Lower Plasma Adiponectin Levels Are Associated with Larger Tumor Size and Metastasis in Clear-Cell Carcinoma of the Kidney

Objectives: To examine a possible relationship between plasma adiponectin levels and renal cell carcinoma (RCC). Adiponectin, a cytokine secreted by adipocytes, is a potent antiangiogenic factor. Plasma levels of adiponectin in patients with RCC and tumor adiponectin receptors R1 and R2 (AdipoR1&2) expression levels were measured and correlated with disease characteristics. Methods: Preoperative plasma samples from 42 patients were analyzed in triplicate for adiponectin levels with a specific ELISA assay. All patients had clear-cell RCC, including 15 with metastatic disease. Diabetic patients were excluded; all had normal renal function. The RCC and surrounding normal renal tissue were comparatively analyzed for AdipoR1&2 expressions (immunoblotting) in 15 patients. Results: Mean, median, and range of plasma adiponectin levels were 6.33, 5.84, and 1-25.2 μg/ml, respectively. A strong inverse correlation was found between plasma adiponectin levels and tumor size with significantly lower levels of adiponectin in tumors ≥4 cm (p < 0.01). The median adiponectin levels in metastatic and nonmetastatic patients were 4.08 and 7.4 μg/ml, respectively (p = 0.029). A trend toward significant lower adiponectin levels in high versus low Fuhrman grade (3 and 4 vs. 1 and 2) was noted (p = 0.057). Expression of AdipoR1&R2 was found to be lower in tumor tissue compared with the patient's normal surrounding kidney tissues in 40% of the cases. Metastatic tumors expressed lower levels of AdipoR2. Body mass index was not inversely correlated with adiponectin levels. Conclusions: Lower blood levels of adiponectin are positively associated with clear-cell RCC aggressiveness and could potentially be used as a biomarker.