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1.
Clin Kidney J ; 14(5): 1364-1370, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34221369

RESUMO

BACKGROUND: Checkpoint inhibitors (CPIs) are used to treat solid organ metastatic malignancies. They act by triggering a vigorous immune response against tumoural cells, preventing their proliferation and metastasis. However, this is not a selective response and can cause immune-related adverse events (irAEs). The kidney can potentially be damaged, with an incidence of irAEs of 1-4%. The most frequent type of toxicity described is acute interstitial nephritis (AIN). METHODS: We conducted a study of patients with solid organ metastatic malignancies treated with immunotherapy who developed acute renal injury and underwent kidney biopsy in the last 14 months at the Vall d'Hebron University Hospital. RESULTS: In all, 826 solid organ malignancies were treated with immunotherapy in our centre, 125 of them (15.1%) developed acute kidney injury (AKI), 23 (18.4% of AKI) visited the nephrology department and 8 underwent kidney biopsy. The most frequent malignancy was lung cancer, in five patients (62%), followed by two patients (25%) with melanoma and one patient (12%) with pancreatic cancer. Four patients (50%) had already received previous oncological therapy, and for the remaining four patients (50%), CPI was the first-line therapy. Five patients (62%) were treated with anti-programmed cell death protein 1, three patients (37%) received anti-programmed death ligand 1 and two (25%) patients were treated in combination with anti-cytotoxic T-lymphocyte antigen 4. The time between the start of CPI and the onset of the AKI ranged from 2 to 11 months. The most frequent urine findings were subnephrotic-range proteinuria, with a mean protein:creatinine ratio of 544 mg/g (standard deviation 147) and eosinophiluria. All patients were biopsied after being diagnosed with AIN. Three patients (37%) received treatment with pulses of methylprednisolone 250-500 mg/day and five patients (62%) received prednisone 1 mg/kg/day. Seven patients (87%) experienced recovery of kidney function and one patient (12%) progressed to chronic kidney disease. CONCLUSIONS: We report on eight patients with CPI-related AIN diagnosed in the last 14 months at our centre. The novel immunotherapy treatment of metastatic solid organ malignancies carries a higher risk of irAEs. The kidney is one of the most commonly affected organs, frequently presenting as an AIN and exhibiting a favourable response to steroid treatment.

2.
Nefrologia (Engl Ed) ; 40(6): 634-639, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32660793

RESUMO

BACKGROUND AND OBJECTIVES: Transjugular renal biopsies (TRB) are an alternative when percutaneous ultrasound renal biopsy is contraindicated. Few sites are currently carrying out this procedure, with limited literature existing on the indications, complications and diagnostic yield thereof. The aim of the study is to analyse the indications, diagnostic yield, safety and complications of percutaneous transjugular renal biopsies in our site over the last 15 years. MATERIAL AND METHODS: Retrospective descriptive study of all transjugular renal biopsies performed in our site, the Hospital Vall d'Hebron, between 2003 and 2018. For this, an exhaustive review of the clinical records of patients subjected to this procedure during the study period was conducted. RESULTS: 56 TRBs were performed during the study period. Out of the patients, 31 were men (55.4%) and 25 were women (44.6%), with a median age of 62 years (IQ range 25-75 [52.5-69.5]). More than half presented with haematuria at the time of biopsy, with a median creatinine of 2.69 mg/dL (IQ 25-75 [1.7-4.3]) and median proteinuria at 24 hours of 2000 mg (IQ 25-75 [0.41-4.77]).The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 140 +/- 26 mmHg and 75 +/- 15 mmHg, respectively. The biopsy was carried out owing to acute kidney failure in 19 patients, chronic kidney disease in 12 patients and nephrotic syndrome in 10 patients; in 15 patients it was carried out for other reasons. The most frequent TRB indication was technical impossibility in 16 of 56 cases (including infracostal kidneys, obesity and COPD), alterations in haemostasis (n = 6), thrombocytopenia (n = 5) and solitary kidney (n = 7). 12.5% of the biopsies were hepato-renal. Histological diagnoses were obtained in two thirds of the renal biopsies. The average number of cylinders obtained was 2.5 ± 1.3, with the average number of glomeruli being 6.6 ± 6.2. The most frequent histological diagnoses were IgA nephropathy, membranoproliferative glomerulonephritis and thrombotic microangiopathy. Three major complications were observed: fornix rupture and two transfusion requirements due to bleeding and subcapsular hematoma. CONCLUSIONS: In our site, TRB allowed for a histological diagnosis in 2/3 of patients for whom percutaneous ultrasound renal biopsy is contraindicated. This allowed us to diagnose and subsequently treat said patients.


Assuntos
Biópsia Guiada por Imagem/métodos , Veias Jugulares , Nefropatias/patologia , Rim/patologia , Injúria Renal Aguda , Adulto , Idoso , Contraindicações de Procedimentos , Creatinina/sangue , Feminino , Hematúria/diagnóstico , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/estatística & dados numéricos , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Proteinúria/diagnóstico , Insuficiência Renal Crônica , Estudos Retrospectivos , Ultrassonografia de Intervenção
3.
Nefrologia ; 36(3): 310-2, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27061865

RESUMO

Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis.


Assuntos
Doença de Fabry/complicações , Doenças Renais Císticas/etiologia , Éxons/genética , Doença de Fabry/diagnóstico , Doença de Fabry/diagnóstico por imagem , Humanos , Doenças Renais Císticas/diagnóstico por imagem , Falência Renal Crônica/etiologia , Pelve Renal/patologia , Masculino , Pessoa de Meia-Idade , Deleção de Sequência , alfa-Galactosidase/genética
4.
J Clin Med ; 4(5): 998-1009, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-26239461

RESUMO

The majority of diabetic patients with renal involvement are not biopsied. Studies evaluating histological findings in renal biopsies performed in diabetic patients have shown that approximately one third of the cases will show pure diabetic nephropathy, one third a non-diabetic condition and another third will show diabetic nephropathy with a superimposed disease. Early diagnosis of treatable non-diabetic diseases in diabetic patients is important to ameliorate renal prognosis. The publication of the International Consensus Document for the classification of type 1 and type 2 diabetes has provided common criteria for the classification of diabetic nephropathy and its utility to stratify risk for renal failure has already been demonstrated in different retrospective studies. The availability of new drugs with the potential to modify the natural history of diabetic nephropathy has raised the question whether renal biopsies may allow a better design of clinical trials aimed to delay the progression of chronic kidney disease in diabetic patients.

5.
J Clin Hypertens (Greenwich) ; 17(12): 963-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26293391

RESUMO

The aim of the current study was to evaluate risk factors associated with hypertension in kidney transplant recipients. The authors recruited 92 consecutive kidney transplant recipients and 30 age-matched patients with chronic kidney disease without history of cardiovascular events. Twenty-four-hour ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound were performed. Serum levels of log-transformed interleukin 6 (Log IL-6), soluble tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were determined. Twenty-four-hour systolic blood pressure (SBP) (P=.0001), Log IL-6 (P=.011), and total number of carotid plaques (P=.013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=.003). Independent predictors of 24-hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=.001), while Log IL-6, serum creatinine, and total number of carotid plaques (P=.0001) were independent predictors of percentage decline of SBP from day to night. These results suggest that subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation.


Assuntos
Aterosclerose/patologia , Hipertensão/patologia , Inflamação/patologia , Transplante de Rim , Adulto , Aterosclerose/sangue , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/sangue , Inflamação/sangue , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso/métodos , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Insuficiência Renal Crônica/cirurgia , Fatores de Risco
6.
Mol Nutr Food Res ; 58(6): 1374-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24668839

RESUMO

Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hibiscus/química , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Humanos , Síndrome Metabólica/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Polifenóis/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
7.
BMC Res Notes ; 6: 306, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23915518

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are renoprotective but both may increase serum potassium concentrations in patients with chronic kidney disease (CKD). The proportion of affected patients, the optimum follow-up period and whether there are differences between drugs in the development of this complication remain to be ascertained. METHODS: In a randomized, double-blind, phase IV, controlled, crossover study we recruited 30 patients with stage 3 CKD under restrictive eligibility criteria and strict dietary control. With the exception of withdrawals, each patient was treated with olmesartan and enalapril separately for 3 months each, with a 1-week wash-out period between treatments. Patients were clinically assessed on 10 occasions via measurements of serum and urine samples. We used the Cochran-Mantel-Haenszel statistics for comparison of categorical data between groups. Comparisons were also made using independent two-sample t-tests and Welch's t-test. Analysis of variance (ANOVA) was performed when necessary. We used either a Mann-Whitney or Kruskal-Wallis test if the distribution was not normal or the variance not homogeneous. RESULTS: Enalapril and olmesartan increased serum potassium levels similarly (0.3 mmol/L and 0.24 mmol/L respectively). The percentage of patients presenting hyperkalemia higher than 5 mmol/L did not differ between treatments: 37% for olmesartan and 40% for enalapril. The mean e-GFR ranged 46.3 to 48.59 ml/mint/1.73 m2 in those treated with olmesartan and 46.8 to 48.3 ml/mint/1.73 m2 in those with enalapril and remained unchanged at the end of the study. The decreases in microalbuminuria were also similar (23% in olmesartan and 29% in enalapril patients) in the 4 weeks time point. The percentage of patients presenting hyperkalemia, even after a two month period, did not differ between treatments. There were no appreciable changes in sodium and potassium urinary excretion. CONCLUSIONS: Disturbances in potassium balance upon treatment with either olmesartan or enalapril are frequent and without differences between groups. The follow-up of these patients should include control of potassium levels, at least after the first week and the first and second month after initiating treatment. TRIAL REGISTRATION: The trial EudraCT "2008-002191-98".


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hiperpotassemia/etiologia , Falência Renal Crônica/complicações , Idoso , Método Duplo-Cego , Feminino , Humanos , Falência Renal Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
8.
Biochim Biophys Acta ; 1820(7): 894-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22503922

RESUMO

BACKGROUND: MicroRNAs have the potential for clinical application. Probable modulation by plant-derived polyphenols might open preventive measures using simple dietary recommendations. METHODS: We assessed the ability of continuous administration of high-dose polyphenols to modulate hepatic metabolism and microRNA expression in diet-induced fatty liver disease in commercially available hyperlipidemic mice using well-established and accepted procedures that included the development of new antibodies against modified quercetin. RESULTS: Weight gain, liver steatosis, changes in the composition of liver tissue, and insulin resistance were all attenuated by the continuous administration of polyphenols. We also demonstrated that metabolites of polyphenols accumulate in immune cells and at the surface of hepatic lipid droplets indicating not only bioavailability but a direct likely action on liver cells. The addition of polyphenols also resulted in changes in the expression of miR-103, miR-107 and miR-122. CONCLUSIONS: Polyphenols prevent fatty liver disease under these conditions. The differential expression of mRNAs and miRNAs was also associated with changes in lipid and glucose metabolism and with the activation of 5'-adenosine monophosphate-activated protein kinase, effects that are not necessarily connected. miRNAs function via different mechanisms and miRNA-mRNA interactions are difficult to ascertain with current knowledge. Further, cell models usually elicit contradictory results with those obtained in animal models. GENERAL SIGNIFICANCE: Our data indicate that plant-derived polyphenols should be tested in humans as preventive rather than therapeutic agents in the regulation of hepatic fatty acid utilization. A multi-faceted mechanism of action is likely and the regulation of liver miRNA expression blaze new trails in further research.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/prevenção & controle , Hibiscus/química , Hiperlipidemias/fisiopatologia , MicroRNAs/genética , Polifenóis/uso terapêutico , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting , Fígado Gorduroso/etiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Aumento de Peso
9.
J Clin Hypertens (Greenwich) ; 7(1): 11-5; quiz 16-7, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15655381

RESUMO

The angiotensin-converting enzyme (ACE) gene has been implicated in the manifestation of the phenotype of malignant hypertension (MH). In 1990 the ACE gene polymorphism characterized by the insertion or deletion of a 287-base pair fragment in the 17q23 chromosome was identified. The DD genotype is associated with increased tissue and circulating ACE levels and elevated angiotensin II. ACE polymorphism was studied in 48 patients with MH, 25 patients with non-MH, and a control group of 78 normotensive individuals by real-time polymerase chain reaction using the LightCycler system (Roche Diagnostics Corporation, Indianapolis, IN). The DD genotype was found statistically more frequently in MH patients than controls (p=0.028; odds ratio, 2.5; confidence interval, 1.1-5.5). Presence of the DD genotype of the ACE gene is more frequent in MH patients than in controls, indicating that this genotype could be a significant risk factor and a predictor for the development of MH.


Assuntos
Cromossomos Humanos Par 17 , Hipertensão Maligna/genética , Peptidil Dipeptidase A/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão Maligna/enzimologia , Masculino , Mutagênese Insercional/genética , Polimorfismo Genético , Estudos Retrospectivos , Fatores de Risco , Deleção de Sequência
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