IgA Nephropathy: Beyond the Half-Century.

In 1968, Jean Berger first introduced the medical world to IgA nephropathy (IgAN). Fifty-five years later, its pathogenesis is still unclear, but treatments such as renin-angiotensin-aldosterone system inhibitors (RAAS-Is), tonsillectomies, and glucocorticoids are currently used worldwide. There have been great strides in the past 20 years since the discoveries of the specific dysregulation of mucosal immunity, galactose-deficient IgA1 (Gd-IgA1), and Gd-IgA1 immune complexes in patients with IgAN. According to these findings, a multi-hit hypothesis was developed, and this multi-hit hypothesis has provided several putative therapeutic targets. A number of novel agents, including molecularly targeted drugs for targets such as APRIL, plasma cells, complement systems, and endothelin, are undergoing clinical trials. Some candidate drugs have been found to be effective, with minimal side effects. Over half a century after the discovery of IgAN, these therapies will soon be available for clinical use.

Post-Operative Kidney Function Using Deep Hypothermic Circulatory Arrest (DHCA) in Aortic Arch Operation.

Background: Although deep hypothermic circulatory arrest (DHCA) is a useful option to protect the central nervous system during aortic arch operations, the influence of simultaneous renal ischemia remains controversial. Patients and Methods: This is a retrospective observational study. Sixty-three patients who underwent thoracic aortic surgery with DHCA and 24 patients who underwent cardiac surgery without DHCA were included in this study. The mean age, preoperative serum creatinine (Cr) level, preoperative estimated glomerular filtration rate (eGFR), peak serum Cr level up to 48 hrs post-operative, elevation rate of Cr compared to the preoperative serum Cr, urine volume rate up to 48 hrs post-operative and AKI staging using the KDIGO criteria were estimated for each patient. Clinical parameters for 3 months after the operation and the 3-month post-operative mortality rate were assessed. Mean values indicating kidney function or distribution of the AKI stages were compared between patients with and without DHCA. Patients with DHCA were further divided according to the duration of ischemia to compare the values for the kidney function of each group, distribution of AKI stages and mortality. Results: The parameters indicating AKI of the patients with DHCA were significantly more severe than those without DHCA. Patients who had undergone an ischemic state for more than 40 min revealed significantly higher peak serum Cr, elevation rate of serum Cr, less urine volume up to 48 hrs post-operative compared with those without DHCA. Distribution of the AKI stages was related to the duration of ischemia. The 3-month post-operative mortality of the patients with DHCA was significantly higher than those without DHCA. Limitations: This study had limitations such as its retrospective design and small number patients, and the data will be required confirmation with other prospective studies. Conclusion: DHCA is closely related to AKI up to 48 hrs post-operative and death during the 3 months following surgery.

The Influence of an Unexpected Switch of Hemodialysis Facilities on the Quality of Life (QOL) in Hemodialysis Patients.

Background: We experienced a sudden breakdown of hemodialysis system during a clinical study of dermal itch and serum BNP concentrations. Patients and Methods: Forty-eight hemodialysis patients were enrolled in the itch-related study. It was intended to improve itch by lowering BNP with supportive communication between the patients and the dialysis staff. We planned to collect data, including visual analogue scale (VAS), dermatology life quality index (DLQI), blood samples and QOL score (KDQOL-SF), four times over a four week interval. The first data was obtained just prior to switching facilities due to a breakdown. The patients underwent hemodialysis in other facilities for two weeks and underwent determination of their clinical data, including QOL scores, three times. Results: While mean blood pressure showed no significant differences, serum albumin, iron and phosphate levels were worsened significantly between pre- and post-relocation. Serum BNP and DLQI showed no significant changes. VAS was significantly worsened. The mean values of the cognitive function in the KDQOL-SF and sleep and the role-physical, role-emotional, social function, dialysis staff's encouragement in SF-36 analysis were identified as statistically significant items by MANOVA. Both SF-12 physical and mental composites were also statistically significant. Although SF-12 physical composites were significant among the patients under 66 yrs of age (median), eight factors were significant among those over 66 yrs. Independent analyses revealed every item that was detected worsened significantly after the switch of facilities. Conclusion: Unexpected switching of hemodialysis facilities severely impacts the QOL for a long duration as well as the patients' symptom and laboratory data.

Immunotactoid Glomerulopathy with Nontuberculous Mycobacterial Infection: A Novel Association.

A 70-year-old woman underwent a renal biopsy due to nephrotic syndrome. She had suffered from nontuberculous mycobacterial infection (NTM) for 14 years. The patient was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type 3 and immunoglobulin (Ig)-associated MPGN based upon LM/erythromycin and IF findings, respectively. In high-magnification imaging, electron-dense deposits showed immunotactoid glomerulopathy (ITG). There was no evidence of hematological cancer, and the patient improved after receiving treatments for NTM. To the best of our knowledge, this patient is the first to show an association between ITG and NTM. Although ITG is generally considered as related to lymphoproliferative disease, it is suggested that ITG is driven by bacterial infection and is a potential outcome of Ig-associated MPGN.

Oxidative stress and Liver X Receptor agonist induce hepatocellular carcinoma in Non-alcoholic steatohepatitis model.

BACKGROUND AND AIM: The incidence of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is progressively increasing. However, the pathophysiology and etiology of NASH progression to HCC are unknown. We hypothesized that steatosis was the key factor in NASH-related hepatocarcinogenesis and aimed to evaluate the effects of long-term liver X receptor (LXR) agonist stimulation on hepatic steatosis induced by a high-fat diet and oxidative stress. METHODS: We used an LXR agonist (T0901317) and CCl4 to induce hepatic steatosis and oxidative stress, respectively. C57BL/6 mice fed with a high-fat diet were treated with either T0901317 + CCl4 (T09 + CCl4 group) or CCl4 alone (CCl4 group). T0901317 (2.5 mg/kg) and CCl4 (0.1 mL/kg) were intraperitoneally administered twice weekly for 24 weeks. RESULTS: The liver-to-body weight ratio was significantly higher in the T09 + CCl4 group than in the CCl4 group. Mice in the T09 + CCl4 group exhibited abnormal lipid metabolism and NASH-like histopathological features. Additionally, all mice in the T09 + CCl4 group developed liver tumors diagnosed as well-differentiated HCC. The genes identified via microarray analysis were related to NASH and HCC development. CONCLUSIONS: By combining long-term LXR agonist stimulation with oxidative stress and a high-fat diet, we successfully reproduced liver conditions in mice similar to those in humans with NASH and progression to HCC. Our results provide new insight into NASH-related HCC progression and therapy.

A novel hydrogel sheet prevents postoperative pancreatic fistula in a rat model.

AIM: To evaluate the efficacy of a novel hydrogel sheet in preventing postoperative pancreatic fistula (POPF). BACKGROUND: Postoperative pancreatic fistula is a life-threatening complication. As no study has reported the use of hydrogel sheets in preventing POPF, their effectiveness for that purpose remains unclear. METHODS: A novel hydrogel sheet made of polyvinyl alcohol (PVA) was prepared by the freeze-thaw method. The pancreatic ducts and surrounding pancreatic parenchyma of rats were transected to induce a pancreatic fistula. Next, the sheet was attached to the transection site. Ascitic fluid amylase and lipase concentrations were measured. Neoveil® , a nonwoven polyglycolic acid (PGA) felt, is already clinically used as an absorbable reinforcing material at pancreatic transection sites. Neoveil® was used for comparison, as was VIEWGEL® , which is marketed as a wound dressing. RESULTS: The hydrogel sheet remained in place 48 hours postoperatively. The ascitic amylase concentrations in the control, VIEWGEL® -treated, Neoveil® -treated, and hydrogel-treated rats, respectively, were 4992.4 ± 5355.7, 1068.4 ± 269.1, 730.2 ± 425.2, and 303.1 ± 240.1 IU/L; the ascitic lipase concentrations were 2279.8 ± 3395.2, 169.5 ± 100.6, 90.4 ± 71.0, and 86.8 ± 59.8 IU/L. The ascitic amylase and lipase levels were significantly lower in the hydrogel group than in the other groups (P < .05). CONCLUSIONS: This novel hydrogel sheet effectively prevents pancreatic fistulas and has promising clinical application potential.

[Salvage Surgery for Unresectable Advanced Esophagogastric Junction Carcinoma with Multiple Liver Metastases after Successful Second-Line Treatment with Nab-Paclitaxel and Ramucirumab Following a Refractory Response to S-1 plus CDDP Therapy-A Case Report].

We report a case of unresectable advanced esophagogastric junction carcinoma that was treated with nab-paclitaxel and ramucirumab, which resulted in complete response and salvage surgery. A 57-year-old male complained of upper abdominal discomfort. While attending a hospital for diabetes mellitus, upper gastrointestinal endoscopy was performed. A tumor protruding from the gastric cardia to the abdominal esophagus was found, and histological examination revealed well-differentiated adenocarcinoma. Multiple liver metastases and para-aortic lymph node metastases were found on abdominal contrast-enhanced CT. The patient was diagnosed with stage Ⅳ cancer, and chemotherapy was performed as unresectable advanced esophagogastric junction carcinoma. S-1 plus CDDP therapy was started as the first-line treatment. After 2 courses of S-1 plus CDDP therapy, tumor markers were elevated. Further, the cancer was judged to be highly toxic and refractory to treatment; therefore, we started nab-paclitaxel and ramucirumab as the secondary treatment. After 4 courses, normalization of tumor markers, disappearance of liver metastases, and marked reduction of enlarged lymph nodes were observed. However, PET-CT showed increased uptake, consistent with the primary lesion. Residual cancer could not be ruled-out; therefore, total gastrectomy was performed. Histopathological examination of the surgically resected specimen showed no residual tumors.

A patient with colitis-associated cancer who developed clinically manifest Crohn's disease only after surgery.

BACKGROUND: Patients with prolonged inflammatory bowel disease have a greater risk of colorectal cancer, known as colitis-associated cancer. Here we describe an unusual case of colitis-associated cancer. CASE PRESENTATION: The subject is a 41-year-old male who has not presented digestive symptoms and has an appreciable medical history. He consulted a nearby doctor with left flank pain. A colonoscopy revealed a lateral spreading tumor (granular-type) in his descending colon. With a clinical diagnosis of cancer, D3 left hemicolectomy was performed and a small intestine stoma was constructed. The pathological diagnosis of the tumor was mucinous adenocarcinoma, pT4a(SE), pN2a, which was associated with dysplasia in the surface area. Post-operative ileus was prolonged and the endoscopic examination revealed longitudinal ulcers in the ileum. These ulcers responded quite well to the administration of infliximab, confirming the final diagnosis of Crohn's disease. Pathological re-examination revealed that the tumor was dysplasia-associated type, and another dysplasia was confirmed near the tumor. Furthermore, mural scars and sporadic lymphoid aggregates were noted in the colon tissues, which suggested pre-existing Crohn's disease. The patient died of peritoneal dissemination of cancer on day 207 after surgery. CONCLUSION: The present case was diagnosed as colitis-associated cancer with clinically latent Crohn's disease, who developed clinically manifest Crohn's disease only after surgery. Our review of literature revealed no cases comparable to ours.

Progressive Renal Dysfunction due to IgG4-Related Kidney Disease Refractory to Steroid Therapy: A Case Report.

Recently, as the number of case reports of IgG4-related kidney disease (IgG4-RKD) has increased, the histopathological features and clinical approach have been clarified. IgG4-RKD generally has a benign prognosis due to the efficacy of steroid therapy and rarely requires dialysis. Herein, we report a case of IgG4-RKD that presented with a subacute onset, advanced to end-stage kidney disease, and finally required maintenance hemodialysis despite steroid therapy. A 75-year-old man was admitted to our hospital for further evaluation of subacute renal failure. Diffuse enlargement of the kidney on computed tomography and increased urinary N-acetyl-ß-D-glucosaminidase and α1-microglobulin levels led us to suspect IgG4-RKD. Upon admission, the laboratory serological findings were as follows: creatinine 3.3 mg/dL, urea nitrogen 46.9 mg/dL, and IgG4 235 mg/dL. Urinalysis showed slight proteinuria without hematuria. Percutaneous renal needle biopsy showed diffuse infiltration of abundant lymphocytes and IgG4-positive plasma cells and storiform fibrosis, which is specific to IgG4-RKD, in the interstitium on light microscopy. Slight linear deposition of C3 was also observed in the tubules on immunofluorescence microscopy, with no electron-dense deposits. He was definitively diagnosed as having IgG4-RKD and started on prednisolone 0.6 mg/kg/day. However, the renal insufficiency continued to progress and hemodialysis was necessary. As the prednisolone was tapered, renal function did not improve and maintenance hemodialysis was started. In conclusion, this case indicates that the prognosis of IgG4-RKD is not necessarily benign and that further studies involving more patients are needed.

Exercise-Induced Acute Kidney Injury in a Police Officer with Hereditary Renal Hypouricemia.

Hereditary renal hypouricemia is characterized by hypouricemia with hyper-uric acid clearance due to a defect in renal tubular transport. Patients with hereditary renal hypouricemia have a higher risk of exercise-induced acute kidney injury (EAKI) and reduced kidney function. Although the best preventive measure is avoiding exercise, there are many kinds of jobs that require occupational exercise. A 27-year-old male police officer suffered from stage 3 AKI after performing a 20-m multistage shuttle run test. His mother had previously been diagnosed as having renal hypouricemia at another facility. The patient had reported having hypouricemia during a health check at a previous police station, but his serum uric acid concentration was within the normal range at our hospital. After treatment, he recovered from EAKI and exhibited low serum uric acid and hyper-uric acid clearance. Since the patient desired to continue his career requiring strenuous exercise, it was difficult to establish a preventive plan against the recurrence of EAKI. Patients with hereditary renal hypouricemia who must undergo strenuous occupational anaerobic exercise are at higher risk of developing EAKI than other workers. The risks of EAKI among patients with hypouricemia should be considered when undergoing physical occupational training.

MPGN Type 3 Associated with Pemphigus Herpetiformis Mimicking PGNMID and Dermatitis Herpetiformis.

A 45-year-old man suffering from dermal blistering disease with proteinuria and hematuria underwent renal biopsy. The renal biopsy specimen suggested proliferative glomerulonephritis with monoclonal IgG deposits under routine light, immunofluorescence and electron microscopy. The staining for IgG subclasses (IgG1 and IgG2) and κ/λ light chain indicated secondary immune complex type MPGN type 3. The patient had been diagnosed as having dermatitis herpetiformis (DH), a phenotype of gluten hypersensitivity prior to the appearance of the renal abnormality. Although common autoantibodies might be related to the pathogenesis of disorders in the skin and kidney, DH is mainly driven by IgA autoantibody, while MPGN is induced by IgG immune complexes. IgA was not observed in the glomeruli by immunofluorescence. Neither the examination for DH specific autoantibodies nor HLA-DQB1 genotype supported the diagnosis of DH. Reassessment of the skin biopsy record revealed that the blister was localized in the epidermis, suggesting pemphigus herpetiformis by IgG class anti-epidermal autoantibody, which also affected the renal disorder.

Evaluation of safety for hepatectomy in a novel mouse model with nonalcoholic-steatohepatitis.

AIM: To investigate whether the liver resection volume in a newly developed nonalcoholic steatohepatitis (NASH) model influences surgical outcome. METHODS: For establishment of a NASH model, mice were fed a high-fat diet for 4 wk, administered CCl4 for the last 2 wk, and administered T0901317 for the last 5 d. We divided these mice into two groups: A 30% partial hepatectomy (PH) of NASH liver group and a 70% PH of NASH liver group. In addition, a 70% PH of normal liver group served as the control. Each group was evaluated for survival rate, regeneration, apoptosis, necrosis and DNA expression after PH. RESULTS: In the 70% PH of NASH group, the survival rate was significantly decreased compared with that in the control and 30% PH of NASH groups (P < 0.01). 10 of 32 mice in the NASH 70% PH group died within 48 h after PH. Serum aspartate aminotransferase (AST) levels and total bilirubin (T-Bil) in the NASH 70% PH group were significantly higher than the levels in the other two groups (AST: P < 0.05, T-Bil: P < 0.01). In both PH of NASH groups, signaling proteins involved in regeneration were expressed at lower levels than those in the control group (P < 0.01). The 70% PH of NASH group also exhibited a lower number of Ki-67-positive cells and higher rates of apoptosis and necrosis than the NASH 30% PH group (P < 0.01). In addition, DNA microarray assays showed differences in gene expression associated with cell cycle arrest and apoptosis. CONCLUSION: The function of the residual liver is impaired in fatty liver compared to normal liver. A larger residual volume is required to maintain liver functions in mice with NASH.

An Acute Case of Granulomatous Amoebic Encephalitis-Balamuthia mandrillaris Infection.

A 74-year-old woman who exhibited drowsiness was referred to our hospital. Enhanced head magnetic resonance imaging (MRI) revealed multiple ring-enhancing lesions and lesions showing partial mild hemorrhaging. The patient gradually progressed to a comatose condition with notable brain deterioration of unknown cause on follow-up MRI. On day nine, the patient inexplicably died, although brain herniation was suspected. Autopsy and histopathology revealed numerous amoebic trophozoites in the perivascular spaces and within the necrotic tissue. Brain immunostaining tested positive for Balamuthia mandrillaris. Infection due to free-living amoeba is rare in Japan; however, it may increase in the near future due to unknown reasons.

Augmentation of Cytolytic Activity in Murine Natural Killer Cells and Inhibition of Tumor Growth by the Ethanol Fraction of Oyster Extract.

A reduced number and/or reduced activity of natural killer (NK) cells, which are important for defense against a variety of cancers and viral infections, occur under various stress conditions and in patients with various diseases. In this article, we report that the 30% to 50% ethanol precipitate of oyster extract (EPOE50) dose-dependently enhanced the activity of mouse spleen NK cells in vitro and in vivo. The activity of EPOE50 was eluted with a molecular weight of about 2000 by gel filtration and was inactivated by periodate but not by proteinase K. The activity of highly purified NK cells was also augmented by EPOE50 but not by oligodeoxyribonucleotide 1585, which mimics bacterial DNA. Administration of EPOE50 to mice stimulated splenic NK cell activity without a change in splenic NK cell populations. Although the proliferation of B16 tumor cells in vitro was slightly stimulated by EPOE50, the growth of B16 melanoma in vivo was dose-dependently suppressed by administration of EPOE50. Taken together, our results indicate that EPOE50 augmented NK cell activity and that its administration to mice inhibited tumor growth presumably through the activation of NK cells and also suggest that the active substance is a sugar-containing oligomer or polymer and is not of bacterial origin.

Novel non-alcoholic steatohepatitis model with histopathological and insulin-resistant features.

Although several non-alcoholic steatohepatitis (NASH) models have been reported to date, few of these models fully reflect the histopathology and pathophysiology of human NASH. The aim of this study was to establish a novel NASH model by feeding a high-fat (HF) diet and administering both carbon tetrachloride (CCl4 ) and the Liver X receptor agonist T0901317. Male C57BL/6J mice were divided into four groups (each n = 5): HF, HF + CCl4 , HF + T0901317, and the novel NASH model (HF + CCl4 + T0901317). CCl4 (0.1 mL/kg) and T0901317 (2.5 mg/kg) were intraperitoneally administered four times and five times, respectively. The livers of the novel NASH model group presented a whitish colour. The serum levels of TNF-α and IL-6 were significantly increased in the novel NASH model group, and mice in this group exhibited histopathological features and insulin resistance reflective of NASH, i.e., macrovesicular hepatic steatosis, ballooning hepatocytes, Mallory-Denk bodies, lobular inflammation and fibrosis. The novel NASH model group presented significantly upregulated expression levels of mRNAs related to lipogenesis, oxidative stress, fibrosis and steatosis and significantly downregulated expression levels of mRNAs related to triglyceride export. We successfully established a novel experimental NASH model that exhibits similar histopathology and pathophysiology to human NASH.

Effects of Cardiac Function with Postoperative Arteriovenous Fistula Blood Flow in Patients with Hemodialysis.

BACKGROUND/AIMS: This study was aimed at evaluating the effect of cardiac function with postoperative arteriovenous fistula (AVF) blood flow in hemodialysis (HD) patients. METHODS: A total of 45 HD patients were examined at the Juntendo University Hospital. The AVF blood flow was measured using ultrasonography, and the cardiac function was measured using echocardiography. Correlation between these parameters and the rate of change in body weight (BW) was analyzed. RESULTS: The number of postoperative days significantly correlated with the AVF blood flow, and it positively correlated with the stroke volume (SV). The postoperative AVF blood flow in patients with reduced ejection fraction (EF) was lower than that in patients with normal EF. The rate of change of BW negatively correlated with that of SV, positively correlated with cardiac output (CO), and positively correlated with CO in patients with an AVF blood flow of more than 1,000 mL/min. CONCLUSION: It appears that the cardiac function can be improved by controlling the BW even in patients with high AVF blood flow.

Predictive factors associated with increased progression to dialysis in early chronic kidney disease (stage 1-3) patients.

BACKGROUND: It has been reported that echocardiographic parameters are independently associated with the progression to dialysis in patients with chronic kidney disease (CKD) (stages 3-5). The objective of the present study was to evaluate whether physical, biochemical, and echocardiographic parameters are associated with the progression to dialysis in early CKD (stage 1-3) patients. METHODS: This retrospective study enrolled 272 CKD patients who underwent echocardiography at the time of diet education, renal biopsy, and the examination of kidney injuries at Juntendo University Hospital, Tokyo, Japan, from 2001 to 2010. All of these CKD patients were classified into stages 1-3. The study patients received regular follow-up at our outpatient clinic in our division. The renal end point was defined as commencement of dialysis. RESULTS: Patients with progression to dialysis were significantly associated with higher levels of left ventricular mass index (LVMI), urinary protein, systolic blood pressure, many kinds of anti-hypertensive drugs, and lower levels of albumin and hemoglobin. In a Cox proportional hazard regression analysis, LVMI [hazard ration (HR) 1.018; 95 % confidence interval (CI) 1.007-1.029; p = 0.002], urinary protein and hemoglobin were independently associated with factors for progression to dialysis in early CKD patients. CONCLUSION: This study of patients in early CKD demonstrated that higher LVMI and urinary protein and that lower levels of hemoglobin in blood were associated with progression to dialysis. LVMI evaluated by echocardiography may identify a high risk of progression to dialysis in early CKD patients.

Improvement of liver function by the administration of oyster extract as a dietary supplement to habitual alcohol drinkers: A pilot study.

Alcoholic liver disease (ALD) is characterized by elevated serum γ-glutamyltransferase (GGT) activity with hepatic steatosis, hepatitis or occasionally fibrosis that may progress to cirrhosis. The potential therapeutic role of oyster extract (OE) or OE-containing dietary supplements (OE supplement) in ALD has seldom been evaluated. In the present study, 84 adults who had an alcohol-drinking habit and marginally high serum GGT levels were enrolled in a randomized, double-blind, placebo-controlled feeding trial to study the effect on alcohol-impaired liver function as reflected by an increased serum level of GGT, as well as the safety, of an OE supplement. The subjects were randomized to receive either an OE supplement (OE group) or placebo (placebo group). There were 42 subjects (31 males and 11 females) in each group, and all the enrolled subjects entered the study. Four individuals (5%) dropped out for reasons unassociated with the study and 6 other subjects were excluded from the efficacy analysis because they did not maintain the required frequency of alcohol intake. As a result, 38 subjects in the placebo group and 36 in the OE group underwent efficacy assessment. Assays of GGT and other liver enzymes were performed at baseline (week 0) and at weeks 4, 8 and 12 of the intervention period. The mean serum levels of GGT in the placebo group gradually increased, while those in the OE group tended to decrease, although no significant within-group differences were observed for either group. A significant between-group difference in the change of mean GGT from baseline was, however, found at week 12 (P=0.049). No OE supplement-associated untoward side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the 12-week intervention. An OE supplement shows promise in reducing risk factors associated with ALD in adults with an alcohol intake habit.

TWEAK/Fn14 system and crescent formation in IgA nephropathy.

BACKGROUND: The TNF-like weak inducer of apoptosis (TWEAK) contributes to kidney inflammation producing secretion by renal cells. The present study examined whether the level of TWEAK is associated with histologic findings in patients with IgA nephropathy (IgAN). METHODS: The levels of urinary TWEAK (uTWEAK) from 116 IgAN patients, 50 non-IgA kidney disease patients, and 50 healthy individuals were measured by ELISA. Histological findings of renal biopsy specimens of patients with IgAN were evaluated according to the Oxford classification and histological classification for IgAN in Japan. We investigated the expression of TWEAK/Fn14 in renal tissues of those patients and assessed the effect of TWEAK in glomerular mesangial cells and podocytes. RESULTS: The levels of uTWEAK in the patients with IgAN and other renal diseases were significantly higher than in the healthy controls (P < 0.001). In the IgAN patients, the levels of uTWEAK correlated significantly with urinary protein excretion and extracapillary proliferation (r = 0.54, P < 0.001 and r = 0.32, P < 0.001, respectively). In a comparison of the levels of uTWEAK at diagnosis with that of follow-up, the levels of uTWEAK in patients with clinical and partial remission decreased significantly. We showed not only increased expression of both TWEAK and Fn14 in IgAN patients with glomerular crescents but also TWEAK-induced cell motility in podocytes. CONCLUSIONS: The relationship between the levels of uTWEAK and clinicopathological findings observed in this study suggests that TWEAK/Fn14 system affects crescent formation and proteinuria in patients with IgAN.

Impact of Body Mass Index on Progression of IgA Nephropathy Among Japanese Patients.

BACKGROUND: The impact of being overweight remains unclear in Asian populations that tend to be lean. The objective of this study is to clarify the impact of body mass index (BMI) and metabolic factors on the prognosis of Japanese patients with IgA nephropathy (IgAN). METHODS: A total of 193 patients with IgAN were divided into three groups equally according to BMI: Group L (lean group, BMI: 15.6-20.1 kg/m(2) ), Group M (middle group, BMI: 20.2-23.0 kg/m(2) ), and Group O (obesity group, BMI: 23.1-31.9 kg/m(2) ). Clinical data at the time of renal biopsy and the progression of the patients after renal biopsy were analyzed. RESULTS: At the time of renal biopsy, hypertension, dyslipidemia, hyperuricemia, and hypercomplementemia in Group O were more significant compared with those in Group L and/or Group M. Uric acid, triglyceride, C3, C4, high-density lipoprotein cholesterol, serum creatinine, systolic blood pressure (BP), and diastolic BP were significantly correlated with BMI. In Group O, the remission of urinary protein over 5 years was significantly delayed using a log-rank test. At the final observation, the BMI of each group was as similar as that at renal biopsy. The patients with aggressive therapy, such as steroid therapy and/or tonsillectomy in Group O did not have major side effects, except for a slight elevation of total cholesterol and low-density lipoprotein cholesterol. CONCLUSION: Even slightly high BMI seems to be a risk factor for progress in Japanese patients with IgAN.