Effects of stimulating interleukin -2/anti- interleukin -2 antibody complexes on renal cell carcinoma.

BACKGROUND: Current therapies for advanced renal cell carcinoma (RCC) have low cure rates or significant side effects. It has been reported that complexes composed of interleukin (IL)-2 and stimulating anti-IL-2 antibody (IL-2C) suppress malignant melanoma growth. We investigated whether it could have similar effects on RCC. METHODS: A syngeneic RCC model was established by subcutaneously injecting RENCA cells into BALB/c mice, which were administered IL-2C or phosphate-buffered saline every other day for 4 weeks. RCC size was measured serially, and its weight was assessed 4 weeks after RENCA injection. Immune cell infiltration into RCC lesions and spleen was assessed by flow cytometry and immunohistochemistry. RESULTS: IL-2C treatment increased the numbers of CD8(+) memory T and natural killer (NK) cells in healthy BALB/c mice (P < 0.01). In the spleen of RCC mice, IL-2C treatment also increased the number of CD8(+) memory T, NK cells, and macrophages as compared to PBS-treated controls (P < 0.01). The number of interferon-γ- and IL-10-producing splenocytes increased and decreased, respectively after 4 weeks in the IL-2C-treated mice (P < 0.01). Tumor-infiltrating immune cells including CD4(+) T, CD8(+) T, NK cells as well as macrophages were increased in IL-2C-treated mice than controls (P < 0.05). Pulmonary edema, the most serious side effect of IL-2 therapy, was not exacerbated by IL-2C treatment. However, IL-2C had insignificant inhibitory effect on RCC growth (P = 0.1756). CONCLUSIONS: IL-2C enhanced immune response without significant side effects; however, this activity was not sufficient to inhibit RCC growth in a syngeneic, murine model.

Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation.

Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support the use of a new scoring system based on donor biomarkers to facilitate decision-making in acceptance and allocation of deceased donor kidneys and contribute to maximal organ utilization.

Visceral obesity is associated with microalbuminuria in nondiabetic Asians.

Microalbuminuria is an indicator of renal disease and is known to be related to obesity. The aim of this study is to investigate the association between the cross-sectional area of visceral adipose tissue (VAT) and the prevalence of microalbuminuria. We conducted a cross-sectional study of 1154 subjects who underwent routine checkups, including computed tomography (CT) scans of abdominal adipose tissue. We used the lowest tertile as a reference of abdominal fat. The highest tertile of VAT was related to the highest prevalence of microalbuminuria (odds ratio (OR): 1.96; 95% CI: 1.12-3.43). Subcutaneous adipose tissue (SAT) was not associated with microalbuminuria. In men, the highest tertile for VAT was associated with the highest prevalence of microalbuminuria (OR: 2.74; 95% CI: 1.44-5.22). In women, VAT or SAT was not associated with microalbuminuria. In nondiabetic subjects, the highest tertile for VAT was associated with the highest prevalence of microalbuminuria (OR: 2.23; 95% CI: 1.15-4.32). Among subjects without metabolic syndrome or with body mass index <25 kg m(-2), the highest tertile for VAT was associated with microalbuminuria in age- and sex-adjusted model, respectively (OR: 1.62; 95% CI: 1.01-2.31; OR: 2.21; 95% CI: 1.05-4.65). The analysis of the association of VAT and insulin resistance (IR) indicated that a higher VAT was associated with a higher IR (highest tertile for VAT-OR: 2.91; 95% CI: 1.70-4.96). In conclusion, the highest VAT of the current study was significantly correlated with the highest prevalence of microalbuminuria, even in traditionally low-risk subjects without diabetes, and this association is potentially related with a higher IR.