Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Am Soc Nephrol ; 31(7): 1539-1554, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32487559

RESUMO

BACKGROUND: Aberrant microRNA (miRNA) expression affects biologic processes and downstream genes that are crucial to CKD initiation or progression. The miRNA miR-204-5p is highly expressed in the kidney but whether miR-204-5p plays any role in the development of chronic renal injury is unknown. METHODS: We used real-time PCR to determine levels of miR-204 in human kidney biopsies and animal models. We generated Mir204 knockout mice and used locked nucleic acid-modified anti-miR to knock down miR-204-5p in mice and rats. We used a number of physiologic, histologic, and molecular techniques to analyze the potential role of miR-204-5p in three models of renal injury. RESULTS: Kidneys of patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy exhibited a significant decrease in miR-204-5p compared with controls. Dahl salt-sensitive rats displayed lower levels of renal miR-204-5p compared with partially protected congenic SS.13BN26 rats. Administering anti-miR-204-5p to SS.13BN26 rats exacerbated interlobular artery thickening and renal interstitial fibrosis. In a mouse model of hypertensive renal injury induced by uninephrectomy, angiotensin II, and a high-salt diet, Mir204 gene knockout significantly exacerbated albuminuria, renal interstitial fibrosis, and interlobular artery thickening, despite attenuation of hypertension. In diabetic db/db mice, administering anti-miR-204-5p exacerbated albuminuria and cortical fibrosis without influencing blood glucose levels. In all three models, inhibiting miR-204-5p or deleting Mir204 led to upregulation of protein tyrosine phosphatase SHP2, a target gene of miR-204-5p, and increased phosphorylation of signal transducer and activator of transcription 3, or STAT3, which is an injury-promoting effector of SHP2. CONCLUSIONS: These findings indicate that the highly expressed miR-204-5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury.

2.
PLoS One ; 15(5): e0225356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32437440

RESUMO

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3'-untranslated regions (3'-UTR) of the (P)RR mRNA. Mutating the binding sites for miR-148a in the 3'-UTR of (P)RR mRNA completely abolished the inhibitory effects of miR-148a on (P)RR expression. In line with our recent findings, reduced (P)RR expression resulted in decreased cellular LDL uptake, likely as a consequence of decreased LDLR protein abundance. Overexpressing the (P)RR prevented miR-148a-induced reduction in LDLR abundance and cellular LDL uptake. Our study supports a new concept that miR-148a is a regulator of (P)RR expression. By reducing (P)RR abundance, miR-148a decreases LDLR protein abundance and consequently cellular LDL uptake.

3.
Iran J Kidney Dis ; 14(2): 107-118, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32165595

RESUMO

INTRODUCTION: Previous studies have shown that TGF-ß1/Smad3 signaling promotes renal fibrosis by inhibiting miR-29. To date, only few studies have reportedon circulating microRNAs in IgA nephropathy (IgAN). However, the plasma expression of miR-29a and its role in patients with IgAN remains unclear. In this study, we attempted to elucidate whether plasma miR-29a expression can be used as a biomarker for monitoring disease states. METHODS: For this study, 15 healthy subjects, 36 patients with untreated renal biopsy-proven IgAN, and 79 patients with IgAN, who were under treatment for a period of 1 year on an average, all of whom had similar age and gender distributions, were included. The plasma expression of miR-29a in each group was explored by real-time PCR, and the relationship between miR-29a expression and clinical, pathological, and prognostic indicators of IgAN was further evaluated. RESULTS: Relative plasma expression of miR-29a in patients with IgAN was significantly lower than that in healthy controls (P < .001), and these changes in plasma miR-29a could be suppressed by treatment (P < .05). Plasma miR-29a was positively correlated with eGFR and negatively correlated with proteinuria and serum creatinine, irrespective of whether or not the patients with IgAN accepted treatment (P < .05). Plasma miR-29a level was negatively correlated with primary pathological parameters such as crescent formation, Lee's and Oxford classification (P < .05). Kaplan-Meier analysis revealed that patients with high plasma expression of miR-29a had better renal function and better response to treatment compared to those with low expression (P < .05). CONCLUSION: Plasma miR-29a could be considered as a biological marker that reflects renal damage and function, to predict the progression of IgAN.

4.
Perit Dial Int ; 40(1): 84-92, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32063147

RESUMO

BACKGROUND: International Society for Peritoneal Dialysis guidelines recommend to routinely monitor the total measured clearance (mCl) of small solutes such as creatinine; however, collection of 24-h urine and peritoneal dialysis (PD) fluid is burdensome to patients and prone to errors. We hypothesized that equations could be developed to estimate mCl (estimated clearance (eCl)) using endogenous filtration markers. METHODS: In the Guangzhou PD Study (n = 980), we developed eCl equations using linear regression in two-third and validated them in the remaining one-third. Reference tests were mCl for urea nitrogen (UN) (mClUN, ml/min) and average mCl for UN and creatinine (mClUN-cr, ml/min/1.73 m2). Index tests were various eCl equations using UN, creatinine, low-molecular-weight proteins (LMWPs) (beta-trace protein (BTP), beta-2 microglobulin (B2M), and cystatin C), demographic variables, and body size. After reexpression of the equations in the combined data set, we analyzed accuracy (eCl within ± 2.0 units of mCl) and the predictive value of eCl to detect a weekly total standard Kt/V (weekly mClUN indexed for total body water) > 1.7 using receiver operating characteristic curve. RESULTS: Mean age of the cohort was 50 ± 15 years, 53% were male; mClUN was 6.9 ± 1.8 and mClUN-cr was 7.5 ± 2.8. Creatinine but not UN contributed to eCl for both mCl. LMWP did not improve accuracy for mClUN (range 88-89%). BTP and B2M improved the accuracy for mClUN-cr (82% vs. 80%); however, differences were small. The area under the curve for predicting a weekly Kt/V > 1.7 was similar for all equations (range 0.79-0.80). CONCLUSIONS: Total small solute clearance can be estimated moderately well in continuous ambulatory PD patients using serum creatinine and demographic variables without urine and dialysate collection.

5.
Clin J Am Soc Nephrol ; 13(12): 1791-1800, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30287424

RESUMO

BACKGROUND AND OBJECTIVES: High-quality epidemiologic data on AKI in children are particularly lacking in developing countries. This study aimed to assess the epidemiology and clinical correlates of AKI among hospitalized children in China. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter study, in a cohort of hospitalized children aged 1 month to 18 years, from 25 general and children's hospitals in China during 2013-2015. We obtained patient-level data from the electronic hospitalization information system and laboratory databases of all children who had at least two serum creatinine tests within any 7-day window during their first 30 days of hospitalization. We identified AKI events according to the creatinine criteria of Kidney Disease Improving Global Outcomes. The in-hospital outcomes of AKI, including mortality, kidney recovery, and length of stay, were assessed. We estimated the corresponding hazard ratios using a Cox proportional hazard model, with adjustment for age, sex, comorbidities, and clinical procedures. RESULTS: A total of 19,908 (20%) patients with AKI were identified among 101,836 pediatric inpatients, of which 7220 (7%) were community acquired and 12,688 (13%) were hospital acquired. Up to 96% of these AKI events were not diagnosed on the discharge records. The cumulative incidence of AKI in infants (28%) was twice that in adolescents (12%). The profiles of risk factors differed between community-acquired and hospital-acquired AKI and varied with age. Diarrhea and sepsis were the top risk factors for community-acquired AKI, each contributing 6% of the risk. Congenital heart disease/cardiac surgery was the major risk factor for hospital-acquired AKI, contributing to 19% of cases. Exposure to nephrotoxic drugs, mostly nonsteroidal anti-inflammatory drugs and proton pump inhibitors, was common in hospitalized children and was associated with a higher risk of AKI. Death occurred in 842 out of 19,908 patients (4%) with AKI versus 450 out of 81,478 children (0.5%) without AKI. The risk of in-hospital death was higher among children with severe AKI, shock, and respiratory failure. Pediatric AKI was associated with longer hospital stay and higher daily cost, even after adjustment for covariates. CONCLUSIONS: Pediatric AKI is common and is substantially underdiagnosed in China.


Assuntos
Lesão Renal Aguda/epidemiologia , Hospitalização/estatística & dados numéricos , Lesão Renal Aguda/terapia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Resultado do Tratamento
6.
Int Urol Nephrol ; 50(11): 2049-2059, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30073617

RESUMO

PURPOSE: The heart and kidney are of utmost importance for the maintenance of cardiovascular (CV) homeostasis. The relationship between cardiac remodeling, especially the left ventricular hypertrophy (LVH) and renal damage reflected by the estimated glomerular filtration rate (eGFR), decline in type 2 diabetes mellitus (T2DM) patients is unclear. And it is also unknown whether cardiac remodeling can be used to assess the eGFR decline in T2DM patients. METHODS: We retrospectively analyzed the relationship between cardiac remodeling especially the LVH and the eGFR decline for 265 patients with T2DM, who were diagnosed between 2011 and 2015 and followed for ≥ 3 months. The parameters of cardiac remodeling were determined using Doppler echocardiography. RESULTS: In the Cox regression model, the parameters of cardiac remodeling were associated with the composite endpoint in different models. These associations were independent of age, body mass index (BMI), history of hypertension, duration of diabetes, the baseline eGFR, 24-h urinary protein, or using angiotensin-converting enzyme inhibitors (ACEI) and (or) angiotensin receptor blockers (ARB). The risk of composite endpoint in patients with T2DM was higher (hazard ratio, 10.832; p < 0.001 for trend) in the group with the highest number of abnormal echocardiographic parameters, than in the group with no abnormal echocardiographic parameters. In receiver operating characteristics (ROC) curve analyses, the parameter of left ventricular posterior wall (LVPW) thickness was superior to the other parameters of cardiac remodeling as represented by the higher area under the curve (AUC) values generated according to the sensitivity and specificity. CONCLUSION: Echocardiographic parameters are strongly correlated with the eGFR decline in patients with T2DM. Moreover, the severity of cardiac remodeling, especially the LVH is closely associated with the eGFR decline in patients with T2DM. Therefore, the recognition of cardiac structural alterations in patients with T2DM may evaluate renal damage at an early stage.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Taxa de Filtração Glomerular , Hipertrofia Ventricular Esquerda/etiologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Ecocardiografia Doppler , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Remodelação Ventricular
7.
J Am Soc Nephrol ; 29(9): 2432-2442, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30054338

RESUMO

BACKGROUND: Current definitions of AKI do not take into account serum creatinine's high variability in children. METHODS: We analyzed data from 156,075 hospitalized children with at least two creatinine tests within 30 days. We estimated reference change value (RCV) of creatinine on the basis of age and initial creatinine level in children without kidney disease or known AKI risk, and we used these data to develop a model for detecting pediatric AKI on the basis of RCV of creatinine. We defined pediatric AKI according to pediatric reference change value optimized for AKI in children (pROCK) as creatinine increase beyond RCV of creatinine, which was estimated as the greater of 20 µmol/L or 30% of the initial creatinine level. RESULTS: Of 102,817 children with at least two serum creatinine tests within 7 days, 5432 (5.3%) had AKI as defined by pROCK compared with 15,647 (15.2%) and 10,446 (10.2%) as defined by pediatric RIFLE (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO), respectively. Children with pROCK-defined AKI had significantly increased risk of death (hazard ratio, 3.56; 95% confidence interval, 3.15 to 4.04) compared with those without AKI. About 66% of patients with pRIFLE-defined AKI and 51% of patients with KDIGO-defined AKI, mostly children with initial creatinine level of <30 µmol/L, were reclassified as non-AKI by pROCK, and mortality risk in these children was comparable with risk in those without AKI by all definitions. CONCLUSIONS: pROCK criterion improves detection of "true" AKI in children compared with earlier definitions that may lead to pediatric AKI overdiagnosis.


Assuntos
Lesão Renal Aguda/diagnóstico , Causas de Morte , Creatinina/sangue , Hospitalização/estatística & dados numéricos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/mortalidade , Adolescente , Fatores Etários , Criança , Pré-Escolar , China , Estudos de Coortes , Bases de Dados Factuais , Feminino , Taxa de Filtração Glomerular/fisiologia , Mortalidade Hospitalar , Humanos , Incidência , Lactente , Testes de Função Renal , Masculino , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Valores de Referência , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais
8.
Theranostics ; 8(6): 1468-1480, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29556335

RESUMO

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically. Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day). Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle. The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats. Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex. Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of ß-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure. The differences in homocysteine levels between low- and high-sodium intakes were significantly associated with the differences in diastolic blood pressure. These associations were significant with or without considering demographic factors. Treatment with ß-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats. Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension.


Assuntos
Aminoácidos/urina , Ácidos Aminoisobutíricos/farmacologia , Aminas Biogênicas/urina , Hipertensão/urina , Cloreto de Sódio na Dieta/urina , Adulto , Ácidos Aminoisobutíricos/urina , Animais , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Dieta/métodos , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Metaboloma/efeitos dos fármacos , Pessoa de Meia-Idade , Ratos , Ratos Endogâmicos Dahl , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/antagonistas & inibidores
9.
Circ Res ; 122(5): 730-741, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29301853

RESUMO

RATIONALE: An elevated level of plasma LDL (low-density lipoprotein) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDLR (LDL receptor) and SORT1 (sortilin-1), independently of the renin-angiotensin system. OBJECTIVES: To investigate the physiological role of (P)RR in lipid metabolism in vivo. METHODS AND RESULTS: We used N-acetylgalactosamine modified antisense oligonucleotides to specifically inhibit hepatic (P)RR expression in C57BL/6 mice and studied the consequences this has on lipid metabolism. In line with our earlier report, hepatic (P)RR silencing increased plasma LDL-C (LDL cholesterol). Unexpectedly, this also resulted in markedly reduced plasma triglycerides in a SORT1-independent manner in C57BL/6 mice fed a normal- or high-fat diet. In LDLR-deficient mice, hepatic (P)RR inhibition reduced both plasma cholesterol and triglycerides, in a diet-independent manner. Mechanistically, we found that (P)RR inhibition decreased protein abundance of ACC (acetyl-CoA carboxylase) and PDH (pyruvate dehydrogenase). This alteration reprograms hepatic metabolism, leading to reduced lipid synthesis and increased fatty acid oxidation. As a result, hepatic (P)RR inhibition attenuated diet-induced obesity and hepatosteatosis. CONCLUSIONS: Collectively, our study suggests that (P)RR plays a key role in energy homeostasis and regulation of plasma lipids by integrating hepatic glucose and lipid metabolism.


Assuntos
Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Metabolismo dos Lipídeos , Obesidade/metabolismo , Receptores de Superfície Celular/metabolismo , Acetil-CoA Carboxilase/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Inativação Gênica , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Complexo Piruvato Desidrogenase/metabolismo , Receptores de Superfície Celular/genética
10.
J Am Soc Nephrol ; 28(12): 3671-3678, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28760751

RESUMO

Our previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2-3 mg/d; mycophenolate mofetil, 0.50-0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P=0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; P<0.01), and the multitarget group had a lower withdrawal rate due to adverse events (1.7% versus 8.9% for azathioprine; P=0.02). In conclusion, multitarget therapy as a maintenance treatment for lupus nephritis resulted in a low renal relapse rate and fewer adverse events, suggesting that multitarget therapy is an effective and safe maintenance treatment for patients with lupus nephritis.


Assuntos
Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Adolescente , Adulto , Idoso , Azatioprina/administração & dosagem , China , Ciclofosfamida/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Prednisona/administração & dosagem , Recidiva , Tacrolimo/administração & dosagem , Resultado do Tratamento , Adulto Jovem
11.
Physiol Genomics ; 49(9): 496-504, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28754823

RESUMO

The activity of fumarase, an enzyme in the tricarboxylic acid cycle, is lower in Dahl salt-sensitive SS rats compared with SS.13BN rats. SS.13BN rats have a Brown Norway (BN) allele of fumarase and exhibit attenuated hypertension. The SS allele of fumarase differs from the BN allele by a K481E sequence variation. It remains unknown whether higher fumarase activities can attenuate hypertension and whether the mechanism is relevant without the K481E variation. We developed SS-TgFh1 transgenic rats overexpressing fumarase on the background of the SS rat. Hypertension was attenuated in SS-TgFh1 rats. Mean arterial pressure in SS-TgFh1 rats was 20 mmHg lower than transgene-negative SS littermates after 12 days on a 4% NaCl diet. Fumarase overexpression decreased H2O2, while fumarase knockdown increased H2O2 Ectopically expressed BN form of fumarase had higher specific activity than the SS form. However, sequencing of more than a dozen rat strains indicated most rat strains including salt-insensitive Sprague-Dawley (SD) rats had the SS allele of fumarase. Despite that, total fumarase enzyme activity in the renal medulla was still higher in SD rats than in SS rats, which was associated with higher expression of fumarase in SD. H2O2 can suppress the expression of fumarase. Renal medullary interstitial administration of fumarase siRNA in SD rats resulted in higher blood pressure on the high-salt diet. These findings indicate elevation of total fumarase activity attenuates the development of hypertension and can result from a nonsynonymous sequence variation in some rat strains and higher expression in other rat strains.


Assuntos
Fumarato Hidratase/genética , Fumarato Hidratase/metabolismo , Variação Genética , Hipertensão/enzimologia , Hipertensão/genética , Animais , Sequência de Bases , Células HEK293 , Humanos , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Dahl , Ratos Sprague-Dawley , Ratos Transgênicos , Análise de Sequência de DNA , Regulação para Cima/genética
12.
Exp Ther Med ; 12(3): 1934-1938, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27602099

RESUMO

Tacrolimus (TAC) has been shown to improve remission from proteinuria in patients with refractory IgA nephropathy (IgAN); however, the efficacy and safety of TAC in such patients have not been fully explored. Therefore, the present study was conducted to evaluate the tolerance to and efficacy of TAC combined with low-dose corticosteroids in patients with refractory IgAN. This was a single-center retrospective study. A total of 28 patients with refractory IgAN were randomly included and received TAC plus corticosteroid; 26 patients received TAC and prednisone, and 2 patients received TAC and methylprednisolone. In addition, all patients were treated with an angiotensin inhibitor. Total urinary protein excretion, serum albumin, blood glucose, complete remission (CR), partial remission (PR), cholesterol, low-density lipoprotein (LDL), serum creatinine (Scr) and estimated GFR (eGFR) were tested at baseline and at 3, 6 and 12 months after the initiation of treatment in all patients. The primary endpoints were CR and PR. Secondary endpoints included changes of Scr, eGFR, clinical data and adverse events. After 12 months, CR was achieved in 40.1% of patients and PR in 43.4%, yielding a total response rate of 83.5%, and the total urinary protein excretion, serum albumin, cholesterol and LDL results were improved significantly compared with those at baseline. Proteinuria and serum albumin results were significantly improved by month 3 of treatment. Two patients relapsed during months 3-6 of follow-up. At the 12-month follow-up, renal function was improved compared with the baseline level as evidenced by eGFR and Scr, respectively. The blood glucose level was stable. One case of pneumococcal pneumonia developed in a patient treated with TAC plus low-dose methylprednisolone and one case of upper gastrointestinal hemorrhage was found in a patient treated with TAC plus low-dose prednisone; both cases completely recovered after treatment. In conclusion, TAC combined with low-dose corticosteroids may be an effective and safe therapeutic option for the treatment of refractory IgAN. However, given the small number of patients in this study, further prospective randomized controlled trials are required with a larger sample of participants and longer follow-up period.

13.
Sci Rep ; 6: 21960, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26916681

RESUMO

Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13(BN26) rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13(BN26) rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7-8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats.


Assuntos
Hipertensão/metabolismo , Nefropatias/metabolismo , Rim/metabolismo , Modelos Animais , Cloreto de Sódio na Dieta/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Animais , Expressão Gênica , Hipertensão/patologia , Rim/patologia , Nefropatias/patologia , Masculino , Ratos , Ratos Endogâmicos Dahl
14.
Kaohsiung J Med Sci ; 31(1): 42-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25600919

RESUMO

The tolerance of mycophenolate mofetil (MMF; Shanghai Roche, China) in Lee Classes III, IV, and V immunoglobulin A nephropathy (IgAN) remains unclear. This article reports nine cases of severe pneumonia (SP), including pneumocystis pneumonia (PCP) and cytomegalovirus (CMV) pneumonia, and its risk factors in MMF plus low-dose corticosteroid-treated patients with Lee Classes III, IV, and V IgAN. Fifty-three patients with IgAN were included in this single-center study. The treatment regimen was MMF (1-1.5 g/d) plus low-dose corticosteroids (0.5 mg/kg/d). SP was defined as diffuse bilateral lung infiltrate with respiratory failure. PCP was diagnosed by detecting the organisms in the sputum and bronchoalveolar lavage. CMV infection was diagnosed through serum screening for CMV-IgG and IgM antibodies and CMV-DNA testing by a real-time polymerase chain reaction assay. The risk factors of SP were analyzed. Nine cases (16.9%) of SP occurred in this study. All SP developed at approximately the 10(th)-14(th) week after the initiation of the regimen: PCP was diagnosed in four cases and CMV infection in two cases. Renal function impairing was more serious in patients with SP than in those without SP, as evidenced by estimated glomerular filtration rate (p = 0.019) and serum creatinine level (p = 0.016). Six of the nine SPs occurred in MMP plus low-dose methylprednisolone group, which was statistically higher than that in the MMF plus low-dose prednisone group (p = 0.000). The incidence of SP in this study was 16.9%. Chronically impaired renal function and the use of methylprednisolone may be the risk factors for SP.


Assuntos
Corticosteroides/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Pneumonia/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , Feminino , Glomerulonefrite por IGA/metabolismo , Humanos , Imunoglobulina A/metabolismo , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
15.
Ann Intern Med ; 162(1): 18-26, 2015 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-25383558

RESUMO

BACKGROUND: Treatment of lupus nephritis (LN) remains challenging. OBJECTIVE: To assess the efficacy and safety of a multitarget therapy consisting of tacrolimus, mycophenolate mofetil, and steroid compared with intravenous cyclophosphamide and steroid as induction therapy for LN. DESIGN: 24-week randomized, open-label, multicenter study. (ClinicalTrials.gov: NCT00876616). SETTING: 26 renal centers in China. PATIENTS: Adults (aged 18 to 65 years) with biopsy-proven LN. INTERVENTION: Tacrolimus, 4 mg/d, and mycophenolate mofetil, 1.0 g/d, versus intravenous cyclophosphamide with a starting dose of 0.75 (adjusted to 0.5 to 1.0) g/m2 of body surface area every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy. MEASUREMENTS: The primary end point was complete remission at 24 weeks. Secondary end points included overall response (complete and partial remission), time to overall response, and adverse events. RESULTS: After 24 weeks of therapy, more patients in the multitarget group (45.9%) than in the intravenous cyclophosphamide group (25.6%) showed complete remission (difference, 20.3 percentage points [95% CI, 10.0 to 30.6 percentage points]; P < 0.001). The overall response incidence was higher in the multitarget group than in the intravenous cyclophosphamide group (83.5% vs. 63.0%; difference, 20.4 percentage points [CI, 10.3 to 30.6 percentage points]; P < 0.001), and the median time to overall response was shorter in the multitarget group (difference, -4.1 weeks [CI, -7.9 to -2.1 weeks]). Incidence of adverse events did not differ between the multitarget and intravenous cyclophosphamide groups (50.3% [91 of 181] vs. 52.5% [95 of 181]). LIMITATION: The study was limited to 24 weeks of follow-up. CONCLUSION: Multitarget therapy provides superior efficacy compared with intravenous cyclophosphamide as induction therapy for LN. PRIMARY FUNDING SOURCE: National Basic Research Program of China, National Key Technology R&D Program.


Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Tacrolimo/uso terapêutico , Adolescente , Adulto , Idoso , Biópsia , Ciclofosfamida/efeitos adversos , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Rim/patologia , Nefrite Lúpica/patologia , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Projetos Piloto , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Indução de Remissão , Tacrolimo/efeitos adversos , Adulto Jovem
16.
Int Urol Nephrol ; 46(8): 1651-4, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24114285

RESUMO

BACKGROUND: Some chronic hemodialysis (HD) patients can maintain normal hemoglobin levels without requiring erythropoiesis-stimulating agents (ESAs). However, the prevalence and the factors associated with this condition in Chinese chronic HD patients have not been reported. The aim of this study was to investigate clinical features, iron metabolism, and other characteristics to survey the prevalence rate and the related factors of this condition among Chinese chronic HD patients. METHODS: A total of 1,318 chronic HD patients participated in this study. The patients were classified into a non-ESA group (n = 11) and an ESA group (n = 1,307). The r-HuEPO-independent (non-ESA) HD patients were defined as having hemoglobin greater than 12 g/dl for more than 6 months without r-HuEPO injection, blood transfusion, or androgen therapy. Epidemiological and laboratory data were collected. Renal sonography was also performed on each patient to evaluate the formation of renal and liver cysts, and the number and size of the cysts were recorded. RESULTS: Approximately 0.84 % of all HD patients were found to be r-HuEPO independent. The non-ESA group had a higher proportion of men (79.6 vs. 58.3 %), a longer duration of renal replacement therapy (RRT) (8.6 ± 6.1 vs. 5.1 ± 3.3 years), a higher prevalence of adult polycystic kidney disease (APKD) (46.3 vs. 9.7 %), a higher prevalence of hepatitis C virus (HCV) liver disease (26.2 vs. 3.2 %, P < 0.01), and had older patients (63.3 ± 13.6 vs. 49.6 ± 13.5 years). Endogenous erythropoietin levels in the non-ESA group were significantly higher than those in the ESA group (61.8 ± 27.1 vs. 29.3 ± 11.7 mU/ml). Non-ESA patients had a significantly higher number of renal (38.1 vs. 13.2 %) and hepatic cysts (9.3 vs. 1.9 %), which were also larger in size (2.9 ± 1.6 vs. 1.3 ± 0.3 cm) compared with those of patients in the ESA group. No significant difference in iron metabolism was found between two groups. In the multivariate Cox analysis, the independent predictor factors for the absence of anemia in these HD patients were the number of renal cysts >6 cysts (95 % CI 1.058-1.405; P = 0.00), endogenous erythropoietin levels (95 % CI 1.139-1.361; P = 0.05), HCV+ liver disease (95 % CI 1.129-1.316; P = 0.01), and time on RRT (95 % CI 1.019-1.263; P = 0.05). CONCLUSIONS: To our knowledge, this study is the first to report on r-HuEPO independence among Chinese HD patients. The prevalence among Chinese chronic HD patients is significantly lower than that reported in the literature. Factors contributing to this condition are complex and multiple. The frequency of this condition is higher in men and in older patients with long-term RRT, in patients with HCV+ liver disease, and in APKD patients. This condition is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.


Assuntos
Anemia/epidemiologia , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Hepatopatias/epidemiologia , Insuficiência Renal Crônica/terapia , Adulto , Fatores Etários , Idoso , Anemia/prevenção & controle , China/epidemiologia , Estudos Transversais , Cistos/diagnóstico por imagem , Cistos/epidemiologia , Eritropoetina/sangue , Feminino , Hemoglobinas/metabolismo , Hepatite C/epidemiologia , Humanos , Ferro/metabolismo , Hepatopatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doenças Renais Policísticas/diagnóstico por imagem , Doenças Renais Policísticas/epidemiologia , Prevalência , Proteínas Recombinantes/uso terapêutico , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/sangue , Fatores de Tempo , Ultrassonografia
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 23(7): 633-4, 2007 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-17618586

RESUMO

AIM: To explore effects of Yishen Decoction on the expression of MMP-9 and TIMP-1 in kidney of mice with IgA nephropathy (IgAN). METHODS: The IgAN model was established by oral administration of bovine serum albumin (BSA) together with the injection of Staphylococcus enterotoxin B (SEB) through caudal vein. The mRNA and protein expression of MMP-9 and TIMP-1 were measured by fluorescent quantitative RT-PCR and immunohistochemistry respectively. RESULTS: No significant differences of mRNA and protein expression of MMP-9 and TIMP-1 were found between the low and high concentration Yishen Decoction treated group. But the expression of TIMP-1 in the Yishen Decoction treated group was lower than that in the IgAN group, while that of MMP-9 was higher than that in the control group. CONCLUSION: The TCM Yishen Decoction can inhibit the abnormal expression of TIMP-1, and strengthen the expression of MMP-9 in kidney of mouse with IgA nephropathy.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glomerulonefrite por IGA/metabolismo , Rim/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Animais , Modelos Animais de Doenças , Glomerulonefrite por IGA/tratamento farmacológico , Imuno-Histoquímica , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Inibidor Tecidual de Metaloproteinase-1/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA