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1.
J Am Soc Nephrol ; 33(9): 1767-1777, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35853713

RESUMO

BACKGROUND: Despite reports of hematuria and proteinuria with rosuvastatin use at the time of its approval by the US Food and Drug Association (FDA), little postmarketing surveillance exists to assess real-world risk. Current labeling suggests dose reduction (maximum daily dose of 10 mg) for patients with severe CKD. METHODS: Using deidentified electronic health record data, we analyzed 152,101 and 795,799 new users of rosuvastatin and atorvastatin, respectively, from 2011 to 2019. We estimated inverse probability of treatment-weighted hazard ratios (HRs) of hematuria, proteinuria, and kidney failure with replacement therapy (KFRT) associated with rosuvastatin. We reported the initial rosuvastatin dose across eGFR categories and evaluated for a dose effect on hematuria and proteinuria. RESULTS: Overall, we identified 2.9% of patients with hematuria and 1.0% with proteinuria during a median follow-up of 3.1 years. Compared with atorvastatin, rosuvastatin was associated with increased risk of hematuria (HR, 1.08; 95% confidence interval [95% CI], 1.04 to 1.11), proteinuria (HR, 1.17; 95% CI, 1.10 to 1.25), and KFRT (HR, 1.15; 95% CI, 1.02 to 1.30). A substantial share (44%) of patients with eGFR <30 ml/min per 1.73 m2 was prescribed high-dose rosuvastatin (20 or 40 mg daily). Risk was higher with higher rosuvastatin dose. CONCLUSIONS: Compared with atorvastatin, rosuvastatin was associated with increased risk of hematuria, proteinuria, and KFRT. Among patients with eGFR <30 ml/min per 1.73 m2, 44% were prescribed a rosuvastatin daily dose exceeding the FDA's recommended 10 mg daily dose. Our findings suggest the need for greater care in prescribing and monitoring rosuvastatin, particularly in patients who receive high doses or who have severe CKD.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Insuficiência Renal Crônica , Humanos , Rosuvastatina Cálcica/efeitos adversos , Atorvastatina/uso terapêutico , Hematúria/induzido quimicamente , Hematúria/epidemiologia , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos
2.
Nord J Psychiatry ; 77(1): 31-35, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35243962

RESUMO

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are used as first-line treatment for many psychiatric diseases, especially major depressive disorder. However, an important side effect of these drugs is the risk of bleeding due to platelet dysfunction. The aim of this study was to determine the frequency of hematuria in patients using SSRI/SNRIs and to compare with a control group. METHODS: This study included patients who were followed up and treated with SSRI/SNRI in the psychiatric outpatient clinic of the Antalya Medical Park Hospital between 1 January 2021 and 31 March 2021 and a control group comprising patients who presented to the medical check-up outpatient clinic between the same dates. Complete urinalysis was performed for all patients and the results were compared between the groups. RESULTS: Each group included 100 patients with a female/male ratio of 1. The mean age was 41.45 ± 13.47 (16-74) years in the study group and 40.51 ± 13.75 (20-70) years in the control group (p = 0.519). Mean duration of SSRI/SNRI use in the study group was 13.35 ± 1.32 (1-64) months. The prevalence of hematuria was 17% in the SSRI/SNRI group and 6% in the control group (p = 0.015). All cases of hematuria were microscopic hematuria. CONCLUSION: Hematuria is significantly more common in patients receiving SSRI/SNRI treatment. The use of SSRI/SNRI should also be taken into account when investigating the etiology of hematuria.


Assuntos
Transtorno Depressivo Maior , Inibidores da Recaptação de Serotonina e Norepinefrina , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Serotonina , Transtorno Depressivo Maior/tratamento farmacológico , Norepinefrina/uso terapêutico , Hematúria/induzido quimicamente , Hematúria/epidemiologia
3.
Eur J Haematol ; 108(6): 510-517, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35266205

RESUMO

OBJECTIVES: To conduct a systematic review of tranexamic acid (TXA) and the risk of renal failure from urinary clots in adult patients with hematuria. METHODS: A systematic review of Medline, Embase, CENTRAL, www. CLINICALTRIALS: gov, and Google Scholar were searched. Randomized control trials (RCTs) and observational studies that assessed the risk of renal failure with use of TXA among adults with hematuria were included. The primary outcome was renal failure due to urinary tract clots with TXA compared to no TXA (or placebo) or comparator. RESULTS: We identified three RCTs (N = 466 patients) and three retrospective cohort studies (N=220 patients), and a total of 342 patients that had hematuria and received TXA. The patient population of the six studies included medical and surgical patients, with two of the three RCTs comprised patients undergoing percutaneous nephrolithotomy, and the third RCT comprised patients undergoing transurethral resection of the prostate. Documentation of renal function before and after TXA administration was documented in only two studies (N = 28 patients), and neither identified worsening renal function in those exposed to TXA. CONCLUSIONS: There are limited studies evaluating the risk of renal failure in patients with hematuria who were exposed to TXA, and the available data does not suggest an increased risk.


Assuntos
Injúria Renal Aguda , Antifibrinolíticos , Ácido Tranexâmico , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Adulto , Antifibrinolíticos/efeitos adversos , Feminino , Hematúria/induzido quimicamente , Hematúria/etiologia , Humanos , Masculino , Ácido Tranexâmico/efeitos adversos
4.
Hinyokika Kiyo ; 68(1): 7-9, 2022 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-35114760

RESUMO

A 76-year-old male patient developed right hydronephrosis due to peritoneal and retroperitoneal dissemination after surgery for gastric cancer. A ureteral stent was inserted, and systemic chemotherapy was introduced for metastatic gastric cancer. Disease progression was observed, and paclitaxel/ramucirumab combination therapy was started as the second-line treatment. After seven courses, severe gross hematuria appeared intermittently, and refractory epistaxis was observed concurrently. No hemorrhagic lesion was found in the imaging test and urethrocystoscopy. The patient received conservative treatment, such as blood transfusion, and further examination was planned. However, hematuria and epistaxis resolved spontaneously during the course of treatment. From the clinical course, it was thought to be a hemorrhagic adverse event due to ramucirumab, and the patient's treatment was therefore changed to another drug. The patient recovered without recurrence of gross hematuria.


Assuntos
Neoplasias Gástricas , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hematúria/induzido quimicamente , Humanos , Masculino , Paclitaxel/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Ramucirumab
5.
N Engl J Med ; 379(13): 1216-1223, 2018 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-30280655

RESUMO

BACKGROUND: In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant. METHODS: We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid-associated coagulopathy. A confirmatory anticoagulant poisoning panel was ordered at the discretion of the treating physician. RESULTS: A total of 34 patients were identified as having synthetic cannabinoid-associated coagulopathy during 45 hospitalizations. Confirmatory anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin poisoning was confirmed in the 15 patients tested. Anticoagulant tests were positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%), bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%). Computed tomography was performed to evaluate abdominal pain and revealed renal abnormalities in 12 patients. Vitamin K1 (phytonadione) was administered orally in all 34 patients and was also administered intravenously in 23 (68%). Red-cell transfusion was performed in 5 patients (15%), and fresh-frozen plasma infusion in 19 (56%). Four-factor prothrombin complex concentrate was used in 1 patient. One patient died from complications of spontaneous intracranial hemorrhage. CONCLUSIONS: Our data indicate that superwarfarin adulterants of synthetic cannabinoids can lead to clinically significant coagulopathy. In our series, in most of the cases in which the patient presented with bleeding diathesis, symptoms were controlled with the use of vitamin K1 replacement therapy. The specific synthetic cannabinoid compounds are not known.


Assuntos
Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/epidemiologia , Canabinoides/efeitos adversos , Vitamina K/uso terapêutico , 4-Hidroxicumarinas/efeitos adversos , 4-Hidroxicumarinas/análise , Dor Abdominal/induzido quimicamente , Adulto , Transtornos da Coagulação Sanguínea/induzido quimicamente , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue , Canabinoides/síntese química , Canabinoides/química , Feminino , Hematúria/induzido quimicamente , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Illinois/epidemiologia , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Varfarina/efeitos adversos , Varfarina/análise
6.
J Stroke Cerebrovasc Dis ; 30(6): 105767, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33823462

RESUMO

OBJECTIVES: Ticagrelor may be superior to aspirin after minor ischemic stroke or TIA, particularly in patients with symptomatic atherosclerotic disease. However, there may be an increased risk of intracerebral hemorrhage in patients with moderate to severe ischemic stroke, and ticagrelor has not been studied in this patient population. Therefore, we sought to evaluate the safety of ticagrelor after moderate or severe ischemic stroke. MATERIALS AND METHODS: Retrospective chart review of all patients admitted with acute ischemic stroke and NIHSS 6 or greater who were discharged on ticagrelor between January 2016 and December 2019. Patients who underwent angioplasty, stenting or carotid revascularization during the hospitalization were excluded. RESULTS: Of 183 patients discharged on ticagrelor, 61 patients were included. Median age was 61 (IQR 52-68); 33 (54%) patients were men. Median NIHSS was 11 (IQR 8-15). Fourteen (23%) patients received IV alteplase and 35 (57%) patients received mechanical thrombectomy. Stroke mechanism was large artery atherosclerosis in 53 (87%) of patients, of which 40 (71%) were deemed intracranial atherosclerosis. Final infarct volume was greater than 10 mL in 32 (52%) patients. Follow-up information was available for 53 (87%) patients; median length of follow-up was 3 (IQR 2-6) months. Six (10%) patients experienced recurrent ischemic stroke. No patients experienced symptomatic intracerebral hemorrhage after initiation of ticagrelor. One (2%) patient experienced major bleeding. CONCLUSIONS: This study provides preliminary evidence supporting the potential safety of ticagrelor following moderate or severe acute ischemic stroke. These findings support the need for future prospective studies.


Assuntos
AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Hemorragia Cerebral/induzido quimicamente , Epistaxe/induzido quimicamente , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hematúria/induzido quimicamente , Humanos , AVC Isquêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Ticagrelor/efeitos adversos , Resultado do Tratamento
7.
Ann Hematol ; 99(4): 839-845, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32025839

RESUMO

Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.


Assuntos
Abatacepte/uso terapêutico , Vírus BK/isolamento & purificação , Ciclofosfamida/efeitos adversos , Cistite/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Hematúria/prevenção & controle , Imunossupressores/efeitos adversos , Mesna/uso terapêutico , Infecções por Polyomavirus/urina , Transplante Haploidêntico , Infecções Tumorais por Vírus/urina , Abatacepte/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Cistite/induzido quimicamente , Cistite/urina , Cistite/virologia , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Hematúria/induzido quimicamente , Hematúria/virologia , Humanos , Imunossupressores/administração & dosagem , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Mesna/administração & dosagem , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/virologia , Urina/virologia , Adulto Jovem
8.
Ther Drug Monit ; 42(4): 548-553, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32079909

RESUMO

BACKGROUND: The alkylating agent cyclophosphamide is used in chemotherapy regimens for various type of cancer. However, cyclophosphamide may lead to toxic side effects on the bladder, namely hemorrhagic cystitis, which can cause hematuria, and, potentially, bladder cancer. These effects are caused by acrolein, a byproduct of cyclophosphamide metabolism. In this study, a method to quantify 3-hydroxypropyl mercapturic acid (3-HPMA) in urine was developed. 3-HPMA is a stable metabolite of acrolein that serves as biomarker of acrolein. METHODS: Urine samples were collected 4 hours after cyclophosphamide administration and analyzed to determine the risk of hematuria. 3-HPMA was analyzed by reverse-phase LC-MS/MS using a triple quadrupole electrospray ionization mass spectrometer in the positive-ion mode. The mobile phase was a 90:10 (vol/vol) mixture of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Multiple reaction monitoring mode was used, with m/z 222.10 → 90.97 for 3-HPMA and 164.10 → 122.02 for the internal standard N-acetyl cysteine (NAC). Samples were prepared by acidification and dilution. RESULTS: The analytical method produced a linear response within the concentration range of 40-10,000 ng/mL. The method was validated in accordance with 2018 FDA guidelines and applied to quantify 3-HPMA in the urine of 40 patients with breast cancer. The measured concentrations ranged from 820.3 to 5596.1 ng/mg creatinine. Seven patients identified with hematuria had low 3-HPMA concentrations of 4445.824 ± 411.17 ng/mg creatinine, and 33 patients without hematuria had low 3-HPMA concentrations of 2419.4 ± 1171.8 ng/mg creatinine. CONCLUSIONS: The method was applicable for the quantification of 3-HPMA in human urine. Large variations in 3-HPMA concentrations were found in 40 patients with breast cancer treated with cyclophosphamide, with a significant difference (P < 0.05) observed between patients with hematuria and those without hematuria.


Assuntos
Acetilcisteína/análogos & derivados , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/urina , Ciclofosfamida/toxicidade , Ciclofosfamida/uso terapêutico , Acetilcisteína/urina , Acroleína/metabolismo , Adulto , Alquilantes/metabolismo , Alquilantes/uso terapêutico , Alquilantes/toxicidade , Biomarcadores/urina , Cromatografia Líquida/métodos , Ciclofosfamida/metabolismo , Feminino , Hematúria/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
9.
Clin Nephrol ; 93(6): 283-293, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32301698

RESUMO

BACKGROUND: There is no systematic or large-scale study in the published literature in which the relationship between drug therapies and renal involvement in ankylosing spondylitis (AS) has been rigorously evaluated. In addition, the sensitivity of the kidneys to drugs varies significantly between races and regional populations. Therefore, the aim of the present study was to investigate the impact of drugs on renal involvement in Chinese AS patients. MATERIALS AND METHODS: The clinical characteristics and biochemical data of 907 AS patients were collected and analyzed, and the differences between patients who had received drugs and those who had not were analyzed using intergroup comparisons to screen out confounding factors. Multivariate logistic regression analysis that corrected for the confounding factors explored the impact of the AS therapeutic drugs on the clinical manifestations of renal involvement. RESULTS: Renal involvement in Chinese AS patients increased significantly following non-steroidal anti-inflammatory drug (NSAID) or conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy, and combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor. For AS patients, NSAID monotherapy increased the probability of hematuria 2.4-fold and the probability of mixed manifestations of renal involvement 3.0-fold. csDMARD monotherapy increased the probability of proteinuria 2.4-fold; combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor increased the probability of hematuria 4.1-fold. In addition, the study found that TNF-α inhibitor monotherapy and combination therapy with NSAIDs or csDMARDs caused no apparent impact on renal involvement in AS patients. CONCLUSION: NSAID or csDMARD monotherapy may significantly increase renal involvement in Chinese AS patients. Combination therapy with TNF-α inhibitor with NSAIDs and csDMARDs should be used prudently.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antirreumáticos/efeitos adversos , Rim/efeitos dos fármacos , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Feminino , Hematúria/induzido quimicamente , Humanos , Modelos Logísticos , Masculino
10.
J Thromb Thrombolysis ; 49(4): 533-539, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32077008

RESUMO

The aim of the study was to compare nationwide time trends of prescribed oral anticoagulants (OAC) with the time trend of genitourinary bleedings (GUB) in Germany from 2005 through 2016. The annual numbers of hospitalized patients with GUB coded as "hematuria", "excessive, frequent and irregular menstruation", "postmenopausal bleeding" or "abnormal uterine and vaginal bleeding" were extracted from the nationwide hospitalization file by the Federal Bureau of Statistics. Hospitalization rates were age-standardized using the German standard population 2011. Defined daily doses (DDD) of prescribed anticoagulants among outpatients for the same calendar period were extracted from reports of the statutory health insurance drug information system. Based on DDD, drug treatment rates per 100,000 person years (py) were calculated. From 2005 to 2016, annual OAC treatment rates per 100,000 py increased by 135.8% (from 901.4 to 2125.9). Until 2011 direct oral anticoagulants (DOAC) represented less than 0.1% of all OAC, but 49.9% in 2016. In the same period age-standardized rates of hospitalizations for hematuria increased continuously (annual change of 1.03 (95% CI 0.94-1.11) per 100,000 py), that of "postmenopausal" (- 1.93; 95% CI - 2.38 to - 1.49) or "excessive, frequent and irregular menstruation" decreased (- 1.25; 95% CI -1.62 to - 0.87) and that of "abnormal uterine and vaginal haemorrhage" remained almost unchanged. From all cases with hematuria 5.3% received at least 1 red blood cell concentrate (RBC) in 2005 and 8.2% in 2016 whereas all cases with the other three types of bleeding counted for 1.9% in 2005 and 3.8% in 2016. The time trends for GUB in all subgroups changed steadily and showed no effect of the disproportional increase of DAOCs until 2011. Our ecologic nationwide comparison of OAC treatment rates in outpatients and hospitalization rates for GUBs revealed that despite increasing OAC treatment rates from 2011 to 2016 the hospitalization rates for GUB showed steady annual changes unaffected by the increasing prescription rates of DOACs since 2011.


Assuntos
Anticoagulantes/efeitos adversos , Prescrições de Medicamentos/estatística & dados numéricos , Hematúria/epidemiologia , Hemorragia Uterina/epidemiologia , Feminino , Alemanha/epidemiologia , Hematúria/induzido quimicamente , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Hemorragia Uterina/induzido quimicamente
11.
Clin Nephrol ; 91(3): 180-186, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30614440

RESUMO

AIMS: To investigate the clinicopathological features and outcomes of adefovir dipivoxil (ADV)-related renal impairment in Chinese patients. MATERIALS AND METHODS: Clinical, pathological, and follow-up data from 15 patients with ADV-related renal impairment were studied. Proximal renal tubular dysfunction (PRTD) was defined by the presence of at least two of the following four abnormalities: hypophosphatemia, hypouricemia, nondiabetic glucosuria, and proteinuria. RESULTS: All patients were treated for 3 - 15 (mean 6.7) years with daily ADV of 10 mg. Renal impairment manifested as PRTD (12, 80%), elevated serum creatinine (12, 80%), and hematuria (2, 13.3%). Mild to moderate tubulointerstitial injury primarily affecting the proximal tubules by light microscopy, and enlarged, dysmorphic mitochondria with loss and disorientation of cristae by electron microscope were identified in all of our cases. Four patients had pathological evidence of IgA nephropathy. The phosphorus, serum uric acid, and creatinine levels were normalized after ADV cessation in 66.7% (8/12) of affected patients, 27.3% (3/11) of affected patients, and 25% (3/12) of affected patients, respectively; proteinuria was eliminated in 7 of 13 affected patients (53.8%); and glucosuria and hematuria both disappeared in all affected patients. These abnormalities had hardly any recovery, and even aggravated with new-onset glucosuria, new-onset hematuria in 3 patients who replaced ADV with tenofovir. CONCLUSION: Nephrotoxicity developed in patients undergoing long-term ADV treatment and was partially reversible after drug cessation. Tubulointerstitial lesions and heteromorphic mitochondria were the predominant pathological changes. Patients with ADV-induced renal impairment should replace ADV with other antiviral agents other than tenofovir.
.


Assuntos
Adenina/análogos & derivados , Antivirais/efeitos adversos , Organofosfonatos/efeitos adversos , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/patologia , Adenina/efeitos adversos , Adulto , Creatinina/sangue , Feminino , Glicosúria/induzido quimicamente , Hematúria/induzido quimicamente , Hepatite B Crônica/tratamento farmacológico , Humanos , Hipofosfatemia/induzido quimicamente , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/patologia , Fósforo/sangue , Proteinúria/induzido quimicamente , Insuficiência Renal/fisiopatologia , Ácido Úrico/sangue
12.
Am J Physiol Renal Physiol ; 315(3): F618-F627, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29993279

RESUMO

Although activation of mouse natural killer T (NKT) cells by α-galactosylceramide (α-GalCer) causes failure of multiple organs, including the kidneys, the precise mechanisms underlying kidney injury remain unclear. Here, we showed that α-GalCer-activated mouse NKT cells injured both kidney vascular endothelial cells and tubular epithelial cells in vitro, causing acute kidney injury (AKI) with hematuria in middle-aged mice. The perforin-mediated pathway was mainly involved in glomerular endothelial cell injury, whereas the TNF-α/Fas ligand pathway played an important role in the injury of tubular epithelial cells. Kidney injury in young mice was mild but could be significantly exacerbated if NKT cells were strongly activated by NK cell depletion alone or in combination with IL-12 pretreatment. When stimulated by a combination of IL-2 and IL-12, human CD56+ T cells, a functional counterpart of mouse NKT cells, also damaged both glomerular endothelial cells and tubular epithelial cells, with the former being affected in a perforin-dependent manner. These data suggest that both mouse NKT cells and human CD56+ T cells are integral to the processes that mediate AKI. Targeting CD56+ T cells may, therefore, be a promising approach to treat AKI.


Assuntos
Injúria Renal Aguda/imunologia , Antígeno CD56/imunologia , Citotoxicidade Imunológica , Hematúria/imunologia , Túbulos Renais Proximais/imunologia , Ativação Linfocitária , Células T Matadoras Naturais/imunologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Fatores Etários , Animais , Antígeno CD56/metabolismo , Linhagem Celular , Técnicas de Cocultura , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Proteína Ligante Fas/metabolismo , Feminino , Galactosilceramidas , Hematúria/induzido quimicamente , Hematúria/metabolismo , Humanos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/metabolismo , Fenótipo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Fatores Sexuais , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
13.
BJU Int ; 121(2): 203-208, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28370882

RESUMO

OBJECTIVES: To evaluate the safety and efficacy of a 2-weekly cabazitaxel schedule in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: During the period October 2013 to February 2016, 43 patients with mCRPC were treated with cabazitaxel (16 mg/m2 , on days 1 and 15 of a 4-week cycle) together with prophylactic granulocyte colony-stimulating factor (G-CSF). The safety profile and efficacy (prostate-specific antigen [PSA] response; biological, clinical or radiological progression-free survival [PFS] and overall survival [OS]) of the treatment were analysed. RESULTS: All patients had received prior docetaxel and 79.1% abiraterone acetate. At inclusion, 46.5% were aged >70 years and 27.9% had an Eastern Cooperative Oncology Group performance status ≥2. Six patients stopped treatment because of toxicity. Grade ≥3 toxicities were: asthenia (16.3%); neutropenia (11.6%); thrombocytopenia (9.3%); diarrhoea (7%), anaemia (4.7%), febrile neutropenia (4.7%) and haematuria (2.3%). In all, 52.4% achieved a ≥30% PSA response and 40.5% had a ≥50% PSA response. The median OS was 15.2 months. CONCLUSION: This prospective pilot study suggests that cabazitaxel 16 mg/m² given 2-weekly has a manageable toxicity profile in docetaxel- and abiraterone acetate-pretreated patients with mCRPC. A prospective phase III trial comparing this regimen with the standard cabazitaxel regimen is planned to confirm these results.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/efeitos adversos , Idoso , Anemia/induzido quimicamente , Antineoplásicos/administração & dosagem , Astenia/induzido quimicamente , Neutropenia Febril Induzida por Quimioterapia/etiologia , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Esquema de Medicação , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hematúria/induzido quimicamente , Humanos , Masculino , Metástase Neoplásica , Projetos Piloto , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem , Trombocitopenia/induzido quimicamente
14.
Pediatr Transplant ; 22(4): e13171, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29569791

RESUMO

Late-onset HC is a well-recognized complication associated with cyclophosphamide/acrolein-induced toxicity. It poses a management challenge when hyperhydration and bladder irrigation do not result in clinical improvement as desired. The data regarding use of hyperbaric oxygen therapy (HBO2) as an early treatment modality in this clinical setting are limited. We present 2 cases, that were refractory to hyperhydration and bladder irrigation but responded to HBO2. They were treated with 20-30 daily sessions over weekdays with 100% oxygen for 90 minutes at 2 atmospheric pressure units (2 atm). Both patients reported improved symptoms within the first 15 sessions, and hematuria diminished by 20 sessions. Hyperbaric oxygen is a less invasive, outpatient therapy that is effective for treatment of HC and is tolerated well by young patients.


Assuntos
Ciclofosfamida/efeitos adversos , Cistite/terapia , Hematúria/terapia , Oxigenoterapia Hiperbárica , Imunossupressores/efeitos adversos , Adolescente , Adulto , Cistite/induzido quimicamente , Feminino , Hematúria/induzido quimicamente , Humanos , Masculino
18.
JAMA ; 318(13): 1260-1271, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28973248

RESUMO

Importance: Antithrombotic medications are among the most commonly prescribed medications. Objective: To characterize rates of hematuria-related complications among patients taking antithrombotic medications. Design, Setting, and Participants: Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014. Exposures: Receipt of an oral anticoagulant or antiplatelet medication. Main Outcomes and Measures: Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria. Results: Among 2 518 064 patients, 808 897 (mean [SD] age, 72.1 [6.8] years; 428 531 [53%] women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio [IRR], 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and 110.72 (difference, 26.5; 95% CI, 25.9-27.0) for those exposed to antiplatelet agents (IRR, 1.31; 95% CI, 1.29-1.33). Patients exposed to antithrombotic agents, compared with patients not exposed to these drugs, were more likely to be diagnosed as having bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85; 95% CI, 1.79-1.92). Conclusions and Relevance: Among older adults in Ontario, Canada, use of antithrombotic medications, compared with nonuse of these medications, was significantly associated with higher rates of hematuria-related complications (including emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria).


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hematúria/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Técnicas de Diagnóstico Urológico , Feminino , Hematúria/terapia , Hospitalização , Humanos , Masculino , Ontário , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/diagnóstico
19.
Cutan Ocul Toxicol ; 36(1): 74-76, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26938860

RESUMO

BACKGROUND: Systemic isotretinoin (13-cis-retinoic acid) is effective in the treatment of acne vulgaris. The most common side effects are mucocutaneous ones. Hematuria seen secondary to isotretinoin treatment is thought to be due to mucosal dryness in the urinary system. This study aims to determine the frequency of hematuria in acne vulgaris patients during isotretinoin treatment. MATERIALS AND METHOD: Eighty-eight subjects aged 16-32 years were included in the study group and 52 subjects were in the control group. The subjects were treated for 6 months and were monitored monthly by complete urine analyzes. They were also examined each month in terms of cheilitis, xerosis, epistaxis, rectal bleeding, fatigue, myalgia, weight loss, dry eye, conjunctivitis, headache, dysuria and pollakiuria. RESULTS: In the study group, 15 subjects (17%) had hematuria at least once during the study, and in the control group, four subjects (7.7%) had hematuria. The difference was not statistically significant (p = 0.118). Among the subjects who had hematuria, 11 of them (73.3%) were female and four of them (33.3%) were male in the study group while all the subjects with hematuria in the control group were female. Hematuria and gender did not show a statistically significant correlation. CONCLUSION: Hematuria was observed in 17% of the study group; this frequency rate was not different from that of the normal population. In subjects having isotretinoin treatment, if all the other reasons or disorders are excluded, one must keep in mind that hematuria may be due to isotretinoin use.


Assuntos
Acne Vulgar/tratamento farmacológico , Fármacos Dermatológicos/efeitos adversos , Hematúria/induzido quimicamente , Isotretinoína/efeitos adversos , Acne Vulgar/urina , Adolescente , Adulto , Fármacos Dermatológicos/uso terapêutico , Feminino , Hematúria/urina , Humanos , Isotretinoína/uso terapêutico , Masculino , Adulto Jovem
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