RESUMEN
Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.
Asunto(s)
Glomerulonefritis por IGA , Glomérulos Renales , Tonsila Palatina , Tonsilectomía , Humanos , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/cirugía , Tonsila Palatina/cirugía , Tonsila Palatina/patología , Femenino , Masculino , Adulto , Glomérulos Renales/patología , Estudios Retrospectivos , Persona de Mediana Edad , Tonsilitis/cirugía , Tonsilitis/patología , Adulto Joven , Inmunoglobulina ARESUMEN
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.
Asunto(s)
Susceptibilidad a Enfermedades , Glomerulonefritis por IGA/etiología , Inmunidad Mucosa , Linfocitos Intraepiteliales/inmunología , Glomérulos Renales/inmunología , Tonsila Palatina/inmunología , Animales , Biomarcadores , Terapia Combinada/métodos , Manejo de la Enfermedad , Progresión de la Enfermedad , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/metabolismo , Glomerulonefritis por IGA/terapia , Humanos , Inmunohistoquímica , Linfocitos Intraepiteliales/metabolismo , Glomérulos Renales/patología , Técnicas de Diagnóstico Molecular , Tonsila Palatina/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
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.
Asunto(s)
Interleucina-6 , Faringitis , Citocinas/genética , Humanos , Interleucina-6/genética , Faringitis/terapia , ARN Mensajero/genéticaRESUMEN
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.
Asunto(s)
Glomerulonefritis por IGA , Biomarcadores , Femenino , Glomerulonefritis por IGA/diagnóstico , Humanos , Inmunoensayo , Inmunoglobulina A , Lectinas , Masculino , Lectinas de Plantas , Polisacáridos , Receptores N-AcetilglucosaminaRESUMEN
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.
Asunto(s)
Glomerulonefritis por IGA/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Anciano , Glomerulonefritis por IGA/patología , Humanos , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , TonsilectomíaRESUMEN
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.
Asunto(s)
Galactosa/metabolismo , Glomerulonefritis por IGA/sangre , Inmunoglobulina A/metabolismo , Adulto , Biomarcadores/sangre , Estudios Transversales , Femenino , Glomerulonefritis por IGA/terapia , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , TonsilectomíaRESUMEN
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.
Asunto(s)
Células Dendríticas/inmunología , Glomerulonefritis por IGA/inmunología , Proteínas de Membrana de los Lisosomas/metabolismo , Proteínas de Neoplasias/metabolismo , Tonsila Palatina/inmunología , Adulto , Western Blotting , Estudios de Casos y Controles , Células Dendríticas/metabolismo , Células Dendríticas/patología , Femenino , Citometría de Flujo , Glomerulonefritis por IGA/metabolismo , Glomerulonefritis por IGA/cirugía , Humanos , Técnicas para Inmunoenzimas , Riñón/inmunología , Riñón/metabolismo , Riñón/patología , Masculino , Tonsila Palatina/metabolismo , Tonsila Palatina/patología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TonsilectomíaRESUMEN
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.
Asunto(s)
Dieta/psicología , Ingestión de Alimentos/psicología , Ingestión de Energía/fisiología , Diálisis Renal/psicología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Peso Corporal , Estudios Transversales , Registros de Dieta , Femenino , Humanos , Japón , Fallo Renal Crónico/psicología , Modelos Lineales , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Because of the well-established annual urinalysis screening system in Japan, the duration of nephropathy (DN) can be estimated in more than half of all patients with IgA nephropathy (IgAN). Treatment using a combination of tonsillectomy and steroid pulse (TSP) therapy has been reported as an effective method for obtaining clinical remission (CR), defined as negative hematuria and proteinuria, in IgAN patients. The present study aims to identify the correlation between DN and CR rate in IgAN patients treated by TSP therapy. METHODS: We retrospectively investigated 830 IgAN patients who were followed up for 81.6 months after TSP therapy. DN could be estimated in 495 of the 830 patients. RESULTS: The CR rate among patients with DN ≤36 months was 87.3% (295/338 patients). The CR rate among patients with DN of 37-84 months was 73.3% (63/86 patients), while that among patients with DN ≥85 months was 42.3% (30/71 patients). The CR rate among the remaining 335 patients in whom DN could not be estimated because of missing annual urinalysis results was 43.6% (146/335 patients). A multivariate Cox regression model using data from the former group of 495 patients showed that DN ≤36 months was a significant predictor of CR (hazard ratio 1.839; 95% confidence interval 1.410-2.398; P < 0.001). CONCLUSION: Shorter DN is associated with higher likelihood of clinical remission in IgAN patients treated by TSP therapy.
Asunto(s)
Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/cirugía , Metilprednisolona/administración & dosificación , Prednisolona/administración & dosificación , Tonsilectomía , Adulto , Factores de Edad , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Quimioterapia por Pulso , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Complejo Antígeno-Anticuerpo/orina , Glomerulonefritis por IGA/diagnóstico , Inmunoglobulina A/orina , Complejos Multiproteicos/orina , Uromodulina/orina , Biomarcadores/orina , Biopsia , Ensayo de Inmunoadsorción Enzimática , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/orina , Humanos , Sensibilidad y EspecificidadRESUMEN
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.
Asunto(s)
Glomerulonefritis por IGA , Tonsilectomía , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/tratamiento farmacológico , Hematuria/etiología , Humanos , Metilprednisolona/efectos adversos , Estudios Retrospectivos , Tonsilectomía/efectos adversos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Carcinoma de Células Escamosas , Virus de la Influenza A , Gripe Humana , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , MetaplasiaRESUMEN
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.
Asunto(s)
Infecciones/terapia , Riñón Poliquístico Autosómico Dominante/complicaciones , Diálisis Renal , Humanos , Infecciones/etiología , Masculino , Persona de Mediana EdadRESUMEN
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.
Asunto(s)
Bacterias/aislamiento & purificación , Disbiosis/microbiología , Glomerulonefritis por IGA/microbiología , Microbiota , Saliva/microbiología , Adulto , Área Bajo la Curva , Bacterias/clasificación , Bacterias/genética , Estudios de Cohortes , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: Chronic kidney disease (CKD) can result from a wide variety of diseases, but whether clinical outcomes differ in the same CKD stages according to the underlying renal disease remains unclear. Clarification of this issue is important for stratifying risk of cardiovascular disease (CVD) and death in patients before dialysis. PATIENTS AND METHODS: The study comprised 2,692 patients recruited from 11 outpatient nephrology clinics, classified by underlying disease of primary renal disease (PRD) (n = 1,306), hypertensive nephropathy (HN) (n = 458), diabetic nephropathy (DN) (n = 283), or other nephropathies (ON) (n = 645). Risks of events such as ischemic heart disease, congestive heart failure, stroke, and all-cause mortality within 12 months were examined by logistic regression analysis in each group. RESULT: During the 12-months' observation from recruitment, 200 cases were lost to follow-up, and 113 cases were introduced to chronic dialysis therapy. A total of 69 CVD events occurred (stroke in 27 cases), and 24 patients died. In total, increased odds ratios (OR) for the events by CKD stage (cf. CKD1 + 2: unadjusted) were CKD3, 1.29 [95% confidence interval (CI), 0.70-2.17]; CKD4, 2.73 (1.55-4.83); and CKD5, 4.66 (2.63-8.23). Regarding events in respective groups, no significant differences were seen by CKD stage except for the group with HN, but significant differences were seen by underlying diseases (cf. PRD: adjusted for confounding factors, including estimated glomerular filtration rate): HN, 2.57 (1.09-6.04); DN, 12.21 (3.90-38.20); and ON, 4.14 (1.93-8.89). CONCLUSION: Risk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Nefropatías Diabéticas/complicaciones , Enfermedades Renales/complicaciones , Enfermedades Renales/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Enfermedad Crónica , Nefropatías Diabéticas/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/mortalidad , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
AIM: The effectiveness of steroid pulse therapy combined with tonsillectomy (ST) has been shown in immunoglobulin A nephropathy (IgAN) patients with moderate or severe urinary abnormalities. The present study aimed to clarify whether the effectiveness may be extrapolated to IgAN with minor urinary abnormalities, and whether the effectiveness may depend on the histological severity with minor urinary abnormalities. METHODS: Data on 388 IgAN patients diagnosed by renal biopsies between 1987 and 2000 in Sendai Shakaihoken Hospital, who presented glomerular haematuria and minimal proteinuria (Asunto(s)
Glomerulonefritis por IGA/complicaciones
, Glomerulonefritis por IGA/terapia
, Glucocorticoides/administración & dosificación
, Hematuria/etiología
, Hematuria/terapia
, Metilprednisolona/administración & dosificación
, Prednisolona/administración & dosificación
, Proteinuria/etiología
, Proteinuria/terapia
, Tonsilectomía
, Adolescente
, Adulto
, Anciano
, Terapia Combinada
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Quimioterapia por Pulso
, Inducción de Remisión
, Estudios Retrospectivos
, Adulto Joven
RESUMEN
Selectivity index (SI) has been reported to reflect the selectivity of proteinuria, and it has a relationship with tubulointerstitial damage. Moreover it has a predictive value on functional outcome. However, it is necessary to measure serum IgG, serum transferrin, urinary IgG, and urinary transferrin to calculate SI. We measured urinary micro-cholesterol (mCHO) levels in sixty-three patients with proteinuria (urinary total protein > or = g/gCr) and compared urinary mCHO/total protein(uTP) ratio and SI. The patients' diseases were minimal change nephrotic syndrome (MCNS, n = 12), focal and segmental glomerular sclerosis (FSGS, n = 12), membranous nephropathy (MN, n = 17), and diabetic nephropathy (DMN, n = 22). Urinary mCHO levels were measured by the ECC method using cholesterol ester hydrolase (CEH) and cholesterol dehydrogenase, and this method was performed conveniently by automatic analyzer. No correlation was observed between urinary mCHO/gCr and serum lipid levels. There was no difference of urinary protein levels among each disease group. We found urinary mCHO/uTP ratio has a good positive correlation with SI(R = 0.722, p < 0.001). Although the difference between ROC curves of SI and urinary mCHO/uTP ratio in distinguishing MCNS from other diseases (FSGS+MN+DMN) did not reach the statistical significance, the area under the curve was larger for mCHO/uTP ratio. These results suggest that measurement of urinary mCHO by ECC method can be a simple and useful tool for predicting selectivity of proteinuria and lipoprotein-loading tubulopathy.
Asunto(s)
Biomarcadores/orina , Colesterol/orina , Proteinuria/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefritis Intersticial/complicaciones , Proteinuria/etiología , Adulto JovenRESUMEN
BACKGROUND: Fluid control in patients on dialysis is an important predictor of outcome but is a difficult restriction to achieve. The authors examined the association between dialysis staff encouragement and fluid control adherence in patients on hemodialysis. METHODS: This cross-sectional study used the dialysis staff encouragement subscale (DSE). The outcome measure was intradialytic weight loss (IWL) of dry weight (DW), with nonadherence defined as IWL/DW greater than 5.7%. Predictors of nonadherence were identified using logistic regression. Odds ratio (OR) was for the occurrence of nonadherence as it correlated with a one standard deviation (SD) decrease in scale score. RESULTS: Seventy-two patients on hemodialysis participated, 45 men (62.5%) and 27 women. The crude OR in DSE score was 1.75 (95% confidence interval [CI]: 1.02 to 3.0) and adjusted odds ratio was 2.51 (95% CI: 0.99 to 6.34). CONCLUSION: Dialysis staff encouragement is important in improving fluid control adherence.
Asunto(s)
Fallo Renal Crónico/terapia , Cooperación del Paciente , Diálisis Renal , Equilibrio Hidroelectrolítico , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Educación Continua en Enfermería , Femenino , Humanos , Control Interno-Externo , Fallo Renal Crónico/dietoterapia , Fallo Renal Crónico/psicología , Masculino , Persona de Mediana Edad , Diálisis Renal/psicología , Estrés PsicológicoRESUMEN
Soluble fibrin (SF) is produced by activated blood coagulation reaction and is useful to diagnose thrombotic diseases. We measured plasma and urine SF levels in nephritic patients to assess the hypercoagulability state associated with the disease. Before they received anti-coagulation or anti-platelet therapies, 60 patients underwent measurement of plasma SF and D-dimer levels by Latex agglutination turbidimetric immnoassay (LA). Urinary SF levels were also measured by LA. Plasma and urinary thrombin antithrombin III complex (TAT) levels were measured by enzyme immunoassay (EIA). Plasma SF levels showed a good correlation with plasma TAT levels but only weak positive correlations were observed between plasma D-dimer and SF or TAT levels. Plasma SF and D-dimer levels were significantly higher in the Iatients with nephrotic-range hypoalbuminemia (< or =3 g/dL) than those without it. Contrarily there was no significant difference in plasma TAT levels between these two groups of patients. In almost all patients, urinary SF levels were under the detection limit. However, TAT was excreted into urine more frequently in patients showing the nephrotic range of hypoalbuminemia at 38.2% than in non-nephrotic patients at 8.0%. Thus, plasma SF levels more precisely indicate activated blood coagulation reaction than plasma TAT levels in nephrotic patients, probably because the plasma SF is not excreted into urine, while plasma TAT is.
Asunto(s)
Biomarcadores/sangre , Fibrina/análisis , Síndrome Nefrótico/complicaciones , Trombofilia/diagnóstico , Trombofilia/etiología , Antitrombina III/orina , Biomarcadores/orina , Fibrina/orina , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Pruebas de Fijación de Látex , Nefelometría y Turbidimetría , Péptido Hidrolasas/sangre , Péptido Hidrolasas/orinaRESUMEN
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.