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Background Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. Methods Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder–decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. Results Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. Conclusions Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan.We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study.The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death.Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death.

We report the case of metformin-associated lactic acidosis (MALA) exacerbated by acute kidney injury (AKI) in a 65-year-old Asian American woman who was an overseas traveler. She had vomiting and diarrhea before arriving in Osaka, Japan, from the Philippines. She suffered from worsening respiratory distress, consciousness loss and anuria the day after coming to Japan. When she arrived at our emergency room via ambulance, she appeared to be in a state shock. Arterial blood gas analysis revealed severe lactic acidosis (pH 6.681, PO2 302 Torr under O2 supplementation, PCO2 15 Torr, HCO3−1.7 mmol/L, and lactate 17.00 mmol/L). She also had renal failure (BUN 108 mg/dL and serum creatinine 8.68 mg/dL) with hyperkalemia (6.1 mEq/L). We collected medical information from family members, and found her prescription medicines including metformin, diuretics and angiotensin-converting enzyme inhibitor (ACEI). We diagnosed her with MALA due to an unintended overdose of metformin resulting from acute kidney injury that can be induced by ACEI and diuretics in the volume-depleted condition. We immediately started hemodialysis therapy. Although she had a temporary cardiopulmonary arrest at the beginning of the treatment, her physical status was gradually improved and the severe acidemia resolved. On hospital day 4, she had urine and no longer needed hemodialysis therapy. On day 14, she was discharged and returned to the United States without noticeable sequelae. This is a case report of an overseas traveler who was successfully rescued through the collection of accurate medical information and understanding of the pathological condition.

Background The hyperosmolar hyperglycemic state (HHS), an acute complication of diabetes mellitus with plasma hyperosmolarity, promotes the secretion of anti-diuretic hormone (ADH) and reduces the storage of ADH. Magnetic resonance T1-weighted imaging reflects ADH storage in the posterior pituitary lobe, which disappears when the storage is depleted. Whether the HHS induces ADH depletion leading to clinical manifestations has been unclear. Case report A 55-year-old Japanese woman was admitted to our center because of mental disturbance and hypotension. She had received lithium carbonate for bipolar disorder and presented with polydipsia and polyuria from 15 years of age. On admission, she had mental disturbance (Glasgow Coma Scale, E4V1M1), hypotension (systolic blood pressure, 50 mmHg), and tachycardia (pulse rate, 123/min). Plasma glucose was 697 mg/dL osmolality was 476 mOsm/kg•H2O, and bicarbonate was 23.7 mmol/L. The diagnoses of HHS and hypovolemic shock were made. During treatment with fluid replacement and insulin therapy, the urine volume continued to be approximately 3 to 4 L/day, and an endocrine examination revealed ADH insufficiency and nephrogenic diabetes insipidus. Desmopressin 10 μg/day and trichlormethiazide 2 mg/day were necessary and administered, and the endogenous ADH secretion improved gradually. The signal intensity of the pituitary posterior lobe, initially decreased on magnetic resonance T1 images, was also improved. Conclusion This patient had ADH insufficiency associated with ADH depletion due to hyperosmolarity and nephrogenic diabetes insipidus. Clinicians should be aware of the risk of the development of critical HHS and relative ADH insufficiency in patients being treated with lithium carbonate.

Hemodialysis is a well-known risk factor for severe infection by putting patients under an immunocompromised state. Such patients are prone to opportunistic pathogen and present with atypical manifestations during infection. Tuberculous meningitis is a central nervous system infection of Mycobacterium tuberculosis, accounting for the highest mortality of all forms of tuberculosis. In fact, the mortality rate of tuberculous meningitis in hemodialysis patients is extremely poor because early clinical diagnosis is difficult. Here, we report a case of tuberculous meningitis in a 61-year-old Indian hemodialysis patient, who presented with fever of unknown origin and was successfully treated with empiric treatment with standard four-drug regimen against tuberculosis. Comprehensive screening of the origin of fever revealed only the positive results of interferon-gamma release assay, which led us to initiate an empiric therapy for tuberculosis, before making a definitive diagnosis by cerebrospinal fluid nested PCR. Soon after the initiation of the treatment, the fever immediately abated. Although the patient experienced a single episode of paradoxical worsening and severe liver injury, she recovered well without any complications. This report provides a clinical course of the disease in a hemodialysis patient, highlighting the importance of early clinical diagnosis and rapid initiation of empirical tuberculosis treatment.

Background Polycystic liver disease is a clinical feature of autosomal dominant polycystic kidney disease, and it can sometimes cause health damage more serious than polycystic kidney. Dialysis therapy can be used for renal failure, but liver transplantation is the only method available for liver failure. Thus, giant and multiple hepatic cysts may affect mortality. However, liver transplantation is not indicated in many cases because of the preserved liver function. Case presentation A 54-year-old Japanese woman with polycystic liver disease was transferred back to our hospital for abdominal pain caused by liver cyst infection with abdominal wall herniation. She had been diagnosed with polycystic liver disease associated with sporadic autosomal dominant polycystic kidney disease 25 years earlier. Although she had several surgical interventions to reduce her liver volume, including right hepatic lobectomy and fenestration for liver cysts in another hospital, she needed further repair of the recurrent incisional herniation with patch graft surgery using fascia lata to cover the herniation site. However, new herniation sites reemerged in the fragile abdominal wall area around the patch, and therefore, she reduced the recurrent abdominal wall herniation by herself. Recurrent intestinal obstructions were luckily released by fasting with decompression treatment via nasogastric tube insertion, but multiple skin ulcers around the enlarged hernia sac gradually developed, and ascites was extremely difficult to control with any medication. At final admission, her abdominal wall was even more prominent, causing shortness of breath, and it spontaneously ruptured many times, which was accompanied by discharge of around 5 liters of ascites each time. She died from sepsis caused by drug-resistant Enterococcus. Conclusions We report a case of autosomal dominant polycystic kidney disease with ruptured abdominal wall resulting from a hepatic cyst enlargement despite multiple laparotomy operations. Throughout the entire disease course, her liver volume increased rapidly, and her quality of life was severely impaired, but she could not undergo liver transplantation after readmission to our hospital. We will discuss the therapeutic strategy for this patient, including the timing and indication for liver transplantation.

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m2 ), moderately impaired (M) (≥30 to

Introduction Recently, nephronophthisis (NPH) has been considered a monogenic cause of end-stage renal disease (ESRD) in adults. However, adult-onset NPH is difficult to accurately diagnose and has not been reported in a cohort study. In this study, we assessed the genetic background and clinicopathologic features of adult NPH. Methods We investigated 18 sporadic adult patients who were suspected as having NPH by renal biopsy. We analyzed 69 genes that cause hereditary cystic kidney disease and compared clinicopathologic findings between patients with and without pathogenic mutations in NPH-causing genes. Results Seven of 18 patients had pathogenic NPH-causing mutations in NPHP1, NPHP3, NPHP4, or CEP164. Compared with patients without pathogenic mutations, those with pathogenic mutations were significantly younger but did not significantly differ in the classic NPH pathologic findings, such as tubular cysts. On the other hand, the number of tubules with thick tubular basement membrane (TBM) duplication, which was defined as >10-μm thickness, was significantly higher in patients with genetically proven adult NPH than in those without pathogenic mutations. α-Smooth muscle actin (α-SMA)-positive myofibroblasts were detected inside thick TBM duplication. Conclusions In adult patients with NPH, thick TBM duplication was the specific finding. Our analysis also suggested that older patients tended to have no pathogenic mutations, even when they were suspected to have NPH by renal biopsy. These findings could be the novel clinical clue for the diagnosis of NPH in adult patients., Graphical abstract

Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are prescribed as conservative or adjunctive therapies for adult idiopathic nephrotic syndrome. However, studies on real‐world practice patterns are scarce. This study aimed to examine the prevalence and incidence of ACEI/ARB prescription and their associated factors. This nationwide cohort study included adult Japanese patients with idiopathic nephrotic syndrome including minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and others. The outcomes were the prevalence of ACEI/ARB prescription at baseline (date of renal biopsy or date of immunosuppressant initiation) and at 2 months after baseline. Of the 326 eligible patients, 122 (37.4%) had already been prescribed ACEIs/ARBs. Of the remaining 204 patients, 67 (32.7%) were newly prescribed within the 2‐month period. MN/FSGS (vs. MCD, adjusted odds ratio [AOR]: 4.96 [95% confidence interval {CI} 2.53–9.72] and 3.95 [95% CI 1.61–9.66], respectively), higher age (per 1‐yr increase, AOR: 1.02 [95% CI 1.00–1.04]), other hypertensive agents (AOR: 2.18 [95% CI 1.21–3.92]), antidiabetic drug (AOR: 6.57 [95% CI 1.77–24.4]) were associated with a higher prevalence of ACEI/ARB prescription. MN (vs. MCD, AOR: 6.00 [95% CI 2.57–14.0]) and higher baseline systolic blood pressure (SBP) (per 10‐mmHg increase, AOR: 1.36 [95% CI 1.09–1.70]) were associated with a higher incidence of ACEI/ARB prescription. On average, incidence of ACEI/ARB prescription increased from 19.2% to 40.8% as baseline SBP increased from 100 to 140 mmHg. Thus, Japanese nephrologists are likely to prescribe ACEIs/ARBs for nephrotic patients with MN or high baseline SBP, even below the hypertensive range.

Introduction Diagnosing renal pathologies is important for performing treatments. However, classifying every glomerulus is difficult for clinicians; thus, a support system, such as a computer, is required. This paper describes the automatic classification of glomerular images using a convolutional neural network (CNN). Method To generate appropriate labeled data, annotation criteria including 12 features e.g., “fibrous crescent”, were defined. The concordance among five clinicians was evaluated for 100 images using kappa coefficient for each feature. Using the annotation criteria, one clinician annotated 10,102 images. We trained the CNNs to classify the features whose average kappa ≧ 0.4 and evaluated their performance using the receiver operating characteristic – area under the curve (ROC–AUC). An error analysis was conducted and the gradient-weighted class activation mapping (Grad-CAM) was also applied; it expresses the CNN’s focusing point with a heat map when the CNN classifies the glomerular image for a feature. Result The average kappa coefficient of the features ranged from 0.28 to 0.50. The ROC–AUC of the CNNs for test data varied from 0.65 to 0.98. Among the features, “capillary collapse” and “fibrous crescent” had high ROC–AUC values of 0.98 and 0.91, respectively. The error analysis and the Grad-CAM visually showed the CNN could not distinguish between two different features that had similar visual structures or occurred simultaneously. Conclusion The differences in the texture or frequency of the co-occurrence between the different features affected the CNN performance; thus, to improve the classification accuracy, methods such as segmentation are required.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein 2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Introduction: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients’ quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. Methods: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels Results: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (β coefficient −6.935, 95% confidence interval, 13.313 to−0.556, p = 0.034). Conclusion: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

Background Renin-angiotensin system inhibitors (RASis) are recommended as the first-line therapy to reduce proteinuria in primary nephrotic syndrome. It is unclear whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy. Methods This retrospective cohort study included adults with primary nephrotic syndrome from causes other than minimal change disease who were enrolled in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, with a 5-year follow-up period, and were not on RASis at enrolment. The exposure was a new RASi prescription, and the outcome was the first CR, defined as a urinary protein level

Background Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. Methods A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. Results Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. Conclusions Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse.This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors.Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively).The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.

Background Bowel perforation in peritoneal dialysis (PD) is mainly caused during the perioperative period. Delayed bowel perforation is difficult to diagnose because of its heterogenous clinical signs and rarity. Previously, the methods to diagnose delayed bowel perforation were invasive, but computed tomography (CT) peritoneography is now employed as a less invasive method. There have been no literature reviews on delayed bowel perforation, including recent cases using CT peritoneography. Delayed bowel perforation before PD initiation has rarely been reported and was mostly after PD initiation. Here, we present a case and literature review of delayed bowel perforation before PD initiation possibly caused by mechanical compression of the PD catheter implanted by the Moncrief–Popovich technique. Case presentation A PD catheter was embedded in a 57-year-old woman with autosomal-dominant polycystic kidney disease, with the distal end of the PD catheter buried under the skin. She had no gastrointestinal symptoms, except renal failure progression, during conservative therapy. Nine months later, she was admitted to our hospital to exteriorize the distal end of the PD catheter. Immediately after the first PD solution was infused into her abdomen, she complained of watery diarrhea. CT peritoneography revealed an outflow of contrast media through the PD catheter into the luminal side of the sigmoid colon, suggesting an interaction between the PD catheter and the colon. Laparoscopic examination revealed that the lateral side of the PD catheter (5 cm from the catheter tip) had adhered to the sigmoid colon and that a small orifice had formed where the side hole of the catheter was attached to the colon. The lesion was entirely surrounded by fibrous tissue that prevented leakage of the intraluminal contents. After restoring the colon with a colostomy, the patient was treated with hemodialysis. Seven months later, she underwent closure of the colostomy. Conclusions Although perforation of the colon by a PD catheter through the side hole is very rare, it is important to consider the interaction of dialysis fluid with the gut if diarrhea or abdominal pain occurs after PD initiation. CT peritoneography may be helpful in identifying the bowel perforation site with minimal invasiveness.

Background Theoretically, atrial natriuretic peptide (ANP), especially low-dose ANP, is beneficial in acute kidney injury (AKI). In this study, we examined whether low-dose ANP is effective in preventing or treating AKI by conducting an updated systematic review for randomized controlled trials (RCTs). Method We searched the Excerpta Medica database (EMBASE), PubMed, and Cochrane CENTRAL databases for RCTs that compare the effects of low-dose ANP (≤ 50 ng/kg/min) with a placebo or conventional therapy in at-risk patients or patients with AKI. The primary outcome was the incidence of new AKI (in prevention RCTs), while the secondary outcomes were in-hospital mortality rate, renal replacement therapy (RRT) requirement, length of hospital and intensive care unit (ICU) stay, incidence of hypotension, and peak serum creatinine levels. The risk-of-bias was evaluated using the Cochrane Collaboration risk-of-bias tool. Trial sequential analysis (TSA) was used for each outcome of interest. Results A total of 18 RCTs (16 prevention and two treatment trials) fulfilled our inclusion criteria. In prevention RCTs, the incidence of new AKI was significantly low in the low-dose ANP group (relative risk [RR] = 0.51; 95% confidence interval [CI] = 0.36–0.72; P = 0.0001) compared to the control group. In addition, the low-dose ANP group showed a significantly reduced RRT requirement in both prevention (RR = 0.17; 95% CI = 0.04–0.64; P = 0.009) and treatment (RR = 0.43; 95% CI = 0.20–0.93; P = 0.03) RCTs. Among secondary outcomes, in some cases, low-dose ANP was associated with a reduction in ICU and in-hospital stay. The risk-of-bias assessment and TSA results indicated that the sample sizes and qualities of the RCTs were insufficient to conclude the efficacy of low-dose ANP. Conclusion Low-dose ANP might be effective in preventing or treating AKI. However, the evidence accumulated so far is not strong enough to demonstrate ANP’s beneficial effects. The next step is to elucidate the effects of low-dose ANP by conducting multicenter, high-quality, large-sample RCTs. Trial registration PROSPERO registry CRD42017068568. Registered 20 June 2017. Electronic supplementary material The online version of this article (10.1186/s13054-019-2330-z) contains supplementary material, which is available to authorized users.

Background : Schizophrenia is a devastating mental disease that affects approximately 1% of the world's population. Breast cancer is the second most common type of cancer in the world that causes death in women. It is often unclear whether patients with schizophrenia receive recommended cancer treatment that met the guideline. This study characterized breast cancer treatment disruptions in schizophrenia patients and sought to identify and resolve correctable predictors of those disruptions. Materials and methods : A retrospective cohort study was conducted on 55 primary breast cancer patients diagnosed with schizophrenia and treated for breast cancer. We evaluated the characteristics of the breast cancer patients with schizophrenia compared to those of 610 breast cancer patients without schizophrenia. Results : Compared to the control group, the schizophrenia group had significantly advanced T and N factors and disease stage. Significantly fewer patients in the schizophrenia group than in the control group received chemotherapy (p Conclusions : Patients with schizophrenia are often diagnosed with breast cancer in advanced stages. In addition, patients with schizophrenia with reduced ADL are less likely to receive chemotherapy or recommended cancer treatment. It is highly recommended that patients with schizophrenia undergo breast cancer screening so that they can be diagnosed early and treated adequately. Micro Abstract : Patients with schizophrenia are often diagnosed with breast cancer in advanced stages. In addition, patients with schizophrenia with reduced ADL are less likely to receive chemotherapy or standard treatment. It is highly recommended that patients with schizophrenia undergo breast cancer screening so that they can be diagnosed early and treated adequately.

Background Pregnancy in dialysis patients is rare but challenging both for nephrologists and obstetricians. Although intensified hemodialysis is effective to achieve favorable clinical outcomes in this clinical setting, the evidence concerning reliable parameters for the optimal dialysis prescription is scarce. Herein, we report a case of a primigravida with advanced maternal age who underwent a normal spontaneous vaginal delivery at full term managed by intensified hemodialysis, and discuss reliable indicators of the appropriate dialysis prescription. Case presentation A 39-year-old primigravida with end-stage renal disease was referred to our department for hemodialysis management during pregnancy. She had a history of multiple gynecologic disorders, including cervical dysplasia, right tubal ectopic pregnancy and spontaneous abortion; consequently, she conceived through in vitro fertilization and embryo transfer. After pregnancy was confirmed, an intensified hemodialysis schedule with weekly duration of 36 hours was employed to prevent volume overload and the accumulation of hyperosmotic substances. Utilizing maternal blood pressure, plasma atrial natriuretic peptide levels and fetal development as indicators of volume status, we incremented her dry weight by 300–400 g per week in the first and second trimester and 100–200 g per week in the third trimester, respectively. Serum urea nitrogen levels were persistently maintained below 50 mg/dL. Throughout pregnancy, fetal growth and development were within normal limits. At 38 weeks and 3 days of gestation, she delivered a healthy child vaginally without complications. To date, the child’s development has been normal, both physically and mentally. Conclusions Pregnancy in dialysis patients with advanced age that leads to a normal childbirth is exceptionally rare. Our case is the hemodialysis patient with the most advanced age who achieves a normal spontaneous vaginal delivery at full term. Considering that cardiovascular system and endogenous metabolism dynamically alter during pregnancy, various clinical parameters should be closely monitored to modify dialysis settings accordingly. Of note, our case suggests that plasma atrial natriuretic peptide level is a useful parameter for the appropriate dry weight. Intensified hemodialysis is an effective and reliable measure that can achieve normal pregnancy in dialysis patients, even in a primigravida with advanced maternal age.

The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593–4.745, p = 0.000) in the multivariate Cox’s model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

Systemic lupus erythematosus (SLE) may be associated with various types of malignancy. However, SLE occurring with ovarian cancer seems rare, and reliable therapeutic approaches for such cases have yet to be identified. We herein report a case of SLE with ovarian cancer that was successfully treated with corticosteroid, plasmapheresis and chemotherapy. This case may provide new insights into treatment approaches for SLE with ovarian cancer.

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.

The lack of high-quality clinical evidences hindered broad consensus on optimal therapies for primary nephrotic syndromes. The aim of the present study was to compare prevalence of immunosuppressive drug use in patients with primary nephrotic syndrome across 6 regions in Japan. Between 2009 and 2010, 380 patients with primary nephrotic syndrome in 56 hospitals were enrolled in a prospective cohort study [Japan Nephrotic Syndrome Cohort Study (JNSCS)], including 141, 151, and 38 adult patients with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), respectively. Their clinical characteristics were compared with those of patients registered in a large nationwide registry of kidney biopsies [Japan Renal Biopsy Registry (J-RBR)]. The regional prevalence of use of each immunosuppressive drug was assessed among adult MCD, MN, and FSGS patients who underwent immunosuppressive therapy in the JNSCS (n = 139, 127, and 34, respectively). Predictors of its use were identified using multivariable-adjusted logistic regression models. The clinical characteristics of JNSCS patients were comparable to those of J-RBR patients, suggesting that the JNSCS included the representatives in the J-RBR. The secondary major immunosuppressive drugs were intravenous methylprednisolone [n = 33 (24.6%), 24 (19.7%), and 9 (28.1%) in MCD, MN, and FSGS, respectively] and cyclosporine [n = 25 (18.7%), 62 (50.8%), and 16 (50.0%), respectively]. The region was identified as a significant predictor of use of intravenous methylprednisolone in MCD and MN patients. Use of intravenous methylprednisolone for MCD and MN differed geographically in Japan. Its efficacy should be further evaluated in a well-designed trial.

IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of IRGN, which needs to be distinguished from IgA nephropathy (IgAN). Thirteen patients with IgA-IRGN (IgA-IRGN group) and 122 with IgAN (IgAN group) were selected from 1788 patients who underwent kidney biopsy between 2000 and 2015 in Kitano Hospital. Data selected included clinical and serological parameters; light and electron microscope findings; immunofluorescence findings; and prognostic parameters like renal and overall survival and creatinine increase by > 50%. In addition, a 26-patient IgAN cohort (matching-IgAN), matching with IgA-IRGN group with respect to age, sex, estimated glomerular filtration rate (eGFR), and proteinuria was segregated for comparison. Compared to IgAN group, IgA-IRGN group were older, had lower hemoglobin, higher CRP, lower eGFR, heavier proteinuria, lower serum albumin, and higher serum IgG and IgA levels (p

Background Secondary hyperparathyroidism (SHPT) is a common complication in patients receiving chronic dialysis therapy. Although cinacalcet can control parathyroid function and bone turnover, preventing ectopic calcification remains challenging. Cinacalcet can also suppress PTH secretion due to parathyroid carcinoma in the same way as it does for parathyroid hyperplasia in the uremic condition. We present a case of parathyroid carcinoma partially controlled by cinacalcet, in which tumorous calcinosis was successfully resolved by total parathyroidectomy. Case presentation A female patient in her forties who had received dialysis for 12 years was referred to our hospital for painful ectopic calcifications on her right hip joint and both knees. Although she had been treated with alfacalcidol and cinacalcet for 2 years, this therapy had been discontinued 6 months earlier as a result of hypercalcemia. The patient exhibited normocalcemia (2.37 mmol/L) and hyperphosphatemia (2.42 mmol/L) with elevated intact parathyroid hormone (707,000 μg/L). Ultrasonography revealed an enlarged parathyroid gland on the left lower side of the thyroid gland. The otolaryngologist surgeons had to perform an en bloc excision to remove this parathyroid gland because of tight adhesions. Histological examination revealed that parathyroid cells had invaded the surrounding skeletal muscle through fibrous capsules, consistent with parathyroid carcinoma. Her joint pain disappeared 2 weeks after parathyroidectomy, and the tumorous calcinosis had largely resolved after 1 year. Conclusions Parathyroid carcinoma is a rare cause of hyperparathyroidism in end-stage kidney disease. Our case indicates that the use of cinacalcet hinders the diagnosis of parathyroid carcinoma in a chronic dialysis patient. When uncontrolled hypercalcemia and/or hyperphosphathemia develop during cinacalcet administration, parathyroidectomy should be considered to prevent a vicious exacerbation of ectopic calcification.

Background Poststreptococcal acute glomerulonephritis (PSAGN) in the elderly tends to have a severe clinical course and often presents with crescentic necrotizing glomerulonephritis in the renal biopsy. However, vasculitis lesions are unusual. Case presentation We present a 71-year-old man who was admitted to our hospital for a recurrent gout attack with a rapid decline of renal function. Low C3 levels and a high anti-streptolysin O titer were observed, while myeloperoxidase- and proteinase 3- antineutrophil cytoplasmic antibody (ANCA) were negative. In addition to cellular crescent and necrosis lesions, diffuse peritubular capillaritis and venulitis as well as small arteriole vasculitis in the glomerular hilus were also apparent. Although granular C3c deposits in the capillary wall and hump lesions were not found, immunofluorescent staining for nephritis-associated plasmin receptor (NAPlr) and in situ zymography for plasmin activity were both positive. We thus diagnosed PSAGN accompanied by small vessel vasculitis. Steroid therapy gradually improved the patient’s renal function, and hemodialysis was discontinued after 1 month. Conclusions In our case, streptococcus infection might have concurrently provoked vasculitis, and NAPlr staining was useful for confirming diagnosis.

Background and objectives Smoking is a well known risk factor of proteinuria in adults; however, clinical studies in children are limited. The purpose of this study is to clarify the associations of maternal smoking during pregnancy and household smoking after the child’s birth with the risk of proteinuria at age 3 years old. Design, setting, participants, & measurements We performed a population–based retrospective cohort study on 44,595 children using data on prenatal health checkups, home visit neonatal health checkups, and health checkups at 4, 9, and 18 months and 3 years of age in Kobe City, Japan. Maternal smoking status (nonsmoker, past smoker, or current smoker) was collected with standardized questionnaires. The outcome of interest was the presence of proteinuria at 3 years of age defined as urinary protein ≥1+. To evaluate the association between child proteinuria and smoking status, we performed multivariate logistic regression model analyses adjusted for confounding factors. Results The prevalence rates of children in the maternal smoking groups (none, past, and current) were 78.9%, 4.4%, and 16.7%, respectively. The frequencies of child proteinuria defined as ≥1+ urinary protein were 1.7% in the current smoking group, 1.6% in the past smoking group, and 1.3% in the nonsmoking group. Maternal smoking during pregnancy was associated with child proteinuria (odds ratio, 1.24; 95% confidence interval, 1.00 to 1.52; P=0.05) in the multiple logistic regression model, although nonmaternal family smoking during pregnancy was not significantly associated with child proteinuria (odds ratio, 0.97; 95% confidence interval, 0.79 to 1.19; P=0.77). We also found a similar association with household smoking after the child’s birth (odds ratio, 1.23; 95% confidence interval, 0.99 to 1.54; P=0.06), although this observation was not significant. Conclusions Maternal smoking during pregnancy was one of the risk factors of childhood proteinuria. We also found a similar association with household smoking after the child’s birth, although this observation was not significant.

A fatal mix-up of a hemofilter with a plasma separator occurred in 2011. The close resemblance between the two blood purification columns commonly used in Japan posed a fundamental risk for such mix-ups. Both the in-hospital case investigation committee and the relevant academic societies have independently proposed the modifications of the dialysate port (D port) of the plasma separator to avoid this type of misuse. To make these devices foolproof, medical professionals, including physicians and clinical engineers, and members of the Medical Technology Association of Japan discussed measures to prevent this type of recurrence. Since new standards were soon to be issued by the International Organization for Standardization (ISO), the modifications were temporarily postponed. In September 2016, the ISO released new standards for small-bore connectors. The shape changes of the D port from the current slip-in type (ISO8637) to the Luer lock type (ISO80369-7) had been already approved by the Ministry of Health, Labor and Welfare of Japan by the end of November 2018, including a temporal use of a converter to connect the current type of D port to the new type of blood circuit. We must address the next issue that the new standard and the older standard coexist in the clinical setting, which may create a new risk.

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search.

Shusuke Hiragi,1,2 Hiroyuki Yamada,1 Tatsuo Tsukamoto,1,3 Kazuki Yoshida,4,5 Naoya Kondo,1 Takeshi Matsubara,1 Motoko Yanagita,1 Hiroshi Tamura,2 Tomohiro Kuroda2 1Department of Nephrology, Graduate School of Medicine, Kyoto University, 2Division of Medical Informatics and Administration Planning, Kyoto University Hospital, Kyoto, 3Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan; 4Department of Epidemiology, 5Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA Background: Acetaminophen (APAP) is frequently used for analgesia and is considered safer than nonsteroidal anti-inflammatory drugs (NSAIDs) for the kidneys. However, there is little epidemiological evidence of the association between APAP and acute kidney injury (AKI).Objectives: To examine the association between APAP and AKI using the self-controlled case series (SCCS) method, which is a novel strategy to control between-person confounders by comparing the risk and reference periods in each patient.Methods: We performed SCCS in 1,871 patients (39.9% female) who were administered APAP and subsequently developed AKI, by reviewing electronically stored hospital information system data from May 2011 to July 2016. We used conditional Poisson regression to compare each patient’s risk and reference period. As a time-varying confounder, we adjusted the status of liver and kidney functions, systemic inflammation, and exposure to NSAIDs.Results: We identified 5,650 AKI events during the 260,549 person-day observation period. The unadjusted incidences during the reference and exposure periods were 2.01/100 and 3.12/100 person-days, respectively. The incidence rate ratio adjusted with SCCS was 1.03 (95% confidence interval [CI]: 0.95–1.12). When we restricted endpoints as stage 2 AKI- and stage 3 AKI-level creatinine elevations, the incidence rate ratios were 1.20 (95% CI 0.91–1.58) and 1.20 (95% CI 0.62–2.31), respectively, neither of which was statistically significant.Conclusion: Our findings added epidemiological information for the relationship between APAP administration and AKI development. The results indicated scarce association between APAP and AKI, presumably supporting the general physicians’ impression that APAP is safer for kidney. Keywords: acetaminophen, acute kidney injury, adverse drug event, self-controlled case series, hospital information system

Background: In order to keep up the optimal iron status in chronic hemodialysis patients, it is important to know how much iron is lost due to hemodialysis. Residual blood associated with the hemodialysis procedure together with blood sampling inevitably causes the loss of iron in chronic hemodialysis patients. Recent advances in hemodialysis techniques might have reduced this complication. In this cross-sectional study, we directly measured total iron loss by hemodialysis. Methods: Two hundred thirty-nine patients who received chronic hemodialysis at Otowa Memorial Hospital were enrolled; 65.7% of patients were men, and mean age was 67 ± 6.4 years (mean ± SD) and 43.2% were diabetic. Residual blood in blood tubing set and dialyzer after rinse back with saline was collected and homogenized. The iron content including free, protein-bound and heme iron was measured using an atomic absorption spectrometry. Results: The mean iron content in residual blood was 1,247.3 ± 796.2 µg (mean ± SD) and the median was 1,002 µg (95% CI 377.6-3,461.6 µg), indicating 160.8 mg (95% CI 58.9-540.0 mg) iron loss annually when hemodialysis was performed 156 times a year. Fifty milliliter whole blood for monthly blood test and another 2 ml of whole blood lost by paracentesis at every dialysis session contains 228.6 and 118.9 mg iron at 11 g/dl hemoglobin, respectively. Therefore, an annual total iron loss due to hemodialysis comes to 508.3 mg (95% CI 406.4-887.5 mg). Conclusions: Five hundred milligram of annual iron supplementation might be sufficient to maintain iron status in hemodialysis patients, which is less than the dose recommended as 1,000-2,000 mg a year. Further study will be required to verify this iron supplementation dosage with recent hemodialysis procedure.

Aim The role of urinary (U-) thioredoxin (Trx), a class of small redox proteins, in physiological and pathological conditions, in addition to its gender specificity, has been insufficiently determined in chronic kidney disease (CKD) patients, especially in diabetes mellitus (DM) nephropathy. Methods U-Trx was measured cross-sectionally in 110 CKD outpatients with estimated glomerular filtration rate (eGFR) of >15 mL/min per 1.73 m2, namely, in 57 type 2 DM patients (male: n = 41, female: n = 16) and 53 non-DM patients (M: n = 33, F: n = 20), as well as 30 healthy controls (M: n = 11, F: n = 19). Comparisons were made among controls, DM and non-DM, and between M and F, with clinical parameters compared in each group. In addition, a comparison between average U-Trx level and the changes of renal function during a one-year period was performed. Results U-Trx was significantly higher in females than in males in controls (P

Pregnancy and membranous nephropathy (MN) can occur concurrently with nephrotic syndrome. However, the pathophysiology of MN associated with pregnancy remains unclear, including the involvement of anti-M-type phospholipase A2 receptor (PLA2R) antibody, the major antigen of idiopathic MN (iMN). A treatment for the condition is also not established. We present the case of a 43-year-old pregnant female with incidental proteinuria and hypoalbuminemia. We made a diagnosis of nephrotic syndrome at 11 week gestation. Renal biopsy revealed iMN using predominant granular staining of IgG4 along the glomerular basement membrane. No secondary cause was identified. Oral glucocorticoid therapy was started from 17 week gestation and induced complete remission at 28 week gestation. A healthy infant was born at 38 week gestation. Glucocorticoid therapy was stopped postpartum without MN relapse. Anti-PLA2R antibody was later found to be positive using serum reserved from before treatment. In conclusion, we presented the case of a pregnant woman with iMN and anti-PLA2R antibodies, whose nephrotic syndrome was successfully controlled with oral glucocorticoids to reach complete remission, even after tapering off the medication. Pregnancy per se might be associated with iMN onset.

It is suggested that altered neuroplasticity contributes to the pathophysiology of schizophrenia and antipsychotics may exhibit some of their therapeutic efficacies by improving neurogenesis and/or proliferation of neural progenitors. The aim of this study is to investigate whether chronic antipsychotics treatment affect neurogenesis in adult mouse hippocampus. Animals were administered olanzapine, quetiapine, clozapine, risperidone, aripiprazole, or haloperidol via the osmotic minipump for 21days and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. BrdU-positive cells in the hippocampus were quantified by stereology. Aripiprazole, quetiapine, clozapine, and olanzapine significantly increased density of BrdU-positive cells in the hippocampus. Interestingly, other antipsychotic drugs had tendency to increasing BrdU-positive cells, whereas haloperidol had propensity to decrease with a marginal significance. These results suggest that differences of neurogenesis among these drugs may, at least in part, account for their pharmacological profiles.

Diabetic nephropathy is a leading cause of end-stage kidney disease in the world. Although various types of treatment for diabetes, hypertension and dyslipidemia have improved prognosis and quality of life in patients with diabetic nephropathy, there still exist some diabetic patients with severe proteinuria showing poor prognosis. This clinical trial, LICENSE, aims to confirm the impact of LDL apheresis on proteinuria exhibiting hyporesponsiveness to treatment. This ongoing trial is a multicenter, prospective study of diabetic patients with severe proteinuria. The objective is to examine the impact of LDL apheresis on proteinuria in patients with diabetic nephropathy. The other subject is to investigate safety of LDL apheresis in these patients. The subjects consist of diabetic patients with serum creatinine (Cr) levels below 2 mg/dL who present severe proteinuria above 3 g/g Cr or 3 g/day and LDL cholesterol above 120 mg/dL. The target number of registered patients will be 35 patients. Urinary protein excretion and renal function will be observed for 24 weeks after the treatment of LDL apheresis. This study will determine the effectiveness and safety of LDL apheresis for diabetic nephropathy patients with severe proteinuria and dyslipidemia.

Soluble fms-like tyrosine kinase-1 (sFlt1), a circulating vascular endothelial growth factor receptor 1 antagonist, is associated with the pathogenesis of pre-eclampsia. Extracorporeal removal of sFlt1 (sFlt1 apheresis) is emerging as a treatment for pre-eclampsia. We performed sFlt1 apheresis for a patient with very early onset pre-eclampsia, beginning at 15 weeks' gestation. She underwent sFlt1 apheresis 13 times from 19 to 23 weeks' gestation. The series of treatments lowered circulating sFlt1, stabilized blood pressure, reduced urinary protein, and preserved renal function, which contributed to a successful prolongation of pregnancy for 4 weeks and a live birth at 23(+3) weeks' gestation. Further studies are necessary for clinical application of sFlt1 apheresis as sFlt1 might have a protective function for the placenta and fetus in pre-eclampsia.

Renal-limited vasculitis (RLV) is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that presents with crescentic glomerulonephritis with no other organ involvement. Although several studies reported patients with crescentic glomerulonephritis who were dual positive for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA or ANCA and anti-glomerular basement membrane (GBM) antibody, patients positive for all three antibodies, i.e., triple-positive patients, were rarely reported. We herein report the case of a male with pauci-immune type crescentic glomerulonephritis positive for MPO-ANCA, PR3-ANCA, and anti-GBM antibody. Renal biopsy led to the definitive diagnosis of RLV with pauci-immune-type crescentic glomerulonephritis. Fluorescence immunostaining showed no linear deposition of IgG on GBM, indicating no involvement of anti-GBM associated diseases. Intensive therapy, including prednisolone, plasma exchange, and intravenous cyclophosphamide, was effective. We report the case of triple-positive patient with crescentic glomerulonephritis, who was successfully treated with glucocorticoid, plasma exchange, and cyclophosphamide, suggesting that treatment for RLV in the patient with serological triple antibodies positivity in the absence of linear IgG deposition could benefit from the combination therapy regimen for plasma exchange and primary induction of remission against microscopic polyangiitis.

Background Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) could improve the hemodynamic status of septic shock patients. As PMX-DHP is an invasive and costly procedure, it is desirable to estimate the therapeutic effect before performing the therapy. However, it is still unclear when this therapy should be started and what type of sepsis it should be employed for. In this study, we retrospectively examined the clinical effect of patients treated with PMX-DHP by using central venous pressure (CVP). Methods Seventy patients who received PMX-DHP for septic shock during the study period were recruited and divided into a low CVP group (n = 33, CVP

The present study was performed to clarify the role of high calcium concentration and the appearance of mononuclear cells at the resorptive site in bone remodeling. Our recent study revealed that the high concentration of extracellular calcium ([Ca2+]e) stimulated DNA synthesis in osteoblastic MC3T3-E1 cells not only directly but also indirectly via monocytes. Human monocyte-conditioned medium (CM) significantly stimulated DNA synthesis and inhibited alkaline phosphatase (ALP) activity. In contrast, when monocytes were cultured at high [Ca2+]e concentrations (more than 3 mM), CM from these monocytes significantly stimulated ALP activity in MC3T3-E1 cells. Such stimulatory effect of CM was not observed at a high magnesium concentration (Mg2+, 5 mM). Treatment of monocytes with the calcium ionophore A23187 did not affect the CM-induced effect on DNA synthesis and ALP activity in these cells. To determine the migration potency of MC3T3-E1 cells and monocytes toward the high [Ca2+]e, chemotaxis assay was performed. The increasing [Ca2+]e (more than 3 mM) induced a chemotactic response of MC3T3-E1 cells as well as monocytes, but the high concentration of Mg2+ (5 mM) did not induce it. On the other hand, treatment with high [Ca2+]e (more than 3 mM) or CM significantly inhibited the 1,25-(OH)2D3-induced formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNC) from their precursors derived from mouse spleen cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: The pathological role of obesity in the progression of glomerular lesions has rarely been studied in primary glomerular diseases. The purpose of this study is to investigate the influence of non-diabetic obesity on clinicopathological findings in IgA nephropathy. Methods: 74 patients with biopsy-proven IgA nephropathy were retrospectively divided into two groups according to the criteria for obesity in Japan: non-obese group (group N: n = 50) with BMI 2, and obese group (group O: n = 24) with BMI ≥25 kg/m2. Clinical and pathological data at the time of renal biopsy were analyzed. Moreover, the outcome of proteinuria in patients treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) was evaluated in different groups after a 1-year follow-up. Results: Urinary protein excretion was significantly greater in the obese group compared to normal-weight patients (p < 0.05). There was no significant difference in the prevalence of hypertension and hyperlipidemia. By light microscopy, the obese group showed significantly larger glomerular size (p < 0.0001). On the other hand, the severity of mesangial matrix expansion and crescent formation revealed no difference between the two groups. By electron microscopy, glomerular basement membrane (GBM) thickness was significantly increased in obese patients (p < 0.001). Among 61 patients who were followed up for 1 year in our institute, 15 patients were treated with ACE-I or ARB without steroids. ACE-I or ARB treatment without steroids tended to reduce proteinuria in the obese patients, but this change did not achieve statistical significance. Conclusions: In IgA nephropathy, obesity induces not only glomerular enlargement but also ultrastructural modification of GBM, which would contribute to increase proteinuria.

Nephronophthisis (NPHP) is a disease characterized by a genetic cause of chronic renal failure in children and adolescents, complicated with several extra-renal manifestations such as retinal defect and/or liver fibrosis. Although it is difficult to establish the correct diagnosis, mutations in six genes (NPHP 1-6) have recently been identified. Here we report the case of a 25-year-old male with NPHP with congenital hepatic fibrosis. He showed microscopic hematuria and moderate proteinuria at 20 years. Renal biopsy revealed severe interstitial fibrosis, diffuse tubular atrophy and microcysts at this time with chronic kidney disease stage III (Cr 2.43 mg/dl). C3c was positive in glomeruli in direct immunofluorescent study. Although his mother belongs to a family with polycystic kidney disease, he did not have a novel genetic background of Arg585Cys mutation in exon 8 of the PKD1 gene. Magnetic resonance angiography (MRA) showed typical portal hypertension with spleno-renal shunt caused by biopsy-proven liver fibrosis. Thus, we diagnosed him as having undetermined renal cystic or tubulo-interstitial disease complicated with membranoproliferative glomerulonephritis (MPGN). Renal transplantation was performed in January 2005 after 2 years of dialysis therapy. He was transported to our emergency room because of severe abdominal pain in December 2005. A computed tomographic scan showed massive ascites, which were caused by rupture of the splenic artery. Despite full intensive care including intraluminal coiling of the ruptured aneurysm and extensive blood transfusion, we failed to rescue him on the next day. The autopsy findings revealed severe atrophy of the bilateral kidney with multiple cysts along the cortico-medullary border. Obvious portal hypertension, resulting from congenital hepatic fibrosis, could account for the rupture of the splenic artery with aneurysm formation under pressure/volume overload. This is the first report of a NPHP patient with the complication of hepatic fibrosis emerging from an ADPKD family. As it remains elusive on the phenotype–genotype of the Japanese NPHP population, a registration system of cystic disease of the kidney is required.