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Glomerular inflammation is a putative aggravation factor for type 2 diabetic nephropathy and urinary thrombin is a novel marker of glomerular inflammation. To clarify the relationship between glomerular inflammation and progression of the nephropathy, we measured urinary thrombin in 118 patients with type 2 diabetic nephropathy at different stages. To investigate the implications of urinary thrombin in the nephropathy, we compared urinary thrombin with expression of tissue factor, the trigger of blood coagulation activation, in glomeruli and with markers of renal injury (estimated glomerular filtration rate (eGFR) and proteinuria). Urinary thrombin was found in 4.9% (3/61), 0.0% (0/12), 29.6% (8/27) and 50.0% (9/18) of patient groups at stages 1, 2, 3 and 4, respectively. Thus, urinary thrombin was negligible in the patients at early stages (stages 1 and 2), but was present predominantly in the patients at advanced stages (stages 3 and 4). Tissue factor was expressed in accumulated macrophages in glomeruli, which indicates that thrombin may be generated in inflamed glomeruli presumably via inflammation-induced activation of the exudated coagulation factors into glomerular tissues and then be excreted in urine. Urinary thrombin was significantly associated with both decreased eGFR and increased proteinuria in type 2 diabetic nephropathy. Therefore, increased urinary thrombin in patients with advanced stages of type 2 diabetic nephropathy suggests that glomerular inflammation may injure the tissues, thereby impairing renal function. Monitoring an effect of anti-diabetic treatments on glomerular inflammation in the patients with type 2 diabetic nephropathy may be a possible application of urinary thrombin.
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Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/orina , Inflamación/complicaciones , Inflamación/orina , Glomérulos Renales/patología , Trombina/orina , Antitrombina III/metabolismo , Biomarcadores/orina , Proteína C-Reactiva/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Inflamación/sangre , Inflamación/fisiopatología , Glomérulos Renales/fisiopatología , Masculino , Persona de Mediana Edad , Péptido Hidrolasas/metabolismo , Proteinuria/complicaciones , Proteinuria/fisiopatología , Tromboplastina/metabolismoRESUMEN
INTRODUCTION: Diagnosing vasculitis is frequently difficult because its clinical symptoms are similar to those of common infectious diseases and other inflammatory disorders. This study focused on chemokine receptor 8 (CCR8) in peripheral blood mononuclear cells to find a new biomarker that distinguishes vasculitis from infectious complications. METHODS: A cross-sectional study was conducted among 113 patients with systemic vasculitis who were referred to Japan Health Care Organization Sendai Hospital from 2014 to 2016, including those with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, anti-glomerular basement membrane disease, lupus nephritis, and Henoch-Schonlein purpura. Peripheral blood mononuclear cells were extracted from blood, and CCR8 expression was examined by real time polymerase chain reaction and flow cytometry. RESULTS: CCR8 gene expression was significantly higher in patients with ANCA-associated vasculitis, which was confirmed by upregulated CCR8 protein expression in flow cytometry (P < 0.001 and P = 0.01, respectively). Neither lupus nephritis nor Henoch-Schonlein purpura showed upregulated CCR8. Elevated CCR8 in the active phase decreased significantly in remission (P = 0.002), which was correlated with decreased serum inflammatory markers. Despite elevated serological inflammatory markers, the CCR8 levels at the time of infection, including bacterial, viral, and fungal, did not increase, indicating that infectious complications did not affect CCR8 expression (P = 0.02). CONCLUSION: CCR8 in peripheral blood mononuclear cells may be a useful diagnostic marker for ANCA-associated vasculitis to differentiate between active vasculitis and infectious inflammation.
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AIM: A recent, growing concern regarding haemodialysis in Japan is a sustained increase in the elderly population. Among very elderly people who start haemodialysis, the prognosis is considered to be poor; however, this has not been fully elucidated. This study aimed to discover the short-term prognosis and related factors in very elderly patients who commence haemodialysis. METHODS: Between January 2008 and December 2013, 122 patients aged ≥85 years at haemodialysis initiation were documented in our hospital. Predictors of 90-day and 1-year mortality after haemodialysis initiation were assessed with Cox proportional hazards regression analysis. Selection of covariates for the multivariate model was based on forward stepwise selection using the probability of a likelihood ratio statistics. RESULTS: The subjects' mean age was 87.4 ± 2.5 years, and 48% were female. The most common cause of death was infection (38% of patients) and the leading cause of infectious death was pneumonia. The 90-day and 1-year survival rates were 81% and 62%, respectively. Suboptimal initiation was a significant prognostic factor for 90-day [hazard ratio (HR) 3.98, 95% confidence interval (CI) 1.18-13.43] and 1-year [HR 3.19, 95% CI 1.51-6.76] mortality after adjusting for confounders in multivariate analysis. CONCLUSION: Very elderly patients who started haemodialysis had a poor prognosis, and suboptimal initiation significantly predicted outcome. Shared decision-making with patients and their families is needed for initiating haemodialysis on the conditions that appropriate information on the expected prognosis is provided.
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Cateterismo Venoso Central/mortalidad , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Diálisis Renal/mortalidad , Poblaciones Vulnerables , Factores de Edad , Anciano de 80 o más Años , Envejecimiento , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia , Causas de Muerte , Catéteres Venosos Centrales , Toma de Decisiones Clínicas , Comorbilidad , Femenino , Anciano Frágil , Fragilidad/diagnóstico , Fragilidad/mortalidad , Evaluación Geriátrica , Humanos , Japón , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/fisiopatología , Masculino , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
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Centro Germinal/patología , Glomerulonefritis por IGA/terapia , Glucocorticoides/administración & dosificación , Tonsila Palatina/patología , Prednisolona/administración & dosificación , Tonsilectomía/métodos , Tonsilitis/patología , Adulto , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Quimioterapia por Pulso , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: An effective approach to prevent hemodialysis vascular access dysfunction is still unclear despite previous studies, which have shown conflicting results of several drugs on vascular access outcomes. In this study, we focused on diabetic hemodialysis patients with native arteriovenous fistula and evaluated the impact of statin treatment on vascular access patency. METHODS: A retrospective cohort study of 268 consecutive patients who newly started hemodialysis due to diabetic nephropathy between January 2011 and December 2013 at Japan Community Health Care Organization Sendai Hospital was performed and the patients were followed for two years. The primary outcome was vascular access dysfunction. Effect of statin treatment was examined using Kaplan Meier analysis and Cox proportional hazard, after adjusting for covariates. RESULTS: The mean follow-up period was 426.7 days, and 117 (52.2%) patients developed vascular access dysfunction. The two-year patency rate was 55.0% among statin users and 36.1% in non-users. Vascular access survival period was significantly longer among statin users (log-rank test, p = 0.004). In multivariable analysis, statin treatment is significantly associated with better vascular access outcomes, in which the hazard ratio was 0.71 (95% CI, 0.52 to 0.97; p = 0.028) in the unadjusted model and 0.63 (95% CI, 0.45 to 0.88; p = 0.007) after adjustment for covariates. CONCLUSIONS: Statin treatment could be associated with improved vascular access dysfunction among diabetic hemodialysis patients.
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Derivación Arteriovenosa Quirúrgica , Nefropatías Diabéticas/terapia , Oclusión de Injerto Vascular/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Diálisis Renal , Grado de Desobstrucción Vascular/efectos de los fármacos , Anciano , Derivación Arteriovenosa Quirúrgica/efectos adversos , Distribución de Chi-Cuadrado , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Background. Tonsillectomy is one of the treatment strategies for immunoglobulin A nephropathy (IgAN). The relationship between the indication of tonsillectomy and the size of palatine tonsils (PTs) in patients with IgAN remains controversial. Methods. This retrospective cohort study investigated 57 patients with IgAN who underwent tonsillectomy combined with steroid pulse therapy (SPT). They were classified into two groups, the hypertrophy group and the nonhypertrophy group, according to the weight of their excised PTs. The effects of tonsillectomy combined with SPT on clinical remission (CR) and the histopathological findings of PTs were compared between the two groups. Results. During the mean follow-up period of 45.5 (range 6-133) months, 78.9% of the patients achieved CR (79.3 versus 78.6%, P = 0.945) and the baseline serum creatinine doubled only in one patient in the nonhypertrophy group (0 versus 3.6%, P = 0.491). No significant difference was observed in the incidence of CR between the two groups by the Kaplan-Meier method (P = 0.839). The predictor for CR, identified in Cox proportional hazards models, was baseline proteinuria [hazard ratio 0.14 (95% CI 0.032-0.621) P = 0.010]. Although macroscopic pus plugs were observed on the surface of PTs in almost 60% of patients in each group, microscopic pus plugs in the crypt and the enlarged interfollicular area were observed in all patients. Conclusions. The treatment effect of tonsillectomy combined with SPT and the pathological features of PTs in IgAN were equal, regardless of the size of the PTs. Therefore, the size of PTs should not be included as a factor when deciding the indication of tonsillectomy for IgAN.
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BACKGROUND: Corticosteroids have been widely used in patients with cholesterol crystal embolism (CCE) and low-density lipoprotein apheresis (LDL-A) was reported to reduce the risk of end-stage renal disease in patients with CCE. This study was designed to evaluate the renoprotective effects of LDL-A in combination with corticosteroids in patients with CCE. METHODS: Thirty-five patients with CCE who, between 2008 and 2013, had shown renal deterioration after vascular interventions were retrospectively evaluated. All patients received corticosteroids; of these, 24 also received LDL-A and 11 did not, designated LDL-A and control groups, respectively. Differences in eGFR (ΔeGFR), 3 months and 1 year after CCE diagnosis, were compared in the two groups. RESULTS: The median estimated glomerular filtration rate (eGFR) in all patients was 38.9 [interquartile range (IQR) 31.9-49.4] ml/min/1.73 m2 at baseline (before vascular intervention). At diagnosis, it was 14.4 (IQR 11.3-21.8) ml/min/1.73 m2. The initial corticosteroid dose was 0.34 ± 0.10 mg/kg/day. The mean number of LDL-A treatment sessions in the LDL-A group was 4.3 ± 1.8. eGFR was increased significantly after LDL-A treatments, from 15.0 (IQR 12.3-20.1) to 19.6 (IQR 14.3-23.6) ml/min/1.73 m2 (P < 0.05). ΔeGFR tended to be higher in the LDL-A than in the control group at 3 months [median 6.5 (IQR 5.1-9.3) vs. 2.6 (IQR -0.6 to 6.3) ml/min/1.73 m2, P = 0.095] and was significantly higher at 1 year [median 7.5 (IQR 5.4-8.7) vs. 2.2 (IQR -3.8 to 5.1) ml/min/1.73 m2, P = 0.019]. CONCLUSIONS: LDL-A plus corticosteroids may restore deteriorated renal function better than corticosteroids alone in patients with CCE.
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Corticoesteroides/uso terapéutico , Eliminación de Componentes Sanguíneos/métodos , LDL-Colesterol/sangre , Embolia por Colesterol/terapia , Fallo Renal Crónico/prevención & control , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Terapia Combinada , Cristalización , Embolia por Colesterol/sangre , Embolia por Colesterol/complicaciones , Embolia por Colesterol/diagnóstico , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/fisiopatología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/etiología , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Anemia greatly affects the development of renal and cardiovascular outcomes in chronic kidney disease (CKD) patients. However, the impact based on CKD stage remains unclear. METHODS: We prospectively followed 2,602 Japanese CKD patients under the care of nephrologists. CKD was defined according to cause, estimated glomerular filtration rate <60 mL/min, and/or proteinuria. Patient outcomes [primary end-points: cardiovascular events (CVEs), all-cause mortality, and end-stage kidney disease (ESKD) requiring renal replacement therapy] were assessed in association with basal hemoglobin (Hb) levels (<10, 10-12 and ≥12 g/dL), stratified by CKD stages. RESULTS: During follow-up, 123 patients developed CVEs, 41 died, and 220 progressed to ESKD. For stages G3, G4 and G5, ESKD frequencies were 2.8, 64.4, and 544.8 person-years, while CVEs and death were 25.6, 45.6, and 76.3 person-years, respectively. The combined endpoint rate was significantly higher in patients with Hb <10 versus Hb 10-12 g/dL, but a higher risk for CVEs and death with Hb <10 g/dL was found only in G3 [hazard ratio (HR) 4.49, (95 % confidence interval (95 % CI) 2.06-9.80)]. In contrast, risk for ESKD with Hb <10 g/dL was found only in G4 [HR 3.08 (95 % CI 1.40-6.79)] and G5 [HR 1.43 (95 % CI 1.01-2.05)]. No increased risks with higher Hb levels were found. CONCLUSION: The impact of renal anemia of Hb <10 g/dL on clinical outcomes differed by CKD stage, with a significantly high risk for CVEs and all-cause mortality in G3 and progression to ESKD in G4 and G5.
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Anemia/etiología , Hemoglobinas/metabolismo , Insuficiencia Renal Crónica/sangre , Adulto , Anciano , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The aim of this study was to determine the efficacy of cyclophosphamide (CY) on anti-neutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA) with renal involvement in Japanese patients. METHODS: Eighty-two patients with newly diagnosed ANCA-positive MPA were enrolled in this retrospective study. Patients were divided into two groups based on whether they received combination therapy with a corticosteroid (CS) plus CY (CY group) or CS alone or with other therapies (non-CY group). The primary outcome was defined as the combination of death and end-stage renal disease (ESRD). RESULTS: The CY and non-CY groups included 29 and 53 patients, respectively. In the non-CY group, 31 patients were treated with CS alone, and 22 with a combination of CS and other therapeutics. The percentage of males and mean Birmingham vasculitis activity scores were higher in the CY group than those in the non-CY group, but other factors such as age, serum creatinine, serum albumin, or CRP at baseline were equivalent in the two groups. No differences were observed in remission rates using induction therapy for the two groups. However, the survival rate 5 years after induction therapy was lower in the CY group than in the non-CY group (0.50 vs. 0.73; P = 0.041), although the hazard ratio of CY for the primary outcome adjusted for all confounding factors was 1.321 [95 % confidence interval (CI), 0.662-2.637; P = 0.171]. CONCLUSIONS: CY may not have an additive effect on induction therapy with CS for Japanese patients with renal vasculitis associated with ANCA-positive MPA.
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Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Poliangitis Microscópica/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Anciano , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Enfermedades Renales/diagnóstico , Enfermedades Renales/inmunología , Enfermedades Renales/mortalidad , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/prevención & control , Masculino , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/mortalidad , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Drugs such as corticosteroids and statins have been used to treat cholesterol crystal embolism (CCE), but the prognosis remains poor. This study evaluated the efficacy of low-density lipoprotein apheresis (LDL-A) in patients with CCE. Patients with CCE who showed renal deterioration after vascular interventions were studied retrospectively. Information on demographic variables, clinical measurements, and medication use was collected. The outcomes were incidence of maintenance dialysis and mortality at 24 weeks. A total of 49 patients with CCE were included, among whom 37 (76%) were diagnosed pathologically and the remainder were diagnosed clinically. The median estimated GFR at baseline and at diagnosis were 40.5 and 13.4 mL/min per 1.73 m(2) , respectively. Corticosteroids were used in 42 patients (86%), statins in 30 patients (61%), and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in 29 patients (59%). LDL-A was performed in 25 patients (LDL-A group), and not in 24 patients (control group). Smoking (100% vs. 72%, P = 0.02), white blood cell count (8900/mm(3) vs. 7000/mm(3) ) and corticosteroid use (96% vs. 75%) were higher in the LDL-A group compared with the control group, but there were no differences in other demographic and clinical parameters between the groups. Patients in the LDL-A group had a lower incidence of maintenance dialysis (2/25 (8%) vs. 8/24 (33%), P < 0.05), and a trend towards lower mortality (2/25 (8%) vs. 7/24 (29%), P = 0.074). These results suggest that LDL-A decreases the risk of maintenance dialysis in severe renal CCE patients after vascular interventions.
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Eliminación de Componentes Sanguíneos , Embolia por Colesterol , Lipoproteínas LDL/sangre , Insuficiencia Renal , Anciano , Anciano de 80 o más Años , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Eliminación de Componentes Sanguíneos/métodos , Eliminación de Componentes Sanguíneos/estadística & datos numéricos , Embolia por Colesterol/sangre , Embolia por Colesterol/complicaciones , Embolia por Colesterol/diagnóstico , Embolia por Colesterol/terapia , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Japón , Masculino , Evaluación de Resultado en la Atención de Salud , Pronóstico , Diálisis Renal/métodos , Diálisis Renal/estadística & datos numéricos , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Crescentic glomerulonephritis (CresGN), an uncommon rapidly progressive disease, is characterized by severe glomerular inflammation with fibrin deposition. The lack of specific CresGN biomarkers delays diagnosis and threatens life. Because fibrin deposits in CresGN glomeruli indicate thrombin generation, we hypothesized that thrombin is excreted in urine and is a specific CresGN biomarker. METHODS: We measured urinary thrombin activity in 200 untreated patients (17 with CresGN, 183 with primary glomerulonephritis) and controls (8 patients with healed CresGN, 11 with nephrosclerosis, and 10 with tubulointerstitial nephritis, and 66 healthy volunteers). CresGN types included 15 pauci-immune and 2 immune complex. We assessed the diagnostic accuracy of thrombinuria in 169 patients with hematuria and proteinuria. Renal biopsy tissues were immunostained for tissue factor and fibrin. We analyzed the relationship of thrombinuria to plasma thrombin-antithrombin complex, hematuria, proteinuria, glomerular filtration rate, glomerular fibrin deposition, antineutrophil cytoplasmic antibodies (ANCAs), and C-reactive protein (CRP). We studied changes in thrombin activities after glucocorticoid treatment in 12 patients with thrombinuria. RESULTS: The highest thrombinuria occurrence was in CresGN (70.6%), followed by membranoproliferative glomerulonephritis (41.7%), IgA nephropathy (9.2%), and acute glomerulonephritis (0%). More than 75% of patients with nonproliferative glomerulonephritis manifested no thrombinuria. No controls had thrombinuria. Thrombinuria showed high CresGN specificity (90.1%) and moderate sensitivity (70.6%) and was detected in 4 of 7 patients with ANCA-negative CresGN. In CresGN, thrombinuria was associated with fibrin deposition in glomerular extracapillary tissue, where monocytes/macrophages expressed tissue factor. Thrombinuria in CresGN was unrelated to plasma thrombin-antithrombin complex, hematuria, proteinuria, glomerular filtration rate, and CRP. After glucocorticoid treatment, thrombinuria in patients with CresGN rapidly disappeared but proteinuria and hematuria persisted. CONCLUSIONS: Thrombinuria was specific for glomerular inflammation, was unaffected by systemic inflammation or coagulation, and demonstrated good diagnostic accuracy for CresGN including ANCA-negative cases. Thrombinuria measurement may provide risk-free diagnosis and screening for CresGN.
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Biomarcadores/orina , Glomerulonefritis/diagnóstico , Trombina/orina , Anciano , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Tasa de Filtración Glomerular , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/fisiopatología , Glomerulonefritis/orina , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Tromboplastina/metabolismoRESUMEN
BACKGROUND: Previous studies established a J-shaped association between blood pressure (BP) and cardiovascular disease (CVD) in chronic kidney disease (CKD), and the different clinical profiles of CVD by ethnicity. However, the adequately lower BP target remains unclear in Asian patients with CKD. METHODS: This prospective observational study included 2,655 Japanese outpatients with CKD under nephrologist care who met the inclusion criteria, namely estimated glomerular filtration rate <60 mL/min and/or presenting proteinuria. The patients were divided by 10-mmHg BP increments by clinical data. The end points were death, cardiovascular events (CVEs), and end-stage kidney disease (ESKD) that requires renal replacement therapy. RESULTS: During a 3.02-year median follow-up, 64 patients died, 120 developed CVEs, and 225 progressed to ESKD. In the adjusted Cox models, the risks of CVEs and all-cause mortality were higher in the patients with systolic BPs (SBPs) < 110 mmHg than in those with SBPs of 130-139 mmHg. Moreover, the risk was higher in those with diastolic BPs (DBPs) < 70 mmHg than in those with DBPs of 80-89 mmHg. Although SBPs ≥ 140 mmHg were associated with higher incidence rates of ESKD, no significant increased risk was associated with BPs < 130/80 mmHg. CONCLUSIONS: SBPs < 110 mmHg and DBPs < 70 mmHg were independent risk factors of CVEs and all-cause mortality. No lower BPs were observed as significant risk factors of progression to ESKD. This study suggests that the lower BP target in Asian patients with CKD should be ≥110/70 mmHg.
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Enfermedades Cardiovasculares/patología , Hipotensión/complicaciones , Riñón/patología , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Adulto , Anciano , Pueblo Asiatico , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Progresión de la Enfermedad , Determinación de Punto Final , Femenino , Tasa de Filtración Glomerular , Humanos , Hipotensión/mortalidad , Japón , Estimación de Kaplan-Meier , Fallo Renal Crónico/etiología , Fallo Renal Crónico/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/mortalidad , Factores de RiesgoRESUMEN
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.
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BACKGROUND: The prevalence of chronic kidney disease (CKD) and its complications, such as cardiovascular disease (CVD), cerebral vascular disease and end-stage kidney disease (ESKD), has been increasingly recognized as a global health problem in Japan. OBJECTIVE: We surveyed the awareness about CKD among medical professionals and the general public in Miyagi Prefecture. Additionally, we considered ways to lower the prevalence of CKD, CVD and ESKD. METHOD: We offered an annual educational lecture on CKD for the general population in Miyagi prefecture from 2010 to 2012. At each lecture, we distributed an anonymous survey to the participants about CKD and its complications. RESULTS: The number of survey respondents was 355, and their mean age was 63.9 years. Awareness about CKD among the participants, excluding medical professionals, was 58.0 %. Terms such as "serum creatinine" and "estimated GFR" were recognized in only about 60% and 40% of the respondents, respectively. Knowledge of risk factors for CKD, such as "elderly person" and "smoker," was at a low level. Furthermore, anemia and osteoporosis were not well-recognized as comorbidities of CKD. CONCLUSION: We found that the participants at the CKD educational lectures had limited knowledge about CKD and its complications; therefore, educational intervention regarding CKD, CVD and ESKD should be continued. Public awareness about CKD must be addressed to reduce CVD not only to prevent ESKD. The educational intervention will require a wide range of specialists in CKD care, general physicians, health nurses, and nutritionists, who contribute to community-based health care.
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Concienciación , Educación en Salud/métodos , Educación en Salud/estadística & datos numéricos , Insuficiencia Renal Crónica , Enfermedades Cardiovasculares/prevención & control , Servicios de Salud Comunitaria , Personal de Salud/educación , Personal de Salud/psicología , Humanos , Japón , Fallo Renal Crónico/prevención & control , Conocimiento , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/prevención & control , Encuestas y CuestionariosRESUMEN
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.
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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
OBJECTIVE: Ambulatory blood pressure (BP) is reportedly associated with target organ damage. However, whether ambulatory BP carries prognostic significance for the development of chronic kidney disease (CKD) has not been confirmed. METHOD: We measured ambulatory BP in 843 participants without CKD at baseline from a general Japanese population and examined the incidence of CKD defined as positive proteinuria or an estimated glomerular filtration rate (eGFR) less than 60âml/min per 1.73 m at health checks. The association between baseline ambulatory BP and CKD incidence was examined using the Cox proportional hazard regression model adjusted for sex, age, BMI, habitual smoking, habitual alcohol consumption, diabetes mellitus, hypercholesterolemia, a history of cardiovascular disease, antihypertensive medication, eGFR at baseline, the number of follow-up examinations, and the year of the baseline examination. RESULTS: The mean age of the participants averaged 62.9â±â8.1 years, 71.3% were women and 23.7% were under antihypertensive medication. During a median follow-up of 8.3 years, 220 participants developed CKD events. The adjusted hazard ratios for CKD in a 1-standard deviation increase in daytime and night-time SBP were 1.13 [95% confidence interval (CI) 0.97-1.30] and 1.21 (95% CI 1.04-1.39), respectively. When night-time and daytime BP was mutually adjusted into the same model, only night-time BP persisted as an independent predictor of CKD. CONCLUSION: Night-time BP is a better predictor of CKD development than daytime BP in the general population. Ambulatory BP measurement is considered useful for evaluating the risk of progression to CKD.
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Presión Sanguínea , Ritmo Circadiano , Fallo Renal Crónico/fisiopatología , Anciano , Femenino , Tasa de Filtración Glomerular , Humanos , Japón , Estudios Longitudinales , Masculino , Persona de Mediana EdadRESUMEN
Dialysis-related amyloidosis is a serious complication of long-term hemodialysis. Its pathogenic mechanism involves accumulation of ß2-microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of ß2-microglobulin, has been available since 1996 to treat dialysis-related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis-related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self-evaluation by patients, worsening of symptoms was inhibited in 84.9-96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis-related amyloidosis in most patients.
Asunto(s)
Amiloidosis/terapia , Hemoperfusión/métodos , Diálisis Renal/efectos adversos , Microglobulina beta-2/metabolismo , Adsorción , Anciano , Amiloidosis/etiología , Amiloidosis/patología , Progresión de la Enfermedad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
A 48-year-old man with chronic lymphocytic leukemia presented with nephrotic syndrome, hematuria, and mild deterioration of renal function. Further analysis using serum immunofixation electrophoresis detected monoclonal immunoglobulin (Ig) M-κ and IgG-κ M-protein. Testing for cryoglobulin in serum was negative. Light microscopy of a renal biopsy specimen showed membranoproliferative glomerulonephritis features with marked mononuclear cell infiltration in the interstitium. On immunofluorescence study, the deposition of IgM heavy chain was predominantly observed with the same distribution of κ light chain, whereas no λ light chain was found. Electron microscopy revealed fine granular deposits in the mesangial, subendothelial, and subepithelial areas, mimicking those observed in the immune complex-mediated glomerulonephritis. These pathological findings were consistent with recently described cases of proliferative glomerulonephritis with monoclonal IgG deposits. Thus, monoclonal IgM deposition can also cause proliferative glomerulonephritis.