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Renal ischemia-reperfusion (I/R) injury is associated with delayed graft function and results in poor long-term graft survival. We previously showed that splenectomy (SPLN) protects the kidney from I/R injury and reduces serum TNF-α levels. Herein, we further investigated the effects of SPLN on inflammatory responses and tissue injury in renal I/R by examining the expression of major inflammatory cytokines and heat shock protein 70 (HSP70). Because it was shown previously that the anti-TNF-α agent infliximab (IFX) attenuated renal I/R injury, we also investigated whether IFX administration mimics the effects of SPLN.The left renal pedicles of adult male Wistar rats were clamped for 45 minutes and then reperfused for 24 hours; right nephrectomy and SPLN were performed immediately. A separate cohort was administered IFX 1 hour before surgery in lieu of SPLN.Serum creatinine and blood urea nitrogen levels were markedly elevated by I/R injury; these increases were significantly reversed by IFX. Furthermore, IFX inhibited the induction of inflammatory cytokines and HSP70 during renal I/R injury. Time-dependent profiles revealed that the expression of inflammatory cytokines was elevated immediately after I/R, whereas levels of HSP70, serum creatinine, and blood urea nitrogen began to rise 3 hours postreperfusion. Macrophages/monocytes were significantly increased in I/R-injured kidneys, but not in those administered IFX. The outcomes of SPLN mirrored those of IFX administration.Splenectomy and TNF-α inhibition both protect the kidney from I/R injury by reducing the accumulation of renal macrophages/monocytes and induction of major inflammatory cytokines.

Ischemic reperfusion (I/R) injury of the kidney is closely associated with delayed graft function, increased acute rejection, and late allograft dysfunction. Splenectomy reduced hepatic I/R injury by inhibiting leukocyte infiltration in the liver, release of TNF-α, cell apoptosis, and expression of caspase-3. Thus, we investigated the effects of splenectomy on renal I/R injury in the rat.Male Wistar rats were assigned to four groups: sham operation (sham group), sham operation+splenectomy (sham+SPLN group), right nephrectomy followed by clamping the left renal pedicle for 30min (I/R 30 group), and I/R 30+splenectomy (I/R 30+SPLN group). Renal function was determined by measuring the concentration of blood urea nitrogen (BUN) and serum creatinine (S-Cr). The serum level of tumor necrosis factor-α (TNF-α) was measured as the marker for inflammation. Left kidneys were obtained 24h after reperfusion. TUNEL assay was assessed for cell apoptosis. Spleens were obtained immediately (0-h group) and 3h after reperfusion (3-h group). The removed spleens were histologically evaluated.The BUN and S-Cr levels were significantly lower in the I/R 30+SPLN group than in the I/R 30 group (p0.05 for both). Apoptotic cells were significantly lower in the I/R 30+SPLN group than in the I/R 30 group. The serum level of TNF-α, which was increased after I/R, was significantly lower in the I/R 30+SPLN group than in the I/R 30 group (p0.05). Spleen weights were significantly lower in the 3-h group than in the 0-h group (p0.05).These results suggest that splenectomy reduces renal I/R injury, and this effect may occur by an anti-inflammatory pathway and inhibition of cell apoptosis.

Objective Encapsulating peritoneal sclerosis (EPS) is a serious complication of continuous ambulatory peritoneal dialysis. Previous studies have created peritoneal sclerosis rat models using daily intraperitoneal injection of chlorhexidine gluconate (CG), but this technique is cumbersome and thickening of the peritoneum makes it difficult to evaluate the injection site. We therefore aimed to make a rat model using a continuous-infusion pump. Methods Various concentrations of CG (5%, 8%, 10%, 12%, and 14%) in ethanol were dissolved in saline within the infusion pumps, each of which was placed in the lower abdominal cavity of a male Wister rat. After a peritoneal equilibration test was performed, the rats were sacrificed and the lower anterior parietal and visceral peritoneum was removed. Each excised peritoneum was analyzed by macroscopic and microscopic examinations, including immunohistochemistry for the expression of transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), and alpha-smooth muscle actin (αSMA). The results were compared with those of control rats injected with ethanol dissolved in saline within the infusion pump and with no-pump rats. Results Two of the 5 rats in the 12% CG group and 3 of the 5 rats in the 14% CG group died of ileus within 14 days. All the rats in the 5%, 8%, and 10% CG groups survived to 28 days. Macroscopic examination in the 10% CG group showed bowel dilatation, bowel adhesion, and bloody ascites, similar to those seen in human EPS patients. All rats in each CG group showed the same extent of thickening of the submesothelial compact zone, proliferation of collagen fibers, and presence of numerous cells and neovascularization. Within same CG groups, an equal degree of thickening was observed at all sites of the peritoneum. TGF-β1, VEGF, and αSMA were highly expressed in the peritoneum of the 10% CG group. Conclusion We developed a novel method of creating a peritoneal sclerosis rat model using a continuous-infusion pump. Our technique is simple and highly reproducible, and will be useful in the study of peritoneal sclerosis mechanisms.

Background/Aims: There is a clear association between one allele of the interleukin-1 receptor-antagonist gene (IL-1RN) and inflammatory diseases in which IL-1 is implicated. We evaluated patient survival and technique survival of peritoneal dialysis (PD) patients, while analyzing independent risk factors, in a PD program. We also tested the association between IL-1RN polymorphism, patient survival and technique survival. Methods: We retrospectively evaluated 129 Japanese CAPD patients undergoing initial treatment in eight centers in Japan. Using PCR, IL-1RN genotype and allele frequencies were determined, and clinical and biochemical variables were recorded at the start of PD. The relation of patient survival or technique survival with IL-1RN polymorphism and those variables was analyzed with a multivariate Cox’s proportional-hazard model. Results: The frequencies of IL-1RN*1/IL-1RN*1 and IL-1RN*1/IL-1RN*2 genotypes were 84.5 and 15.5%, respectively. Median patient survival was 37.0 months, and overall patient survival was 92.8 and 87.9% at 2 and 5 years, respectively. Age, cardiovascular disease and serum albumin were found to be independent predictors of patient survival. Median technique survival was 32 months. PD failure occurred in 37 patients, with technique survival rates of 92.0 and 72.7% at 2 and 5 years, respectively. Serum albumin, peritonitis and the presence of the IL-1RN*2 genotype were found to be independent predictors of technique survival. Conclusion: Serum albumin was the strongest predictive factor for mortality and technique failure in PD. Technique failure was also affected by IL-1RN polymorphism in this patient population.

本研究では腎移植と透析療法間における骨代謝に対する影響の違いを調べる目的にて, radiographic absorptiometryの一方法であるdigital image processing method (DIP法) を用いて測定した骨塩量および骨代謝パラメーターを腎移植患者と透析患者間において比較検討した.対象は山口大学泌尿器科にて経過観察中で移植後6か月以上経過し移植腎機能良好な腎移植患者27名 (腎移植群) と, 岩国中央病院にて血液透析施行中の透析患者26名 (透析群) であり, 年齢, 性別, 治療期間には両群間において有意差を認めなかった. 各群における骨塩量 (ΣGS/D, MCI) と各骨代謝パラメーターとの相関をみると, 腎移植群においては有意な相関関係は認めなかったが, 透析群においてはΣGS/Dと透析期間, Al-P, またMCIと透析期間, C-PTH, Al-Pとの間にそれぞれ有意な相関関係を認めた.両群間での骨塩量の比較では, ΣGS/Dは腎移植群では2.61±0.33mmAl, 透析群では2.30±0.52mmAlであり, 腎移植群において有意に高値であった (p

The prophylactic effect of 5'-deoxy-5-fluorouridine (5'-DFUR) has not been fully studied in superficial bladder cancer. The aims of this work were to investigate the prophylactic effects of 5'-DFUR in terms of tumor recurrence after transurethral resection of bladder tumor (TURBT) and to study whether thymidine phosphorylase (TdRPase) immunostaining predicts tumor recurrence.A total of 112 patients with pTa or pT1 bladder cancer were eligible for the analysis and were allocated to either an adjuvant group (TURBT+5'-DFUR; n = 47; initial 23 months) or a control group (TURBT alone; n = 65, final 23 months). Tumor specimens were studied immunohistochemically using anti-TdRPase antibody.Tumor recurrence was observed in 54 of the patients (48%) after a median follow-up period of 26.8 months. No significant clinico-pathologic bias was observed between the two groups. Although patients in the adjuvant group had a significantly higher recurrence-free survival rate than those in the control group when considering 78 patients with pathological T1 tumors (p = 0.0272) and 65 patients who did not recur within 12 months (p = 0.001), overall there was no significant difference between the two groups. Multivariate analysis revealed that 5'-DFUR administration was the strongest predictor of late tumor recurrence, which was defined as development of recurrence 12 months after TURBT (hazard ratio 5.744; 95% CI 1.495-30.45; p = 0.0094). Immunostaining did not predict prophylactic effects of 5'-DFUR. Mild, reversible toxicity was found in 9/58 (15.5%) of the cases evaluated.Oral administration of 5'-DFUR after TURBT did not prevent tumor recurrence in the overall cohort, although this novel drug may have a prophylactic effect in patients belonging to several subgroups.

At the haemodialysis centres of nine hospitals in Japan, microbial contamination of treated water (reverse osmosis method), acid and bicarbonate concentrates, and dialysate was investigated. Among these fluids used in haemodialysis, the dialysate was most frequently contaminated and had the highest concentration of bacteria. Of 40 dialysate samples analysed, 42.5% showed a bacterial count of more than 2000cfu/mL, which was above the Association for the Advancement of Medical Instrumentation (AAMI) standard. However, among the 40 samples from 20 dialysis machines, all six dialysate samples from three dialysis machines that used an ultrafiltration membrane in the circuit before the entrance of the dialysate into the dialyser, showed a bacterial count of ≤10cfu/mL. In addition, when an ultrafiltration membrane was used in the circuit before the entrance of the dialysate into the dialyser for four dialysis machines showing dialysate samples contaminated with 10 4 –10 5 cfu/mL the bacterial count in dialysate samples from these machines became zero. Because dialysis machines are susceptible to microbial contamination, it is necessary to take measures such as placing an ultrafiltration membrane into the circuit before the entrance of dialysate into the dialyser.

TACROLIMUS, a potent immunosuppressive drug, has been associated with improved kidney graft survival, although there is an increased incidence of posttransplant diabetes mellitus (PTDM). PTDM is a serious complication of immunosuppressive drugs that increases the risk of both graft loss and patient death, and predisposes patients to diabetic complications, including retinopathy and neuropathy. We reported here two cases of PTDM under a tacrolimus-based immunosuppression.

Recurrence of immunoglobulin (Ig) A nephropathy following kidney transplantation has been described as occurring in 40% to 60% of cases. Although this type of recurrence was considered a benign condition for a long time, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We present 2 cases of recurrent IgA nephropathy following kidney transplantation. In case 1, renal function remained stable with a creatinine level of 1.2 mg/dL at 5 months after diagnosis and 61 months after transplantation. In case 2, the patient lost his graft and returned to regular hemodialysis at 36 months after diagnosis and 125 months after kidney transplantation.