Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
1.
Int J Mol Sci ; 25(15)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39125734

RESUMO

Chronic beryllium disease (CBD), or berylliosis, is an interstitial lung disease caused by the chronic inhalation of finely particulate beryllium, frequently mistaken for sarcoidosis. It is rarely associated with skin nodular lesions, asymptomatic granulomatous hepatitis or calcium nephrolithiasis. To date, it has never been reported as a diffused multi-organ granulomatous disease. A 60-year-old Pakistani man, a former excavation worker with ancient history of suspected sarcoidosis, underwent a left nephroureterectomy for suspected papillary kidney carcinoma. The histopathological analysis showed a benign non-necrotic granulomatous infiltration of the renal pelvis and ureter. Six months later, he suffered from two consecutive episodes of acute kidney failure. Bladder biopsies found similar noncaseous granulomatosis and kidney biopsies showed interstitial nephritis. Known for suspected asthma, sleep apnea, and usual interstitial pneumonia, the patient would regularly consult for episodes of pyrexia, chills, nocturnal coughing, and wheezing. As kidney function gradually worsened, he ultimately started hemodialysis and was transferred to our facility. A positive blood beryllium lymphocyte proliferation test confirmed the diagnosis of CBD. This original report is the first description of multi-organ berylliosis with diffused urothelial granulomatosis and pseudo-tumor. The patient's pulmonary disease is minimal compared with renal and urinary tract involvement, eventually responsible for end-stage kidney disease. Berylliosis usually responds to glucocorticoids. This case report highlights the importance of evoking the diagnosis of CBD in the presence of any granulomatosis, even extra-thoracic, especially if associated with pulmonary symptoms, however atypical.


Assuntos
Beriliose , Berílio , Humanos , Masculino , Pessoa de Meia-Idade , Beriliose/diagnóstico , Beriliose/patologia
2.
BMC Nephrol ; 24(1): 116, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37106351

RESUMO

BACKGROUND: Peritoneal dialysis (PD) depends upon a functioning and durable access to the peritoneal cavity. Many techniques exist to insert a peritoneal catheter, showing similar outcomes and benefits. Blind percutaneous insertion represents a bedside intervention predominantly performed by nephrologists requiring only local anesthesia, sedation and minimal transcutaneous access. Although current guidelines recommend insertion techniques allowing visualization of the peritoneal cavity, the blind percutaneous approach is still widely used and has been proven safe and effective to bring durable peritoneal dialysis access. Herein, we described a rare case of jejunal perforation secondary to blind PD catheter placement, and conduct a review of the current medical literature describing early bowel perforations secondary to PD catheter placement, gathering descriptions of symptomatology and outcomes and their relations to the insertion technique. CLINICAL PRESENTATION: We herein describe the case of a 48 year-old patient with a history of appendectomy who suffered from triple jejunal perforation after blind percutaneous insertion and subsequent embedment of his peritoneal catheter. Accurate diagnosis was made 1 month after insertion due to atypical clinical presentation and because physicians had no access to the peritoneal cavity after catheter embedment. After surgical repair and broad-spectrum antibiotics, the patient was switched to HD. CONCLUSION: Early catheter-related visceral injury is a rare, yet threatening condition that is almost always causing a switch to hemodialysis or death. Our review highlights that laparoscopic catheter placement might bring better outcomes if perforation occurs, as it allows immediate diagnosis and treatment. On the contrary, catheter embedment may delay clinical diagnosis and therefore bring worse outcomes.


Assuntos
Perfuração Intestinal , Laparoscopia , Diálise Peritoneal , Humanos , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Cateterismo/métodos , Cateteres de Demora/efeitos adversos , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Laparoscopia/efeitos adversos , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia
3.
Int J Mol Sci ; 24(22)2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38003685

RESUMO

In patients hospitalized for severe COVID-19, the incidence of acute kidney injury (AKI) is approximately 40%. To predict and understand the implications of this complication, various blood and urine biomarkers have been proposed, including neutrophil gelatinase-associated lipocalin (NGAL), chemokine (C-C motif) ligand 14 (CCL14), cystatin C, leucine aminopeptidase (LAP), and soluble urokinase plasminogen activator (suPAR). This study, conducted between mid-January and early May 2021, aimed to assess the diagnostic and prognostic capabilities of these biomarkers in a cohort of COVID-19 patients monitored during the initial two weeks of hospitalization. Among the 116 patients included in this study, 48 developed AKI within the first three days of hospitalization (41%), with 29 requiring intensive care unit (ICU) admission, and the overall mortality rate was 18%. AKI patients exhibited a statistically significant increase in urinary LAP levels, indicating acute tubular injury as a potential mechanism underlying COVID-19-related renal damage. Conversely, urinary NGAL and CCL-14 excretion rates did not differ significantly between the AKI and non-AKI groups. Importantly, elevated plasma suPAR and cystatin C levels upon admission persisted throughout the first week of hospitalization and were associated with unfavorable outcomes, such as prolonged ICU stays and increased mortality, irrespective of AKI development. In conclusion, this study underscores the early predictive value of urinary LAP levels in identifying acute tubular injury in COVID-19-induced AKI. Moreover, elevated plasma suPAR and cystatin C levels serve as valuable prognostic markers, offering insights into the short-term morbidity and mortality risks among COVID-19 patients, regardless of AKI occurrence. These findings shed light on the complex interplay between COVID-19, renal injury, and biomarkers with diagnostic and prognostic potential.


Assuntos
Injúria Renal Aguda , COVID-19 , Humanos , Lipocalina-2 , Cistatina C , Prognóstico , Seguimentos , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Estudos Prospectivos , COVID-19/complicações , COVID-19/diagnóstico , Biomarcadores , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Teste para COVID-19
4.
Clin Nephrol ; 98(3): 155-161, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35818813

RESUMO

Acute granulomatous tubulointerstitial nephritis (GTIN) is a rare finding in renal biopsy. Differential diagnosis is facilitated when GTIN is associated with granulomatous bilateral anterior uveitis (GBAU). Nevertheless, differentiation between a rare form of granulomatous tubulointerstitial nephritis and uveitis syndrome (TINU) and sarcoidosis can be challenging. We report a case of biopsy-proven GTIN with concomitant GBAU, leading to a dead-end diagnosis. We discuss workup and propose a diagnostic algorithm based on a literature review. We also report a successful treatment of ophthalmologic and renal relapse using mycophenolate mofetil.


Assuntos
Nefrite Intersticial , Uveíte Anterior , Uveíte , Doença Aguda , Humanos , Ácido Micofenólico/uso terapêutico , Nefrite Intersticial/complicações , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/etiologia , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Uveíte Anterior/etiologia
5.
Arch Toxicol ; 93(11): 3345-3366, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602497

RESUMO

Exposure to aristolochic acid (AA) is associated with human nephropathy and urothelial cancer. The tumour suppressor TP53 is a critical gene in carcinogenesis and frequently mutated in AA-induced urothelial tumours. We investigated the impact of p53 on AAI-induced nephrotoxicity and DNA damage in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with 3.5 mg/kg body weight (bw) AAI daily for 2 or 6 days. Renal histopathology showed a gradient of intensity in proximal tubular injury from Trp53(+/+) to Trp53(-/-) mice, especially after 6 days. The observed renal injury was supported by nuclear magnetic resonance (NMR)-based metabonomic measurements, where a consistent Trp53 genotype-dependent trend was observed for urinary metabolites that indicate aminoaciduria (i.e. alanine), lactic aciduria (i.e. lactate) and glycosuria (i.e. glucose). However, Trp53 genotype had no impact on AAI-DNA adduct levels, as measured by 32P-postlabelling, in either target (kidney and bladder) or non-target (liver) tissues, indicating that the underlying mechanisms of p53-related AAI-induced nephrotoxicity cannot be explained by differences in AAI genotoxicity. Performing gas chromatography-mass spectrometry (GC-MS) on kidney tissues showed metabolic pathways affected by AAI treatment, but again Trp53 status did not clearly impact on such metabolic profiles. We also cultured primary mouse embryonic fibroblasts (MEFs) derived from Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice and exposed them to AAI in vitro (50 µM for up to 48 h). We found that Trp53 genotype impacted on the expression of NAD(P)H:quinone oxidoreductase (Nqo1), a key enzyme involved in AAI bioactivation. Nqo1 induction was highest in Trp53(+/+) MEFs and lowest in Trp53(-/-) MEFs; and it correlated with AAI-DNA adduct formation, with lowest adduct levels being observed in AAI-exposed Trp53(-/-) MEFs. Overall, our results clearly demonstrate that p53 status impacts on AAI-induced renal injury, but the underlying mechanism(s) involved remain to be further explored. Despite the impact of p53 on AAI bioactivation and DNA damage in vitro, such effects were not observed in vivo.


Assuntos
Ácidos Aristolóquicos/toxicidade , Dano ao DNA , Fibroblastos/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Mutagênicos/toxicidade , Proteína Supressora de Tumor p53/genética , Animais , Ácidos Aristolóquicos/metabolismo , Células Cultivadas , Citocromo P-450 CYP1A1/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Expressão Gênica/efeitos dos fármacos , Testes de Função Renal , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutagênicos/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética
6.
Clin Nephrol ; 88(12): 359-363, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28992849

RESUMO

Myoglobinuric acute kidney injury (AKI) is a severe condition requiring early therapeutic strategies. Early recognition and treatment are crucial to reduce morbidity and mortality rate. Here, we report a kidney recipient with severe rhabdomyolysis and AKI secondary to parvovirus B19 infection. Initiation of hemodialysis with the super high-flux filter Theralite® (Gambro, cut-off 45 kDa, 2.1 m2) resulted in the clearance of myoglobin from 61 to 71% after 3 hours. Elimination rates of IL-6 and ß2-microglobulin were ~ 30 - 64% and 55 - 71% after 3 hours, respectively. Renal graft function rapidly recovered. The place of this effective but expensive procedure still needs to be defined and validated in high-risk patients.
.


Assuntos
Injúria Renal Aguda/etiologia , Transplante de Rim/efeitos adversos , Mioglobinúria/etiologia , Diálise Renal/métodos , Injúria Renal Aguda/terapia , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Mioglobinúria/terapia , Rabdomiólise/terapia
7.
Int J Mol Sci ; 18(2)2017 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-28146082

RESUMO

The term "aristolochic acid nephropathy" (AAN) is used to include any form of toxic interstitial nephropathy that is caused either by ingestion of plants containing aristolochic acids (AA) as part of traditional phytotherapies (formerly known as "Chinese herbs nephropathy"), or by the environmental contaminants in food (Balkan endemic nephropathy). It is frequently associated with urothelial malignancies. Although products containing AA have been banned in most of countries, AAN cases remain regularly reported all over the world. Moreover, AAN incidence is probably highly underestimated given the presence of AA in traditional herbal remedies worldwide and the weak awareness of the disease. During these two past decades, animal models for AAN have been developed to investigate underlying molecular and cellular mechanisms involved in AAN pathogenesis. Indeed, a more-in-depth understanding of these processes is essential to develop therapeutic strategies aimed to reduce the global and underestimated burden of this disease. In this regard, our purpose was to build a broad overview of what is currently known about AAN. To achieve this goal, we aimed to summarize the latest data available about underlying pathophysiological mechanisms leading to AAN development with a particular emphasis on the imbalance between vasoactive factors as well as a focus on the vascular events often not considered in AAN.


Assuntos
Ácidos Aristolóquicos/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Nefrite Intersticial/etiologia , Animais , Ácidos Aristolóquicos/química , Ácidos Aristolóquicos/metabolismo , Nefropatia dos Bálcãs/diagnóstico , Nefropatia dos Bálcãs/epidemiologia , Nefropatia dos Bálcãs/etiologia , Biópsia , Transformação Celular Neoplásica/induzido quimicamente , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Fibrose , Humanos , Neoplasias Renais/etiologia , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/epidemiologia , Estresse Oxidativo
8.
Exp Physiol ; 101(1): 193-206, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26442795

RESUMO

Aristolochic acid (AA) nephropathy (AAN), a progressive tubulointerstitial injury of toxic origin, is characterized by early and transient acute tubular necrosis. This process has been demonstrated to be associated with reduced nitric oxide (NO) production, which can disrupt the regulation of renal function. In this study, we tested the hypothesis that L-arginine (L-Arg) supplementation could restore renal function and reduce renal injury after AA intoxication. C57BL/6 J male mice were randomly subjected to daily i.p. injection of either sterile saline solution or AA (2.5 mg kg(-1)) for 4 days. To determine whether AA-induced renal injuries were linked to reduced NO production, L-Arg, a substrate for NO synthase, was supplemented (5%) in drinking water. Mice intoxicated with AA exhibited features of rapid-onset acute kidney injury, including polyuria, significantly increased plasma creatinine concentrations, proteinuria and fractional excretion of sodium (P < 0.05), along with severe proximal tubular cell injury and increased NADPH oxidase 2 (Nox2)-derived oxidative stress (P < 0.05). This was associated with a significant reduction in NO bioavailability. L-Arg supplementation in AA-treated mice significantly increased NO bioavailability, which in turn improved renal function (creatininaemia, polyuria, proteinuria, fractional excreted sodium and N-acetyl-ß-D-glucosaminidase enzymuria) and renal structure (tubular necrosis and tubular cell apoptosis). These changes were associated with significant reductions in Nox2 expression and in production of reactive oxygen species and with an increase in antioxidant concentrations. Our results demonstrate that preservation of NO bioavailability leads to renal protection in AA-induced acute kidney injury by reducing oxidative stress and maintaining renal function.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Ácidos Aristolóquicos , Óxido Nítrico/uso terapêutico , Injúria Renal Aguda/patologia , Animais , Arginina/farmacologia , Creatinina/sangue , GMP Cíclico/urina , Rim/patologia , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Poliúria/induzido quimicamente , Poliúria/prevenção & controle , Proteinúria/induzido quimicamente , Proteinúria/prevenção & controle , Sódio/urina , Superóxido Dismutase/metabolismo
9.
Mediators Inflamm ; 2016: 7651024, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27493452

RESUMO

Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX), efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)), a useful biomarker of RTX response in other autoimmune diseases, and memory (CD3(-)CD19(+)CD20(+)IgD(-)CD27(+)CD38(-)) and naive (CD3(-)CD19(+)CD20(+)IgD(+)CD27(-)CD38(low)) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow-up after RTX. RTX induced complete disappearance of CD19(+) B cells, plasmablasts, and memory B cells as soon as day 15. Despite severe CD19(+) lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells (days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more rapidly than memory B cells but still remained elevated as compared to day 0 of RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case report suggests that, besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN.


Assuntos
ADP-Ribosil Ciclase 1/imunologia , Biomarcadores/metabolismo , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/metabolismo , Rim/metabolismo , Rim/fisiologia , Plasmócitos/imunologia , Plasmócitos/metabolismo , Receptores da Fosfolipase A2/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Antígenos CD19/metabolismo , Antígenos CD20/metabolismo , Complexo CD3/metabolismo , Humanos , Imunoglobulina D/metabolismo , Rim/imunologia , Masculino , Pessoa de Meia-Idade , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
10.
Transpl Int ; 28(2): 199-205, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25377421

RESUMO

Intravesical instillation of bacillus Calmette-Guerin (BCG) is the treatment of choice for non-muscle-invasive bladder cancer (NMIBC) of high grade and/or carcinoma in situ. This study evaluated the feasibility, efficacy, and tolerance of BCG instillations in eight kidney recipients for end-stage aristolochic acid nephropathy (AAN), a condition at high risk of urothelial carcinoma, and diagnosed for NMIBC. Five of them had relapsed after mitomycin C treatment. Tolerance to BCG was evaluated clinically and regular follow-up with fluorescence cystoscopy was performed along with renal graft function monitoring. Immunosuppression doses were adjusted and prophylactic anti-tuberculous treatment given to reduce risks of graft rejection and infection. After a mean follow-up period of 50 months, seven of the eight patients are free of relapse and kidney graft function remained unchanged. Tolerance was good, except for one episode of fever and one early discontinuation because of subjective discomfort. No systemic tuberculous infection was observed. This is the first clinical observation of successful BCG therapy for NMIBC in patients given transplant for end-stage AAN. Under standardized conditions, immunotherapy based on intravesical BCG is feasible, effective, and well tolerated in renal transplantation.


Assuntos
Ácidos Aristolóquicos/toxicidade , Vacina BCG/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Adulto , Idoso , Feminino , Seguimentos , Humanos , Falência Renal Crônica/induzido quimicamente , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/patologia
11.
Planta Med ; 81(5): 363-72, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25798640

RESUMO

This in vitro study aimed to determine the effects of a Panax ginseng extract on aristolochic acid-mediated toxicity in HK-2 cells. A methanolic extract of ginseng (50 µg/mL) was able to reduce cell survival after treatment with 50 µM aristolochic acid for 24, 48, and 72 h, as evidenced by a resazurin reduction assay. This result was confirmed by a flow cytometric evaluation of apoptosis using annexin V-PI staining, and indicated higher apoptosis rates in cells treated with aristolochic acid and P. ginseng extract compared with aristolochic acid alone. However, P. ginseng extract by itself (5 and 50 µg/mL) increased the Ki-67 index, indicating an enhancement in cellular proliferation. Cell cycle analysis excluded a P. ginseng extract-mediated induction of G2/M cell cycle arrest such as the one typically observed with aristolochic acid. Finally, ß-catenin acquisition was found to be accelerated when cells were treated with both doses of ginseng, suggesting that the epithelial phenotype of renal proximal tubular epithelial cells was maintained. Also, ginseng treatment (5 and 50 µg/mL) reduced the oxidative stress activity induced by aristolochic acid after 24 and 48 h. These results indicate that the ginseng extract has a protective activity towards the generation of cytotoxic reactive oxygen species induced by aristolochic acid. However, the ginseng-mediated alleviation of oxidative stress did not correlate with a decrease but rather with an increase in aristolochic acid-induced apoptosis and death. This deleterious herb-herb interaction could worsen aristolochic acid tubulotoxicity and reinforce the severity and duration of the injury. Nevertheless, increased cellular proliferation and migration, along with the improvement in the epithelial phenotype maintenance, indicate that ginseng could be useful for improving tubular regeneration and the recovery following drug-induced kidney injury. Such dual activities of ginseng certainly warrant further in vivo studies.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Aristolóquicos/efeitos adversos , Nefropatias , Rim/efeitos dos fármacos , Panax/química , Extratos Vegetais , Regeneração/efeitos dos fármacos , Aristolochia/química , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Interações Medicamentosas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular , Ginsenosídeos/análise , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Humanos , Técnicas In Vitro , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , beta Catenina/metabolismo
12.
J Appl Toxicol ; 35(12): 1520-30, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25663515

RESUMO

Aristolochic acids (AA) are nephrotoxic and profibrotic agents, leading to chronic kidney disease. As some controversial studies have reported a nephroprotective effect of exogenous recombinant human bone morphogenetic protein (rhBMP)-7 in several models of renal fibrosis, we investigated the putative effect of rhBMP-7 to prevent progressive tubulointerstitial damage after AA intoxication in vitro and in vivo. In vitro, the toxicity of AA on renal tubular cells was demonstrated by an increase in vimentin as well as a decrease in ß-catenin expressions, reflecting a dedifferentiation process. Increased fibronectin and interleukin-6 levels were measured in the supernatants. Enhanced α-SMA mRNA levels associated to decreased E-cadherin mRNA levels were also measured. Incubation with rhBMP-7 only prevented the increase in vimentin and the decrease in ß-catenin expressions. In vivo, in a rat model of AA nephropathy, severe tubulointerstitial lesions induced by AA after 10 and 35 days (collagen IV deposition and tubular atrophy), were not prevented by the rhBMP-7 treatment. Similarly, rhBMP-7 did not ameliorate the significant increase in urinary concentrations of transforming growth factor-ß. In summary, our in vitro data demonstrated a poor beneficial effect of rhBMP-7 to reverse cell toxicity while, in vivo, there was no beneficial effect of rhBMP-7. Therefore, further investigations are needed to confirm the exact role of BMP-7 in progressive chronic kidney disease.


Assuntos
Ácidos Aristolóquicos/toxicidade , Proteína Morfogenética Óssea 7/uso terapêutico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/prevenção & controle , Animais , Proteína Morfogenética Óssea 7/administração & dosagem , Linhagem Celular , Fibronectinas/metabolismo , Fibrose , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/urina , Resultado do Tratamento , Vimentina/biossíntese , beta Catenina/metabolismo
13.
Pharm Biol ; 53(7): 985-94, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25495691

RESUMO

CONTEXT: Acute kidney injury (AKI) is often encountered in patients receiving cisplatin (CisPt), a chemotherapeutic drug that induces numerous toxic side effects. Techniques used to limit nephrotoxicity during CisPt treatment are not fully effective; about a third of patients experience AKI. New nephroprotective strategies, including pharmacological approaches, must be developed. OBJECTIVE: The present study investigated the nephroprotective potential of Angelica sinensis (Oliv.) Diels (Apiaceae) root towards CisPt tubulotoxicity. MATERIALS AND METHODS: HK-2 cells were incubated with CisPt (10 µM) and/or with a methanolic extract of A. sinensis (AS). Nephroprotective capacity was evaluated by means of cellular viability (resazurin assay) and apoptosis (annexin-V/PI staining), oxidative stress generation (H2DCF-DA oxidation), Ki-67 index (immunofluorescence), cell cycle analysis (DNA staining), cell migration rate (scratch assay), extracellular matrix deposition (collagen determination), and ß-catenin relocalization. RESULTS: CisPt decreased cell viability [76% versus Ctrl], which was associated with an increased apoptosis. Simultaneous treatment with 50 µg/ml AS enhanced cell survival [84% versus Ctrl] and decreased the apoptosis rate. AS could not alleviate CisPt-induced oxidative stress; but doses of 5 and 50 µg/ml raised the Ki-67 index [135 and 244% versus Ctrl] and cell migration rates [1.2 and 1.3-fold versus Ctrl]. Finally, both doses of AS limited the amount of collagen deposition [121.6 and 119.6% for 5 and 50 µg/ml, respectively, versus 131.0% for CisPt-treated cells] and prevented the relocalization of ß-catenin from the membrane to the nucleus. CONCLUSION: These results confirm the nephroprotective potential of A. sinensis and require further investigations aiming at identifying its active compounds.


Assuntos
Injúria Renal Aguda/prevenção & controle , Angelica sinensis , Cisplatino/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Túbulos Renais/efeitos dos fármacos , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Raízes de Plantas , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico
14.
Int J Cancer ; 135(2): 502-7, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24921086

RESUMO

Aristolochic acid (AA) causes aristolochic acid nephropathy (AAN), first described in women in Belgium accidently prescribed Aristolochia fangchi in a slimming treatment, and also Balkan endemic nephropathy (BEN), through probable dietary contamination with Aristolochia clematitis seeds. Both nephropathies have a high risk of urothelial cancer, with AA being the causative agent. In tissues of AAN and BEN patients, a distinct DNA adduct, 7-(deoxyadenosin-N6-yl)-aristolactam I (dA-AAI), has been detected. DNA adducts can be removed through DNA repair, they can result in mutations through erroneous DNA replication or they can cause cell death. The dA-AAI adduct induces AT to TA transversions in the tumor-suppressor TP53 gene in experimental systems, matching TP53 mutations observed in urothelial tumors from AAN cancer cases. Using thin-layer chromatography 32P-postlabeling and mass spectrometric analysis we report the detection of dA-AAI in renal DNA from 11 Belgian AAN patients over 20 years after exposure to AA had ceased. Our results showed that dA-AAI is an established biomarker of AA exposure, and that this biomarker can be demonstrated to be persistent decades after a distinct AA exposure. Further, the persistence of dA-AAI adducts appears to be a critical determinant for the AA mutational fingerprint frequently found in oncogenes and tumor suppressor genes recently identified by whole genome sequencing of AA-associated urothelial tumors. The potential for exposure to AA worldwide is high; the unprecedented long-term persistence of dA-AAI provides a useful long-term biomarker of exposure and attests to the role of AA in human urothelial malignancy.


Assuntos
Ácidos Aristolóquicos/efeitos adversos , Nefropatia dos Bálcãs/induzido quimicamente , Biomarcadores/análise , Adutos de DNA/análise , Mutagênicos/efeitos adversos , Adulto , Idoso , Cromatografia em Camada Fina , Feminino , Humanos , Rim/química , Rim/patologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade
15.
Kidney Int ; 86(6): 1260-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25007166

RESUMO

Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Membranas Artificiais , Diálise Renal/métodos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Materiais Revestidos Biocompatíveis , Falha de Equipamento , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal/terapia , Cloreto de Sódio/administração & dosagem , Resultado do Tratamento
16.
Kidney Int ; 85(3): 611-23, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24304883

RESUMO

AMP-activated protein kinase (AMPK) is an important energy sensor that may be critical in regulating renal lipid accumulation. To evaluate the role of AMPK in mediating renal lipid accumulation, C57BL/6J mice were randomized to a standard diet, a high-fat diet, or a high-fat diet plus AICAR (an AMPK activator) for 14 weeks. Renal functional and structural studies along with electron microscopy were performed. Mice given the high-fat diet had proximal tubule injury with the presence of enlarged clear vacuoles, and multilaminar inclusions concurrent with an increase of tissue lipid and overloading of the lysosomal system. The margins of the clear vacuoles were positive for the endolysosomal marker, LAMP1, suggesting lysosome accumulation. Characterization of vesicles by special stains (Oil Red O, Nile Red, Luxol Fast Blue) and by electron microscopy showed they contained onion skin-like accumulations consistent with phospholipids. Moreover, cholesteryl esters and phosphatidylcholine-containing phospholipids were significantly increased in the kidneys of mice on a high-fat diet. AMPK activation with chronic AICAR treatment prevented the clinical and structural effects of high-fat diet. Thus, high-fat diet contributes to a dysfunction of the lysosomal system and altered lipid metabolism characterized by cholesterol and phospholipid accumulation in the kidney. AMPK activation normalizes the changes in renal lipid content despite chronic exposure to lipid challenge.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Rim/metabolismo , Metabolismo dos Lipídeos , Albuminúria/prevenção & controle , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Colesterol/metabolismo , Dieta Hiperlipídica , Resistência à Insulina , Rim/patologia , Camundongos Endogâmicos C57BL , Mitocôndrias/fisiologia , Obesidade/prevenção & controle , Ribonucleotídeos/farmacologia
17.
Am J Kidney Dis ; 64(5): 696-705, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24856872

RESUMO

BACKGROUND: The 2009 KDIGO (Kidney Disease: Improving Global Outcomes) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 (25[OH]D) levels<30ng/mL in patients treated with maintenance hemodialysis, but does not provide a specific treatment protocol. STUDY DESIGN: 2-center, double-blind, randomized, 13-week, controlled trial followed by a 26-week open-label study. SETTING & PARTICIPANTS: 55 adult maintenance hemodialysis patients with 25(OH)D levels<30ng/mL were recruited from June 2008 through October 2009. INTERVENTION: Cholecalciferol, 25,000IU, per week orally versus placebo for 13 weeks, then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. OUTCOMES: Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks. Secondary outcomes included the percentage of patients with normal calcium, phosphorus, and intact parathyroid hormone (iPTH) blood levels. Safety measures included incidence of hypercalcemia and hypervitaminosis D. MEASUREMENTS: Blood calcium and phosphate were measured weekly; iPTH, 25(OH)D, 1,25-dihydroxyvitamin D3 (1,25[OH]2D), and bone turnover markers, trimonthly; fetuin A and fibroblast growth factor 23 (FGF-23) serum levels and aortic calcification scores were determined at weeks 0 and 39. RESULTS: The primary end point significantly increased in the treatment group compared with the placebo group (61.5% vs 7.4%; P<0.001), as well as 1,25(OH)2D levels (22.5 [IQR, 15-26] vs 11 [IQR, 10-15]pg/mL; P<0.001) and the proportion of patients achieving the target calcium level (76.9% vs 48.2%; P=0.03). Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups. The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group. LIMITATIONS: Small size of the study population. CONCLUSIONS: Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective, safe, inexpensive, and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients. Further evaluation of clinical end points is suggested.


Assuntos
Colecalciferol/administração & dosagem , Colecalciferol/sangue , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Idoso , Método Duplo-Cego , Feminino , Fator de Crescimento de Fibroblastos 23 , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vitamina D/sangue
18.
Nephrol Dial Transplant ; 29(11): 2020-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24166461

RESUMO

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.


Assuntos
Nefropatia dos Bálcãs , Consenso , Gerenciamento Clínico , Programas de Rastreamento/métodos , Nefropatia dos Bálcãs/classificação , Nefropatia dos Bálcãs/diagnóstico , Nefropatia dos Bálcãs/terapia , Humanos
19.
J Appl Toxicol ; 34(12): 1311-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24155209

RESUMO

Renal proximal tubular epithelial cells are the main targets of toxic drugs such as cisplatin (CisPt), an alkylating agent indicated for the treatment of solid organ tumors. Current techniques aiming at reducing nephrotoxicity in patients receiving CisPt are still not satisfactory as they can only partially prevent acute kidney injury. New nephroprotective strategies remain to be developed. In the present in vitro study, schizandrin (Schi) and schizandrin B (Schi B), major phytochemicals from Schisandra chinensis (Turcz.) Baill. fruits, were tested on HK-2 cells along four processes that could help alleviate CisPt toxicity. Results indicated that: (i) both Schi and Schi B enhanced cell survival via reducing apoptosis rate; (ii) only Schi showed moderate effects towards modulation of regeneration capacities of healthy cells; (iii) both Schi and Schi B limited extracellular matrix deposition; and (iv) both compounds could help preventing dedifferentiation processes via the ß-catenin pathway. Schi and Schi B present promising activities for future development of protective agents against CisPt nephrotoxicity.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Ciclo-Octanos/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Lignanas/farmacologia , Compostos Policíclicos/farmacologia , Substâncias Protetoras/farmacologia , Técnicas de Cultura de Células , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colágeno/biossíntese , Ciclo-Octanos/isolamento & purificação , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Frutas/química , Humanos , Túbulos Renais Proximais/patologia , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Policíclicos/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Schisandra/química
20.
Ann Intern Med ; 158(6): 469-77, 2013 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-23552405

RESUMO

It has been 20 years since the first description of a rapidly progressive renal disease that is associated with the consumption of Chinese herbs containing aristolochic acid (AA) and is now termed aristolochic acid nephropathy (AAN). Recent data have shown that AA is also the primary causative agent in Balkan endemic nephropathy and associated urothelial cancer. Aristolochic acid nephropathy is associated with a high long-term risk for renal failure and urothelial cancer, and the potential worldwide population exposure is enormous. This evidence-based review of the diagnostic approach to and management of AAN draws on the authors' experience with the largest and longest-studied combined cohort of patients with this condition. It is hoped that a better understanding of the importance of this underrecognized and severe condition will improve epidemiologic, preventive, and therapeutic strategies to reduce the global burden of this disease.


Assuntos
Ácidos Aristolóquicos/efeitos adversos , Nefropatias/induzido quimicamente , Preparações de Plantas/efeitos adversos , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatia dos Bálcãs/diagnóstico , Nefropatia dos Bálcãs/epidemiologia , Nefropatia dos Bálcãs/terapia , Humanos , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Nefropatias/fisiopatologia , Nefropatias/terapia , Fatores de Risco , Neoplasias Urológicas/induzido quimicamente , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/fisiopatologia , Neoplasias Urológicas/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA