Epipharyngeal Abrasive Therapy Down-regulates the Expression of Cav1.2: A Key Molecule in Influenza Virus Entry.

BACKGROUND/AIM: Influenza A virus (IAV) infection causes an inflammatory response to the respiratory mucosa. The viral glycoprotein hemagglutinin (HA) binds to the sialylated voltage-dependent Ca2+ channel (Cav1.2) in ciliated epithelium. The binding of HA and sialylated Cav1.2 is considered essential to IAV infection, entry, and IAV-induced Ca2+ oscillation. The epipharynx comprises the ciliated epithelium, which is the initial target for viruses that cause upper respiratory tract infections. Previously, we showed that epipharyngeal abrasive therapy (EAT), a treatment for chronic epipharyngitis in Japan, which scratches the epipharyngeal mucosa with a cotton swab containing zinc chloride, induces squamous metaplasia. In this study, we evaluated whether squamous metaplasia by EAT affects the expression patterns of Cav1.2. PATIENTS AND METHODS: The study subjects were seven patients who had not been treated with EAT and 11 patients who had. For the immunohistochemical assessment of the epipharyngeal mucosa, the staining intensity of Cav1.2 was described using the immunohistochemical score (IHC score). RESULTS: The IHC scores for Cav1.2 in the EAT-treated group was 4.19-fold lower than those in the non-treated group (p=0.0034). CONCLUSION: EAT down-regulates the expression of Cav1.2, a key cell surface molecule in influenza virus entry via squamous metaplasia. Thus, EAT may be a simple method for preventing influenza infection.

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis.

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

Development and Evaluation of a Robust Sandwich Immunoassay System Detecting Serum WFA-Reactive IgA1 for Diagnosis of IgA Nephropathy.

Aberrant glycosylation of IgA1 is involved in the development of IgA nephropathy (IgAN). There are many reports of IgAN markers focusing on the glycoform of IgA1. None have been clinically applied as a routine test. In this study, we established an automated sandwich immunoassay system for detecting aberrant glycosylated IgA1, using Wisteria floribunda agglutinin (WFA) and anti-IgA1 monoclonal antibody. The diagnostic performance as an IgAN marker was evaluated. The usefulness of WFA for immunoassays was investigated by lectin microarray. A reliable standard for quantitative immunoassay measurements was designed by modifying a purified IgA1 substrate. A validation study using multiple serum specimens was performed using the established WFA-antibody sandwich automated immunoassay. Lectin microarray results showed that WFA specifically recognized N-glycans of agglutinated IgA1 in IgAN patients. The constructed IgA1 standard exhibited a wide dynamic range and high reactivity. In the validation study, serum WFA-reactive IgA1 (WFA+-IgA1) differed significantly between healthy control subjects and IgAN patients. The findings indicate that WFA is a suitable lectin that specifically targets abnormal agglutinated IgA1 in serum. We also describe an automated immunoassay system for detecting WFA+-IgA1, focusing on N-glycans.

Role of Palatine Tonsil and Epipharyngeal Lymphoid Tissue in the Development of Glomerular Active Lesions (Glomerular vasculitis) in Immunoglobulin A Nephropathy.

Hematuria is an essential symptom of immunoglobulin A nephropathy (IgAN). Although the etiology of hematuria in IgAN has not been fully elucidated, it is thought that the rupture of the glomerular basement membranes caused by intra-capillary leukocyte influx, so-called glomerular vasculitis, is the pathological condition responsible for severe hematuria. Glomerular vasculitis are active lesions that exist in the glomeruli of acute phase IgAN and it is important because it is suspected to make the transition to segmental glomerular sclerosis (SGS) as a repair scar lesion in the chronic phase, and the progression of SGS would eventually lead to glomerular obsolescence. Worsening of hematuria concomitant with acute pharyngitis is common in patients with IgAN; therefore, elucidating the relationship between the immune system of Waldeyer's ring, including the palatine tonsil and epipharyngeal lymphoid tissue, and the glomerular vasculitis may lead to understanding the nature of IgAN. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. Hyperactivation of innate immunity via upregulation of Toll-like receptors in the interfollicular area of the palatine tonsil and epipharyngeal lymphoid tissue, followed by enhanced fractalkine/CX3CR1 interactions, appears to play an important role in the development of glomerular vasculitis in IgAN. As latent but significant epipharyngitis is present in most patients with IgAN, it is plausible that acute upper respiratory infection may contribute as a trigger for the innate epipharyngeal immune system, which is already upregulated in a chronically inflamed environment. Given that epipharyngitis and its effects on IgAN are not fully understood, we propose that the so-called "epipharynx-kidney axis" may provide an important focus for future research.

Pre-treatment hematuria and crescents predict estimated glomerular filtration rate trajectory after methylprednisolone pulse therapy with tonsillectomy for IgA nephropathy.

BACKGROUND: Glomerular hematuria and proteinuria are typical manifestations of IgA nephropathy (IgAN). However, hematuria severity is not considered a useful marker of the potential benefits of corticosteroid administration as proteinuria severity only is included in the current guidelines. METHODS: In this retrospective cohort study, we enrolled 133 patients diagnosed with IgAN through biopsy. We calculated the 2-year estimated glomerular filtration rate (eGFR) slope (mL/min/1.73m2/year) and eGFR trajectory after methylprednisolone pulse therapy using mixed effects models stratified by the Oxford classification and three categories of pre-treatment hematuria: mild [urinary red blood cells (URBCs) < 10/high-power field (HPF)], moderate (URBCs 10-30/HPF), and severe (URBCs ≥ 30/HPF). RESULTS: The severe pre-treatment hematuria group showed a significantly higher likelihood of having crescents (odds ratio (OR), 4.3; 95% confidence interval (CI), 1.7-10.9). In the longitudinal analysis of 103 patients, most of whom underwent tonsillectomy, the severe pre-treatment hematuria group had a significantly higher 2-year eGFR slope after methylprednisolone pulse therapy than the mild and moderate hematuria groups (mild, -0.52 ± 1.97; moderate, -0.32 ± 1.99; severe, 1.44 ± 3.20 mL/min/1.73m2/year). Patients with C2 scores showed a significantly higher 2-year eGFR slope after methylprednisolone pulse therapy than those with C0 and C1 scores (C0, -0.38 ± 1.74; C1, 0.81 ± 3.02; C2, 3.29 ± 3.68 mL/min/1.73m2/year). Analyses of eGFR trajectory after methylprednisolone pulse therapy revealed that the eGFR improved only in patients with severe pre-treatment hematuria or C2 score (Pinteraction with time < 0.001). CONCLUSIONS: The eGFR is likely to improve after methylprednisolone pulse therapy with tonsillectomy in IgAN patients with severe pre-treatment hematuria or a high percentage of crescents.

A case of autosomal dominant polycystic kidney disease with amelioration of refractory cyst infections following prolonged hemodialysis time.

Renal cyst infection is a frequent and serious problem in patients with autosomal dominant polycystic kidney disease (ADPKD). Cyst infection is often a refractory complication of treatment that leads to sepsis and death in patients with ADPKD. It was previously reported that a higher dose of dialysis demonstrated clearly better survival than shorten-time dialysis. The relationship between the frequency of cyst infection episodes in hemodialysis (HD) patients with ADPKD and the dialysis dose has not yet been fully elucidated. In this report, we describe a case of an HD patient with ADPKD that was provided elongation of HD time from 4-h twice weekly HD to 8-h thrice weekly nocturnal HD. As a result, the frequency of cyst infection episodes decreased from 10.0 to 1.5 days a month. Our findings suggest that prolonged HD time might contribute to amelioration of refractory cyst infections in patients with ADPKD.

Dysbiosis in the Salivary Microbiome Associated with IgA Nephropathy-|A| |Japanese Cohort Study.

IgA nephropathy is one of the leading causes of chronic kidney disease in Japan. Since the origin and mechanisms by which IgA nephropathy develops currently remain unclear, a confirmed disease diagnosis is currently only possible by highly invasive renal biopsy. With the background of the salivary microbiome as a rich source of biomarkers for systemic diseases, we herein primarily aimed to investigate the salivary microbiome as a tool for the non-invasive diagnosis of IgA nephropathy. In a comparison of salivary microbiome profiles using 16S rRNA amplicon sequencing, significant differences were observed in microbial diversity and richness between IgA nephropathy patients and healthy controls. Furthermore, recent studies reported that patients with IgA nephropathy are more likely to develop inflammatory bowel diseases and that chronic inflammation of the tonsils triggered the recurrence of IgA nephropathy. Therefore, we compared the salivary microbiome of IgA nephropathy patients with chronic tonsillitis and ulcerative colitis patients. By combining the genera selected by the random forest algorithm, we were able to distinguish IgA nephropathy from healthy controls with an area under the curve (AUC) of 0.90, from the ulcerative colitis group with AUC of 0.88, and from the chronic tonsillitis group with AUC of 0.70. Additionally, the genus Neisseria was common among the selected genera that facilitated the separation of the IgA nephropathy group from healthy controls and the chronic tonsillitis group. The present results indicate the potential of the salivary microbiome as a biomarker for the non-invasive diagnosis of IgA nephropathy.

The epipharynx-kidney axis triggers glomerular vasculitis in immunoglobulin A nephropathy.

Macroscopic hematuria concomitant with acute pharyngitis is a characteristic feature of immunoglobulin A nephropathy (IgAN). Although the underlying mechanism of worsening hematuria has not been fully elucidated, activation of the innate immune system of nasopharynx-associated lymphoid tissue is thought to play an important role. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. As latent but significant epipharyngitis presents in most IgAN patients, it is plausible that acute pharyngitis due to airway infection may contribute as a trigger of the epipharyngeal innate immune system, which is already upregulated in the chronically inflamed environment. The aim of this review was to discuss the mechanism of epipharynx-kidney axis involvement in glomerular vasculitis responsible for the worsening of hematuria in IgAN.

Steroid pulse therapy transiently destroys the discriminative histological structure of tonsils in IgA nephropathy: Tonsillectomy should be performed before or just after steroid pulse therapy.

OBJECTIVE: Tonsillectomy combined with steroid-pulse therapy is a widely accepted method for the treatment of IgA nephropathy (IgAN) in Japan. However, the indication of tonsillectomy for IgAN is still controversial, and the timing of tonsillectomy is not clearly defined for the protocol of this therapy. Based on the results of a randomized control trial in Japan, the Evidence-Based Clinical Practice Guidelines for IgA nephropathy 2014 (edited in Japan) recommended tonsillectomy combined with steroid-pulse therapy for Grade C1. However, this is not widely accepted worldwide. To clarify the validity and timing of tonsillectomy, we evaluated how the three-consecutive steroid-pulse therapy method affects the tonsil tissues of IgAN patients. METHODS: We examined tonsil specimens from 35 IgAN patients and 8 chronic tonsillitis patients. We compared the proportion of follicular area to total tonsillar area and the number of germinal centers between each group on hematoxylin and eosin stained pathological specimens to clarify the histopathological characteristics of tonsils from IgAN patients. Based on these findings, we examined the tonsils of patients after three-consecutive steroid-pulse therapy treatments (n=34) to determine the influence of this therapy on the tonsil tissues of IgAN patients. Moreover, we observed chronological changes in tonsil tissues after steroid-pulse therapy. RESULTS: The extrafollicular area was enlarged in IgAN patients before steroid-pulse therapy compared with chronic tonsillitis patients. Just after steroid-pulse therapy, the follicles became very small with blurry outlines, and the number of germinal centers was remarkably decreased. With a gradual decrease in oral prednisolone, the tonsil tissue structure was gradually restored. CONCLUSION: Tonsillectomy combined with steroid-pulse therapy is considered a reasonable treatment for IgAN. Steroid-pulse therapy-induced histological changes in tonsils were transient, indicating tonsillectomy should be performed before or just after steroid-pulse therapy.

Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA).

The epipharynx is an immunologically active site even under normal conditions, and enhanced immunologic activation is prone to occur in response to an upper respiratory infection, air pollution, and possibly to vaccine adjuvants. Due to the potential link between the central nervous system and immune function, a relationship between epipharyngitis and autonomic nervous disturbance as well as autoimmune disease has been suggested. Various functional somatic symptoms have been described after human papillomavirus (HPV) vaccination, although a causal relationship has not been established. We examined the epipharynx in young women showing functional somatic symptoms following HPV vaccination. Surprisingly, despite having minimal symptoms involving the pharynx, all patients were found to have severe epipharyngitis. In addition, significant improvement in symptoms was seen in most patients who underwent epipharyngeal treatment. Thus, we speculate that the chronic epipharyngitis potentially caused by the vaccine adjuvant may be involved in the pathogenesis of functional somatic syndrome (FSS) post-HPV vaccination. Further, we suggest that epipharyngeal treatment may be effective for various types of FSS regardless of the initial cause, as well as for some autoimmune diseases, and that this may be an important direction in future research.

Comparisons of amino acids, body constituents and antioxidative response between long-time HD and normal HD.

Introduction Oxidative stress is one of the main mediators of progression of chronic kidney diseases (CKD). Nuclear factor E2-related factor 2 (Nrf2) is the transcription factor of antioxidant and detoxifying enzymes and related proteins which play an important role in cellular defense. Long-time hemodialysis (HD) therapy (8 hours) has been considered to be more beneficial compared to normal HD therapy (4 hours). We investigated oxidative response related to Nrf2 in peripheral blood mononuclear cells (PBMCs) of long-time HD and normal HD patients. Methods Eight adult long-time HD therapy patients (44.5 ± 3.0 years) and 10 normal HD therapy patients (68.1 ± 2.7 years) were enrolled. PBMCs were isolated and processed for expression of Nrf2 and its related genes by qRT-PCR. Plasma indoxyl sulfate, amino acids, and body constituents were measured. Findings Plasma indoxyl sulfate was significantly low after long-time HD therapy compare to that of normal HD therapy. Although, skeletal muscle mass, lean body mass, mineral and protein were significantly decreased 2 months in normal HD patients, those in long-time HD patients were significantly increased after 2 months. Almost of amino acids were significantly decreased after HD therapy in both HD therapies. Plasma amino acids were significantly low in long-time HD patients compared to normal HD patients. In PBMCs, the expression of Nrf2 was significantly decreased and hemooxygenase-1 expression was significantly increased in long-time HD compared to normal HD. Conclusion These observations indicate the beneficial effects of in long-time HD in improving oxidative stress in patients.

Immunosuppressive therapy for active IgA nephropathy is effective and safe, even in "elderly" patients.

Proportions of elderly aged ≥65 and ≥75 within Japan will increase to 30 and 20 %, respectively, in 2025, when "Baby-Boom Generations" will reach the age of 75 years. Okabayashi and colleagues report that even in elderly patients with IgA nephropathy (IgAN), immunosuppressive treatment can reduce proteinuria, with no adverse events. Their findings remind us of recent finding from STOP-IgAN study; additional immunosuppressive therapy to intensive supportive care [specifically renin-angiotensin system (RAS) inhibitors (RASi)] did not improve the outcome. If STOP-IgAN makes doctors believe that immunosuppression is not necessary, many patients could lose opportunity to eliminate their kidney disease. Indeed, we have experienced patients with IgAN, who despite hematuria, could not undergo renal biopsy or immunosuppressive treatment at another facility because of low proteinuria, and exhibited advanced lesions in their renal biopsy at our institution. The discrepancy between Okabayashi's and STOP-IgAN study was derived not only from differences in population age (≥60 years vs. 18-70 years). STOP-IgAN excluded the crescentic IgAN, whereas Okabayashi et al. found active manifestations (hematuria, mesangial proliferation, and cellular/fibrocellular crescent). Therefore, immunosuppressive therapy is required even in elderly patients. In STOP-IgAN, RASi were used first, and then immunosuppressive agent was additionally used. RASi has important implications to reduce glomerular capillary pressure and to suppress the intrarenal RAS activity. However, immunosuppressant should be administered initially to cure hematuria. In fact, microscopic-hematuria was resolved in only 16 and 42 % of two-assigned groups in STOP-IgAN, respectively. Okabayashi et al. provided a timely message regarding the significance of immunosuppressive treatment of IgAN.

Prominent hyperplasia of renin-producing juxtaglomerular apparatus after chronic and complete blockade of the renin-angiotensin system in adult IgA nephropathy.

Juxtaglomerular apparatus (JGA) hyperplasia rarely happened in renal biopsy and has been controversial clinically, because synthesis and secretion of renin were susceptible to the effect of clinical condition and medication. Here we present the case of a 39-year-old who got JGA hyperplasia of IgA nephropathy (IgAN) after long-term inhibition of the renin-angiotensin system (RAS) with an angiotensin receptor blocker (ARB), and a direct renin inhibitor (DRI) in combination with a diuretic. He was diagnosed with IgAN in his first renal biopsy, and was treated with supra-maximal dosages of ARB, DRI and a diuretic. In the second biopsy, because of the massive proteinuria and occurrence of steroid-induced diabetes, it was revealed that the area and the number of JGA cells were strikingly increased in observed glomeruli. Immunohistopathologically, the both specimens were stained by human renin antibody. The hyperplastic JG cells contained a large amount of renin granules. Putative renin granules were observed in some interstitial cells adjacent to an afferent arteriole by electron microscopy. The increasing response of renin granules co-localized in prominent JGA hyperplasia should be worried while physicians treat hypertensive patients with potent RAS inhibitors and diuretics even though they have diabetes. This is the first report showing a clinical course of forming prominent JGA hyperplasia directly after a full combination of RAS inhibitors and diuretics in adult IgA nephropathy.

Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy.

BACKGROUND: The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity. METHODS: We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3-5 years. RESULTS: Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B. CONCLUSION: Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.

Five cases of tonsillectomy and steroid pulse therapy for recurrent immunoglobulin A nephropathy after kidney transplantation.

Five cases of recurrent immunoglobulin A nephropathy (IgAN) after kidney transplantation were successfully treated by tonsillectomy and steroid pulse therapy (SPT). The clinical background and pathology in the five cases were different, but good results were obtained in all of them. In cases 1 and 2, mild recurrent IgAN developed and failed to remit after tonsillectomy alone, but a remission was achieved in both cases after SPT. In case 3, highly active recurrent IgAN with crescent lesions developed 13 years after kidney transplantation, and a remission was achieved after SPT. In case 4, renal biopsy specimens showed pathological findings of recurrent IgAN with tubulitis, and hematuria and proteinuria resolved after SPT. In case 5, the biopsy findings indicated recurrent IgAN with chronic rejection. Tonsillectomy was followed by resolution of the proteinuria, and a remission was achieved after SPT. In conclusion, SPT is effective in inducing a remission of recurrent IgAN when tonsillectomy alone fails.

Clinical and immunological implications of increase in CD208+ dendritic cells in tonsils of patients with immunoglobulin A nephropathy.

BACKGROUND: The therapeutic effect of tonsillectomy for immunoglobulin A nephropathy (IgAN) has been widely recognized, but the mechanism by which tonsillar immunity leads to glomerulonephritis has been unclear. We investigated subtypes and localization of dendritic cells (DCs) in tonsils and looked for relationships between the tonsillar DCs and the clinical features and renal histological changes of patients with IgAN. METHODS: We examined tonsils from 33 IgAN patients, using as control tonsillar specimens from subjects without glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels of these DC markers were evaluated using real-time polymerase chain reaction. The clinical data and histological results obtained evaluating renal biopsy tissues were statistically compared with immunological data. RESULTS: Of the five subtypes of DCs, CD208(+) DCs were significantly increased in the tonsils of IgAN patients compared with that of controls. Furthermore, the number of CD208(+) DCs in the tonsils was positively and linearly correlated with the proportion of crescentic glomeruli in renal biopsy tissues and with the urinary protein level. Only few CD208(+) cells, however, were found in the kidney biopsy specimens of IgAN patients. CONCLUSIONS: These observations suggest that increased CD208(+) DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present results support the therapeutic significance of tonsillectomy for IgAN patients.

Interpersonal psychosocial factors associated with underreported dietary energy intake in hemodialysis patients.

OBJECTIVE: To examine the association between degree of underreporting energy intake and psychosocial (including interpersonal and personal) factors among hemodialysis patients in Japan. DESIGN: We conducted a cross-sectional study. Predictors of difference were identified using multiple linear regression analysis. SETTING: Study was conducted at a public hospital and a dialysis clinic in a single district in northeast Honshu, Japan. SUBJECTS: Participants were hemodialysis outpatients. Patients aged more than 20 years and undergoing treatment for end-stage renal disease for at least 6 months were included. Exclusion criteria were diagnosis of depression, a mental disease, or dementia. MAIN OUTCOME: The outcome measure was the difference in reported energy intake defined by the differences between a brief administered dietary history questionnaire and diet record stratified by standardized weight. RESULTS: Seventy patients undergoing hemodialysis participated (44 men [62.9%] and 26 women [37.1%]). Of these, 54.3% underreported energy intake (by >10%). Sex (male) and employment status (employed) were statistically associated with energy intake underreporting. A lower score of dialysis staff encouragement was associated with greater energy intake underreporting (ß coefficient = 3.89 kcal/standardized weight, 95% confidence interval: 0.89 to 6.90; P = .012). CONCLUSION: Degree of underreporting energy intake is significantly associated with interpersonal psychosocial factors among hemodialysis patients in Japan. The interpersonal relationship with encouragement by the dialysis staff is important in improving the accuracy of reporting energy intake among dialysis patients.

The complex of immunoglobulin A and uromodulin as a diagnostic marker for immunoglobulin A nephropathy.

BACKGROUND: The only tool to diagnose immunoglobulinn A nephropathy (IgAN) is renal biopsy which requires hospitalization; moreover, renal biopsy has a risk of critical bleeding. Therefore, a non-invasive method for accurate diagnosis of IgAN is desirable and a must-to-have tool for the clinics. For this purpose, we evaluated the diagnostic value of the IgA-uromodulin complex in the urine of patients with IgAN for its feasibility and adequacy. METHOD: We determined the IgA-uromodulin complex as a candidate for a diagnostic marker of IgAN by immunoprecipitation, liquid chromatography-mass spectrometry (LC-MS) and Western blot analysis. The enzyme-linked immunosorbent assay (ELISA) for the IgA-uromodulin complex was developed and applied to urine samples obtained from various kidney disease patients. RESULT: One hundred and three of 126 urine samples (81.7%) from IgAN patients were positive for the IgA-uromodulin complex, while only 25 out of 94 urine samples (26.6%) in other kidney disease patients were positive. Sensitivity was 81.7%, specificity was 73.4%, and diagnosis efficiency was 78.2%. The complex was negative in eight urine samples obtained from patients with Alport syndrome which is almost impossible to discriminate from IgAN by routine urinalysis. CONCLUSION: Detection of the urinary IgA-uromodulin complex by ELISA is a useful non-invasive method to diagnose IgAN.