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Far-infrared radiation therapy (FIRT), which utilizes an invisible electromagnetic wave, has demonstrated its ability to improve vascular access flow for hemodialysis (HD) patients. Although previous overseas studies revealed the beneficial effects of FIRT on HD patients by improving vascular function, no study in Japan has examined the clinical efficacy of FIRT for such patients. Therefore, we aimed to evaluate the usefulness of FIRT for HD patients. We paid particular attention on secondary vascular access (VA) patency of HD patients. Eighteen patients who had undergone vasodilation of VA vessels or vascularization more than once were selected from approximately 70 outpatients receiving HD in the Dialysis Unit of the Juntendo University Hospital. FIRT was administered for 40 min during HD three times per week for 1 year to the not frequent VA treatment (nf-VAT) group, for which VA intervention had been performed no more than two times during the 1 year, and to the frequent VA treatment (f-VAT) group, for which VA intervention had been performed three times or more over the 1 year. Variables including VA treatment interval were compared between those groups. The nf-VAT group did not require VA re-treatment during the study period. The VA treatment interval was significantly prolonged in the f-VAT group. The fistula diameter expanded, and intimal thickening improved significantly in the nf-VAT group. Oxidized low-density lipoprotein cholesterol levels decreased slightly. This study suggested that FIRT is effective for improving secondary VA patency. UMIN, UMIN000011965. Registered 4 October 2013, Japanese: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000013960 , English: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013960

This study aimed to identify the ideal timing and setting for measuring blood pressure (BP) and determine whether the left ventricular mass index (LVMI) is an independent risk factor associated with increased cardiovascular events in hemodialysis (HD) patients. BP and LVMI were measured at baseline and at 6 and 12 months after HD initiation. BP was monitored and recorded at nine different time points, including before and after HD over a one-week period (HDBP). The mean BP measurement was calculated as the weekly averaged BP (WABP). LVMI was significantly correlated with home BP, in-office BP, HDBP, and WABP. Receiver operating characteristic analysis indicated that the cutoff LVMI value for cardiovascular events was 156 g/m2. LVMI and diabetes mellitus were significant influencing factors for cardiovascular events (hazards ratio (95% confidence interval): diabetes mellitus, 2.84 (1.17,7.45), LVMI &gt, 156 g/m2, 2.86 (1.22,6.99)). Pre-HDBP, post-HDBP, and WABP were independently associated with higher LVMI in the follow-up periods. Hemoglobin and human atrial natriuretic peptide (hANP) levels were associated with LVMI beyond 12 months after HD initiation. Treatment of hypertension, overhydration based on hANP, and anemia may reduce the progression of LVMI and help identify HD patients at high risk for cardiovascular events.

Objective The present study was designed to identify the clinical characteristics that permit the differential diagnosis of hereditary angioedema (HAE) and mast cell-mediated angioedema (Mast-AE) during the first consultation. Methods The medical histories and laboratory data of 46 patients with HAE and 41 patients with Mast-AE were compared. Results The average age of onset in the HAE group (19.8±9.0 years) was significantly lower than that in the Mast-AE group (35.2±12.0 years). The incidence of familial angioedema (AE) in the HAE group (73.9%) was significantly higher than that in the Mast-AE group (9.7%). The frequency of history of AE in the extremities, larynx, or gastrointestinal tract was significantly higher in the HAE group. The frequency of AE episodes of the lips and eyelids was significantly lower in the HAE group. The serum C4 concentration and CH50 titer were lower than the normal limit in 91.3% and 45.6% of the patients in the HAE group, respectively; in Mast-AE group the serum C4 concentration and CH50 titer were significantly lower than the normal limit in 4.8% and 0% of the patients, the difference between the two groups was statistically significant. A C1-inhibitor (C1-INH) activity level of

Background Hereditary angioedema (HAE) is an autosomal dominant disease caused by deficiency of C1 esterase inhibitor. Symptoms of HAE include edema, which can potentially cause suffocation. Some patients with HAE exhibit immunological abnormalities, which could prevent an accurate diagnosis. Low levels of complement components are characteristic of HAE and in other settings are thought to reduce elimination of apoptotic cells and immune complex (IC). Thus, we aimed to experimentally clarify the mechanism of immunological abnormalities using sera from HAE patients. Methods Serum samples from 18 patients with HAE were collected when free from angioedema attack and compared with normal human pooled sera (NHPS) from 20 healthy volunteers. Opsonization was measured as the rate of phagocytosis of apoptotic Jurkat cells by macrophages differentiated from THP-1 cells incubated with serum. IC solubilization in serum was analyzed by quantifying peroxidase released from a synthetic IC composed of peroxidase and anti-peroxidase antibodies. Anti-C1q antibody levels were detected using an enzyme-linked immunosorbent assay. Results Serological immunological abnormalities were detected in 12 patients. Opsonization in serum samples from each patient with HAE was lower than that in NHPS (∼20% versus 70%, respectively). The rate of IC solubilization was lower in serum from HAE patients than NHPS. Some patients had high serum anti-C1q antibody levels with increased serum IC levels. Conclusions Sera from patients with HAE exhibit anti-C1q antibodies, with a lower capacity for opsonization and IC solubilization. This may be associated with immunological abnormalities and should be investigated further to facilitate accurate diagnosis of HAE.

Background: Mesangioproliferative glomerulonephritis is the most common type of chronic glomerulonephritis (CGN). However, the clinical characteristics and prognosis are not fully understood in patients without Immunoglobulin A (IgA) deposition. To explore the clinical and pathological characteristics of patients with mesangioproliferative glomerulonephritis without IgA deposition (N-IgAN), we performed dual retrospective analyses. Methods: A single-center study was performed in 60 patients with biopsy-proven N-IgAN. 98 ageand sex-matched IgA nephropathy (IgAN) patients were randomly selected as a control group. The clinical and histopathological data at the time of renal biopsy were compared between N-IgAN and IgAN. In a second study, the data for 477 patients who had undergone maintenance renal replacement therapy (RRT) was collected and examined for the causal primary diseases. Results: Duration from onset of renal symptoms to renal biopsy in patients with N-IgAN (71.2 ± 123.3 months) was significantly longer than that in patients with IgAN (65.9±74.9 months) (p=0.0328). Urinary protein excretion in N-IgAN patients (0.6±1.1 g/gCr) was significantly lower than that in IgAN (1.0 ± 1.3 g/gCr) (p < 0.0001). Ratio of global sclerosis, segmental sclerosis, crescents, interstitial mononuclear cell infiltration, interstitial fibrosis, and tubular atrophy were significantly lower in N-IgAN patients. Of the 477 patients who had undergone maintenance RRT, 95 patients had CGN (19.9%). Among them, 37 patients had received a renal biopsy, only one patient was N-IgAN (1%). Conclusion: It appears that N-IgAN can be recognized as a benign disease entity in comparison with IgAN.

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/m2), Group M (middle group, BMI: 20.2–23.0 kg/m2), and Group O (obesity group, BMI: 23.1–31.9 kg/m2). 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.

Obstructive sleep apnea (OSA) is complicated with heart failure (HF); however, the reason for this is not well understood. Craniofacial anatomic risk factors may contribute to OSA pathogenesis in HF patients. However, there are no data about cephalometric findings among OSA patients with HF. Consecutive patients with HF and OSA (defined as total apnea–hypopnea index (AHI) ≥15/h) were enrolled. As controls, OSA patients without HF but matching the test group in age, BMI, and obstructive AHI were also enrolled. Overall, 17 OSA patients with HF and 34 OSA patients without HF were compared. There are no significant differences in the characteristics or polysomnographic parameters between 2 groups. In the cephalometric findings, compared with patients without HF, patients with HF showed a significantly greater angle between the line SN to point “A” (SNA) and a longer inferior airway space and greater airway area. However, the tongue area of patients with HF was more than those without HF. The craniofacial structures of OSA patients with HF were different from those without HF. OSA patients with HF had an upper airway anatomy that is more likely to collapse when sleeping while recumbent, despite having a larger airway space.

Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis throughout the world. A majority (approx. 60%) of patients with IgAN experience disease exacerbations associated with an acute respiratory or gastrointestinal illness that appears to represent a viral infection. However, the exact mechanism of the disease exacerbation by viral infection is not understood, especially at the cellular and molecular levels. Here we report that glomerular podocytes express the major sensors for double-stranded RNA (dsRNA), a common byproduct of viral replication. In addition to these receptors, Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I)-like helicases (RLHs), podocytes express the collateral proteins required to support intracellular signaling. The pathways that mediate responses to dsRNA are fully functional in podocytes. The transcription factor interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-ĸB) are phosphorylated and translocate to the nucleus, and dsRNA increases synthesis of proteins driven by IRF3 (P54, P56 and P60) or NF-ĸB (interleukin 8 and A20). Furthermore, dsRNA suppresses podocyte cell migration, alters the expression of a panel of podocyte essential proteins (nephrin, podocin and CD2-associated protein or CD2AP) and changes transepithelial albumin flux. These effects are dsRNA sensor-specific: TLR3-/- podocytes do not respond to extracellular dsRNA, while intracellular dsRNA has no effect on podocytes bearing a dominant negative form of the major active RLH. These results demonstrate that innate responses to viruses can disturb podocyte cell function in vitro.

Background. The aim of the present study was to explore the significance of extraglomerular (Bowman’s capsule and/or arteriole) C3 (ex-C3) deposits in IgA nephropathy (IgAN). Methods. One hundred and seventy patients with IgAN were divided into two groups: Group A (n = 79), patients who did not have ex-C3 deposits, and Group B (n = 91), patients who had ex-C3 deposits. Results. At the time of renal biopsy, Group B was characterized by a marked increase in diastolic blood pressure, total cholesterol, triglyceride and low-density lipoprotein-cholesterol compared with those of Group A. After 4 years, the estimated glomerular filtration rate (eGFR) in Group B was significantly worse than that of Group A. Upon examination by electron microscopy, the arteriolar dense deposits in Group B were found to occur in significantly higher amounts than in Group A. One hundred and thirty-four patients underwent a 3-year follow-up study after intervention and were re-divided by therapeutic factors as follows: ‘conventional therapy’, treatment with anti-hypertensive drugs and/or anti-platelet drugs, and ‘aggressive therapy’, additional treatment with either tonsillectomy or corticosteroid. Patients treated with conventional therapy in Group B had significantly higher body mass index and levels of C3 and CH50 compared with other Groups. Aggressive therapy was significantly effective in urinary protein reduction in both Group A and Group B. Except for the patients who received aggressive therapy in Group A, the levels of the eGFR gradually declined. Conclusions. It appears that IgAN patients who have ex-C3 deposits have worse clinical outcomes.

Background. We have recently demonstrated that hemodialysis (HD) patients have significantly higher levels of functional complement activity (FCA) in all three pathways, i.e. the classical pathway, alternative pathway and lectin pathway (LP), than in age-matched controls, though the role of FCA during HD still remains unknown. Methods. Serial plasma or serum samples were obtained from five patients during HD in order to investigate the kinetics of complement components. The levels of the C5b-9 complex, the FCA of the three pathways, a derivative of C3a (C3a desArg) and a derivative of C5a (C5a desArg) in the samples were analyzed. Results. The levels of the C5b-9 complex at 60 min were significantly increased when compared with those at 0 min. Functional activities for all three pathways showed different patterns so the same tendency between pathways was not observed. The levels of C3a desArg and C5a desArg at 60 min were markedly increased when compared with those at 0 min. A Spearman’s rho test showed a strong positive correlation between functional LP activity and C5a desArg. Conclusions. These findings lead to new insights into the FCA during HD and suggest that functional LP activity has an important role in C5 activation.

Mannose-binding lectin (MBL), L-ficolin and MBL associated serine protease-2 (MASP-2) are molecules involved in initiation of the lectin pathway (LP) in the complement system. Although MBL deficiency is observed in almost 10% of healthy people, studies of associations between MBL deficiency and end-stage renal disease (ESRD) remain rare. The objective of the present study is to clarify the significance of the LP in maintenance hemodialysis (HD) patients, especially in terms of MBL levels. Two hundred and forty-four HD patients who had been followed up for 74±84months and 199 healthy controls were included in this study. Measurements of serum concentrations of MBL, L-ficolin, and MASP-2 were performed. Low serum MBL levels (

A 55-year-old woman presented with heavy proteinuria (6.2 g/day) in April 2007. Because monoclonal IgG-k was detected in serum and urine samples, bone marrow aspiration and renal biopsy were performed. She was diagnosed with plasma cell dyscrasia because a bone marrow aspiration specimen showed plasma cells at 6.1%. Renal tissues revealed the formation of nodular glomerulosclerosis which was negative for Congo-red staining. Renal immunohistochemistry showed positive staining for kappa light chains in the nodular lesions, proximal tubules and part of Bowman's capsules. Her renal involvement was diagnosed as light chain deposition disease. Proteinuria disappeared and renal function stabilized after high-dose chemotherapy and autologous stem cell transplantation. It appears that an early initiation of active therapy such as high-dose chemotherapy and autologous stem cell transplantation may be beneficial for patients with light chain deposition disease.

The aim of this study was to explore the association between the serum concentration of complement component 3 (C3) and a variety of metabolic parameters. The study involved 125 patients in our outpatient clinic. Anthropometric and clinical laboratory data were collected and statistical associations between the serum concentration of C3 and other parameters were evaluated in a cross‐sectional as well as a prospective manner. A group of male patients with metabolic syndrome (Mets, n=35) were characterized by marked increase in serum concentrations of C3, body mass index (BMI), waist circumference, hemoglobin (Hb) A1c, insulin resistance (HOMA‐IR), triglyceride, uric acid, urinary protein, and Hb. In a one‐way analysis of variance of all subjects, the serum concentration of C3 was significantly elevated as the number of items of complying with the Mets diagnostic criteria increased. In 60 of 125 patients who did not have diabetes and were given anti‐lipogenetic medication, the serum concentration of C3 showed significant positive associations with serum levels of CH50, insulin, HOMA‐IR, total cholesterol, hematocrit, LDL‐c, C4, Hb, triglyceride, BMI, and albumin. In a prospective follow‐up evaluation (n=35), there was a significant positive association between ΔC3 (the second concentration of serum C3 minus the first concentration of serum C3)and ΔHOMA‐IR (the second concentration of HOMA‐IR minus the first concentration of HOMA‐IR). In conclusion, in Japanese patients, there is evidence implicating C3 concentration as a marker of Mets coinciding with insulin resistance. J. Clin. Lab. Anal. 24:113–118, 2010. © 2010 Wiley‐Liss, Inc.

A 49-year-old man with pulmonary sarcoidosis was admitted to our hospital because of nephrotic syndrome. Renal biopsy revealed membranous nephropathy and granulomatous interstitial nephritis. DNA and cell membrane constituents of Propionibacterium acnes were detected in the patient’s glomeruli and tubular epithelial cells. Treatment with corticosteroids and an antimicrobial agent resulted in remission of the nephrotic syndrome. This is the second case in which components of P. acnes were found in renal tissue, suggesting latent pathogenesis of P. acnes infection in renal sarcoidosis.

Mannose-binding lectin (MBL), L-ficolin and H-ficolin are human serum lectins, all of which form complexes with MBL-associated serine proteases (MASP). The lectin-MASP complexes bind to the surface of microbes, leading to activation of the lectin pathway of complement. Enzyme-linked immunosorbent assays (ELISA) of the lectin pathway activity reported so far determined the activity via either MBL or L-ficolin, but an assay of activity via plural host defense lectins has not been established. To measure the lectin pathway activation mediated by plural lectins simultaneously, we developed an ELISA system in which N-acetylglucosamine-pentamer conjugated to dipalmitoylphosphatidylethanolamine (GN5-DPPE) was employed as a ligand for the lectins. In our ELISA system, both purified MBL and L-ficolin isolated from serum diluted in a buffer containing high ionic NaCl bound to GN5-DPPE and activated C4. Purified H-ficolin was not capable of binding to GN5-DPPE. MBL and L-ficolin in MBL-sufficient serum also bound to GN5-DPPE and activated C4. Mannose and N-acetylgalactosamine inhibited binding of MBL and L-ficolin to GN5-DPPE, respectively. MBL-deficient serum that had been depleted of L-ficolin did not exhibit C4 activation, but addition of both or either purified MBL and/or L-ficolin to the serum restored the activation in a dose-dependent manner. Thus, C4 cleaving activity could be evaluated with the co-existence of MBL and L-ficolin in vitro. In conclusion, we propose a novel method using GN5-DPPE for investigating the MBL- and L-ficolin-dependent lectin pathway and anticipate that this method will be useful in innate immunity and clinical research.

Peritoneal calcification is one of the complications of peritoneal dialysis (PD). It can become serious, leading to severe abdominal pain and even death. Possible mediators of peritoneal calcification in PD patients are assumed to include acetate buffer, overdosage of vitamin D, repeated peritonitis, hypertonic dialysate, calciphylaxis and secondary hyperparathyroidism (SHPT). However, the mechanism and treatment of peritoneal calcification are controversial. Few reports have appeared on improvement of peritoneal calcification after parathyroidectomy (PTX) for SHPT of long duration. We report herein the case of a 48-year-old man on dialysis for 17 years including PD for 14 years. In 1989, he was admitted to hospital because of end-stage renal disease (ESRD), and started treatment with PD. Abdominal computed tomography (CT) first showed peritoneal calcification in August 2002. Peritoneal calcification did not improve despite conventional treatment including discontinuation of PD, control of calcium phosphate product to less than 55 mg2/dl2, removal of the peritoneal catheter and empirical prednisolone (PSL) usage. The intact parathyroid hormone (i-PTH) level was increased over 1,000 pg/ml and extra-osseous calcification occurred. Total PTX was performed in November 2004. Postoperatively, the i-PTH level decreased immediately and calcium phosphate product was maintained in the reference range. Abdominal CT after PTX showed improvement of peritoneal calcification in September 2005. It appeared that PTX could be used to treat patients with persistent peritoneal calcification not responding to conventional treatment. It was postulated that SHPT might play a crucial role in accelerating peritoneal calcification in PD patients.

Background: The necessity of nasal packing for patients who undergo endoscopic nasal surgery remains controversial concerning hypoxic episodes during sleep. This study was designed to characterize patients with sleep disturbance during nasal packing. Methods: The patients were evaluated for nasal resistance using the anterior active rhinomanometric test and for oxygen saturation by pulse oxymetry before and after surgery. Results: Thirty-five patients (mean age: 45.4 ± 16.7 years old, mean BMI: 23.6 ± 2.6 kg/m2) underwent nasal surgery and received bilateral total nasal packing. Nineteen patients with nasal packing showed decreased oxygen saturation (Worsened group), whereas improvement of oxygen saturation during nasal packing was recognized in 16 patients (unchanged group). BMI and preoperative rhinomanometric test showed significantly higher scores in the unchanged group than in the worsened group. Conclusions: Oxygen saturation during postoperative nasal packing (PNP) should be monitored more carefully in patients with low body mass index (BMI) or preoperative low nasal resistance of air flow.

Purpose: The purpose of this study was to acquire a hyperpolarized (HP) 3He image of the mouse lung and to estimate 3He T1 in the lung from wash-out curve analysis under spontaneous respiration. Materials and Methods: We first tested the K-Rb hybrid method for the spin-exchange optical pumping (SEOP) of 3He using a home-built noble gas polarizer operated at atmospheric pressure and then applied it to MR imaging and spectroscopy of the mouse lung. The longitudinal relaxation time (T1) of 3He in the mouse lung was estimated under spontaneous respiration by exploiting a novel method in which SF6 gas at thermal equilibrium was utilized in combination with the HP 3He gas in the quantitative wash-out curve analysis. This method utilizes the difference in the profile of the wash-out curve of HP 3He and SF6 at thermal equilibrium. That is, the slope of the 3He wash-out curve in the semi-logarithmic plots is affected by 3 factors, including RF pulse angle, respiration, and T1, whereas the slope of the SF6 wash-out curve is only the function of respiratory term. Results: A 3He lung image was obtained successfully, and we were able to estimate successfully 3He T1 in the mouse lung under spontaneous respiration using a novel method; the estimated T1 value was 68±25 s, which was reasonable compared with the value calculated from the literature data measured during breath-hold. Conclusion: We succeeded in acquiring the first 3He image of mouse lung in vivo in this country, and our proposed method of estimating 3He T1 in the lung under spontaneous respiration is noninvasive and readily applied to animals and would be useful to evaluate the alveolar gas exchange function as well as oxygen partial pressure (pO2) in lungs of animals.

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.

Background Urinary (U)-complement components have been detected in patients with proteinuric renal diseases, and complement activation via the alternative pathway (AP) is believed to play a role in renal tubular damage. The present study aimed to examine the regulation of complement AP activation in patients with renal tubular damage by focusing on the balance between properdin (P) and factor H (fH). Methods In the in vivo studies, U concentrations of P, fH and membrane attack complex (MAC) were measured in patients with renal diseases using an enzyme-linked immunosorbent assay (ELISA), and their relationships with the clinical data were evaluated. In the in vitro studies, human proximal tubular epithelial cells (PTECs) were incubated with normal human serum (NHS), P-depleted serum (PDS), purified P and/or fH. Changes in cell morphology and phenotype were assessed by microscopy, real-time polymerase chain reaction (PCR), immunostaining and a cell viability assay. Results The U-P, fH and MAC concentrations were significantly higher in patients with renal disease than in normal controls and correlated with the U-protein and tubular damage markers. Furthermore, multivariate analysis revealed a relationship between P levels and tubular damage markers. There were no significant changes in morphology and mRNA expression in the AP components (P, fH, fB, C3, C5 and C9) after the addition of up to 25% NHS. Dose-dependent depositions of P or fH were observed after the addition of P or fH on PTECs. Depositions of P were not inhibited by fH in a mixture of a fixed concentration of P and a variable concentration of fH, and vice versa. Preincubation with the fixed concentration of P before the addition of NHS or PDS increased the depositions of P, C3 and MAC compared with incubation with intact NHS or intact PDS only; the depositions of C3 and MAC showed a serum-dependent trend. Preincubation with P before NHS addition significantly suppressed cell viability without causing morphological changes. Conclusions In the pathogenesis of renal tubular damage, P can directly bind to PTECs and may accelerate AP activation by surpassing fH regulation.

Mannose-binding lectin (MBL), L-ficolin and MBL associated serine protease-2 (MASP-2) are molecules involved in initiation of the lectin pathway (LP) in the complement system. Although MBL deficiency is observed in almost 10% of healthy people, studies of associations between MBL deficiency and end-stage renal disease (ESRD) remain rare. The objective of the present study is to clarify the significance of the LP in maintenance hemodialysis (HD) patients, especially in terms of MBL levels. Two hundred and forty-four HD patients who had been followed up for 74±84months and 199 healthy controls were included in this study. Measurements of serum concentrations of MBL, L-ficolin, and MASP-2 were performed. Low serum MBL levels (0.1µg/mL) in the patients were confirmed by examination of a point mutation in the Mbl-2 gene. Seventeen HD patients (7%) and 20 healthy controls (10%) had MBL deficiency. During the follow-up period, 99 patients died. There was no significant difference in the frequency of deaths by infectious diseases between MBL deficient and non-deficient patients. In both patients and healthy controls with MBL deficiency, the serum concentration of L-ficolin tended to be high, and that of MASP-2 was significantly high (P0.05). MBL deficiency is not a risk factor for HD induction or life-threatening infections. It is postulated that the elevation of concentration of the two components of the LP, L-ficolin and MASP-2, may compensate for the insufficient activity of the LP in MBL deficiency.

Background The complement system is vital for innate immunity and is implicated in the pathogenesis of inflammatory diseases and the mechanism of host defense. Complement deficiencies occasionally cause life-threatening diseases. In hemodialysis (HD) patients, profiles on complement functional activity and deficiency are still obscure. The objectives of the present study were to measure the functional complement activities of the classical pathway (CP), lectin pathway (LP) and alternative pathway (AP) using a novel method and consequently to elucidate the rates of deficiencies among HD patients. Methods In the present study, 244 HD patients at one dialysis center and 204 healthy controls were enrolled. Functional complement activities were measured simultaneously using the Wielisa®-kit. The combination of the results of these three pathway activities allows us to speculate which candidate complement is deficient; subsequently, the deficient complement was determined. Results All three functional complement activities were significantly higher in the HD patients than in the control group (P < 0.01 for all cases). After identifying candidates in both groups with complement deficiencies using the Wielisa®-kit, 16 sera (8.8%) with mannose-binding lectin (MBL) deficiency, 1 serum (0.4%) with C4 deficiency, 1 serum (0.4%) with C9 deficiency, and 1 serum (0.4%) with B deficiency were observed in the HD group, and 18 sera (8.8%) with MBL deficiency and 1 serum (0.5%) with B deficiency were observed in the control group. There were no significant differences in the 5-year mortality rate between each complement-deficient group and the complement-sufficient group among the HD patients. Conclusion This is the first report that profiles complement deficiencies by simultaneous measurement of functional activities of the three complement pathways in HD patients. Hemodialysis patients frequently suffer from infections or malignancies, but functional complement deficiencies do not confer additional risk of mortality.

Immunoglobulin A nephropathy (IgAN) is characterized by mesangial cell proliferation and mesangial expansion with mesangial depositions of IgA. We have found that electron-dense deposits (EDD) are often observed in areas other than paramesangial areas in glomeruli. To compare electron microscopic findings with light microscopic findings and clinical data, we examined the biopsies from 178 patients with IgAN. Patients were divided into two groups: group A had only paramesangial deposits and group B had deposits not only in paramesangial areas but also in other areas. All patients examined in this study had EDD in glomerular paramesangial areas. Thirty-six patients were included in group B. Cellular crescent formation in glomeruli and urinary protein in group B were significantly higher than those in group A (P < 0.01). Serum albumin and estimated glomerular filtration rate (eGFR) in group B were significantly lower than those in group A (P < 0.05). Group B showed a significant positive correlation with histological severity, which is defined in the Japanese Clinical Guidelines on IgAN. In patients with broad distribution of EDD, urinary protein was significantly increased (P < 0.05). Detailed observation of EDD distribution has an impact on evaluation of the disease activity of IgAN.

A 77-year-old diabetic man newly contracted pulmonary mucormycosis. A rapidly progressing clinical course including severe worsening of pneumonia and renal failure culminated in death. This patient presented with hypocomplementemia and dermal vasculitis. Autopsied organs were examined by histological technique. Lung tissues showed pulmonary artery thrombosis and extensive alveolar invasion by Mucor hyphae with depositions of immunoglobulins, mannose-binding lectin (MBL) and C1q. The right internal jugular vein was occluded by thrombi containing numerous hyphae. The glomerular change was a hallmark of extra-capillary proliferative glomerulonephritis, which was overlying diabetic nephropathy. Depositions of IgM, C3 and C4 on glomeruli were also detected. Electron microscopy showed electron-dense deposits in the mesangial area and the wall of the afferent arteriole. This report shows evidence of complement opsonization of Mucor hyphae and refers to mucormycosis that developed small-sized vasculitis with complement activation.

The link between glomerular IgA nephropathy (IgAN) and T helper 2 (Th2) response has been implicated, however, the mechanisms are poorly defined because of the lack of an appropriate model. Here we report a novel murine model characterized by lineage-restricted deletion of the gene encoding MAD homologue 4 (Smad4) in T cells (Smad4(co/co;Lck-cre) ). Loss of Smad4 expression in T cells results in overproduction of Th2 cytokines and high serum IgA levels. We found that Smad4(co/co;Lck-cre) mice exhibited massive glomerular IgA deposition, increased albumin creatinine ratio, aberrant glycosylated IgA, IgA complexed with IgG1 and IgG2a, and polymeric IgA, all known features of IgAN in humans. Furthermore, we examined the β1, 4-galactosyltransferases (β4GalT) enzyme which is involved in the synthesis of glycosylated murine IgA, and we found reduced β4GalT2 and β4GalT4 mRNA levels in B cells. These findings indicate that Smad4(co/co;Lck-cre) mice could be a useful model for studying the mechanisms between IgAN and Th2 response, and further, disruption of Smad4-dependent signaling in T cells may play an important role in the pathogenesis of human IgAN and contributing to a Th2 T cell phenotype.