Search

Wiskott–Aldrich syndrome (WAS) is an X-chromosome recessive immunodeficiency disease characterized by the triad of thrombocytopenia, eczema, and susceptibility to infection owing to WAS protein gene abnormalities. Kidney transplantation is rarely offered to WAS patients with end-stage renal disease because of concerns that thrombocytopenia and immune disorders may affect the clinical outcome. Here, we report the case of a 20-year-old kidney transplant patient who developed end-stage renal disease owing to immunoglobulin (Ig)A nephropathy caused by WAS. Despite recurrent IgA nephropathy and T-cell-mediated rejection 7 months after transplantation, two rounds of steroid pulse therapy attenuated his renal function and urinary abnormality. His serum creatinine level was maintained at approximately 1.5 mg/dL 1 year after transplantation. No other WAS-related complications were observed throughout the clinical course. Although WAS can cause poor prognosis in kidney transplant patients, careful follow-up may allow kidney transplantation to be performed.

OBJECTIVES To compare the urinary pH, recurrence-free survival (RFS), and safety of adjuvant intravesical therapy in patients with non-muscle-invasive bladder cancer (NMIBC) receiving mitomycin C (MMC) therapy and MMC + cytosine arabinoside (Ara-C) therapy. PATIENTS AND METHODS A total of 165 patients with NMIBC from six hospitals were randomly allocated to two groups: weekly instillation of MMC + Ara-C (30 mg/30 mL + 200 mg/10 mL) for 6 weeks and the same instillation schedule of MMC (30 mg/40 mL). The primary outcome was RFS, and secondary outcomes were urinary pH and toxicity in the two groups. RESULTS A total of 81 and 87 patients were randomised into the MMC and MMC + Ara-C groups, respectively. Overall, the RFS in the MMC + Ara-C group was significantly longer (P = 0.018) than that in the MMC group. A similar significant difference was detected in patients with intermediate-risk NMIBC, but not in those with high-risk NMIBC. The mean (SD) urinary pH was significantly higher in the MMC + Ara-C group than in the MMC group, at 6.56 (0.61) vs 5.78 (0.64) (P 7.0 in the MMC and MMC + Ara-C groups was 6.3% and 26.7%, respectively (P

BACKGROUND Identifying characteristics of patients at high risk of poor adherence before transplantation would be advantageous. However, the optimal approach for characterizing such patients remains unknown.We aimed to evaluate the association between factors for hemodialysis nonadherence and post-transplant renal prognosis. We hypothesized that these factors would influence post-transplantation adherence and worsen renal prognosis. MATERIAL AND METHODS We reviewed patients on hemodialysis who underwent kidney transplantation at our hospital between 2000 and 2017 to identify risk factors associated with poor prognosis. The patients' background and pre-transplantation data, known hemodialysis nonadherence factors, serum phosphate and potassium levels, and interdialytic weight gains were evaluated. The primary endpoint was renal death. We also evaluated the fluctuation of calcineurin inhibitor concentration and weight gain after transplantation. RESULTS Seventy-seven patients were eligible, and the mean observational period was 83.2 months (standard deviation, 50.5). Thirteen patients reached the endpoint.Cox proportional hazards regression analysis showed that pre-transplantation serum phosphate level was a risk factor for renal death (p, Annals of transplantation, 24, pp.260-267; 2019

Background High-dose methotrexate (HD-MTX) therapy has been used to treat a wide range of oncological malignancies. While the therapy can be tolerated with hydration, urine pH control, and leucovorin rescue therapy, HD-MTX is cytotoxic and can cause renal failure. There have been several case reports of HD-MTX toxicity in patients with solid tumors; however, few case series of hematological malignancies have been published. Patients with hematological malignancies tend to be administered many concomitant drugs, which can affect the elimination of MTX and result in acute kidney injury. Case presentation Here, we present three cases of HD-MTX-induced acute kidney injury in patients with hematological malignancies. Several blood purification methods were used to attempt to eliminate MTX. Conclusions Rapid elimination of MTX is needed for patients with higher serum MTX concentrations to avoid additional cytotoxic effects, especially in patients who have experienced many complications. Although the most effective method for MTX elimination remains unknown, the results of our retrospective survey suggest that combined modalities, such as hemodialysis and plasma exchange, may be suitable for treatment of patients with hematological malignancies.

Intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, has been reported to be a diagnostic marker of intestinal ischemia and a prognostic marker in critically ill patients. However, the kinetics of I-FABP in renal failure patients is unknown. We sought to identify I-FABP levels in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on hemodialysis (HD) and to identify the manner in which the I-FABP levels change.Adult patients who were admitted for elective cardiac surgery with either normal renal function (NRF), CKD, or ESKD on HD were enrolled. Serum I-FABP levels in NRF and CKD patients and in ESKD patients before and after HD were determined.A total of 124 patients were evaluated: 47 NRF, 53 CKD, and 24 ESKD. The I-FABP levels of the CKD patients and pre-HD ESKD patients were significantly higher than those of the NRF patients (P = 0.018 and P 0.001, respectively). I-FABP levels were significantly negatively correlated with the estimated glomerular filtration rate in NRF and CKD patients (Spearman's ρ = -0.313, P = 0.002). In addition, I-FABP levels in ESKD patients were significantly lower after HD than those before HD (P 0.001).I-FABP levels in CKD and pre-HD ESKD patients were significantly higher than those in NRF patients. In addition, I-FABP was significantly eliminated by HD in patients with ESKD. Clinicians and researchers should consider this aspect of I-FABP when using it as a diagnostic and prognostic marker in patients with renal insufficiency.

Background The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. Conclusions In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

A 38-year-old man underwent peritoneal dialysis (PD) in May 2011 due to chronic renal failure with chronic glomerulonephritis. In early February 2012, he underwent laparoscopy to salvage and correct a malpositioned PD catheter. The laparoscopic intra-abdominal findings revealed turbid ascites and multiple fibrin lumps, despite the patient's lack of history of peritonitis. Based on these findings, in addition to the presence of continuous inflammation and ascites, a diagnosis of pre-encapsulating peritoneal sclerosis was suspected, and the treatment was switched from PD to hemodialysis. The administration of prednisolone at a dose of 20 mg/day and peritoneal lavage resulted in a decrease in the ascites and fibrin lumps., Internal Medicine, 53(7), pp.767-770; 2014

Background: High serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient's prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage. Methods: This cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis. Results: Of the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43-4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50-10.4; P = 0.005)had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07-2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23-1.59; P < 0.001). Conclusions: Although the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient's calcium level., BMC Nephrology, 20(1), art.no.210; 2019

Metastatic pulmonary calcification, defined as calcium deposition in the intact lung, is commonly seen in patients with chronic renal failure, and it is known to be a benign clinical condition when detected by chance in an asymptomatic patient. Here we report the case of a 33-year-old woman who developed rapid and aggressive metastatic pulmonary calcification shortly after a living donor kidney transplantation, which induced acute antibody-mediated rejection. The patient's metastatic pulmonary calcification was successfully improved by extensive treatment for graft rejection, the correction of her accompanying primary hyperparathyroidism, and medical treatment with a bisphosphonate and sodium thiosulfate. Aggressive pulmonary calcification is reported as a rare complication seen in patients who have undergone a failed renal transplantation. A failed renal graft and accompanying secondary hyperparathyroidism seem to accelerate metastatic calcification. Most of the patients who develop aggressive pulmonary calcification suffer from the rapid progression of dyspnea and occasionally fever, and they die of respiratory failure. Pulmonary calcification should be considered in a patient developing dyspnea and unexplained pulmonary infiltrate, especially in the context of renal graft rejection; otherwise the prognosis of the patient will be very poor.

We report the clinical and pathological findings of a case of de novo minimal change disease (MCD) after ABO-incompatible living kidney transplantation. A 62-yr-old man with end-stage renal disease associated with type I diabetes received ABO-incompatible kidney transplantation from his 58-yr-old wife. Although allograft function was excellent immediately after surgery, massive proteinuria (35 g/d) appeared on post-transplantation day 5. After the allograft biopsy taken on post-transplantation day 6, he was treated with 12 cycles of plasma exchange, but the nephrotic-range proteinuria showed no remission. The biopsy specimen showed no significant pathological findings on light microscopy, but electron microscopy showed diffuse effacement of podocyte foot processes. Based on the diagnosis of de novo MCD, the patient received intravenous methylprednisolone pulse therapy, followed by high-dose steroid maintenance therapy. The steroid therapy induced complete remission of nephrotic syndrome and stable allograft function immediately, which was also maintained at one yr after the transplantation.

Summary Patients on hemodialysis are at higher risk of renal cell carcinoma probably because of inflammatory and immune system disorders. The aim of this study was to clarify the pathologic roles of 2 phenotypes of mast cells, mast cell tryptase and mast cell chymase, and their correlation with stem cell factor and protease-activated receptor 2 in patients with renal cell carcinoma on hemodialysis. The densities of mast cell tryptase and mast cell chymase and expressions of stem cell factor and protease-activated receptor 2 were examined in 35 patients with hemodialysis-renal cell carcinoma and 39 with non–hemodialysis-renal cell carcinoma who were diagnosed and treated in our hospital. Protein expression was examined by immunohistochemistry. The proliferation index represented the number of Ki-67–positive cells. There were no significant differences in clinicopathologic features between the 2 groups. Mast cell tryptase densities in intratumoral (8.3 per high-power field) and peritumoral areas (8.7 per high-power field) were higher in hemodialysis-renal cell carcinoma than non–hemodialysis-renal cell carcinoma (2.7 and 5.3 per high-power field). No such significant correlations were detected in mast cell chymase. In hemodialysis-renal cell carcinoma, intratumoral mast cell tryptase density correlated with the proliferation index ( P = .039 and P = .008, respectively) and also with stem cell factor and protease-activated receptor 2 expression. Our results emphasize the important roles of mast cell tryptase in cancer cell proliferation and recurrence in hemodialysis-renal cell carcinoma. Stem cell factor and protease-activated receptor 2 seem to up-regulate mast cell tryptase functions in these patients. The results suggest collaborative effects of stem cell factor, mast cell tryptase, and protease-activated receptor 2 on the malignant potential of hemodialysis-renal cell carcinoma.

症例は61歳，女性．慢性糸球体腎炎を原疾患とする慢性腎不全にて1996年腹膜透析（peritoneal dialysis：PD）導入となった．1998年12月と1999年1月に細菌性腹膜炎の既往があった．腹膜の石灰化がありPD歴10年と長期に腹膜透析を行っていたことから，2006年8月に血液透析へ完全移行し，その1か月後にPDカテーテルを抜去された．カテーテル抜去後より次第に腹水の増加と腹部膨満感の増悪，CRPの上昇，腹膜石灰化の進行を認めた．2007年4月にはイレウス状態となったことから被嚢性腹膜硬化症（encapsulating peritoneal sclerosis：EPS）の発症が疑われ，精査加療目的で当科入院となった．身体所見では著明なるいそうと微熱があり，検査所見では持続性のCRP上昇を，腹部CTでは腹膜の石灰化を認めた．EPSの加療目的でステロイド療法を開始したが，CRPの高値が持続したことから腹腔洗浄目的で5月30日にPDカテーテル留置術（再挿入）を施行した．腹水の除去に伴い，CRPや腹水中のIL-6の値は改善を認めた．難治性EPSに対し，ステロイド内服とカテーテル再挿入による腹水除去が奏功した1例を経験した．

A simple capillary electrophoretic method was developed for simultaneous determination of mycophenolic acid (MPA) and its metabolites, acyl glucuronide (AcMPAG) and phenol glucuronide (MPAG), in human serum. The method utilized only running buffer in the separation, prior acidification of serum, and extraction with ethyl acetate. Separation was performed by capillary zone electrophoresis using 20 mM sodium acetate--acetic acid (pH 4.9) as running buffer, applied voltage of 15 kV, and UV detection at 217 nm. Each electrophoretic run was completed within 14 min. The optimized method demonstrated good performance concerning specificity, linearity (r > 0.998), sensitivity (limit of detection: for MPA, 0.10 μg/ml; for AcMPAG, 0.10 μg/ml; MPAG, 0.42 μg/ml), accuracy (87--108%) and precision (, Journal of Pharmaceutical and Biomedical Analysis, 47(1), pp.201-206; 2008

OBJECTIVES Lymphangiogenesis is associated with tumor progression in various cancers and is regulated by vascular endothelial growth factors (VEGFs). However, little is known about the pathologic roles of lymphangiogenesis in renal cell carcinoma (RCC). We investigated the relationships between various clinicopathologic features and lymphangiogenesis, angiogenesis, and expression of VEGFs in RCC. METHODS The TNM stage and grade of 107 conventional RCC were reviewed. Lymph vessel density (LVD) and microvessel density (MVD) were measured by quantitative immunohistochemistry using anti-D2-40 antibody and anti-CD34 antibody, respectively. Expression levels of VEGF-A, B, C, and D were examined by immunostaining. RESULTS D2-40-positive lymphatic vessels were detected mainly in the peritumoral area. However, no significant difference was found between LVD in peritumoral areas of the RCC tissues and the normal kidney (P = 0.238). Intratumoral D2-40-positive lymphatic vessels were detected in only six specimens, and neither intratumoral nor peritumoral LVD correlated with the clinicopathologic features. VEGF-A expression correlated with MVD (r = 0.50, P

Matrix metalloproteinase (MMP)-10 is associated with malignant aggressiveness in various cancers, but its importance has not been investigated in conventional renal cell carcinoma (CRCC). The purpose of this study was to determine the clinical significance and malignant potential of MMP-10 in human CRCC tissues.Specimens were obtained from 103 CRCC patients who underwent radical surgery and were examined by immunohistochemistry for MMP-10 expression. The proportions of Ki-67-stained cells (proliferation index: PI) and densities of CD34-positive vessels (microvessel density: MVD) were measured by a computer-aided image analysis system. The relationships between MMP-10 expression and clinicopathologic features and various parameters including tumour size, PI, MVD, and survival were investigated by univariate and multivariate analyses.MMP-10 expression was mainly detected in cancer cell cytoplasm, and 45 (43.7%) CRCCs were considered MMP-10-positive. MMP-10 expression correlated with grade (p=0.006) and pT stage (p0.001), and it was a significant and independent factor for high pT stage in multivariate analysis model. MMP-10 expression was associated with MVD (p = 0.022) but not tumour size or PI. MMP-10 expression in CRCC was a significant predictor of poor outcome by log-rank test (p = 0.013) but not by multivariate analysis.MMP-10 seems to play an important role in renal cancer cell invasion and is a potentially useful therapeutic target to prevent CRCC tumour progression.

We report two cases of primary non-functioning kidney from the same non-heart beating donor (NHBD). A 42-yr-old man received a renal transplant from a NHBD. The donor was a 38-yr-old male who died of neck spinal injury. The warm ischemic time was 61 min. One h after reperfusion, the graft became edematous and congested in the presence of normal and adequate vascular anastomosis and lack of renal vein thrombosis. The one-h biopsy specimen showed acute tubular necrosis and severe congestion with occasional platelet aggregates in glomerular capillaries. The graft was resected on post-transplantation day 6. Graftectomy specimen revealed renal cortical necrosis. The contralateral kidney of the same donor was transplanted into a 54-yr-old male. The one-h biopsy specimen showed tubular degeneration and neutrophil infiltration in peritubular capillaries, but no glomerular congestion or thrombus. The recipient died on post-transplantation day 4. Although the cause of death was unknown, necropsy of the renal graft showed renal cortical necrosis, similar to case 1. Ischemia/ reperfusion injury was considered the cause of non-functioning kidney in both cases, because of long warm ischemic time. The biopsy specimens at zero-h from both grafts showed focal tubular degeneration only without distinct necrosis, indicating it is difficult to predict viability based on the pathological findings at zero-h or one-h biopsies. There is a need for further understanding of clinical and histological patterns in order to define the criteria of viability of kidney transplant.

Background: Chronic allograft nephropathy (CAN), associated with late-allograft dysfunction is caused by alloantigen-dependent and -independent mechanisms, and eventually leads to interstitial fibrosis (ci). Activation of complement cascade is considered to be a poor prognostic marker of graft survival. This study was designed to examine the relationship between the expression of C4d and heat-shock protein 47 (HSP47, a collagen-specific chaperone) in the development of interstitial fibroproliferative lesions in CAN. Methods: Sixty-three renal allograft biopsy specimens, obtained from 48 patients, were examined for the expression of C4d, HSP47, CD68 and α-smooth muscle actin (α-SMA) by immunohistochemistry. Double-staining was performed to determine the colocalization of C4d and HSP47. The relationship of between the expression of C4d, HSP47, CD68 and α-SMA and the clinical and histopathological parameters were statistically analysed. Results: No expression of C4d was noted in the tubulointerstitium including peritubular capillary (PTC) of the control kidney. C4d was expressed in PTC in one-third of allograft renal tissues with morphological evidences of CAN. The interstitial cells around the fibrotic areas of the PTC of CAN were positive for the expression of HSP47. The deposition of C4d in PTC correlated with interstitial expression of HSP47 around the PTC. Most HSP47 expressing cells were phenotypically altered myofibroblasts, as determined by the dual staining of α-SMA. Conclusions: The increased expression of HSP47 positively correlated with the expression of C4d in PTC, and might contribute to the progression of interstitial ci in CAN.

Accelerated atherosclerosis is a major complication in patients on haemodialysis (HD). Macrophage colony-stimulating factor (MCSF) is a representative regulator of activation of monocytes and macrophages, and plays important roles in the development of atherosclerosis in HD patients. However, the long-term predictive value of the serum MCSF level for the development of aortic calcification under HD conditions has not been reported.Serum MCSF level was measured in 40 HD patients. The aortic calcification index (ACI) was also calculated on computed tomography once each year for 6 years. Predictive value was examined by logistic regression analysis.At baseline, there was a significant correlation between serum MCSF and ACI (r = 0.43, P0.01). A significant increase in ACI was first noted at 4 years post-baseline and the increase was maintained thereafter in the high MCSF group. No such changes were noted in the low MCSF group. Univariate analysis identified high levels of calcium x phosphorus product, triglyceride, C-reactive protein (CRP), MCSF and presence of diabetes mellitus as significant predictors for increased ACI at 6 years. However, among these five factors, high levels of CRP and MCSF were the only independent and significant predictors (odds ratio = 24.0, P = 0.03 and odds ratio = 22.8, P = 0.02, respectively).Our results demonstrated that MCSF is associated with the process of atherosclerosis in HD patients. Furthermore, the serum MCSF level is an independent long-term predictor of increased ACI. These results provide useful information for preventive strategies against atherosclerotic disease under HD conditions.

We report the clinicopathological courses of two recipients of kidneys retrieved from the same non-heart beating donor (NHBD). A 52-year-old man received a renal transplant from an NHBD. The donor was a 66-year-old woman who died of subarachnoid haemorrhage. The recipient was immunosuppressed by basiliximab, tacrolimus (TAC), mycophenolate mofetil (MMF), methyl prednisolone (MP), and antilymphocyte globulin (ALG). On post-operative day (POD) 21, haemodialysis therapy was withdrawn, however, their serum creatinine (s-Cr) level failed to improve. Four transplant biopsies were performed (1 h and POD 46, 74, and 114). The biopsy showed tubular degeneration but no evidence of TAC nephrotoxicity. The last biopsy after discontinuation of TAC demonstrated acute rejection of borderline grade. The s-Cr level at discharge was 5.0 mg/dL. The contra-lateral kidney was transplanted into a 31-year-old female and showed early functioning, with an s-Cr level at discharge of 1.8 mg/dL. Biopsy examination on POD 38 showed a recovery of tubular degeneration. The causes of delayed graft function and persistently high level of s-Cr in Case 1 remain unclear. Various factors, including donor-related factors, recipient-related factors, TAC nephrotoxicity, acute rejection, and urinary tract infection could all be associated with this condition.

Aim: Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM) as well as those undergoing hemodialysis (HD). The purpose of this study is to investigate the frequency and severity of ED in HD patients with DM and those without DM. In addition, we examined the relationship between erectile function and several risk factors, including presence of DM and hemoglobin A1c levels in HD patients. Methods: This study involved 180 patients on HD, including 66 HD patients with DM (DM-HD) and 114 patients without DM (non-DM-HD). We evaluated erectile function using an abridged five-item version of the international index of erectile function (IIEF-5). Logistic regression analysis was used to investigate the relationship between presence of ED and several risk factors. Results: The total score of IIEF-5 in DM-HD patients (9.5 ± 4.2) was significantly lower than in non-DM-HD patients (13.5 ± 5.7). The prevalence of severe ED was 42.4% and 18.4% in DM-HD patients and non-DM-HD patients, respectively. Age, cardiovascular disease history, and DM were identified as independent risk factors for the presence of ED. Furthermore, age and elevated hemoglobin A1c levels were identified as independent risk factors for the presence of severe ED. Conclusion: DM-HD patients are more likely to have ED, and particularly severe forms of ED, than non-DM-HD patients. DM and elevated hemoglobin A1c levels were associated with the presence of ED or severe ED, respectively. Aging was identified as an independent factor in both ED and severe ED.

We report severe arteriolar lesion mimicking drug-induced arteriolopathy in a renal allograft of a 37-year-old Japanese male, who has been treated by conventional immunosuppressive therapy but not administered cyclosporin or tacrolimus for 16 years after renal transplantation. Renal biopsy also showed glomerular changes including transplant glomerulopathy and features of chronic vascular rejection. The cause of the arteriolar lesion remains uncertain. Although its pathogenesis may be multi-factorial, long-term usage of conventional immunosuppressive agents and/or vascular rejection may contribute to the occurrence of the arteriolar lesion. We propose that biopsy study is needed for further understanding of histopathological behaviours of renal grafts in long-term survivors.

Objective To assess the relationship between serum ferritin levels (a useful marker for diagnosing and staging renal cell carcinoma, RCC) and tumour status in RCC of 7 cm diameter. Patients and methods Serum ferritin levels were measured using an enzyme immunoassay in 101 patients before treatment for RCC. The largest diameter of the primary tumour was measured in the pathological specimens. The correlation between serum ferritin levels and histopathological status was assessed retrospectively in all patients, and separately in the 67 patients with tumours of 7 cm diameter. Results For the whole group, lymph node metastasis, distant metastasis, extracapsular invasion, vascular invasion and nuclear grade were significantly different (P

Plasma exchange is used frequently in renal diseases for the removal of the humoral components of immune responses. Various pathological circulating factors are recognized in primary and secondary renal diseases. Recent advances in medical technology have allowed a wider clinical application of plasmapheresis in the clinical management of a variety of conditions. However, the clinical efficacy of plasmapheresis in renal diseases is still controversial. In this article, we review the therapeutic use of apheresis in different renal diseases.

近年, 透析患者の増加に伴い, 動脈硬化性疾患の合併は大きな問題となっている. 腹部大動脈瘤 (abdominal aortic aneurysm, AAA) や閉塞性動脈硬化症 (arteriosclerosis obliterans, ASO) は, その治療として外科手術を要することがあり, 透析患者の生命予後, quality of lifeの観点からも重要な疾患である. 今回我々は, 当院における透析患者のAAA4例およびASO3例の血行再建術症例の臨床的検討を行った.AAAの症例は年齢45-61歳で, 全例高血圧を伴い, 透析導入後6か月-6年であった. 2症例が腹痛ないし背部痛を訴えたが, 2症例は腹部腫瘤触知が発見の契機であった. 4例ともinfrarenal typeで, 3例にY graft, 1例にstraight graft置換を施行し, 全例とも予後は良好である.3例のASOは年齢51-67歳で, 2例で高血圧を伴い, 発症は透析導入後5年4か月-19年3か月とAAAに比し長期間の症例が多かった. いずれの症例も, 下肢痛・間歇性跛行・足趾壊死などの症状, 所見を認めた. 2例は左側のiliac～popliteal arteryの閉塞で, 自己大伏在静脈によるfemoro-popliteal bypass術を施行, 他の1例は右側のcommon～external iliac arteryの閉塞で, femoro-femoral cross over bypass術を2回施行した. 術後1例は予後良好であるが, 2例はASO以外の死因で死亡した.近年, 手術手技の向上および周術期の透析管理の進歩により, 透析患者に対し安全に手術が施行し得るようになってきたが, ASOの症例は, 必ずしも予後が良好でない場合もあり, 治療法選択, 手術時期に対するさらなる検討が必要と思われた.

Objective: A planned primary analysis of a Phase II study of S-1 demonstrated that the drug was active and tolerable in Japanese patients with cytokine-refractory metastatic renal cell carcinoma. Furthermore, pharmacogenomic analysis suggested that low expression of thymidylate synthase mRNA may have been associated with clinical outcome in terms of overall response rate and progression-free survival. Here, we report the results of the final analysis assessing the efficacy and safety of S-1 including overall survival. Methods: Patients with renal cell carcinoma were eligible if they had had at least one regimen of cytokine for metastatic disease. S-1 was orally administered on Days 1‐28 of a 42-day cycle until disease progression. The primary endpoint was the overall response rate, and the secondary endpoint included progression-free survival, overall survival and safety. Results: A total of 45 patients were treated with S-1 and were fully assessable for efficacy and safety. At the final analysis, a response was seen in 11 patients (overall response rate, 24.4%; 95% confidence interval: 12.9‐39.5%), including two patients who achieved a complete response. The final median progression-free and overall survival were 9.2 and 42.8 months, respectively. The safety profile of S-1 was favorable. It was suggested that there was no relation between overall survival and the expression level of thymidylate synthase. Conclusion: This final analysis confirms that S-1 treatment is effective and safe in patients with cytokine-refractory renal cell carcinoma.

Background: Although the percentage of patients with renal cell carcinoma (RCC) extending into venous systems is unexpectedly high, the prognostic impact and independency of venous tumor thrombus-related factors on overall survival (OS) remain controversial. Furthermore, the prognostic impact of various clinicopathologic factors including tumor thrombus-related factors on OS may change with elapsed years after the intervention and also with follow-up duration of participants. The aim of the study is to explore independent and universal predictive preoperative and intraoperative clinicopathologic factors on OS in patients with RCC extending into venous systems using subgroup analysis in terms of restricted follow-up duration and yearly-based survivors.Methods: Between 1980 and 2009, 292 patients diagnosed with RCC with venous tumor thrombus were retrospectively registered for this study. The prognostic impacts of various clinicopathologic and surgical treatment factors including levels of venous thrombus, venous wall invasion status and likelihood of aggressive cytoreductive operation, were investigated using Kaplan-Meier method and following multivariate Cox proportional hazards model for all patients and those still alive at 1, 2, and 3 years of follow-up. To investigate the impact of follow-up duration on the statistical analyses, multivariate logistic regression analyses were used to explore prognostic factors using restricted data until 1, 2, and 3 years of follow-up.Results: The median follow-up duration was 40.4 months. The 5-year OS was 47.6%. Several independent predictive factors were identified in each subgroup analysis in terms of yearly-based survival and restricted follow-up duration. The presence of tumor thrombus invading to venous wall was independently related to OS in the full-range follow-up data and in survivors at 2 and 3 years of follow-up. Using restricted follow-up data until 1, 2, and 3 years of follow-up, many independent predictive factors changed with follow-up duration, but surgical category could be universal and independent predictive factors.Conclusion: The most universal factors affecting improvement both in short-term and long-term survivals could be cytoreductive surgery and absence of venous wall invasion. It may mean that feasible aggressive cytoreductive operation following more reliable preoperative imaging for predicting venous wall invasion status would improve OS for patients with RCC extending into venous systems., BMC Cancer, 13(1), 447; 2013

死体腎移植後にmanidipine hydrochloride (manidipine) にて乳び腹水をきたしたCAPD患者の1例を報告する.症例は36歳, 男性. 死体腎移植レシピエントで術後1日目より高血圧のためmanidipine 20mg分2の投与を開始した. 約96時間後にCAPD排液の混濁, 微熱, 軽度の腹痛がみられ, 身体所見では左下腹部 (移植腎部付近) 圧痛があり, 腹膜炎が強く疑われた. CAPD排液の検査では性状は黄色混濁, 無臭. 沈渣は細胞数正常. 培養では細菌および真菌とも陰性. 生化学分析で脂質成分の増加 (特に, トリグリセライド), などが見られた. 以上より乳び腹水と診断した. 原因はmanidipineによる強力な末梢血管拡張作用によるリンパ管の拡張が考えられ, manidipineの投与を中止したところ速やかに消失した. また, 混濁時に除水量の著しい増加も見られ, manidipineによる限外濾過能の改善によるものと思われた.CAPD患者において乳び腹水による身体的影響はほとんどないが, 本例のように腎移植患者では免疫能低下があり, 乳び腹水にもしも腹膜炎が合併した時, 診断が遅れ重症になることも考えられるため, なるべくmanidipineの投与を中止したほうがよいと思われる.

Tc-99m MAG3 renal scintigraphy was performed before and after transcatheter steel coil embolization in a 55-year-old man with an aneurysmal type left renal arteriovenous fistula (AVF). Before embolization, dynamic renal scintigraphy revealed characteristic accumulation compatible with the hemodynamics of an aneurysmal type AVF in the vascular phase. Embolization changed the split renal function in the treated side, and shunt flow through the fistula disappeared. Dynamic renal scintigraphy might be very useful in evaluating patients with hemodynamic renal AVF scheduled for transcatheter embolization.

Objective To determine the clinical usefulness of Bosniak's classification of cystic renal masses, the differentiation of which remains difficult despite significant advances in diagnostic imaging. Patients and methods The computed tomography (CT) findings of all histopathologically examined cystic renal masses diagnosed at our institution were analysed retrospectively; 35 patients with cystic renal masses were treated between 1986 and 1998. Tissues surgically removed were examined pathologically and the final diagnosis compared with the preoperative CT category of Bosniak's classification. Results The histopathological examined showed cystic renal cell carcinoma in 21 patients, a benign renal cyst in 12, haemangiosarcoma in one and transitional cell carcinoma in one. Most of the 35 masses (26, 74%) were found incidentally during evaluation for an unrelated disease or a routine health check. All 11 masses of Bosniak category I were benign and one category II mass was malignant. All 10 masses of category III and 12 of category IV were malignant. Conclusions Bosniak's classification is useful for differentiating category I, III and IV cystic renal masses. There were too few samples to allow meaningful conclusions to be drawn for category II renal masses. It is critical to differentiate between complicated cysts of category II and III because of the major implications for prognosis and clinical management.

Bone scan is performed as part of the evaluation of bone metastasis. We assessed the diagnostic value of bone scan in patients with renal cell carcinoma.Bone scan was performed at presentation in 205 patients with confirmed renal cell carcinoma. Abnormal hot areas were further evaluated by x-ray, computerized tomography or surgery.Of the 56 patients (27%) with an abnormal bone scan 32 (57%) had osseous metastatic lesions. Overall bone metastasis was present in 34 of the 205 patients (17%). Bone scan had 94% sensitivity and 86% specificity. Of the 124 patients with clinically localized, stages T1-2N0M0 disease exclusive of bone metastasis 6 (5%) had bone metastasis only, whereas 28 of 81 (35%) with locally advanced or metastatic disease had bone metastasis, including 12 (35%) who complained of bone pain and 19 (56%) who presented with other symptoms due to local tumor growth or metastasis at other sites. Three patients (9%) were asymptomatic. There was osseous metastasis without other metastasis, enlarged regional lymph nodes or bone pain in 7 patients, including 1 with stage T1b (2% of all with that stage), 2 with stage T2 (5%), 1 with stage T3a (4%), 1 with stage T3b (6%), 1 with stage T3c (14%) and 1 with stage T4 (6%) disease.Bone scan may be omitted in patients with stages T1-3aN0M0 tumors and no bone pain because of the low proportion of missed cases with bone metastasis.

Purpose This phase II multicenter trial was conducted to evaluate the activity and safety of S-1 in Japanese patients with metastatic renal cell carcinoma (mRCC). We also examined the relation between response and mRNA expression levels of enzymes involved in the metabolism of fluorouracil (FU). Methods Patients with mRCC who had received nephrectomy in whom cytokine-based immunotherapy was ineffective or contraindicated were studied. S-1 was administered orally at 80-, 100-, or 120-mg daily, assigned according to body surface area, on days 1 to 28 of a 42-day cycle. The primary end point was the objective response rate. The mRNA expression levels of FU-related enzymes were measured by reverse-transcriptase polymerase chain reaction in formalin-fixed, paraffin-embedded specimens of tumors obtained at nephrectomy. Results A total of 45 eligible patients were enrolled. Eleven (24.4%) of 45 patients had partial responses to S-1, and 28 (62.2%) had stable disease. Median progression-free survival was 9.2 months. The severity of most adverse events was mild to moderate. The most common grade 3/4 drug-related adverse events were neutropenia (8.9%) and anorexia (8.9%). The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048), and progression-free survival was significantly longer in patients whose TS mRNA expression levels were below the median value, as compared with those with higher levels (log-rank test, P = .006). Conclusion S-1 is active against cytokine-refractory mRCC. Quantification of TS mRNA levels in tumors before treatment may facilitate prediction of the response of mRCC to S-1.

Distant metastasis of malignant neoplasm to the oral soft tissue is extremely rare. We report a case of renal cell carcinoma (RCC) metastasizing to the tongue. A 47-year-old man visited our hospital with chief complaint of a lump on the middle third of the dorsum of his tongue and the lesion fell off from the tongue. Although histopathological diagnosis of the mass was granuloma teleangiectaticum, similar nodule reappeared in the same area 2 weeks later. The second lesion was composed of granuloma teleangiectaticum and aggregation of neoplastic clear cells in ductal arrangement. The clear cells were immunohistochemically positive for EMA and CD10. The abdominal CT scan revealed a 5.5 cm mass in the left kidney, suggesting RCC. Thus, the lingual lesion was consistent with metastatic RCC. There has been no recurrence for 2 years after the radical nephrectomy and local excision of the tongue., The original publication is available at www.springerlink.com, Medical oncology, 28(4), pp.1389-1394; 2011

Multiloculated renal cell carcinoma and multilocular renal cyst with renal cell carcinoma are uncommon diseases. We report on 2 cases of multiloculated renal cell carcinoma. To our knowledge 16 cases of multiloculated renal cell carcinoma and multilocular renal cyst with renal cell carcinoma have been previously described in detail. The authors review the literature and discuss the aetiology and diagnosis of the disease.

Purpose: The expression of matrix metalloproteinase-7 (MMP-7) correlates with the malignant potential of various tumors and patient survival. We investigated the clinical and prognostic significance of MMP-7 expression in cancer cells and endothelial cells in human renal cell carcinoma (RCC).Experimental Design: We reviewed tissue samples of 156 patients with RCC who had undergone radical operation. MMP-7 expression was examined by immunohistochemistry. Sections containing MMP-7-positive vessels were also stained for CD34. The density of MMP-7-positive vessels was determined by a computer-aided image analysis system. Multivariate analysis was done to assess relevant variables for invasion, metastasis, and cause-specific survival.Results: The proportion of MMP-7-expressing tumor cells were significantly higher (P < 0.001) than that of normal cells. MMP-7-positive vessels were considered blood vessels based on staining for CD34, and their density was increased in tumor areas. The proportion of MMP-7-expressing cancer cells and density of MMP-7-positive vessels correlated with grade, pathologic tumor stage, and metastasis. Multivariate analysis showed that MMP-7 expression on cancer cells correlated with pathologic tumor stage only, whereas MMP-7-positive vessel density correlated with metastasis only. The elevated status of MMP-7 in cancer tissues was an independent predictor for cause-specific survival (odds ratio, 8.61; P = 0.040) by multivariate analysis.Conclusions: Our results showed that MMP-7 influences tumor progression by regulating invasion and angiogenesis. Multivariate analysis showed that MMP-7 status of cancer tissues was strong predictor of poor prognosis. Our results suggest that MMP-7 targeting treatment may be a potential target against RCC.

Chronic allograft nephropathy (CAN), associated with late-allograft dysfunction is caused by alloantigen-dependent and -independent mechanisms, and eventually leads to interstitial fibrosis (ci). Activation of complement cascade is considered to be a poor prognostic marker of graft survival. This study was designed to examine the relationship between the expression of C4d and heat-shock protein 47 (HSP47, a collagen-specific chaperone) in the development of interstitial fibroproliferative lesions in CAN.Sixty-three renal allograft biopsy specimens, obtained from 48 patients, were examined for the expression of C4d, HSP47, CD68 and alpha-smooth muscle actin (alpha-SMA) by immunohistochemistry. Double-staining was performed to determine the colocalization of C4d and HSP47. The relationship of between the expression of C4d, HSP47, CD68 and alpha-SMA and the clinical and histopathological parameters were statistically analysed.No expression of C4d was noted in the tubulointerstitium including peritubular capillary (PTC) of the control kidney. C4d was expressed in PTC in one-third of allograft renal tissues with morphological evidences of CAN. The interstitial cells around the fibrotic areas of the PTC of CAN were positive for the expression of HSP47. The deposition of C4d in PTC correlated with interstitial expression of HSP47 around the PTC. Most HSP47 expressing cells were phenotypically altered myofibroblasts, as determined by the dual staining of alpha-SMA.The increased expression of HSP47 positively correlated with the expression of C4d in PTC, and might contribute to the progression of interstitial ci in CAN.

Introduction Most donors in Japan have been non–heart-beating donors (NHBD), so-called “marginal donors.” In Western countries kidney transplants from NHBD have also been increasing. We analyzed 120 kidneys harvested from NHBD with regard to organ procurement, renal function, graft survival, and the donor factors that affected graft survival. Methods Donors were moved into the operating room after cardiac arrest. A double-balloon catheter was inserted into the abdominal aorta via laparotomy. In situ cooling by Euro-Collins solution was started at 500 mL/min. We did not performed cannulation into the femoral artery or vein prior to cardiac arrest. Results Warm ischemia time (WIT) was 18.6 minutes. Among 108 kidneys (90%) used for transplantation, 102 kidneys functioned. There were no cases of bilateral nonfunctioning kidneys. The delayed graft function (DGF) rate was 86%; however, the death-censored graft survival was 80.0% at 5 years and 62.9% at 10 years. Kidneys implanted after more than 24 hours of total ischemia time required a significantly longer period of hemodialysis. Donor risk factors that affected graft survival included WIT ≥ 20 minutes, donor age ≥ 50 years, and serum creatinine level at admission > 1.0 mg/dL. Conclusions Organ procurement without cannulation prior to cardiac arrest entailed a long WIT and a high DGF rate. However, the graft survival was good. It has been necessary to use grafts from NHBD despite the inherent risk factors. It is important to reduce kidney damage both at the organ procurement and during the posttransplant management.

Patients with sarcomatoid renal cell carcinoma are rare and have poor survival. We evaluated 14 patients who had renal cell carcinoma with a sarcomatoid component between 1982 and 2000. There were 9 men and 5 women with a median age of 59.5 years (range 32 to 77). Seven patients had a tumor on the right side and 7 on the left side. Thirteen patients had some symptoms and 11 had metastases at the initial visit. Most of them were stage T4 and high nuclear grade cancer and showed elevated acute phase reactants. There were 7 patients followed by interferon therapy, and the cause-specific 5-year survival rate was less than 10%. We confirmed that renal cell carcinoma with a sarcomatoid component often showed local invasion, distant metastasis and poor prognosis.

We report severe arteriolar lesion mimicking drug-induced arteriolopathy in a renal allograft of a 37-year-old Japanese male, who has been treated by conventional immunosuppressive therapy but not administered cyclosporin or tacrolimus for 16 years after renal transplantation. Renal biopsy also showed glomerular changes including transplant glomerulopathy and features of chronic vascular rejection. The cause of the arteriolar lesion remains uncertain. Although its pathogenesis may be multi-factorial, long-term usage of conventional immunosuppressive agents and/or vascular rejection may contribute to the occurrence of the arteriolar lesion. We propose that biopsy study is needed for further understanding of histopathological behaviours of renal grafts in long-term survivors.

The nature of effectors of interferon (IFN)-alpha or IFN-gamma-induced killer cell activity remains unclear. The aim of this study was to examine killer cell activity induced by IFN-alpha alone, IFN-gamma alone or a combination of both in patients with renal cell carcinoma (RCC) and to determine the phenotypic patterns of these effectors. The study group included 14 patients (12 men and 2 women, median age 64 years, range 36-77) with confirmed RCC. Peripheral blood mononuclear cells (PBMC) from RCC patients or normal volunteers were cultured with IFN-alpha alone, IFN-gamma alone or a combination of both. Cytotoxic activity was assayed against ACHN cells. Subpopulations of effector cells in IFN-induced killer cell activity were characterized by cell sorting. The most effective type of IFN and the optimal concentration of IFN necessary to induce the maximal killer cell activity varied among RCC patients. The killer activity induced by a combination of IFN-alpha and IFN-gamma was significantly greater than that induced by IFN-alpha or IFN-gamma alone. The greatly increased killer activity induced by IFN-alpha and IFN-gamma was seen in the subpopulations CD3(-) CD16(+), CD3(-) CD56(+) and subpopulation CD3(+)CD4(-), CD3(-)CD16(+), CD3(-)CD56(+), CD57(+)CD16(-), respectively. An optimal type of IFN and optimal concentration of IFN seem to increase the effective rate of treatment of RCC. In addition, the role of IFN-alpha seems to be different from that of IFN-gamma in host defense against RCC. A combination treatment with IFN-alpha and IFN-gamma seems to be suitable to increase the effective rate if we could reduce the side effects of IFNs.

The nature of effectors of interferon (IFN)-alpha or IFN-gamma-induced killer cell activity remains unclear. The aim of this study was to examine killer cell activity induced by IFN-alpha alone, IFN-gamma alone or a combination of both in patients with renal cell carcinoma (RCC) and to determine the phenotypic patterns of these effectors. The study group included 14 patients (12 men and 2 women, median age 64 years, range 36-77) with confirmed RCC. Peripheral blood mononuclear cells (PBMC) from RCC patients or normal volunteers were cultured with IFN-alpha alone, IFN-gamma alone or a combination of both. Cytotoxic activity was assayed against ACHN cells. Subpopulations of effector cells in IFN-induced killer cell activity were characterized by cell sorting. The most effective type of IFN and the optimal concentration of IFN necessary to induce the maximal killer cell activity varied among RCC patients. The killer activity induced by a combination of IFN-alpha and IFN-gamma was significantly greater than that induced by IFN-alpha or IFN-gamma alone. The greatly increased killer activity induced by IFN-alpha and IFN-gamma was seen in the subpopulations CD3(-) CD16(+), CD3(-) CD56(+) and subpopulation CD3(+)CD4(-), CD3(-)CD16(+), CD3(-)CD56(+), CD57(+)CD16(-), respectively. An optimal type of IFN and optimal concentration of IFN seem to increase the effective rate of treatment of RCC. In addition, the role of IFN-alpha seems to be different from that of IFN-gamma in host defense against RCC. A combination treatment with IFN-alpha and IFN-gamma seems to be suitable to increase the effective rate if we could reduce the side effects of IFNs.

Donor-specific blood transfusion (DST) improves allograft survival, although the exact mechanism(s) is not completely understood. The purpose of this study was to determine the role of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) in DST-protective effects, using a rat cardiac transplantation model. Lewis rats (RT-1 1 ) were transfused with fully allogeneic ACI rats (RT-l a ) blood (DST group) or Lewis syngeneic blood (ST) through the portal vein 7 days prior to allogeneic cardiac transplantation. Posttransplantation, aminoguanidine (AG)-treated rat received continuous intravenous infusion of AG, an inhibitor of inducible nitric oxide synthase (iNOS). The survival times of grafted hearts were 5.7±0.5, 6.8±0.8 and 9.2±1.2 days in ST, ST/AG, and DST groups ( n =6 for each group), respectively. Inhibition of iNOS in ST/AG group prolonged allograft survival, but it was shorter than that in DST rats. Serum nitrite/nitrate levels on postgrafting day 5 were significantly higher in ST than in ST/AG and DST groups, but were similar in ST/AG and DST groups. These results were confirmed by immunohistochemical staining with anti-iNOS antibody. Serum PGE 2 concentrations in DST rats were significantly higher than in ST and ST/AG groups. Our results suggest that DST prolongs graft survival by enhanced production of PGE 2 with a resultant suppression of immune activation. In addition, DST-induced prolongation of graft survival may be partially mediated by NO suppression.

Background. Various clinical and biochemical parameters are currently in use for monitoring allograft rejection. However, the mechanism of allograft rejection is complex and it is frequently difficult to obtain a prompt and accurate diagnosis. We examined the usefulness of OK432-induced killer cell activity as an immunological monitoring system for acute renal rejection after renal transplantation. Methods. Twenty-four renal transplant recipients, seven patients on haemodialysis, and 10 normal volunteers were enrolled in our study. The killer cell activity of peripheral blood mononuclear cells was induced by culturing these cells with the immunopotentiator, OK432, a heat and penicillin-treated lyophilized powder of the Su-strain of Streptococcus pyogenes. Results. The OK432-induced killer cell activity of renal transplant recipients without acute rejection (stable recipients) was significantly lower than in normal volunteers. In four renal transplant recipients with acute rejection, the killer cell activity was significantly higher than in stable recipients. In three recipients suffering from opportunistic infections, killer cell activity was significantly suppressed compared with stable recipients. Conclusions. Our new test utilizing OK432-induced killer cell activity is potentially useful for monitoring the immunological state and complications after renal transplantation.