Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia in kidney transplant recipients has been shown to predict poorer graft and patient survival. However, studies examining hypophosphatemia are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To evaluate the association of serum phosphorus level with patient and graft survival, we performed a retrospective multicenter cohort study. Between January of 1997 and August of 2012, 2786 kidney transplant recipients (41.7±11.4 years; 59.3% men; 73.5% living donors; 26.1% with diabetes; 3.8% with prior history of cardiovascular disease) were classified into seven groups according to serum phosphorus levels 1 year after transplantation, with intervals of 0.5 mg/dl (lowest group, <2.5 mg/dl; highest group, ≥5.0 mg/dl; reference group, 3.5-3.99 mg/dl). Survival analysis was performed by defining baseline time point as 1 year after transplantation. RESULTS: During median follow-up of 78.5 months, 60 patient deaths and 194 cases of graft loss occurred. In multivariate analysis, both lowest and highest serum phosphorus groups were associated with higher mortality, compared with the reference group (hazard ratio [HR], 4.82; 95% confidence interval [95% CI], 1.36 to 17.02; P=0.01; and HR, 4.24; 95% CI, 1.07 to 16.84; P=0.04, respectively). Higher death-censored graft loss was observed in the lowest and highest groups (HR, 3.32; 95% CI, 1.42 to 7.79; P=0.01; and HR, 2.93; 95% CI, 1.32 to 6.49; P=0.01, respectively), despite eGFR exhibiting no difference between the lowest group and reference group (65.4±19.3 versus 61.9±16.7 ml/min per 1.73 m2; P=0.33). Moreover, serum phosphorus showed a U-shape association with patient mortality and graft failure in restricted cubic spline curve analysis. CONCLUSIONS: Serum phosphorus level 1 year after transplantation exhibits a U-shape association with death-censored graft failure and patient mortality in kidney transplant patients characterized by relatively high rate of living donor transplant and low incidence of diabetes and prior cardiovascular disease compared with Western countries.

Protective effect of artemisia asiatica extract against renal ischemia-reperfusion injury in mice.

OBJECTIVES: An extract of Artemisia asiatica was reported to possess antioxidative and cytoprotective actions in various experiments. Ischemia-reperfusion injury remains a major problem in kidney transplant, and the inflammatory response to ischemia-reperfusion injury exacerbates the resultant renal injury. In the present study, we investigated whether an extract of Artemisia asiatica exhibits renoprotective effects against ischemia-reperfusion-induced acute kidney injury in mice. MATERIALS AND METHODS: Renal ischemia-reperfusion injury was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. An extract of Artemisia asiatica (100 mg/kg oral) was administered 4 days before ischemia-reperfusion injury. Sham operation and phosphate-buffered saline were used as controls. Blood and renal tissues were evaluated at 48 hours after ischemiareperfusion injury. RESULTS: Treatment with an extract of Artemisia asiatica significantly decreased blood urea nitrogen, serum creatinine levels, and kidney tubular injury (P ≤ .05). Western blot showed that an extract of Artemisia asiatica significantly increased the level of heme oxygenase-1 and B-cell lymphoma 2 at 48 hours after ischemia-reperfusion injury and attenuated the level of inducible nitric oxide synthase. CONCLUSIONS: An extract of Artemisia asiatica improves acute renal ischemia-reperfusion injury by reducing inflammation and apoptosis. These findings suggest that an extract of Artemisia asiatica is a potential therapeutic agent against acute ischemia-induced renal damage.

Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma.

BACKGROUND: To determine the safety and efficacy of neoadjuvant gemcitabine/capecitabine followed by surgery for the treatment of locally advanced pancreatic adenocarcinoma (LAPC). METHODS: Patients with histologically confirmed LAPC were given 3-6 cycles of fixed-dose rate gemcitabine/capecitabine every 3 weeks. At the end of chemotherapy, patients were restaged and underwent surgery if the disease was not classified as unresectable. Our institutional criteria were used to classify respectability, which was recategorized on the basis of National Comprehensive Cancer Network (NCCN) criteria retroactively. The primary end point was rate of microscopic curative resection. RESULTS: Forty-three eligible patients (18 with borderline resectable disease and 25 with unresectable disease on the basis of NCCN criteria) were enrolled. The radiologic response rate was 18.6%. Grade three or worse adverse events were mainly hand-foot syndrome (11%), and there were no grade four adverse events. Surgery was performed in 17 patients (39.5%); pathologic curative resection (R0) was achieved in 14 patients (32.5%) among total 43 patients, and 82.3% (14/17) among the 17 resected patients. With 43-month follow-up, the median overall was 16.6 months with a median progression-free survival of 10.0 months. Median overall survival was 23.1 months in patients who underwent surgery and 13.2 months in patients who could not complete the surgery (P = .017). CONCLUSION: A subset of patients with borderline or unresectable pancreatic cancer could be performed curative tumor resection after neoadjuvant chemotherapy. Some patients might be benefit on survival from neoadjuvant chemotherapy after surgical resection.

Comparison between CT colonography and double-contrast barium enema for colonic evaluation in patients with renal insufficiency.

OBJECTIVE: To compare the CT colonography (CTC) and double-contrast barium enema (DCBE) for colonic evaluation in patients with renal insufficiency. MATERIALS AND METHODS: Two sequential groups of consecutive patients with renal insufficiency who had a similar risk for colorectal cancer, were examined by DCBE (n = 182; mean ± SD in age, 51 ± 6.4 years) and CTC (n = 176; 50 ± 6.7 years), respectively. CTC was performed after colon cleansing with 250-mL magnesium citrate (n = 87) or 4-L polyethylene glycol (n = 89) and fecal tagging. DCBE was performed after preparation with 250-mL magnesium citrate. Patients with colonic polyps/masses of ≥ 6 mm were subsequently recommended to undergo a colonoscopy. Diagnostic yield and positive predictive value (PPV) for colonic polyps/masses, examination quality, and examination-related serum electrolyte change were retrospectively compared between the two groups. RESULTS: Both the CTC and DCBE were positive for colonic polyps/masses in 28 (16%) of 176 and 11 (6%) of 182 patients, respectively (p = 0.004). Among patients with positive findings, 17 CTC and six DCBE patients subsequently underwent a colonoscopy and yielded a PPV of 88% (15 of 17 patients) and 50% (3 of 6 patients), respectively (p = 0.089). Thirteen patients with adenomatous lesions were detected in the CTC group (adenocarcinoma [n = 1], advanced adenoma [n = 6], and non-advanced adenoma [n = 6]), as compared with two patients (each with adenocarcinoma and advanced adenoma) in the DCBE group (p = 0.003). Six (3%) of 176 CTC and 16 (9%) of 182 DCBE examinations deemed to be inadequate (p = 0.046). Electrolyte changes were similar in the two groups. CONCLUSION: In patients with renal insufficiency, CTC has a higher diagnostic yield and a marginally higher PPV for detecting colorectal neoplasia, despite a similar diagnostic yield for adenocarcinoma, and a lower rate of inadequate examinations as compared with DCBE.

Anti-inflammatory effects of Artemisia princeps in antigen-stimulated T cells and regulatory T cells.

OBJECTIVES: The aim was to investigate the anti-inflammatory effects of Artemisia princeps extract on the activity of anti-CD3/CD28-stimulated CD4(+)CD25(-) T cells and antigen-expanded regulatory T cells. METHODS: CD4(+)CD25(-) T cells were activated with coated anti-CD3 and anti-CD28 and cultured in the presence or absence of various concentrations of A. princeps extract. The cultures were pulsed on Day 6 with [(3)H]thymidine and, after harvesting the cells, [(3)H]thymidine incorporation was measured. For analysis of interleukin-2 and interferon-gamma secreted from CD4(+)CD25(-) T cells, culture supernatants were collected on Days 2 and 6. For the analysis of interleukin-10 secreted from the CD4(+)CD25(-) T cells and expanded regulatory T cells, supernatants were collected after 2 and 7 days, respectively. Cytokine levels were determined using an enzyme-linked immunosorbent assay. Potential medicinal components of the A. princeps extract were determined using gas chromatography-mass spectrometry. KEY FINDINGS: A. princeps (30 microg/ml) effectively suppressed proliferation of CD4(+)CD25(-) T cells that were stimulated with anti-CD3/CD28 without causing cytotoxicity in spleen cells incubated under conditions lacking antigen stimulation. A. princeps inhibited production of the pro-inflammatory cytokines interleukin-2 and interferon-gamma in anti-CD3/CD28-stimulated CD4(+)CD25(-) T cells. Also, the extract slightly increased production of the anti-inflammatory cytokine interleukin-10 in these cells. In regulatory T cells expanded by anti-CD3/CD28, A. princeps increased production of interleukin-10 and Foxp3. CONCLUSIONS: The results suggest that A. princeps may be useful in the treatment of autoimmune diseases and organ transplantation rejection by inhibiting proliferation of inflammatory T cells, suppressing inflammatory processes in antigen-stimulated CD4(+)CD25(-) T cells and increasing activity of expanded regulatory T cells.

Anti-inflammatory action of Cudrania tricuspidata on spleen cell and T lymphocyte proliferation.

This study examined whether an extract of Cudrania tricuspidata shows anti-proliferative effects in anti-CD3/CD28-mediated spleen and CD4+CD25- T cells and decreases the production of the proinflammatory cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in anti-CD3/CD28-mediated CD4+CD25- T cells. The proliferation of anti-CD3/CD28-mediated spleen cells and CD4+CD25- T cells was effectively suppressed by C. tricuspidata. This extract, however, did not show cytotoxicity in spleen cells under conditions where the antigen was not stimulated using CCK-8 analysis. C. tricuspidata also decreased the production of the pro-inflammatory cytokines IL-2 and IFN-gamma by selective inhibition of this extract on proliferating cells in anti-CD3/CD28-mediated CD4+CD25- T cells. These results suggest that C. tricuspidata may be useful in the treatment of autoimmune diseases and organ transplantation through the inhibitory action of T cells in inflammation.