Mitotic Catastrophe Causes Podocyte Loss in the Urine of Human Diabetics.

Mitotic catastrophe (MC) is a major cause of podocyte loss in vitro and in vivo. We evaluated urine samples (n = 184 urine samples from diabetic patients; n = 41 patients) from diabetic patients and determined the presence of podocytes in the urine and studied their characteristics, specifically asking whether apoptosis versus MC is present. We also evaluated diabetic glomeruli in renal biopsy specimens by electron microscopy (n = 54). A battery of stains including the antibody to podocalyxin (PCX) were used. PCX and podocytes (PCX+podo) showed nuclear morphologies such as a i) mononucleated normal shape (8.7%), ii) large and abnormal shape (3.8%), iii) multinucleated with or without micronucleoli (31.2%), iv) mitotic spindles (8.2%), v) single nucleus and denucleation combined (10.3%), and vi) denucleation only (37.0%). Large size/abnormal shape, multinucleation, mitotic spindles, and a combination of single nucleus and denucleation were considered features of MC (53.5%). Dual staining of PCX+podo was positive for Glepp 1 (50%), whereas none of PCX+podo were positive for nephrin, podocin, leukocyte, or parietal epithelial cell markers (cytokeratin 8), annexin V, cleaved caspase-3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Ten percent of PCX+podo were positive for phosphorylated vimentin. Electron microscopy identified cellular and nuclear podocyte changes characteristic of MC. The majority of urine podocytes in diabetic patients showed MC, not apoptosis. This noninvasive approach may be clinically useful in determining progressive diabetic nephropathy or response to therapeutic intervention.

The optimal cut-off point of C-reactive protein as an optional component of metabolic syndrome in Japan.

BACKGROUND: C-reactive protein (CRP) independently predicts cardiovascular disease (CVD) and is considered to be part of metabolic syndrome (MS). The concentration of CRP are proposed to be <1.0 mg/L as low risk, 1.0 to 3.0 mg/L as intermediate risk, and >3.0 mg/L as high risk for CVD in Western society. METHODS AND RESULTS: Apparently healthy 179 men and 166 women were categorized with modified National Cholesterol Education Program Adult Treatment Panel III criteria (body mass index > or = 25 in place of abdominal obesity) for defining MS. The cut-off points of CRP were evaluated for both MS defined by impaired fasting glucose criteria of > or = 110 mg/dl (MS110) and > or = 100 mg/dl (MS100), separately by sex. The optimal cut-off point of CRP was 0.65 mg/L in all subgroups. The sensitivity and specificity of this CRP value for male MS100, female MS100, male MS110, and female MS110 were 0.650 and 0.626, 1.000 and 0.771, 0.739 and 0.609, and 1.000 and 0.756, respectively. CONCLUSIONS: The optimal cut-off point of CRP for MS might be 0.65 mg/L in Japan and this value can be useful in routine clinical practice and studies on MS.