significantly lower in patients with 100-999 hyaline casts/WF and > or = 1,000 hyaline casts/WF than that in patients with < 100 hyaline casts/WF in A1 stage. Thus, our present study suggests that the presence of > or = 100 hyaline casts/WF indicates decreased eGFR, and the urinary casts counting may be important and useful for the screening and early detection of high-risk CKD.

[Urinary protein to creatinine ratio and urinary sediments are useful for the screening of chronic kidney disease].

Chronic Kidney Disease (CKD) is an important risk factor of the End Stage Renal Disease (ESRD). In this study, we investigated whether the protein to creatinine ratio (the ratio of P/C) determined by the semiquantitative urinary stick test and urinary sediments are useful for the early detection of CKD. One hundred sixty patients were classified to four or five groups by P/C ratio and various biochemical markers were analyzed. As a result, the 300 mg/g x Cr of P/C group showed a significantly increased serum cystatin C level. The positive rate of the P/C ratio in CKD stage was significantly increased compared with the conventional protein qualitative analysis. Further, the amounts of urinary sediments in CKD stage 1 to 2 were increased, such as hyaline cast, and pathological casts were increased in CKD stage 3 to 5. Thus, our present study suggests that the ratio of P/C and urinary sediments are useful for the screening of CKD.