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A 37-year-old African–British man was referred to our hospital for detailed examination because of persistent fever, swelling and pain in both ankle joints, and blurred vision for two months. Inguinal lymph node biopsy showed a large number of epithelioid granulomas without necrosis. Granulomatous anterior uveitis, nephropathy, high serum angiotensin-converting enzyme activity, and high serum-soluble interleukin-2 receptor were observed, and the diagnosis of systemic sarcoidosis was made. His serum creatinine was 1.4 mg/dL and hematuria, leukocyturia, and urine protein were also seen. The renal biopsy finding was mesangial proliferative glomerulonephritis, with no findings of granuloma formation or tubular interstitial nephritis. Immunofluorescence staining showed deposition of IgG, C3, and C1q in the mesangial region. IgG3 was dominant in subclass staining. There was no monoclonality on kappa and lambda staining. Electron microscopy showed predominant deposition in the mesangial region with some subepithelial and endothelial deposition. His hematuria and leukocyturia disappeared with steroid therapy, suggesting sarcoidosis-related nephropathy. A case of systemic sarcoidosis with mesangial proliferative glomerulonephritis showing predominant deposition of IgG in the mesangial region is presented. No cases of such histological findings have been reported so far, and it is necessary to analyze further cases to clarify the pathogenic significance of the renal biopsy findings observed in this case.

Renin-angiotensin-aldosterone system (RAAS) is primarily involved with pathological mechanism of developing hypertensive emergencies. However, none of clinical practice guidelines mention RAAS blockers for the treatment of hypertensive emergencies. A 44 year-old woman presented with severe hypertension, brain stem posterior reversible encephalopathy syndrome and severe acute kidney injury (AKI). We started anti-hypertensive therapy with continuous intravenous nitroglycerin and oral calcium channel blocker (CCB) and spironolactone. Since severe AKI persisted despite this therapy, we administered losartan potassium, which resulted in improvement in her blood pressure and creatinine. Clinical course of our patient suggests that timely initiation of ARB and spironolactone for hypertensive emergencies could be beneficial in terms of blood pressure control and for protection of target organs from this condition.

Background This article is a duplicated publication from the Japanese version of “2019 JSDT Guidelines for Peritoneal Dialysis” with permission from the Japanese Society for Dialysis Therapy (JSDT). This clinical practice guideline (CPG) was developed primarily by the Working Group on Revision of Peritoneal Dialysis (PD) Guidelines of the Japanese Society for Dialysis Therapy. Recently, the definition and creation process for CPGs have become far more rigorous; traditional methods and formats no longer adhere to current standards. To improve the reliability of international transmission of our findings, CPGs are created in compliance with the methodologies developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group. Part 2 of this PD guideline is the first CPG developed by our society that conforms to the GRADE approach. Methods Detailed processes were created in accordance with the Cochrane handbook and the GRADE approach developed by the GRADE working group. Results Clinical question (CQ)1: Is the use of renin-angiotensin system inhibitors (RAS inhibitors), such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), effective in PD patients? Recommendation: We suggest the usage of RAS inhibitors (ACEI and ARB) in PD patients (GRADE 2C). CQ2: Icodextrin or glucose solution: which is more useful as a dialysate among patients with PD? Recommendation: We suggest using icodextrin when managing body fluids in PD patients (GRADE 2C). CQ3: Is it better to apply or not apply mupirocin/gentamicin ointment to the exit site? Recommendation: We suggest not applying mupirocin/gentamicin ointment to the exit sites of PD patients (GRADE 2C). CQ4: Which surgical approach is more desirable when a PD catheter is placed, open surgery or laparoscopic surgery? No recommendation. CQ5: Which administration route of antibiotics is better in PD patients with peritonitis, intravenous or intraperitoneal? Recommendation: We suggest intraperitoneal administration of antibiotics in PD patients with peritonitis (GRADE 2C). Note: The National Insurance does not currently cover intraperitoneal administration. CQ6: Is peritoneal dialysis or hemodialysis better as the first renal replacement therapy in diabetic patients? No recommendation. Conclusions In the future, we suggest that society members construct their own evidence to answer CQs not brought up in this guideline, and thereby show the achievements of Japan worldwide.

BackgroundIcodextrin enhances peritoneal filtration for patients on peritoneal dialysis (PD). However, clinically important outcomes have not yet been analyzed using authentic, objective statistical methods. The present systematic review aimed to determine the risks and benefits of icodextrin compared with a glucose-based solution with respect to clinically important and patient-centered outcomes.MethodsWe systematically investigated only randomized controlled trials (RCTs) by adopting the Cochrane Database of Systematic Review (2014) and searched the CENTRAL, MEDLINE, and EMBASE databases for eligible studies reported in the literature. The quality of the evidence was assessed using the GRADE approach.ResultsWe finally evaluated important outcomes in 13 RCTs. Icodextrin significantly decreased the number of reported episodes of uncontrolled fluid overload in four RCTs that involved 236 patients (relative risk [RR], 0.31; 95% confidence interval [CI], 0.12 to 0.82; moderate certainty evidence). However, the inclusion of icodextrin for peritoneal ultrafiltration did not significantly differ in six RCTs involving 252 patients (mean difference [MD], 186.76 mL; 95% CI, − 47.08 to 420.59; low certainty evidence). Regarding other clinically important outcomes, all-cause mortality in 10 RCTs involving 1106 patients (RR, 0.75; 95% CI, 0.33 to 1.71; low certainty evidence) and technical survival in five RCTs involving 470 patients (RR, 0.57; 95%CI, 0.29 to 1.12; low certainty evidence) were not significant. Urine volume in four RCTs involving 136 patients, residual renal function in five RCTs involving 181 patients and peritoneal function measured as the ratio of solute concentration in dialysate and plasma (D/P ratio) in two RCTs involving 105 patients were not specifically affected by icodextrin, and the results for adverse events were similar between icodextrin and glucose PD solutions.ConclusionIcodextrin could relieve uncontrolled fluid overload without adding risk. However, a significant effect on clinically relevant outcomes such as technical survival and overall patient survival was not suggested. More trials are required to increase the statistical power and to verify the value of icodextrin in clinical practice.Trial registrationPROSPERO,CRD42018104360

Background There is no evidence on how to use the information from bioimpedance analysis (BIA) devices in clinical management, including setting of target dry weight (DW), or improving outcomes in hemodialysis (HD) patients. Methods Here, we investigate preferable cut off values of fluid status (extracellular water/total body water ratio; ECW/TBW) detected by a new and more accurate BIA device (Seca®) in 78 HD patients. Results Patients with an ECW/TBW of more than 45% and human atrial natriuretic peptide (HANP) value of > 50 pg/mL had a higher blood pressure and cardio-thoracic ratio on chest x-ray examination.Conclusions Our results suggests that ECW/TBW of more than 45% and HANP value of > 50 pg/mL were overhydrated and had a worse prognosis.

One third of the patients with chronic kidney disease (CKD) develop cognitive impairment, which is also an independent risk factor for mortality. However, the concise mechanism of cerebro-renal interaction has not been clarified. The present study examines the effects of uremic toxins on neuronal cells and analyzes the pathological condition of the brain using mouse hippocampal neuronal HT-22 cells and adenine-induced CKD model rats. Among the uremic toxins analyzed, indoxyl sulfate, indole, 3-indoleacetate, and methylglyoxal significantly decreased viability and glutathione level in HT-22 cells. The mixture of these uremic toxins also decreased viability and glutathione level at a lower dose. Adenine-induced CKD rat showed marked renal damage, increased urinary oxidative stress markers, and increased numbers of pyknotic neuronal cells in hippocampus. CKD rats with damaged hippocampus demonstrated poor learning process when tested using the Morris water maze test. Our results suggest that uremic toxins have a toxic effect on hippocampal neuronal cells and uremic CKD rats shows pyknosis in hippocampus., Cerebro-renal interaction; Cognitive impairment; Chronic kidney disease; Uremic toxins.

Background Complications of acute kidney injury (AKI) are common in patients with coronavirus disease in 2019 (COVID-19). However, clinical characteristics of COVID-19-associated AKI are poorly described. We present two cases of severe COVID-19 patients with AKI. Case presentation A 77-year-old woman was suspected of having vancomycin-associated AKI, and a 45-year-old man was suspected of having heme pigment-induced AKI caused by rhabdomyolysis. The granular cast, which is known to be a valuable diagnostic tool for confirming the diagnosis of acute tubular necrosis, was detected in both patients at the onset of AKI. Interestingly, both patients also developed microscopic hematuria at the occurrence of AKI, and one patient had elevated d-dimer and low platelet levels simultaneously. Conclusions Some reports suggested that COVID-19-associated microangiopathy contributed to the kidney damage. Therefore, it is possible that our patients might have accompanied renal microangiopathy, and that this pathological background may have caused exaggerated tubular damage by vancomycin or heme pigment. The etiology of AKI in patients with COVID-19 is multifactorial. Superimposition of nephrotoxin(s) and virus-associate intra-renal microangiopathy may be a crucial trigger of kidney injury leading to severe AKI in COVID-19 patients. Therefore, in COVID-19 patients, risk factors for AKI should be taken into consideration to prevent its progression into severe AKI.

Background Hyperuricemia is highly prevalent in chronic kidney disease (CKD) patients, but the evidence for a relationship between uric acid (UA) and clinical outcomes in CKD patients is limited and inconsistent. We hypothesized that UA has a different impact on clinical outcomes according to the underlying disease causing CKD. Methods This study prospectively investigated the associations between UA and renal and non-renal outcomes according to the underlying disease causing CKD in 2,797 Japanese patients under the care of nephrologists. The patients were categorized into four groups: primary renal disease (n = 1306), hypertensive nephropathy (n = 467), diabetic nephropathy (n = 275), and other nephropathy (n = 749). The renal outcome was defined as end-stage renal disease (ESRD), and the non-renal outcome was defined as a composite endpoint of cardiovascular events (CVEs) and all-cause mortality. Results During a median 4.8-year follow-up, 359 (12.8%) patients reached the renal outcome, and 260 (9.3%) reached the non-renal outcome. In the all-patient analysis, hyperuricemia was not associated with the risks for renal and non-renal outcomes, but in primary renal disease (PRD) and hypertensive renal disease (HTN) patients, hyperuricemia was significantly associated with non-renal outcomes. Per 1 mg/dl higher UA level, multivariable adjusted hazard ratio was 1.248 (95% CI: 1.003 to 1.553) for PRD, and 1.250 (1.035 to 1.510) for HTN. Allopurinol did not reduce the risks for renal and non-renal outcomes, both in all patients and in the subgroup analysis. Conclusions The effect of hyperuricemia on clinical outcomes in CKD patients varies according to the underlying disease causing CKD. Hyperuricemia is an independent risk factor for non-renal outcomes in primary renal disease and hypertensive renal disease patients. Allopurinol did not decrease the risks for renal and non-renal outcomes.

Introduction A recent study suggested that orally dosed ferric citrate hydrate (FC) corrects renal anemia in patients on hemodialysis (HD), suggesting biological differences in effects of iron supplementation using different routes of administration. To address this issue, the present study compared oral FC with i.v. saccharated ferric oxide (FO) in stable HD patients. Methods Participants comprised 6 patients administered 3 consecutive protocols in the first HD session of the week in a fasting state: nothing given, as control (C); oral load of FC (480 mg iron), and 5 minutes of i.v. FO (40 mg iron). Iron dynamics in the body and biological impact on redox-inflammation status during the study (6 hours) were examined. Results Significant increases in serum iron and transferrin saturation were seen with both FC and FO. Regarding total iron-binding capacity as the sum of serum iron and unsaturated iron-binding capacity, no changes were found in FC, whereas significant increases were seen in FO (appearance of non–transferrin-binding iron [NTBI]), despite the lower serum iron levels in FO. Compared with C, increases were seen in serum myeloperoxidase (oxidative marker) with accompanying significant decreases in thioredoxin (antioxidant) in FO, whereas no changes were found in FC. Conclusion Oral FC differs from i.v. FO in areas such as less NTBI generation and less induction of oxidative stress. The result indicates potential clinical benefits of oral FC in terms of iron supplementation for renal anemia in HD patients.

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

Background The definition and guideline of sepsis and septic shock were recently updated. The aim of this study is to evaluate the ability of Third Consensus Definitions of Sepsis and Septic Shock (Sepsis-3) to predict outcomes among patients with community-acquired sepsis receiving continuous renal replacement therapy (CRRT). Methods We conducted a retrospective observational study between January 2013 and December 2015 in a single university hospital. From 368 patients receiving CRRT for various reasons, 64 patients who suffered from community-acquired sepsis and required CRRT were selected and evaluated using the current and previous sepsis criteria. We additionally assessed infection characteristics. The primary outcome was 28-day mortality, and the secondary outcome was in-hospital mortality. Results Of the 64 participants (70.3% male, median age 66.5 years), 33 (51.6%) administered antimicrobials before admission. The most common source of infections was pneumonia, and 27 participants (42.2%) had positive cultures. The Sepsis-3 criteria identified 64 cases (100%) as sepsis at the start of CRRT, while the previous criteria identified 44 cases (68.8%). According to the Sepsis-3 criteria, the 28-day mortality of sepsis and septic shock were 31.3% (20/64) and 46% (17/37), and in-hospital mortality was 43.8% (28/64) and 62.2% (23/37), respectively. Septic shock diagnosed using the Sepsis-3 criteria predicted mortality (log-rank P = 0.0001); however, using the previous criteria was not associated with mortality (log-rank P = 0.437). Among variables, lactate levels ≥ 2 mmol/L and SOFA score ≥ 14 were significantly associated with mortalities, with an optimal cutoff value for lactate of 1.8 mmol/L (AUC 0.777, sensitivity 85.7%, specificity 58.3%). Although age ≥ 65 years predicted in-hospital mortality, and pre-hospital antimicrobial therapy tended to be associated with 28-day mortality, we did not detect any association between outcomes and the CRRT regimen or general risk factors (e.g., acute kidney injury, serum creatinine levels, and comorbidities). Conclusions Our data suggests that the Sepsis-3 criteria predicted survival more accurately than the previous criteria among patients with community-acquired sepsis receiving CRRT. This is based on lactate levels and SOFA scores being strongly associated with mortality.

Background Improved biocompatibility of peritoneal dialysis solution (PDS) is crucial for peritoneal membrane preservation, thereby ensuring long-term peritoneal dialysis (PD) and preventing encapsulating peritoneal sclerosis. We previously reported the protective effect of molecular hydrogen (H2) on mesothelial cells from PDS in nonuremic rats. Summary In the present study, we examined the effect of H2-containing PDS (commercially available neutral pH type) regarding the protection of peritoneal tissue in experimental chronic kidney disease rats. Furthermore, we conducted a 2-week clinical trial in which H2-containing PDS was used in place of standard PDS and its feasibility was examined. In the experimental study, test solutions were injected through the subcutaneous port into the abdomen for 3 weeks. Histological study revealed a significant increase in the number of mesothelial cells and a significant decrease in peritoneal thickness in the H2-PD group as compared to the control and PD groups. Also, results of immunostaining analysis revealed increased vimentin and apoptotic cells in the membrane of the PD group, indicating that H2 may play a role in ameliorating PDS-induced peritoneal injury and preserving peritoneal integrity. In the clinical trial with 6 prevalent PD patients, all subjects completed the study with no adverse effects. Moreover, there were substantial changes in surrogate markers, such as increased CA125 and mesothelin, in the effluent in selected cases, suggesting enhanced mesothelial regeneration by H2. Key Message: H2-enriched PDS is a candidate novel PDS with improved biocompatibility. Further, our results support the significance of H2-PD clinical trials in the future.

Background Peritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H2) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H2 on the peritoneal membrane of experimental PD rats. Method Eight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8–11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H2PD group (PD solution with dissolved H2 at 400 ppb). Furthermore, the influence of iron (FeCl3: 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H2PD groups). The H2PD solution was manufactured by bathing a PD bag in H2-oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis. Results In the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H2PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H2PD group. Conclusion H2-dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.

Tissue accumulation of advanced glycation end products (AGE) is thought to contribute to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has been reported to be an independent predictor of mortality associated with CVD in Caucasian patients on chronic hemodialysis. The aim of this study was to assess the predictive value of skin autofluorescence on all-cause and cardiovascular mortality in non-Caucasian (Japanese) patients on chronic hemodialysis. Baseline skin autofluorescence was measured with an autofluorescence reader in 128 non-Caucasian (Japanese) patients on chronic hemodialysis. All-cause and cardiovascular mortality was monitored prospectively during a period of 6 years. During the follow-up period, 42 of the 128 patients died; 19 of those patients died of CVD. Skin autofluorescence did not have a significant effect on all-cause mortality. However, age, carotid artery intima-media thickness (IMT), serum albumin, high-sensitivity C-reactive protein (hsCRP), skin autofluorescence and pre-existing CVD were significantly correlated with cardiovascular mortality. Multivariate Cox regression analysis showed skin autofluorescence (adjusted hazard ratio [HR] 3.97; 95% confidence interval [CI]1.67-9.43), serum albumin (adjusted HR 0.05; 95% CI 0.01-0.32), and hsCRP (adjusted HR 1.55; 95% CI 1.18-2.05) to be independent predictors of cardiovascular mortality. The present study suggests that skin autofluorescence is an independent predictor of cardiovascular mortality in non-Caucasian (Japanese) patients on chronic hemodialysis.

At 14:46 on 11 March 2011, northeastern Japan was struck by a major earthquake measuring 9.0 on the Richter scale (the Great East Japan Earthquake). Several reports have suggested a transient blood pressure (BP) increase after a major earthquake, but its impact on BP in chronic dialysis patients has not been reported. In a retrospective review of 25 hemodialysis patients who were residents of Koriyama City, changes in the morning home BP after the earthquake were investigated. Home systolic and diastolic BPs were significantly elevated 1 week after the earthquake (158 ± 16 mm Hg vs. 151 ± 13 mm Hg, P

Although recent studies showed anti-PLA2R antibody plays a crucial role in idiopathic membranous nephropathy (IMN), detailed HLA mapping and interaction between the HLA genes and PLA2R1 have not been investigated in IMN. We genotyped across the PLA2R1 gene and the HLA region, using 183 IMN patients and 811 healthy controls. Five SNPs around the PLA2R1 gene were significantly associated with IMN. In addition to the two SNPs previously reported to be strongly associated with IMN, rs3749119 and rs35771982 (OR 3.02 and 2.93, P = 3.24E-14 and 4.64E-14, respectively), two novel intronic SNPs (rs2715928 and rs16844715) were also identified as IMN-associated SNPs (OR = 2.30 and 2.51, P = 3.15E-10 and 5.66E-13, respectively). In the HLA gene analysis, DRB1*1501 and DQB1*0602 were strongly associated with IMN (P = 1.14E-11 and 1.25E-11, respectively). The interaction was strongest between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the intronic SNP rs2715928 (OR = 17.53, P = 4.26E-26). Furthermore, positive interaction was also observed between HLA-DRB1*15:01 - HLA-DQB1*06:02 and the missense SNP rs35771982 (OR = 15.91, P = 2.76E-29), which is in strong linkage disequilibrium with 5′UTR SNP rs3749119, and intronic SNP rs16844715 (OR = 15.91, P = 2.30E-26) for IMN. Neither HLA-DRB1*15:01 nor HLA-DQB1*06:02 was associated with steroid responsiveness, overall survival and renal survival during the observation period of mean 11 years though limited number of analysis.

Blood pressure (BP) transiently increases after major earthquakes. Although home BP increased in hypertensive patients after the Great East Japan Earthquake (measuring 9.0 on the Richter scale) on March 11th, 2011, such profiles in patients with chronic kidney disease (CKD) have not been investigated. This retrospective single-center observational study included 38 patients with CKD at the predialysis stage [male, n = 27 (71 %); mean age 66.0 years; mean estimated glomerular filtration rate (eGFR) 46.0 mL/min/1.73 m²] who lived in Fukushima City. We compared their morning BP between two and four weeks after the quake with that of a control group of 39 non-CKD patients with hypertension. Systolic BP (SBP) remained elevated for one week after the quake in the CKD and non-CKD groups [before vs. after the quake 133.7 ± 15.6 vs. 136.9 ± 16.9 (p = 0.017) and 129.9 ± 7.8 vs. 133.3 ± 9.3 mmHg (p = 0.009), respectively]. Increases in SBP in the morning after the quake were statistically significant in the group with but not in that without CKD (7.1 and 3.4 mmHg; p = 0.038 and 0.221, respectively). Multivariate analysis revealed that a low eGFR was an independent risk factor for elevated SBP after the quake. The quake caused acute changes in the home BP and the fact that BP elevation correlated with renal function suggests a possible mechanism of CKD, such as enhanced activity of the sympathetic nervous system in such patients.

BACKGROUND At 1446 on 11 March 2011, northeastern Japan was struck by a major earthquake measuring 9.0 on the Richter scale. There have been several reports of transient blood pressure increases after a major earthquake, but the impact of a major earthquake on blood pressure in chronic kidney disease (CKD) patients has not been fully investigated. METHODS Changes in clinic blood pressure following the earthquake were investigated in 132 hypertensive patients with stage 3 and 4 CKD who were residents of Fukushima City. RESULTS Both systolic and diastolic blood pressures were significantly elevated 1-3 weeks after the earthquake compared with before the earthquake (134 ± 19 mm Hg vs. 138 ± 20 mm Hg, P = 0.02 for systolic; 76 ± 13 mm Hg vs. 79 ± 12 mm Hg, P = 0.01 for diastolic), and these values returned to baseline by 5-7 weeks after the earthquake. Multiple logistic regression analysis identified male sex (odds ratio (OR), 0.35; 95% confidence interval (CI), 0.14-0.86; P = 0.02), mean blood pressure at baseline (OR, 0.92; 95% CI, 0.86-0.96; P < 0.01), and sympatholytic medications, such as α-blockers, β-blockers, or central sympatholytics (OR, 0.23; 95% CI, 0.07-0.76; P = 0.01), as independent factors related to elevation of mean blood pressure 1-3 weeks after the earthquake in CKD patients. CONCLUSIONS Blood pressure was significantly increased after a major earthquake in hypertensive patients with stage 3 and 4 CKD. During the first 3 weeks after the earthquake, blood pressure control was associated with the use of sympatholytic medications.

Stress corrosion cracking (SCC) simulation code has been developed for the evaluation of SCC behavior in specimens in the shape of field components. The code utilizes numerical calculation of stress/strain states at a crack tip using finite element methods and a formula describing the crack tip reaction kinetics containing unknown environmental parameters. The applicability of this simulation code was investigated by applying the code to the evaluation of SCC behavior in a mock-up of a bottom mounted instrumentation tube for a pressurized water reactor subjected to complex stress/strain states. The results indicate that crack growth rate in a component suffering from certain environments can be estimated using the developed SCC simulation code with pre-determined unknown parameters, using the experimental crack growth rate data measured on other specimens in the same environment.

The primary objective of this study is to develop a quantitative model to predict the effects of materials, environment and mechanics such as loading configuration on environmentally-assisted cracking (EAC) of stainless steels in high-temperature water. It has basically been accepted that crack propagation in oxygenated high temperature water is controlled by a slip-dissolution and/or deformation-oxidation mechanism. According to this mechanism, the crack-tip strain rate is an extremely important mechanical parameter for determining the crack growth rates. Based upon a formulation obtained by combining Faraday’s equation with an elastic plastic analysis of the strain singularity at a growing crack-tip in work hardening materials, a theoretical formulation of crack-tip strain rate has been derived for plane strain and plane stress conditions. The FEM analysis for 3D crack growth can be compared to the theoretical 2D analysis. In this paper, we first make a CCP (Center Crack Plane) model, and performed a 3-dimensional Finite Element Analysis (3D-FEA) to evaluate the crack-tip stain rate paying attention to the element mesh size and to the loading history. After optimization these parameters, the calculated crack-tip strain distribution, including its logarithmic singularity, was founded to agree well with the theoretical distribution. The significance of the crack-tip strain rate upon the crack-tip strain distribution and crack growth rate was demonstrated. The specimen size effects on crack growth rates were discussed from this point of crack-tip strain distribution. Finally, we focused on the importance of crack-tip strain rate as a unique mechanical parameter that controls the crack growth rate.

Background and aim It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation. Subjects and method 262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups. Results In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors. Conclusion The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment.

Hyperuricemia is associated with the onset of chronic kidney disease (CKD) and renal disease progression. Febuxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has been reported to have a stronger effect on hyperuricemia than conventional therapy with allopurinol. However, few data are available regarding the clinical effect of febuxostat in patients with CKD.A prospective, randomized, open-label, parallel-group trial was conducted in hyperuricemic patients with stage 3 CKD. Patients were randomly assigned to treatment with febuxostat (n = 21) or to continue conventional therapy (n = 19). Treatment was continued for 12 weeks. The efficacy of febuxostat was determined by monitoring serum uric acid (UA) levels, blood pressures, renal function, and urinary protein levels. In addition, urinary liver-type fatty acid-binding protein (L-FABP), urinary albumin, urinary beta 2 microglobulin (β2MG), and serum high sensitivity C-reactive protein were measured before and 12 weeks after febuxostat was added to the treatment.Febuxostat resulted in a significantly greater reduction in serum UA (-2.2 mg/dL) than conventional therapy (-0.3 mg/dL, P0.001). Serum creatinine and estimated glomerular filtration rate changed little during the study period in each group. However, treatment with febuxostat for 12 weeks reduced the urinary levels of L-FABP, albumin, and β2MG, whereas the levels of these markers did not change in the control group.Febuxostat reduced serum UA levels more effectively than conventional therapy and might have a renoprotective effect in hyperuricemic patients with CKD. Further studies should clarify whether febuxostat prevents the progression of renal disease and improves the prognosis of CKD.

BACKGROUND: Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD). METHODS: Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis. RESULTS: Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004). CONCLUSIONS: Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.

A histological subtype of acute postinfectious glomerulonephritis (APIGN), the garland pattern, is identified not only by characteristic histological findings, but also by severe clinical course as compared with typical APIGN. However, since the morbidity of APIGN has decreased globally, there have been few reports on this disease form in developed countries during the last two decades. Herein, we report a case of adolescent garland-pattern APIGN with IgA-dominant deposits, presenting with severe nephrotic syndrome and protracted hematuria and proteinuria. We also review the clinical and histological features of 13 previously reported cases in Japan and compare them with our present case. In our review, we confirmed IgA deposition in at least three of these patients, in whom urinary protein excretion tended to be greater than those patients without IgA. Greater awareness of this condition is necessary to ensure appropriate follow-up of the clinical course of patients with garland-pattern APIGN with IgA deposition.

Aftercare for the prevention of a secondary health disaster in survivors of major earthquakes

A 75-year-old woman presented with rapidly progressive glomerulonephritis with positive results for anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). Corticosteroid therapy was successfully introduced. However, 7 months later, magnetic resonance imaging revealed marked swelling in the falx cerebri and high density regions were apparent on gallium scintigraphy, leading to diagnosis of hypertrophic cranial pachymeningitis (HCP). Symptoms improved with intensified corticosteroid therapy, but radiological examination 9 months later revealed right nasal sinus inflammation accompanied by osteolytic change. Granulomatosis with polyangiitis (Wegener's) was finally diagnosed. HCP is an important complication in MPO-ANCA-related vasculitis, and needs to be considered during the clinical course.

OBJECTIVE Albuminuria is thought to reflect generalized endothelial dysfunction. In hypertensive patients, albuminuria increases the risk of cardiovascular disease (CVD) events. Therefore, screening for albuminuria is critical for stratifying risks in hypertensive patients. However, a limited number of Japanese studies have performed quantitative examinations of albuminuria. The objective of this study was to examine the utility of the CLINITEK MICROALB CREATININE TEST for albuminuria screening. MATERIALS The CLINITEK MICROALB CREATININE TEST consists of a urine test strip that assesses albumin excretion corrected for the urine creatinine levels in only 60 seconds without the need for any special facilities. The CLINITEK MICROALB CREATININE TEST was performed in 5,647 Japanese hypertensive patients, excluding diabetic patients, and the clinical significance of the test was evaluated. RESULTS According to the CLINITEK MICROALB CREATININE TEST, the A1 (albumin creatinine ratio: ACR

Models of two-dimensional and three-dimensional subsurface fracture networks are proposed on the basis of “fractal geometry” to describe geothermal water flow. Using this fracture network model, as well as the single fracture model and the permeable zone model, a parameter study of the performance of Hot Dry Rock geothermal energy extraction systems, such as the changes in output water temperature and thermal output with time, is performed. The results show a strong dependence of the system performance on geothermal reservoir characteristics, such as the fracture density of the rock mass. The fracture network model proposed here can describe the performance of reservoirs which vary between the single fracture model and the permeable zone model, and is expected to bridge the gap between the two models. It is confirmed that the performance of geothermal energy extraction systems can be predicted as a function of the fracture density of the rock mass by using the fracture network model.

Objective Anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)- related nephritis constitutes 60% of rapidly progressive glomerulonephritis (RPGN) in Japan. The reported 1-year survival rate is over 80%, however, the long-term prognosis remains unknown. We therefore investigated the prognosis and factors affecting the clinical course of patients. Methods We retrospectively investigated 74 patients (female, n=42; median age, 73.0 years) with MPO-ANCA-related nephritis. The patients were admitted to Fukushima Medical University and two affiliated hospitals between 2000 and 2010. Results Median estimated GFR (eGFR) was 12.1 mL/min/1.73 m2 at admission. The Birmingham Vasculitis Activity Score (BVAS version 3: max 63 points) at diagnosis and at 4 weeks after start of treatment were 15.0 and 5.0, respectively. Twenty-three patients (31%) died during a median observation period of 30.5 months. Sixteen patients (22%) presented with end-stage renal disease (ESRD) at the initial phase, and needed regular dialysis therapy. Multivariate Cox proportional hazards model analysis revealed that renal death at the initial phase was a significant risk factor for all-cause death (Hazard ratio, 5.72; 95% confidence interval, 2.49-13.09; p 6, evaluated 4 weeks after start of treatment, is an independent risk factor for ESRD and patient survival. Conclusion This is the first investigation to demonstrate clinical features focusing on MPO-ANCA-related nephritis. Renal death at the initial phase of treatment is a powerful risk factor for all-cause death in patients with MPO-ANCA-related nephritis. Patients at high risk of death and ESRD could be stratified according to BVAS.

A new radical operation for Hirschsprung's disease, i.e., rectal myotomy with colectomy, the aim of which is to minimize pelvic dissection and to preserve the rectal wall as much as possible, was performed in 11 cases of Hirschsprung's disease. It can be used on young infants, and rectal sensation is preserved. The result was satisfactory in all but one child.

Measurement of intraluminal anorectal pressures and cineradiographic studies were carried out on 15 infants and children with Hirschsprung's disease and 18 patients who had undergone radical operation for the disease. The results were compared with those obtained from 50 normal infants and children. It was revealed that the chronic and severe constipation seen in Hirschsprung's disease was caused by lack of propulsive movement in aganglionic portion of the colon and absence of normal recto-sphincteric reflex. Studies on postoperative infants revealed that propulsive movement of the ano-rectrum and ordinary recto-sphincteric reflex were recovered in patients treated by rectal myotomy with colectomy or Lynn's rectal myectomy. On the other hand, recto-sphincteric reflex was not restored in those who had undergone Swenson's rectosigmoidectomy.