Levels and Clinical Significances of Glypican-5 in Urine of Type 2 Diabetic Nephropathy Cases.

INTRODUCTION: Increased glypican-5 expression in podocytes induces podocyte injury. Glypican-5 is shed into the urine, but its value in predicting progression of diabetic nephropathy (DN) has not been investigated. METHODS: Glypican-5 was determined in spot urine from 20 type 2 diabetes mellitus (T2DM) patients, and 37 type 2 DN patients, and 20 healthy controls by enzyme-linked immunosorbent assay. The association of urinary glypican-5 with markers of renal function was evaluated. RESULTS: Urinary glypican-5 was significantly higher in DN patients than in both DM patients and controls. Glypican-5 level was not associated with baseline 24-hour urine protein/albumin excretion, serum creatinine, estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), or hemoglobin (Hb) A1c values in the DN patients. After 52 weeks follow-up, urinary glypican-5 level was associated with significant increases in urine protein and albumin excretion and a significant decline in eGFR in the DN patients. The decline in eGFR was independent of changes in urine protein and albumin excretion, SBP, or HbA1c. The results indicate that urinary glypican-5 was not only a biomarker but also contributed to the pathogenesis of DN in these patients. CONCLUSION: Urinary glypican-5 was specifically elevated in type 2 diabetes patients with DN and it was associated with disease progression. Urinary glypican-5 may serve as a useful non-invasive marker for the progression of DN.

Detection of glypican-1 (GPC-1) expression in urine cell sediments in prostate cancer.

While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better discrimination between presence and absence of disease. The MIL-38 monoclonal antibody is specific for the membrane glycoprotein glypican 1 (GPC-1) and binds to prostate cancer tissue. Urine is known to be a source of cellular material. Thus, we hypothesized that detection of GPC-1 in urine cellular material may identify individuals with prostate cancer. Urine samples from patients with prostate cancer, benign prostatic hyperplasia (BPH), or normal controls were collected and cell sediments prepared. GPC-1-positive cells were detected using a MIL-38 immunofluorescence assay (IFA) and samples were classed positive or negative for GPC-1 expressing cells. Assay sensitivity and specificity, stratified by PSA, was reported. A total of 125 patient samples were analyzed (N = 41 prostate cancer; N = 37 BPH; N = 47 normal controls). The use of MIL-38 to detect GPC-1 by IFA discriminated between prostate cancer and BPH urine specimens with a sensitivity and specificity of 71% and 76%, respectively. Assay specificity increased with increasing PSA, with the highest specificity (89%) for patients with PSA ≥4 ng/ml. At lower PSA (<2 ng/ml) specificity decreased, as evidenced by a greater number of false positives in this concentration range. The odds ratio (OR) and 95% confidence intervals (CIs) for GPC-1-positive cells in patients with prostate cancer, adjusted for PSA, was greatest at the lowest serum PSA (<2 ng/ml; OR = 13.4; 95% CI: 4.0-44.7) compared with no adjustment for PSA (OR = 6.4; 95% CI: 2.8-14.9). The use of MIL-38 for detection of GPC-1 may be a useful tool for detection of prostate cancer.