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BACKGROUND: Antineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. In this study, we aim to investigate the role of CD206+ mono-macrophages in AGN. METHODS: 27 AGN patients (14 active AGN, 13 remissive AGN) together with healthy controls (n = 9), disease controls (n = 6) and kidney function adjusted controls (n = 9) from Department of Nephrology, Ruijin hospital were recruited. Flow cytometry was used to study proportion of CD206+ cells in peripheral blood. Immunohistochemistry for CD206 staining was performed and CD206 expression was scored in different kidney regions. Serum soluble CD206 (sCD206) was measured by enzyme-linked immunosorbent assay (ELISA). We also generated murine myeloperoxidase (MPO) (muMPO) ANCA by immunizing Mpo-/- mice. Mouse bone marrow-derived macrophages (BMDMs) from wild C57BL/6 mice and peripheral blood mononuclear cell (PBMC) derived macrophages from healthy donors were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression. RESULTS: The proportion of peripheral CD206+CD68+ cells in active AGN patients were significantly higher than that in remissive patients (p < 0.001), healthy controls (p < 0.001) and kidney function adjusted controls (p < 0.001). Serum sCD206 level in active AGN patients was higher than that in healthy controls (p < 0.05) and remissive patients (p < 0.01). Immunohistochemistry showed CD206 was highly expressed in different kidney regions including fibrinoid necrosis or crescent formation, glomeruli, periglomerular and tubulointerstitial compartment in active AGN patients in comparison with disease controls. Further studies showed MPO ANCA could induce CD206 expression in BMDMs and PBMC derived macrophages and such effects could be reversed by its inhibitor AZD5904. CONCLUSION: ANCA could induce CD206 expression on mono-macrophages and CD206+ mono-macrophages are activated in AGN. CD206 might be involved in the pathogenesis of AAV and may be a potential target for the disease.
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Anticuerpos Anticitoplasma de Neutrófilos , Glomerulonefritis , Animales , Ratones , Glomerulonefritis/metabolismo , Glomerulonefritis/patología , Leucocitos Mononucleares/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Peroxidasa/metabolismoRESUMEN
OBJECTIVES: Renal risk score (RRS) and chronicity score (CS) are both newly proposed tools to predict end stage renal disease (ESRD) which could be applicable in antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis patients. Their predictive value has not been fully studied and compared. METHODS: 252 patients with newly biopsy-proven ANCA-associated renal vasculitis were retrospectively studied at the Department of Nephrology, Ruijin Hospital, China. Patients were evaluated with RRS and CS for clinical factors, pathological lesions and outcome. Their predictive value of renal survival was also compared. RESULTS: The median RRS score point at diagnosis was 6 (interquartile range [IQR] 0-9) and CS score point was 4 (IQR 3-7). In accordance with severity of RRS category and CS grade, percentage of hypertensive patients, dialysis dependency, and level of proteinuria increased accordingly. Significant differences were found regarding dialysis dependency within RRS and CS groups (p<0.001 and p<0.01 respectively). The addition of RRS or CS scoring scheme to the base model of dialysis dependency significantly improved discrimination. The C statistic, integrated discrimination improvement and net reclassification improvement were significantly increased by adding either RRS/CS or both. Furthermore, RRS had better ROC. CONCLUSIONS: Among ANCA associated renal vasculitis patients, RRS and CS achieved similar discrimination, but the discrimination of RRS was superior.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , China , Humanos , Riñón , Estudios RetrospectivosRESUMEN
BACKGROUND: Acute kidney injury (AKI) is a critical clinical syndrome characterised by a rapid decrease in renal filtration, with the accumulation of products of metabolism such as creatinine and urea. In recent years, the incidence of AKI has increased not only in critically ill hospitalised patients but also in community patients. Also, the prognosis of AKI is poor and treatment is limited in these populations. The increasing incidence and poor prognosis may be the reasons why more investigators are involved in epidemiological and risk factor analysis of AKI. AIMS: To investigate the effects of these risk factors on outcomes in both community-acquired and hospitalised AKI populations to provide certain guidance for clinics and to explore the prognostic value of prealbumin on all-cause mortality in patients with community-acquired and post-operative AKI. METHODS: From 2000 to 2010, 477 patients diagnosed with AKI and treated in the Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University, were enrolled in the community-acquired AKI (CA-AKI) group and 138 patients diagnosed with AKI after an operation were enrolled in the post-operative AKI (PO-AKI) group. Data were collected at AKI onset and 1 year after discharge and analysed retrospectively. RESULTS: Compared with PO-AKI patients, more patients in CA-AKI group had chronic kidney disease, obesity and hyperlipidaemia, and fewer patients had cerebrovascular disease (CVD), anaemia, shock or arrhythmia. Risks for CA-AKI were atherosclerosis, CVD, arrhythmia, multiple organ dysfunction syndrome and usage of vasoactive agents, and risks for PO-AKI were elderly, arrhythmia and requirement of renal replacement therapy. A higher level of serum PA was associated with a better outcome in the CA-AKI group (hazard ratio 0.92, 95% confidence interval 0.85-0.996) and PO-AKI group (hazard ratio 0.91, 95% confidence interval 0.84-0.99). In the CA-AKI group, the cumulative survival rate of patients with a normal PA level (PA >20 mg/dL) was higher than that among patients with a lower PA (PA ≤20 mg/dL; 95.4% vs 88.3%, P = 0.031). Similarly, in the PO-AKI group, a normal PA level was associated with a higher survival rate (74.1% vs 47.6%, P = 0.019). CONCLUSION: Serum PA may serve as a prognostic marker for CA-AKI and PO-AKI, and further research is warranted to confirm this finding.
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Lesión Renal Aguda , Albúmina Sérica , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Anciano , China/epidemiología , Mortalidad Hospitalaria , Humanos , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy caused by inactivating mutations in the SLC12A3 gene. Although hundreds of different mutations across the SLC12A3 gene have been reported worldwide, data from mainland China are limited. We investigated the clinical manifestations and genetic features of Chinese patients with GS. METHODS: Fifty-four unrelated Chinese patients with clinically diagnosed GS were included. Clinical manifestations and biochemical parameters were collected and analyzed. All exons and flanking regions of the SLC12A3 and CLCNKB genes were screened by direct sequencing. RESULTS: Weakness was the most commonly reported symptom in this cohort of patients with GS. In gender-based analyses, higher systolic blood pressure and urine protein excretion were observed in male patients. For genetic screening, 2 pathogenic SLC12A3 mutations were identified in 38 patients (70.4%), 1 mutation in 11 patients (20.4%) and no mutation in 5 patients (9.3%). In total, 42 distinct pathogenic mutations throughout SLC12A3 were identified; 16 were novel, including 9 missense, 1 deletion, 1 insertion, 3 splice site and 2 nonsense mutations. Eleven mutations were recurrently found in different patients. Among them, T60M and D486N were identified in 11 individuals. No CLCNKB mutations were found. CONCLUSION: Sixteen novel SLC12A3 pathogenic mutations were identified in a cohort of Chinese patients with GS. T60M and D486N were most frequent and appear to be important candidate alleles in Chinese patients with GS.
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Pueblo Asiatico/genética , Canales de Cloruro/genética , Síndrome de Gitelman/genética , Adolescente , Adulto , Alelos , China , Estudios de Cohortes , Exones/genética , Femenino , Pruebas Genéticas , Genotipo , Humanos , Masculino , Mutación , Fenotipo , Análisis de Secuencia de ADN , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , Adulto JovenRESUMEN
BACKGROUND: Traditionally, antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is histologically characterized by pauci-immune glomerulonephritis. However, more and more literature has reported immune complex (IC) deposits to be found in renal specimen from patients with AAV. The role that these IC deposits play in the development of AAV, as well as their clinical and pathological significance, is worthy of studying. OBJECTIVES: The objective of this study was to analyze the clinical and pathological characteristics of Chinese patients with AAV having renal IC deposition. METHODS: A retrospective study was performed on 34 patients with AAV in Shanghai Ruijin Hospital with renal IC deposition. Clinical and pathological data were collected and studied and compared with other 76 AAV patients having classic pauci-immune glomerulonephritis. RESULTS: Thirty-four patients were enrolled in this study, with a mean age of 56.4 ± 16.4 years and a male-female ratio of 1:1.3 (19/15). Twenty-seven patients (79.4%) had impaired renal function, with an average serum creatinine of 4.4 ± 3.2 mg/dL. C3 (82.4%) and immunoglobulin M (50%) were the most common IC deposits observed in the kidneys. During the follow-up (median, 39 months), 6 patients (17.7%) died, and 11 (32.4%) finally progressed to end-stage renal disease despite immunosuppressive therapy. Compared with patients having classic pauci-immune glomerulonephritis, patients with renal IC deposits had similar clinical and laboratory features except for more proteinuria (2374 ± 2221 vs 1444 ± 1956 mg/24 h, P = 0.002), a higher prevalence of nephrotic syndrome (30.3% vs 9.6%, P = 0.007) and hypocomplementemia (86.8 ± 33.1 vs 110 ± 45.5 mg/dL, P = 0.029), and also a higher risk for progressing to end-stage renal disease (32.4% vs 13.1%, P = 0.018). CONCLUSIONS: Patients with AAV with renal IC deposition might have a worse renal prognosis than those having classic pauci-immune glomerulonephritis.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Complejo Antígeno-Anticuerpo/metabolismo , Enfermedades del Complejo Inmune/diagnóstico , Enfermedades del Complejo Inmune/patología , Riñón/metabolismo , Riñón/patología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , China , Comorbilidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glomerulonefritis/diagnóstico , Glomerulonefritis/mortalidad , Glomerulonefritis/patología , Humanos , Enfermedades del Complejo Inmune/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Síndrome Nefrótico , Prevalencia , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitute a subgroup of life-threatening diseases which affects the kidney in more than half of the patients at diagnosis. Currently, little has been published focusing on AAV patients with dialysis. We analysed AAV patients with chronic dialysis to provide more detailed information. METHODS: From 1997 to 2011, AAV patients complicated by renal involvement resulting in end-stage renal disease (ESRD) and had undergone haemodialysis (HD) or peritoneal dialysis (PD) for at least 3 months in Shanghai Ruijin hospital were retrospectively analysed in this study. Their data were also compared to those without dialysis at the same time. RESULTS: We enrolled 49 AAV patients with chronic dialysis. 41 required dialysis at initial presentation and rest 8 progressed to ESRD during follow-up. 19 HD patients died and 6 PD patients died during follow-up, and infection was the most common cause among the patients. There was no significant difference regarding survival between HD patients and PD patients (p>0.05). However anaemia and level of triglyceride was more significantly improved in HD patients at the end of observation (p<0.05, p<0.05 respectively). Compared with patients without dialysis dependency, dialysis patients presented higher percentage of hypertension (p<0.01), more severe renal involvement and higher BVAS (p<0.01). For the outcome, survival was significantly higher in non-dialysis patients (p<0.05). CONCLUSIONS: Patients with AAV experienced a high rate of renal failure and dialysis dependence. Our study suggests that haemodialysis and peritoneal dialysis are two comparable dialysis modalities for AAV patients with ESRD. However, AAV patients with dialysis dependency had worse outcome in comparison with those without dialysis.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Fallo Renal Crónico , Riñón/inmunología , Diálisis Peritoneal , Diálisis Renal , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/sangre , China/epidemiología , Creatinina/sangre , Hemoglobinas/análisis , Humanos , Estimación de Kaplan-Meier , Riñón/fisiopatología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/etiología , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/métodos , Diálisis Peritoneal/estadística & datos numéricos , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Diálisis Renal/estadística & datos numéricos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIM: To investigate diabetic retinopathy (DR) prevalence in Chinese renal-biopsied type 2 diabetes mellitus (T2DM) patients with kidney dysfunction, and to further evaluate its relationship with diabetic nephropathy (DN) incidence and the risk factors for DR development in this population. METHODS: A total of 84 renal-biopsied T2DM patients were included. Fundus and imaging examinations were employed for DR diagnosis. Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups. Risk factors on DR development were analyzed with multiple logistic regression. RESULTS: DR prevalence was 50% in total. The incidences of DN, non-diabetic renal disease (NDRD) and mixed-type pathology were 47.6%, 19.0% and 33.3% in the DR group respectively, while 11.9%, 83.3% and 4.8% in the non-DR group. Systolic blood pressure, ratio of urinary albumin to creatine ratio, urinary albumin, 24-hours urinary protein, the incidence and severity of DN histopathology were found statistically increased in the DR group. Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development [odds ratio (OR)=21.664, 95% confidential interval (CI) 5.588 to 83.991, P<0.001 for DN, and OR=45.475, 95%CI 6.949 to 297.611, P<0.001 for mixed-type, respectively, in reference to NDRD)], wherein DN severity positively correlated. CONCLUSION: Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.
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BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive disease of renal tubulopathy, primarily characterized by hypokalemic metabolic alkalosis with significant hypomagnesemia, low urinary calcium, secondary aldosteronism and normal blood pressure. Both hypokalemia and hypomagnesemia were reported to cause impaired glucose tolerance and/or insulin resistance, but it is unclear whether impaired glucose tolerance and/or insulin resistance are common in GS patients. METHODS: An oral glucose tolerance test was performed among 16 GS patients and 12 healthy adults as control subjects. Fasting glucose and serum insulin levels were measured and the values of glucose and serum insulin after 30, 60, 120 and 180 min were also measured after an oral glucose load. The area under curve (AUC) of glucose and insulin was calculated. RESULTS: One patient had isolated impaired fasting glucose, 2 had isolated impaired glucose tolerance, and 1 had combined impaired fasting glucose and glucose tolerance. Six patients were diagnosed with type 2 diabetes mellitus. Compared with a healthy normal control group, GS patients showed a higher AUC glucose level [16.1 (IQR 12.5-25.4 mEq · h/l) vs. 13.0 (IQR 11.9-13.7 mEq · h/l); p < 0.05] and AUC insulin level [81.0 (IQR 58.9-138 µU · h/ml) vs. 46.4 (IQR 35.6-63.3 µU · h/ml); p < 0.01]. GS patients showed a delay of insulin secretion peak which was observed 120 min after a glucose load. Homeostasis model assessment of insulin resistance in GS patients was significantly higher than in control volunteers. Quantitative insulin sensitivity check index and insulin sensitivity index composite in the GS group were significantly lower than in the control group. CONCLUSION: Abnormal glucose metabolism and insulin secretion is common in GS patients. It is speculated that hypokalemia and hypomagnesemia may be the main cause.
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Glucemia/metabolismo , Síndrome de Gitelman/metabolismo , Resistencia a la Insulina , Insulina/sangre , Adolescente , Adulto , Área Bajo la Curva , Estudios de Casos y Controles , China , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Síndrome de Gitelman/complicaciones , Prueba de Tolerancia a la Glucosa , Homeostasis , Humanos , Insulina/metabolismo , Secreción de Insulina , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVES: Antineutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitis (AASV) constitutes a group of life-threatening diseases and renal involvement is its most severe and common manifestation. Acute kidney injury (AKI) is common in patients with AASV but the value of RIFLE criteria is still unclear in those patients. METHODS: We performed a retrospective study on patients with AASV in Shanghai Ruijin Hospital from 1997 to 2008. RESULTS: A total of 147 ANCA-associated renal vasculitis patients were studied and 92 developed AKI at diagnosis. According to RIFLE classification, 8 (8/147, 5.44%) patients had AKI-R, 15 (15/147, 10.20%) had AKI-I and 69 (69/147, 46.94%) had AKI-F. Our results demonstrated that more hypertensive patients and higher BVAS were found in patients with AKI-F than those in other groups (p<0.01 and p<0.01, respectively). Survival rate was significantly lower among patients with advanced RIFLE categories during remission-induction therapy (p<0.05). Survival rate of 1 year and total survival rate were significantly lower among patients with advanced RIFLE categories (p<0.01, p=0.001, respectively). Cox regression analysis demonstrated that advanced RIFLE categories were associated with a worse prognosis of the patients (OR=1.706, 95%CI: 1.262-2.307, p<0.01). The area under the ROC curve for mortality was 0.718 (95% CI: 0.63-0.81, p<0.001). CONCLUSIONS: The RILFE criteria is a valid measurement of both prognosis and progression in patients with AASV.
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Lesión Renal Aguda/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Lesión Renal Aguda/clasificación , Lesión Renal Aguda/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/clasificación , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Pueblo Asiatico , China/epidemiología , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
BACKGROUND: To investigate clinical characteristics and risk factors of Chinese patients with post-operative acute kidney injury (PO-AKI). METHODS: Patients with PO-AKI in Ruijin Hospital from December 1997 to December 2005 were retrospectively studied. RESULTS: Patients' mean age was 62.2 ± 18.1 years. There were 111 males and 57 females. The mean serum creatinine at diagnosis was 370.41 ± 320.92 µmol/L and the mean estimated glomerular filtration rate was 33.56 ± 24.24 mL/min. For the outcome of the patients, 38 died and the mortality rate was 22.6%. There were 17 patients (10.1%) with Acute Dialysis Quality Initiative-RIFLE (risk-injury-failure-loss-end classification) phase R, 21 (12.5%) with phase I, and 130 (77.4%) with phase F. There was no significant difference in mortality regarding patients who underwent different types of surgeries. For the risk factors related to PO-AKI, acute tubular necrosis (ATN) increased relative risk of mortality PO-AKI (odds ratio = 7.089, 95% confidence interval = 2.069-24.288, p < 0.001). Multivariate regression models showed that ATN had a positive correlation with mortality of PO-AKI. CONCLUSIONS: PO-AKI is one of the most common causes of AKI in patients who underwent operations. Special attention should be paid to risk factors related to PO-AKI in order to improve prognosis.
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Lesión Renal Aguda , Complicaciones Posoperatorias , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , China , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: The pathogenesis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is unclear and the prognosis is poor. Few studies have been published focusing on Chinese patients with TTP-HUS. We performed a retrospective study on the clinical characteristics and outcome of Chinese patients with TTP-HUS. METHOD: Patients with TTP-HUS, admitted to our hospital from 1998 to 2006, were retrospectively analyzed. RESULTS: There were 26 females and 6 males in our study. Fifteen patients had systemic lupus erythematosus (SLE)-associated TTP-HUS; 2 had pregnancy-associated TTP-HUS; 1 had antiphospholipid syndrome-associated TTP-HUS; 2 had drug-associated TTP-HUS; 4 had malignant angionephrosclerosis- associated TTP-HUS; 3 had vasculitis-associated TTP-HUS, and the remaining 5 had idiopathic TTP-HUS. Twenty-six patients had acute kidney injury and 21 had nephrotic syndrome. Hypertension was found in 31 patients. For the treatment, 15 patients had plasmapheresis, 12 had continuous veno-venous hemodiafiltration and 14 had hemodialysis. Eighteen patients were treated with intravenous immunoglobulin. Corticosteroids were used in patients with idiopathic TTP-HUS. For the patients with SLE-associated TTP-HUS, corticosteroids and immunosuppressant were used. Outcome was poor: 6 patients died; 17 recovered from renal insufficiency; 5 progressed to chronic renal failure, and 4 were dependent on hemodialysis. CONCLUSIONS: Most of our patients had secondary TTP-HUS. SLE-associated TTP-HUS is the most common form of TTP-HUS. Early diagnosis and treatment can improve prognosis. An immunosuppressant together with corticosteroids could improve prognosis in some patients.
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Síndrome Hemolítico-Urémico/tratamiento farmacológico , Síndrome Hemolítico-Urémico/mortalidad , Inmunosupresores/uso terapéutico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/mortalidad , Adolescente , Adulto , Niño , China/epidemiología , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND/AIMS: Primary antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) used to have poor prognosis, and renal involvement is its most common manifestation. Few studies have been published focusing on AASV patients with poor prognosis. METHODS: From 1997 to 2006, 101 patients with ANCA-associated renal vasculitis (70 microscopic polyangiitis, MPA; 14 Wegener's granulomatosis, WG; 3 Churg-Strauss syndrome, CSS; 14 renal limited vasculitis, RLV) were diagnosed in Shanghai Ruijin Hospital and 26 deaths were recorded among them. Patients' data were retrospectively analyzed. RESULTS: Patients with WG, MPA and RLV made up for 23.1% (6/26), 65.4% (17/26) and 11.5% (3/26) of all deaths. No deaths were observed among CSS patients. Infection alone accounted for 13 deaths. Infection together with pulmonary involvement of active vasculitis accounted for 3. Organ-specific involvement of active vasculitis alone caused 8 deaths. Others died of acute myocardial infarction or gastric carcinoma. Compared with patients who survived, nonsurvivors had more severe renal insufficiency and older age (p < 0.01). There was no significant difference regarding clinical presentation at diagnosis and cause of death between patients who survived first remission-induction treatment and those who did not. Infection remained the major cause of death. CONCLUSION: Infection is the major cause of death in patients with ANCA-associated renal vasculitis, and treatment response might not correlate to severity of disease in patients with poor prognosis. Rational use of immunosuppressants could improve the prognosis.
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Anticuerpos Anticitoplasma de Neutrófilos , Enfermedades Renales/inmunología , Vasculitis/inmunología , Vasculitis/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Causas de Muerte , Femenino , Humanos , Infecciones , Enfermedades Renales/mortalidad , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Insuficiencia Renal , Estudios Retrospectivos , Vasculitis/terapiaRESUMEN
Early detection of acute kidney injury is difficult due to lack of known biomarkers; previous studies have tried to identify new biomarkers for detecting acute kidney injury at an early stage. MicroRNA, a 21-23 nucleotide noncoding RNA molecule, has emerged as a desirable marker in the diagnosis and prognosis of various diseases. This study aims to identify the expression profile of microRNA in ischemia-reperfusion-induced kidney injury and determine the possibility of using the candidate microRNA as biomarker for the detection of I/R-induced kidney injury. Based on the established rat model of I/R-induced kidney injury, a microarray analysis of rat urine was performed at the beginning of operation (0 h) as well as 72 h post operation. To validate the results, urine samples from 71 patients who underwent cardiac surgery were collected, after which urinalysis was conducted to determine the microRNA concentration. An alternative expression profile of microRNAs was detected in rat urine. The quantitative validation of microRNA showed that the expression of miR-30c-5p, miR-192-5p, and miR-378a-3p was elevated significantly in urine post operation, which was consistent with those of the microarray analysis and earlier than kidney injury molecule-1 (KIM-1). In patients with acute kidney injury, increased levels of miR-30c-5p and miR-192-5p were also detected 2 h post operation, and miR-30c-5p showed preferable diagnostic value compared with protein-based biomarkers. In conclusion, an aberrant expression profile of microRNA was detected in rat urine based on the established ischemia-reperfusion animal model. Both miR-30c-5p and miR-192-5p served as important potential diagnostic markers for I/R-induced kidney injury. Impact statement Firstly, one differentiating factor in our study is that the candidate miRNAs were screened in a controlled animal model rather than in patients with acute kidney injury (AKI) to ensure the purity of the cause of disease and to avoid possible effects of comorbidities on the spectrum of urine miRNA. This ensured the presence of only the relevant candidate miRNA (that associated with I/R injury); and what's more, the alterative expression of miR-192-5p and miR-30c-5p in animal model, patients with AKI, and cell model was confirmed simultaneously, which is likely to be more convincing. Secondly, the candidate miRNAs were screened sequentially at regular time points, which covered the initiation, progression, and partial repair stages, thus ensuring that no significant miRNAs were omitted in the screening process, and miR-biomarkers in 2 h post operation showed preferable diagnostic performance.
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Lesión Renal Aguda/orina , MicroARNs/orina , Daño por Reperfusión/orina , Lesión Renal Aguda/diagnóstico , Animales , Biomarcadores/orina , Línea Celular , Modelos Animales de Enfermedad , Humanos , Túbulos Renales/citología , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/diagnóstico , TranscriptomaRESUMEN
OBJECTIVE: Renal vasculitis is one of the most common manifestations of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) and renal histology is a key predictor of the outcome. A new histopathologic classification was proposed and validated, but the results are still debated. METHODS: We performed a retrospective analysis to validate the histopathologic classification and performed a metaanalysis to evaluate its predictive value. There were 186 patients with ANCA-associated renal vasculitis diagnosed at Ruijin Hospital who were enrolled in the retrospective study. The metaanalysis considered the data for 1601 patients. RESULTS: In our retrospective study, patients with focal class had the best renal outcome while patients with mixed class had the worst (p < 0.001). Metaanalysis showed that patients with focal class had better renal outcome than did those with crescentic class [risk ratio (RR) 0.23, 95% CI 0.16-0.34, p < 0.00001], with no evidence of heterogeneity (I2 = 0%, p = 0.96). Patients with crescentic class had better renal outcome than did those with sclerotic class (RR 0.52, 95% CI 0.41-0.64, p < 0.00001), with no evidence of heterogeneity (I2 = 2%, p = 0.43). We did not find statistical significance regarding renal outcome between mixed and crescentic classes (RR 1.14, 95% CI 0.91-1.43, p = 0.27), with no evidence of heterogeneity (I2 = 23%, p = 0.19). The retrospective study showed that lung and upper respiratory tract involvement were the most common extrarenal manifestations. CONCLUSION: We demonstrated the clinical utility of histopathologic classification in determining renal outcome in patients with AAV. Metaanalysis showed that patients with focal class had the best outcome while sclerotic class had the worst.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Riñón/patología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Biopsia , Progresión de la Enfermedad , Humanos , Riñón/inmunología , Pronóstico , Estudios RetrospectivosRESUMEN
In this study, rat models of acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) and HK-2 cell models of hypoxia-reoxygenation (H/R) were established to investigate the expression of inhibitor of DNA binding 1 (ID1) in AKI, and the regulation relationship between ID1 and hypoxia-inducible factor 1 alpha (HIF-1α). Through western blot, quantitative real-time PCR, immunohistochemistry, and other experiment methods, the induction of ID1 after renal I/R in vivo was observed, which was expressed mainly in renal tubular epithelial cells (TECs). ID1 expression was upregulated in in vitro H/R models at both the protein and mRNA levels. Via RNAi, it was found that ID1 induction was inhibited with silencing of HIF-1α. Moreover, the suppression of ID1 mRNA expression could lead to decreased expression and transcription of HIF-1α during hypoxia and reoxygenation. In addition, it was demonstrated that both ID1 and HIF-1α can regulate the transcription of twist. This study demonstrated that ID1 is induced in renal TECs during I/R and can regulate the transcription and expression of HIF-1α.
Asunto(s)
Lesión Renal Aguda/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Proteína 1 Inhibidora de la Diferenciación/biosíntesis , Túbulos Renales Distales/metabolismo , Daño por Reperfusión/genética , Lesión Renal Aguda/patología , Animales , Hipoxia de la Célula/genética , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Expresión Génica , Silenciador del Gen , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proteína 1 Inhibidora de la Diferenciación/genética , Túbulos Renales Distales/patología , ARN Mensajero/biosíntesis , Ratas , Daño por Reperfusión/patologíaRESUMEN
OBJECTIVE: To describe and analyze the clinical characteristics of acute kidney injury (AKI) patients with preexisting chronic heart failure (CHF) and to identify the prognostic factors of the 1-year outcome. METHODS: A total of 120 patients with preexisting CHF who developed AKI between January 2005 and December 2010 were enrolled. CHF was diagnosed according to the European Society of Cardiology guidelines, and AKI was diagnosed using the RIFLE criteria. Clinical characteristics were recorded, and nonrecovery from kidney dysfunction as well as mortality were analyzed. RESULTS: The median age of the patients was 70 years, and 58.33% were male. 60% of the patients had an advanced AKI stage ('failure') and 90% were classified as NYHA class III/IV. The 1-year mortality rate was 35%. 25.83% of the patients progressed to end-stage renal disease after 1 year. Hypertension, anemia, coronary atherosclerotic heart disease and chronic kidney disease were common comorbidities. Multiple organ dysfunction syndrome (MODS; OR, 35.950; 95% CI, 4.972-259.952), arrhythmia (OR, 13.461; 95% CI, 2.379-76.161), anemia (OR, 6.176; 95% CI, 1.172-32.544) and RIFLE category (OR, 5.353; 95% CI, 1.436-19.952) were identified as risk factors of 1-year mortality. For 1-year nonrecovery from kidney dysfunction, MODS (OR, 8.884; 95% CI, 2.535-31.135) and acute heart failure (OR, 3.281; 95% CI, 1.026-10.491) were independent risk factors. CONCLUSION: AKI patients with preexisting CHF were mainly elderly patients who had an advanced AKI stage and NYHA classification. Their 1-year mortality and nonrecovery from kidney dysfunction rates were high. Identifying risk factors may help to improve their outcome.
RESUMEN
OBJECTIVE: To investigate the prevalence of cardiovascular disease (CVD) in a Chinese patient population with different stages of chronic kidney disease (CKD). METHODS: Six hundred and two CKD patients who were hospitalized in Ruijin Hospital between Jan. 2004 and Jan. 2006 were selected. Patients' medical histories and the results of laboratory tests were reviewed. RESULTS: The prevalence of CVD in 602 patients with CKD stages 1 to 5 was 1.28%, 17.24%, 22.86%, 33.33%, 56.2% respectively. The prevalence of CVD in CKD stage 5 patients with dialysis was 78.51%. In all the patients, the prevalence of coronary artery disease (CAD), left ventricular hypertrophy (LVH), and congestive heart failure (CHF) was 8.64% (52/602), 26% (154/602), and 13% (78/602), respectively. Regarding co-morbidities of CVD, 34.52% of patients had 2 or more of the above abnormalities. The prevalence of CAD in patients with CKD stages 1 to 5 respectively was 1.28%, 5.75%, 7.86%, 10.26%, 12.33%;LVH was 0%, 11.49%, 16.43%, 29.49%, 44.75%; and CHF was 0%, 3.45%, 3.57%, 8.97%, 28.77%. CONCLUSION: The occurrence of CVD started from CKD stage 1 and increased with the progression of CKD. The screening and prevention of CVD should begin at CKD stage 1.