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Exhaustive exercise is known to induce acute renal damage. However, the precise mechanisms remain unclear. We investigated the effects of macrophage depletion on exhaustive exercise-induced acute renal damage. Male C57BL/6 J mice were divided into four groups: sedentary with control liposome (n=8), sedentary with clodronate liposome (n=8), exhaustive exercise with control liposome (n=8), and exhaustive exercise with clodronate liposome (n=8). Mice were treated with clodronate liposomes or control liposomes intraperitoneally for 48 h before undergoing exhaustive exercise. Renal function and renal histology were tested at 24 h. The expression levels of kidney injury molecule (KIM)-1 and inflammatory cytokines in kidney tissues were measured by quantitative RT-PCR, and KIM-1 concentration was semi-quantified by immunostaining. As a result, exhaustive exercise increased macrophage infiltration into the kidney. However, clodronate reduced it. Although exhaustive exercise resulted in an increase in KIM-1 mRNA expression levels and concentration, injection of clodronate liposome reduced it. In addition, TUNEL positive apoptotic cells were increased after exercise, but significantly reduced by clodronate. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the kidney after exhaustive exercise. These results suggest that macrophages play a critical role in increasing renal damage by regulating inflammation.
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Ácido Clodrônico , Lipossomos , Animais , Ácido Clodrônico/metabolismo , Ácido Clodrônico/farmacologia , Citocinas/genética , Citocinas/metabolismo , Interleucina-6/metabolismo , Rim/fisiologia , Lipossomos/metabolismo , Lipossomos/farmacologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent's targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient's nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.
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Rivaroxaban (Riv), a direct factor Xa (FXa) inhibitor, exerts anti-inflammatory effects in addition to anticoagulation. However, its role in cardiovascular remodeling is largely unknown. We tested the hypothesis that Riv attenuates the progression of cardiac hypertrophy and fibrosis induced by continuous activation of the renin-angiotensin system (RAS) in renin-overexpressing hypertensive transgenic (Ren-Tg) mice. We treated 12-week-old male Ren-Tg and wild-type (WT) mice with a diet containing Riv (12 mg/kg/day) or a regular diet for 4 weeks. After this, FXa in plasma significantly increased in Ren-Tg mice compared with WT mice, and Riv inhibited this increase. Left ventricular wall thickness (LVWT) and the area of cardiac fibrosis evaluated by Masson's trichrome staining were greater in Ren-Tg mice than in WT mice, and Riv decreased them. Cardiac expression levels of the protease-activated receptor (PAR)-2, tumor necrosis factor-α, transforming growth factor (TGF)-ß1, and collagen type 3 α1 (COL3A1) genes were all greater in Ren-Tg mice than in WT mice, and Riv attenuated these increases. To investigate the possible involvement of PAR-2, we treated Ren-Tg mice with a continuous subcutaneous infusion of 10 µg/kg/day of the PAR-2 antagonist FSLLRY for 4 weeks. FSLLRY significantly decreased LVWT and cardiac expression of PAR-2, TGF-ß1, and COL3A1. In isolated cardiac fibroblasts (CFs), Riv or FSLLRY pretreatment inhibited the FXa-induced increase in the phosphorylation of extracellular signal-regulated kinases. In addition, Riv or FSLLRY inhibited FXa-stimulated wound closure in CFs. Riv exerts a protective effect against cardiac hypertrophy and fibrosis development induced by continuous activation of the RAS, partly by inhibiting PAR-2.
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Renina , Rivaroxabana , Animais , Cardiomegalia/patologia , Inibidores do Fator Xa/farmacologia , Inibidores do Fator Xa/uso terapêutico , Fibrose , Masculino , Camundongos , Miocárdio/patologia , Receptor PAR-2 , Renina/genética , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêuticoRESUMO
BACKGROUND/AIM: Viral infection often exacerbates proteinuria, which has been suggested to be due to antiviral responses of podocytes. We examined the effect of polyinosinic-polycytidylic acid (polyIC) on the expression of retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in differentiated human podocytes in culture. MATERIALS AND METHODS: The podocytes were treated with 2 ng/ml to 500 µg/ml of polyIC for 3 to 36 h, and also transfected with siRNA against RIG-I and MDA5. F-actin staining was performed to assess actin reorganization. RESULTS: PolyIC induced the expression of RIG-I and MDA5 in dose- and time-dependent manner, accompanied with interferon-ß (IFN-ß) and interleukin-6 (IL-6) up-regulation and actin reorganization. Temporal knockdown of RIG-I by siRNA decreased IFN-ß expression, while MDA5 siRNA inhibited IFN-ß and IL-6 expression. Actin reorganization was attenuated by RIG-I and MDA5 knockdown. CONCLUSION: RIG-I and MDA5 may play a role in the antiviral responses of podocytes.
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Melanoma , Podócitos , Proteína DEAD-box 58/genética , RNA Helicases DEAD-box/genética , Humanos , Inflamação/genética , Helicase IFIH1 Induzida por Interferon/genética , Tretinoína/farmacologiaRESUMO
OBJECTIVE: The focus of this review was to elicit the mechanistic logic of the experimental and clinical study designs of natriuretic peptides (NP) in acute kidney injury (AKI) and to understand their respective outcomes. METHODS: Online search of PubMed and manual review of articles. Randomized trials, observational and physiologic studies of NPs and AKI were extracted. Rationale, design and study outcomes were analyzed. RESULTS: In experimental models of AKI, infusion of NP prevented post-ischemic fall in renal blood flow (RBF) or improvement in RBF, GFR, diuresis and natriuresis and demonstrated anti-inflammatory properties. NPs were most effective in the early stages of AKI, also in established phase of AKI but their effectiveness were limited to the time of infusion. Hypotension was a major side-effect. Based on these observations, preliminary clinical studies were performed which demonstrated improved urine output, RBF and GFR and reduced need for dialysis. However, randomized, controlled trials failed to demonstrate improvement in dialysis-free survival in different cohorts and study designs. Although NPs reduced the incidence of AKI in the postoperative period in cardiac surgery, it was not associated with improved long-term survival. In contrast to randomized trials, meta-analysis reported favorable results. CONCLUSIONS: Reasons for the divergence of experimental and clinical outcomes of NPs in AKI are discussed in this review article.
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Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Anti-Inflamatórios/uso terapêutico , Humanos , Peptídeos Natriuréticos/uso terapêutico , Diálise RenalRESUMO
BACKGROUND: The impact of distance between donor and recipient hospitals on outcomes in cadaveric kidney transplantations is unknown. We investigated the association between inter-hospital distance and outcomes in cadaveric kidney transplantations in Japan. METHODS: We retrospectively analyzed 363 cadaveric kidney transplantations between 2002 and 2017 in Japan. Inter-hospital distance, graft transport time, total ischemic time (TIT), and graft survival were compared between our hospital and national transplantation cohort in Japan. Estimated glomerular filtration rate (eGFR) 1 month and 1 year after transplantation was compared between cadaveric and living-donor kidney transplantations in our hospitals. Additionally, inter-hospital distances among the seven geographical regions in Japan were assessed. RESULTS: There were 12 and 351 cadaveric kidney transplantations at our hospital and in Japan, respectively. Mean inter-hospital distance at our hospital (217 ± 121 km) was significantly longer than that of the national cohort (53 ± 80 km; P < 0.001). Mean TIT and graft survival for our hospital and national cohort were 539 ± 200 min and 91% and 491 ± 193 min and 81%, respectively. Mean eGFRs 1 year after cadaveric and living-donor transplantations at our hospitals were comparable (47 ± 16 vs. 47 ± 15 mL/min/1.73 m2). The comparison among seven regions in Japan indicated a regional difference in inter-hospital distance with an association between area (km2) and inter-hospital distance (km). CONCLUSIONS: Despite the longer inter-hospital distance at our hospital, TIT and transplant outcomes were acceptable in our cases. In addition, geographical inequity in graft allocation in Japan was suggested.
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Isquemia Fria , Transplante de Rim/estatística & dados numéricos , Meios de Transporte/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Ethylene glycol intoxication causes severe metabolic acidosis and acute kidney injury. Fomepizole has become available as its antidote. Nevertheless, a prompt diagnosis is not easy because patients are often unconscious. Here we present a case of ethylene glycol intoxication who successfully recovered with prompt hemodialysis. CASE PRESENTATION: A 52-year-old Japanese male was admitted to a local hospital due to suspected food poisoning. The patient presented with nausea and vomiting, but his condition rapidly deteriorated, with worsening conscious level, respiratory distress requiring mechanical ventilation, hypotension, and severe acute kidney injury. He was transferred to the university hospital; hemodialysis was initiated because of hyperkalemia and severe metabolic acidosis. On recovering consciousness, he admitted having ingested antifreeze solution. Thirty-seven days after admission, the patient was discharged without requiring HD. CONCLUSIONS: We reported a case of ethylene glycol intoxication who presented with a life-threatening metabolic acidosis. In a state of severe circulatory shock requiring catecholamines, hemodialysis should be avoided, and continuous hemodiafiltration may be a preferred approach. However, one should be aware of the possibility of intoxication by unknown causes, and hemodialysis could be life-saving with its superior ability to remove toxic materials in such cases.
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BACKGROUND: Direct-acting antivirals (DAAs) dramatically improve the treatment of hepatitis C virus (HCV) infections. However, the effects of DAAs on extra-hepatic manifestations such as HCV-associated glomerulonephritis, especially in cases with renal dysfunction, are not well elucidated. CASE PRESENTATION: A 69-year-old Japanese woman was diagnosed as having chronic hepatitis C, genotype 1b at the age of 55. She presented with hypertension, microscopic hematuria, proteinuria, renal dysfunction, purpura, and arthralgia at the age of 61. She also had hypocomplementemia and cryoglobulinemia. Renal biopsy revealed membranoproliferative glomerulonephritis (MPGN), and she was diagnosed as having HCV-associated cryoglobulinemic MPGN. She declined interferon therapy at the time and was treated with antihypertensive medications as well as oral corticosteroid that were effective in reducing proteinuria. However, when the corticosteroid dose was reduced, proteinuria worsened. She began antiviral treatment with daclatasvir/asunaprevir (DCV/ASV). Clearance of HCV-RNA was obtained by 2 weeks and sustained, and liver function was normalized. In addition, microhematuria turned negative, proteinuria decreased, hypocomplementemia and estimated glomerular filtration rate were improved, whereas cryoglobulinemia persisted. She completed 24 weeks of therapy without significant adverse effects. CONCLUSION: In a case of HCV-associated cryoglobulinemic MPGN with renal dysfunction, DCV/ASV -based DAAs ameliorated microhematuria, proteinuria and renal function without significant side effects.
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Crioglobulinemia/prevenção & controle , Glomerulonefrite Membranoproliferativa/etiologia , Glomerulonefrite Membranoproliferativa/prevenção & controle , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Isoquinolinas/administração & dosagem , Sulfonamidas/administração & dosagem , Idoso , Antivirais/administração & dosagem , Carbamatos , Crioglobulinemia/diagnóstico , Crioglobulinemia/etiologia , Feminino , Glomerulonefrite Membranoproliferativa/diagnóstico , Hepatite C/diagnóstico , Humanos , Pirrolidinas , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
BACKGROUND: In this study, we investigated the relationship between serum uric acid (SUA) and renal function in a unique patient cohort wherein SUA levels fluctuate during the course of standard care. METHODS: Correlation coefficients between SUA and serum creatinine (SCr) and kinetic estimated GFR (KeGFR) were retrospectively investigated in acute myeloid leukemia (AML) patients, and statistically significant and clinically relevant determinants were studied in multiple regression models. RESULTS: One hundred and twenty-six patients were included in the analysis. Baseline SUA was associated with an increased risk for acute kidney injury (AKI; OR 1.27, 95% CI 1.1-1.5, p = 0.003) and laboratory tumor lysis syndrome (OR 1.26, 95% CI 1.1-1.5, p = 0.005). Prophylactic uric acid-lowering therapy and hydration resulted in lower SUA values from baseline in 88.1% of the patients, the lowest values were observed on post-induction day 1 (20.4% reduction). Significant linear correlations were observed between SUA and SCr (r = 0.35, p < 0.001) values with a significant inverse correlation between SUA and KeGFR on day 1 (r = -0.33, p < 0.001) that persisted through day 4. By subgroup analysis, patients with primary AML (r = -0.49, p < 0.001), baseline SUA >5.5 mg/dl (r = -0.41, p = 0.002) and baseline eGFR >60 ml/min/1.73 m2 (r = -0.51, p < 0.001) demonstrated robust relationships between SUA and KeGFR. The relationship was more robust when the groups were combined (primary AML plus baseline SUA >5.5 mg/dl plus baseline eGFR >60 ml/min/1.73 m2, r = -0.52, p < 0.001). CONCLUSION: The demonstration of linear relationship between SUA and SCr and inverse relationship between SUA and KeGFR reinforces the emerging translational physiological evidence regarding the role of uric acid in AKI.
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Taxa de Filtração Glomerular , Ácido Úrico/sangue , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Estudos de Coortes , Creatinina/sangue , Feminino , Humanos , Testes de Função Renal , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Lise Tumoral/sangue , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/fisiopatologiaRESUMO
BACKGROUND: Fibrin deposition within glomeruli is commonly seen in kidney biopsy specimens, suggesting enhanced coagulant activity. Tissue factor (TF) is a coagulation factor which is also related to various biological effects, and TF is upregulated by hypoxia in cancer cells. Recently, hypoxic podocyte injury has been proposed, therefore, we investigated TF expression in hypoxia. METHODS: Conditionally immortalized human podocytes were differentiated and treated under hypoxic or normoxic conditions. mRNA expressions of TF and tissue factor pathway inhibitor (TFPI) were analyzed by quantitative RT-PCR. Protein levels of TF and TFPI were tested by enzyme-linked immunosorbent assay. We employed small interfering RNA (siRNA) to temporary knockdown early growth response protein 1 (Egr-1), hypoxia-inducible factor-1α (HIF-1α) and TF. The expression of CD2-associated protein (CD2AP) mRNA and phalloidin staining was examined to assess podocyte injury. RESULTS: Hypoxia increased mRNA expression of TF (6 h: 2.3 ± 0.05 fold, p < 0.001, 24 h: 5.6 ± 2.4 fold, p < 0.05) and suppressed TFPI (6 h: 0.54 ± 0.04 fold, p < 0.05, 24 h: 0.24 ± 0.06 fold, p < 0.001) compared with normoxia. Similarly, protein levels of TF were increased and TFPI were decreased. Egr-1 siRNA did not change TF mRNA expression. Pyrrolidine dithiocarbamate (PDTC), a nuclear factor kappa B (NF-κB) inhibitor, significantly reduced hypoxia induced TF expression, and HIF-1α knockdown further increased TF. Hypoxia resulted in decreased CD2AP and actin reorganization in podocytes, and these changes were attenuated by TF siRNA. CONCLUSION: Hypoxia increased the expression of TF in human podocytes NF-κB dependently. TF may have a critical role in the hypoxic podocyte injury.
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NF-kappa B/metabolismo , Oxigênio/metabolismo , Podócitos/metabolismo , Tromboplastina/metabolismo , Citoesqueleto de Actina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Hipóxia Celular , Linhagem Celular , Cobalto/farmacologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Imunofluorescência , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lipoproteínas/genética , Lipoproteínas/metabolismo , NF-kappa B/antagonistas & inibidores , Faloidina/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/patologia , Pirrolidinas/farmacologia , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Tiocarbamatos/farmacologia , Tromboplastina/genética , Fatores de Tempo , Transfecção , Regulação para CimaRESUMO
BACKGROUND: We previously showed that phospholipase C (PLC)-δ1 activity was enhanced by 3-fold in patients with coronary spastic angina (CSA). We also reported that p122Rho GTPase-activating protein/deleted in liver cancer-1 (p122RhoGAP/DLC-1) protein, which was discovered as a PLC-δ1 stimulator, was upregulated in CSA patients. We tested the hypothesis that p122RhoGAP/DLC-1 overexpression causes coronary spasm. METHODS AND RESULTS: We generated transgenic (TG) mice with vascular smooth muscle (VSM)-specific overexpression of p122RhoGAP/DLC-1. The gene and protein expressions of p122RhoGAP/DLC-1 were markedly increased in the aorta of homozygous TG mice. Stronger staining with anti-p122RhoGAP/DLC-1 in the coronary artery was found in TG than in WT mice. PLC activities in the plasma membrane fraction and the whole cell were enhanced by 1.43 and 2.38 times, respectively, in cultured aortic vascular smooth muscle cells from homozygous TG compared with those from WT mice. Immediately after ergometrine injection, ST-segment elevation was observed in 1 of 7 WT (14%), 6 of 7 heterozygous TG (84%), and 7 of 7 homozygous TG mice (100%) (p<0.05, WT versus TGs). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in TG, but not in WT mice, despite of the similar response to prostaglandin F2α between TG and WT mice (n = 5). Focal narrowing of the coronary artery after ergometrine was documented only in TG mice. CONCLUSIONS: VSM-specific overexpression of p122RhoGAP/DLC-1 enhanced coronary vasomotility after ergometrine injection in mice, which is relevant to human CSA.
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Vasoespasmo Coronário/metabolismo , Vasos Coronários/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Músculo Liso Vascular/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Angina Pectoris/metabolismo , Animais , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Regulação para Cima/fisiologiaRESUMO
BACKGROUND: It is sometimes challenging to diagnose unsusual cases of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulopathy (ITG), the rare causes of nephrotic syndrome. CASE PRESENTATION: A 75-year-old Japanese woman presented with nephrotic syndrome, microhematuria and renal insufficiency. Renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) with IgM and weak C3 deposition. Congo red stain was negative. Electron microscopy demonstrated massive fibrils in the subendothelium, mesangium and subepithelium. The fibrils were partially parallel, partially curved and 17 nm in diameter. Cryoglobulin, hepatitis B virus (HBV) antigen, hepatitis C virus (HCV) antibody or antinuclear antibody were negative. CONCLUSION: We report a case of MPGN associated with peculiar non-amyloid fibril deposition corresponding to neither FGN nor ITG.
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Glomerulonefrite Membranoproliferativa/patologia , Idoso , Feminino , HumanosRESUMO
BACKGROUND: Mesangial proinflammatory chemokine/cytokine expressions via innate immunity play a pivotal role in the pathogenesis of glomerulonephritis. CXCL1/GROα is a strong neutrophil chemoattractant cytokine and reportedly plays an important role in regional inflammatory reactions. However, detailed signaling of mesangial CXCL1 expression induced by viral or "pseudoviral" immunity remains to be determined. METHODS: We treated normal human mesangial cells (MCs) in culture with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expression of CXCL1 by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR and enzyme-linked immunosorbent assay. To elucidate the poly IC-induced signaling pathway for CXCL1 expression, we subjected the cells to RNA interference against Toll-like receptor (TLR) 3, retinoic acid-inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), interferon (IFN)-ß, nuclear factor (NF)-κB p65 and IFN regulatory factor (IRF) 3. We also conducted an immunofluorescence study to examine mesangial CXCL1 expression in biopsy specimens from patients with lupus nephritis (LN) and IgA nephropathy (IgAN). RESULTS: We found that activation of TLR3 signaling could induce the expression of CXCL1 in MCs. NF-κB, IRF3 and IFN-ß, but neither RIG-I nor MDA5, were found to be involved in mesangial CXCL1 expression in this setting. Induction of CXCL1 by poly IC was inhibited by pretreatment of cells with dexamethasone. Intense glomerular CXCL1 expression was observed in biopsy specimens from patients with LN, whereas only a trace staining occurred in specimens from patients with IgAN. CONCLUSION: TLR3 signaling also contributes to the CXCL1 expression in MCs. These observations further support the implication of viral and "pseudoviral" immunity in the pathogenesis of inflammatory renal diseases, especially in LN.
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Quimiocina CXCL1/biossíntese , Quimiocina CXCL1/genética , Células Mesangiais/metabolismo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Anti-Inflamatórios/farmacologia , Células Cultivadas , Dexametasona/farmacologia , Glomerulonefrite por IGA/metabolismo , Humanos , Imunidade Celular/genética , Nefrite Lúpica/metabolismo , Poli I-C/farmacologia , Interferência de RNA , RNA de Cadeia Dupla/biossíntese , Transdução de Sinais/genéticaRESUMO
BACKGROUND: The aim of the study was to investigate the effects of serum uric acid (SUA) on acute kidney injury (AKI) in patients undergoing cardiac surgery. METHODS: Prospectively collected data from a previous study were analyzed to investigate the relationship between SUA and AKI as assessed by neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine (SCr) and kinetic estimated glomerular filtration rate (KeGFR). RESULTS: Patients undergoing cardiovascular surgery (n = 37) were included. SUA was measured at postoperative 1 h. Statistically significant correlations were present between SUA and NGAL measured at postoperative 1 h (r = 0.39, p = 0.008), 6 h (r = 0.31, p = 0.029) and 24 h (r = 0.31, p < 0.001), respectively. Significant correlations were also noted between SUA and SCr measured on postoperative day 1 (r = 0.41, p = 0.006), day 2 (r = 0.29, p = 0.042) and day 3 (r = 0.42, p = 0.009). Negative correlations were demonstrated between SUA and day 1 (r = -0.44, p = 0.007), day 2 (r = -0.43, p = 0.007), day 3 (r = -0.44, p = 0.006 and day 4 KeGFR (r = -0.35, p = 0.035). The inverse relationship of SUA and KeGFR was also demonstrated with a different method (Jelliffe) of measurement. CONCLUSIONS: A reduction in glomerular filtration rate (GFR) can lead to a rise in SUA. However, in this study, we are able to show that SUA at 1 h (maximal dilution time) effectively predicts subsequent changes in urinary NGAL, SCr, KeGFR, and the development of AKI. Thus, these findings suggest that uric acid precedes and predicts acute changes in renal function and cannot be ascribed to a simple relationship in which a reduced GFR raises SUA.
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Injúria Renal Aguda/sangue , Procedimentos Cirúrgicos Cardíacos , Taxa de Filtração Glomerular , Ácido Úrico/sangue , Proteínas de Fase Aguda , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/cirurgia , Creatinina/sangue , Feminino , Humanos , Lipocalina-2 , Lipocalinas/sangue , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/uso terapêutico , Projetos Piloto , Período Pós-Operatório , Estudos Prospectivos , Proteínas Proto-Oncogênicas/sangue , Fatores de Tempo , Ácido Úrico/metabolismoRESUMO
BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) and concurrent membranous nephropathy (MN) are very rare combination. Their causal relationship has been suggested, but not determined. CASE PRESENTATION: A 73-years-old male with 5-year history of proteinuria underwent an operation for his sigmoid colon cancer. Seven months later, he was referred to a nephrology division due to an exacerbating renal function and hypoalbuminemia. Laboratory examination revealed positive MPO-ANCA in the serum. A renal biopsy revealed a necrotizing extracapillary proliferative glomerulonephritis with crescents, demonstrating MPO-ANCA-GN. Whereas, immunofluorescent staining documented granular deposition of immumoglobulin (Ig) G and C3 along the capillary wall and electron microscopy showed subepithelial deposits in the glomerular basement membrane demonstrating MN. Immunofluorescent staining of IgG subclass showed positive IgG1, IgG2, negative IgG3 and weak positive IgG4 suggested the possibility of malignancy-associated MN. CONCLUSION: Combination of MPO-ANCA-GN and MN are rare. Although the causal relationship has been suggested in some cases, we should consider all the possibilities including idiopathic MN and secondary MN associated with malignancy, drug use or infection.
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Anticorpos Anticitoplasma de Neutrófilos/análise , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite/diagnóstico , Peroxidase/análise , Idoso , Glomerulonefrite/complicações , Glomerulonefrite Membranosa/complicações , Humanos , MasculinoRESUMO
PURPOSE: Serum uric acid (SUA) is a novel risk factor for acute kidney injury (AKI), which adversely affects renal blood flow autoregulation, glomerular filtration rate (GFR), and promotes inflammation and angiogenesis. This pilot study investigated the effect of lowering SUA therapy on AKI, by using traditional and non-traditional markers. MATERIALS AND METHODS: In this prospective, double-blind, placebo-controlled, randomized pilot trial, 26 hyperuricemic patients undergoing cardiac surgery were randomized to receive rasburicase or placebo in the preoperative period. RESULTS: Subjects receiving rasburicase showed no difference in serum creatinine compared with the control group receiving placebo. Despite no difference in primary endpoint, the rasburicase group had less evidence of renal structural injury as reflected by urine neutrophil-associated lipocalin (uNGAL) concentrations, especially in subjects with higher SUA levels, more severe renal dysfunction (baseline GFR ≤ 45 mL/min/1.73 m(2)) or heart failure (left ventricular ejection fraction ≤45 %). CONCLUSIONS: In this study, rasburicase showed no benefit on postoperative serum creatinine in hyperuricemic subjects undergoing cardiac surgery. However, the observation that markers of structural renal injury such as uNGAL tended to be lower in rasburicase-treated subjects suggests potential different effects of uricase treatment on hemodynamic alterations in renal function versus structural mechanisms of kidney injury.
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Injúria Renal Aguda/prevenção & controle , Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias/prevenção & controle , Urato Oxidase/uso terapêutico , Ácido Úrico/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
Nephrotic syndrome is a rare complication of hematopoietic cell transplantation. It has been suggested that nephrotic syndrome may represent a limited form of graft-versus-host disease although the pathological link between these two entities remains unclear. In this paper, we report a case of a 61-year-old female who underwent nonmyeloablative allogenic stem cell transplantation for T-cell prolymphocytic leukemia and subsequently developed biopsy proven minimal change disease shortly after cessation of her immunosuppression therapy. Urinary CD80 was markedly elevated during active disease and disappeared following corticosteroid-induced remission. We hypothesize that alloreactive donor T cells target the kidney and induce podocyte expression of CD80 that results in proteinuria from limited 'graft versus host' disease.
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Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Nefrose Lipoide/etiologia , Podócitos/imunologia , Antígeno B7-1/urina , Feminino , Humanos , Pessoa de Meia-Idade , Proteinúria/etiologia , Transplante HomólogoRESUMO
BACKGROUND: We have reported that children with biopsy-proven minimal change disease (MCD) express CD80 (also known as B7.1) in their podocytes and excrete high levels of CD80 in their urine during active nephrotic syndrome. We also reported that polyIC, a Toll-like receptor 3 ligand, increases CD80 mRNA and protein expression in cultured human podocytes dose-dependently, with actin re-organization and a reduction in synaptopodin expression. METHODS: To determine the effect of polyIC in the kidney, we subjected mice to systemic injection of polyIC or phosphate buffered saline. RESULTS: Mice injected with polyIC developed significant proteinuria with increased urinary CD80 excretion. Glomeruli from mice injected with polyIC were normal by light microscopic examination, but showed increased CD80 production in podocytes by immunofluorescence staining. In isolated glomeruli from mice injected with polyIC, expressions of CD80 and interleukin 10 significantly increased with a mild non-significant increase in CTLA-4, and synaptopodin expression decreased significantly. CONCLUSIONS: Our study demonstrates that systemically administered polyIC can induce transient proteinuria and urinary CD80 excretion with an increase in CD80 production in podocytes, increased glomerular CD80 and reduced synaptopodin expression. These findings may be relevant to the pathogenesis of proteinuria in MCD.
Assuntos
Antígeno B7-1/metabolismo , Glomérulos Renais/efeitos dos fármacos , Nefrose Lipoide , Podócitos/efeitos dos fármacos , Poli I-C/farmacologia , Proteinúria/induzido quimicamente , Receptor 3 Toll-Like/metabolismo , Animais , Antivirais/farmacologia , Antígeno B7-1/genética , Antígeno B7-1/urina , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas Imunoenzimáticas , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Podócitos/metabolismo , Podócitos/patologia , Proteinúria/metabolismo , Proteinúria/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 3 Toll-Like/genéticaRESUMO
BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR)--tyrosine kinase inhibitor (TKI) is used for the patients with EGFR-mutant lung cancer. Recently, phase III studies in the patients with EGFR-mutant demonstrated that EGFR-TKI monotherapy improved progression-free survival compared with platinum-doublet chemotherapy. The echinoderm microtubule-associated protein-like 4 (EML4)--anaplastic lymphoma kinase (ALK) fusion oncogene represents one of the newest molecular targets in non-small cell lung cancer (NSCLC). Patients who harbor EML4-ALK fusions have been associated with a lack of EGFR or KRAS mutations. CASE PRESENTATION: We report a 39-year-old patient diagnosed as adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene. We treated this patient with erlotinib as the third line therapy, but no clinical benefit was obtained. CONCLUSION: We experienced a rare case with EGFR mutation and EML4-ALK. Any clinical benefit using EGFR-TKI was not obtained in our case. The therapeutic choice for the patients with more than one driver mutations is unclear. We needs further understanding of the lung cancer molecular biology and the biomarker information.
Assuntos
Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Proteínas de Fusão Oncogênica/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Adulto , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , MasculinoRESUMO
BACKGROUND: We hypothesized that post-operative serum uric acid (SUA) may be associated with acute kidney injury (AKI). METHODS: In this prospective, observational study, the relationships between SUA, urine neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin-18 (uIL-18), serum monocyte chemoattractant protein-1 (sMCP-1) and tumor necrosis factor-alpha (sTNF-alpha), and incidence of AKI were determined. SUA were divided into tertiles and their association with AKI investigated. RESULTS: A total of 100 cardiac surgery patients were included for analyses. The 1st, 2nd, and 3rd SUA tertiles were associated with 15.1%, 11.7%, and 54.5% incidence of AKI, respectively. The 3rd SUA tertile, compared to the referent 1st tertile, was associated with an eightfold (OR 8.38, CI95% 2.13-33.05, p=0.002) increased risk for AKI. Patients with AKI on post-operative day 1 (n=11) were then excluded for the purpose of determining the predictive value of SUA to diagnose AKI on postoperative day 2 and during hospital stay. In comparison to the referent 1st tertile, the 3rd tertile SUA was associated with an eightfold increased risk for AKI on post-operative day 2 (adjusted OR 7.94, CI95% 1.50-42.08, P=.015) and a five-fold increased risk for AKI during hospital stay (OR 4.83, CI95% 1.21-19.20, P=.025), respectively. SUA (Area Under Curve, AUC 0.77 (CI95% 0.66-0.88, P<.001), serum creatinine (0.73, CI95% 0.62-0.84, P<.001) and sTNF-alpha (0.76, CI95% 0.65-0.87, P<.001) had the best diagnostic performance measured by the Receiver Operating Characteristics curves. CONCLUSIONS: We conclude that post-operative SUA is associated with an increased risk for AKI and compares well to conventional markers of AKI.