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2.
BMC Cardiovasc Disord ; 21(1): 508, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674646

RESUMO

BACKGROUND: Catheter ablation is an established therapy for atrial fibrillation (AF), but recurrence after ablation remains a great challenge. Additionally, little is known about the effect of renal function on the efficiency of AF ablation. This study aimed to evaluate the predictors of the prognosis of catheter ablation for AF, especially the effect of renal function. METHODS: A total of 306 drug-refractory symptomatic patients with AF who underwent first-time catheter ablation were enrolled in the present study. Individuals underwent circumferential pulmonary vein isolation for paroxysmal AF and stepwise ablation for persistent AF. RESULTS: The follow-up time was 27.2 ± 19.5 months, 202 patients (66.01%) were free of atrial tachyarrhythmia (non-recurrence group), and the other 104 patients experienced recurrence (recurrence group). The recurrence group had a larger left atrial diameter (LAD) and left atrial volume (LAV), a higher LAV index (LAVI) (both, p < 0.01), and a lower estimated glomerular filtration rate (eGFR) (53.5 ± 14.4 vs. 65.5 ± 13.3 ml/min/1.732, p < 0.001) and creatinine clearance rate (CCr) (85.2 ± 26.1 vs. 101.5 ± 29.4 ml/min, p < 0.05). Multivariate logistic regression indicated both eGFR (p = 0.002) and LAVI (p < 0.001) as independent associated factors for long-term recurrence after single catheter ablation; multivariate Cox proportional hazard regression with backward feature selection identified both eGFR (HR: 0.93, 95% CI: 0.91-0.95, p < 0.001) and LAVI (HR: 1.32, 95% CI: 1.25-1.40, p < 0.001) as independent prognostic factors for recurrence when adjusting other clinical variables. CONCLUSIONS: Decreased eGFR and elevated LAVI may facilitate the long-term recurrence of atrial tachyarrhythmia after catheter ablation for AF.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Taxa de Filtração Glomerular , Átrios do Coração/anatomia & histologia , Insuficiência Renal/fisiopatologia , Adulto , Idoso , Fibrilação Atrial/complicações , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Recidiva , Insuficiência Renal/complicações , Estudos Retrospectivos , Fatores de Risco
3.
Med Sci Monit ; 27: e932096, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383727

RESUMO

BACKGROUND The thyroid state significantly influences renal function. However, a direct link between thyroid and kidney dysfunction has not been identified. Thyroid hormones affect cardiac output and vascular resistance, and thus can modify kidney perfusion. This prospective study aimed to test the association between renal cortical perfusion (RCP) estimated in color Doppler sonographic dynamic tissue perfusion measurement (DTPM) with thyroid hormones in 36 patients treated with levothyroxine following total thyroidectomy for resectable thyroid cancer. MATERIAL AND METHODS Blood tests, blood pressure monitoring, and DTPM of the renal cortex were performed. To exclude possible reading errors, the intrarater reliability of the ultrasound perfusion measurement method was estimated. RESULTS The absolute difference between the 2 ultrasound RCP measurements was 5.2±4.4%. RCP correlated significantly with free thyroxine (FT4) (r=0.46; p=0.006) but not with triiodothyronine and thyroid-stimulating hormone. In the adjusted to age backward stepwise multivariable regression analysis model, including estimated glomerular filtration rate, mean arterial pressure, and FT4, only FT4 was independently associated with RCP (R²=0.21; p=0.006). CONCLUSIONS Renal cortical perfusion is independently associated with free thyroxine, which can contribute to renal function abnormalities in the condition of impaired thyroid function. This small prospective study from a single center showed that the renal cortex's color Doppler sonographic dynamic tissue perfusion measurement had very good intraobserver reproducibility.


Assuntos
Córtex Renal/diagnóstico por imagem , Imagem de Perfusão/métodos , Complicações Pós-Operatórias/diagnóstico , Insuficiência Renal/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tiroxina/sangue , Adolescente , Adulto , Estudos de Viabilidade , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Córtex Renal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Insuficiência Renal/sangue , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Reprodutibilidade dos Testes , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/complicações , Tireoidectomia/efeitos adversos , Tiroxina/administração & dosagem , Ultrassonografia Doppler em Cores , Adulto Jovem
4.
Clin J Am Soc Nephrol ; 16(8): 1210-1220, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34099500

RESUMO

BACKGROUND AND OBJECTIVES: Bacterial infection-related GN occurs concurrent to or after known or unknown infections. It is important to understand the clinical implications of the bacterial isolates, antimicrobial resistance patterns, and effect of latency-based classification on kidney and patient outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 501 consecutive adults diagnosed with bacterial infection-related GN between 2005 and 2017 were included from a biopsy registry of 15,545 patients at a single center in South India, and follow-up data were collected from electronic medical records until December 2019. Latency was defined as time between resolution of infection and onset of GN, which was classified as parainfectious, peri-infectious, or postinfectious GN. Longitudinal kidney and patient outcomes were studied. RESULTS: The mean age of the cohort was 40 (± 15) years, 6% were above 65 years, and 330 (66%) were men. Diabetes was present in 93 (19%) patients. Seventy percent (353 of 501) of patients had known infections, with the median latent period for parainfectious (115 of 353, 33%), peri-infectious (97 of 353, 27%), and postinfectious (141 of 353, 40%) GN being 0, 5 (4-7), and 15 (10-31) days, respectively. The most common predisposing organism was Streptococcus pyogenes (137 of 353, 39%). Drug-resistant nonstreptococcal bacteria were methicillin-resistant Staphylococcus aureus (25%, four of 16), extended-spectrum ß-lactamases (20%, 12 of 59), and carbapenem-resistant organisms (10%, six of 59). Twenty of 22 (91%) of the drug-resistant organisms were isolated from the parainfectious group. The most common site of infection was skin in peri- (23 of 97, 24%) and postinfectious GN (61 of 141, 43%), and urinary tract in parainfectious GN (35 of 115, 30%). Of 321 patients with >3 months of follow-up, 48 (15%) developed kidney failure over a median period of 10 (2-37) months and 14 (4%) died. Parainfectious GN, eGFR<30 ml/min per 1.73 m2, moderate-to-severe interstitial fibrosis and tubular atrophy, and nontreatment with renin-angiotensin system blockers were significant risk factors for progression to kidney failure by a Cox proportional-hazards model. CONCLUSIONS: Along with clinical and histologic predictors, parainfectious GN caused predominantly by nonstreptococcal and drug-resistant bacterial infections was associated with poor kidney prognosis.


Assuntos
Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Glomerulonefrite/microbiologia , Glomerulonefrite/fisiopatologia , Insuficiência Renal/fisiopatologia , Adulto , Atrofia , Biópsia , Carbapenêmicos , Farmacorresistência Bacteriana , Feminino , Fibrose , Taxa de Filtração Glomerular , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Humanos , Rim/patologia , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Sistema de Registros , Insuficiência Renal/etiologia , Estudos Retrospectivos , Fatores de Risco , Dermatopatias Bacterianas/complicações , Dermatopatias Bacterianas/microbiologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes , Fatores de Tempo , Infecções Urinárias/complicações , Adulto Jovem , beta-Lactamases
5.
Cancer Chemother Pharmacol ; 88(3): 543-553, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34117512

RESUMO

PURPOSE: SN-38, a pharmacologically active metabolite of irinotecan, is taken up into hepatocytes by organic anion transporting polypeptide (OATP) 1B1. The effects of functional OATP1B1 521T>C on the pharmacokinetics of SN-38 remain controversial. Here, we prospectively examined the effects of OATP1B1 function on the area under the plasma total or unbound concentration-time curve (tAUC or uAUC) of SN-38 by assessing OATP1B1 521T>C and the plasma levels of endogenous OATP1B1 substrates, coproporphyrin (CP)-I and III, in cancer patients treated with irinotecan. METHODS: We enrolled cancer patients who were treated with an irinotecan-containing regimen and did not have severe renal failure. The total and unbound concentrations of SN-38 in the plasma were measured by high-performance liquid chromatography. AUC values were calculated and normalized to the actual irinotecan dose (AUC/dose). The OATP1B1 521T>C was analyzed by direct sequencing. Concentrations of the endogenous substrates in plasma before irinotecan treatment (baseline) were determined by liquid chromatography with tandem mass spectrometry. RESULTS: Twenty-two patients with a median estimated glomerular filtration rate of 74.8 mL/min (range 32.6-99.6) were examined. Both tAUC/dose and uAUC/dose were associated with the grade of neutropenia; however, they were not associated with OATP1B1 521T>C or baseline CP-I and III levels. It is worth noting that these baseline concentrations were significantly higher in patients with OATP1B1 521C, supporting functional changes in OATP1B1. CONCLUSION: The contribution of OATP1B1 activity to inter-patient variability in the systemic exposure to SN-38 is likely minimal in patients without severe renal failure.


Assuntos
Irinotecano/administração & dosagem , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Neoplasias/tratamento farmacológico , Insuficiência Renal/fisiopatologia , Idoso , Área Sob a Curva , Cromatografia Líquida , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular , Humanos , Irinotecano/efeitos adversos , Irinotecano/farmacocinética , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Prospectivos , Índice de Gravidade de Doença , Espectrometria de Massas em Tandem , Inibidores da Topoisomerase I/administração & dosagem , Inibidores da Topoisomerase I/efeitos adversos , Inibidores da Topoisomerase I/farmacocinética
6.
Ann Vasc Surg ; 76: 449-453, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33905849

RESUMO

OBJECTIVE: Patients with functioning renal allografts may need ligation of pre-existing hemodialysis conduits. Chronic immunosuppression for renal allografts may adversely affect wound healing and perioperative complications following these procedures. We sought to analyze outcomes following elective ligation and resection of symptomatic arteriovenous (AV) access in immunosuppressed patients with renal allografts no longer requiring dialysis at a high-volume renal transplant hospital. METHODS: We retrospectively reviewed procedure codes for hemodialysis access resection and revision from 2014-2020 at a single academic tertiary care hospital. Patients who underwent complete or subtotal dialysis access resection with a functioning renal allograft were included for analysis of preoperative, operative, and postoperative outcomes. We performed descriptive statistics, and student's t-test using Microsoft Excel. RESULTS: Thirty-four patients met inclusion criteria. The majority were male, 56%, and the most common causes of renal failure were hypertension and diabetes, respectively. Ligation and resection of proximal upper extremity access was performed in 68%. The mean operative time was 126 minutes with pain being the most common indication for intervention. Four patients required arterial reconstruction. Mean postoperative follow-up was 13 months. Arm pain and swelling resolved in 100% and 88% of patients following AV access resection, respectively. No impairment in mean postoperative glomerular filtration rates were noted. One patient required hemodialysis and died three months after fistula resection following complications from treatment of a newly diagnosed neuroendocrine tumor and subsequent fungemia, CONCLUSION: Elective operative resection of symptomatic AV access may be performed safely in immunosuppressed patients with functioning renal transplants. The risk of allograft impairment and/or failure as a result of AV access resection in our series was low. Elective ligation and resection can be achieved with low mortality, excellent symptomatic relief, and few wound complications despite chronic immunosuppression.


Assuntos
Derivação Arteriovenosa Cirúrgica , Implante de Prótese Vascular , Hospitais com Alto Volume de Atendimentos , Imunossupressores/uso terapêutico , Transplante de Rim , Diálise Renal , Insuficiência Renal/terapia , Idoso , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Ligadura , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/diagnóstico , Insuficiência Renal/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
7.
Pharmacol Res Perspect ; 9(2): e00734, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33689224

RESUMO

The primary aim of this study was to examine the effect of severe renal impairment (SRI) on the pharmacokinetics of lemborexant, a dual orexin receptor antagonist indicated for the treatment of insomnia. A phase 1 multicenter, single-dose, open-label, parallel-group study was conducted in subjects with SRI not requiring dialysis (estimated glomerular filtration rate 15-29 ml/min/1.73 m2 ; n = 8) compared with demographically matched healthy subjects with normal renal function (n = 8). Plasma levels of lemborexant and its metabolites were measured over 240 h following a single oral 10-mg dose administered in the morning. Relative to subjects with normal renal function, lemborexant maximum plasma concentration (Cmax ) was similar, whereas area under the plasma concentration-time curve from zero to time of last quantifiable concentration (AUC(0-t) ) and AUC from zero to infinity (AUC(0-inf) ) were about 1.5-fold higher in subjects with SRI. The geometric mean ratios (90% confidence interval) were 104.8 (77.4-142.0), 150.5 (113.2-200.3), and 149.8 (113.1-198.6) for Cmax , AUC(0-t) , and AUC(0-inf) , respectively. In both groups, the median lemborexant time to Cmax (tmax ) was 1 h, and the mean unbound fraction of lemborexant was ~7%. For the M4, M9, and M10 metabolites, Cmax was reduced ~20% and exposure (AUC(0-t) and AUC(0-inf) ) was ~1.4- to 1.5-fold higher in subjects with SRI versus healthy subjects; tmax was delayed ~1.5-2 h for M4 and M10. All treatment-emergent adverse events were mild or moderate. Lemborexant pharmacokinetics were not sufficiently altered to warrant a dose adjustment for subjects with renal impairment.


Assuntos
Antagonistas dos Receptores de Orexina/farmacocinética , Piridinas/farmacocinética , Pirimidinas/farmacocinética , Eliminação Renal/fisiologia , Insuficiência Renal/metabolismo , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Adolescente , Adulto , Idoso , Área Sob a Curva , Feminino , Taxa de Filtração Glomerular/fisiologia , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas dos Receptores de Orexina/administração & dosagem , Antagonistas dos Receptores de Orexina/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Insuficiência Renal/diagnóstico , Insuficiência Renal/fisiopatologia , Índice de Gravidade de Doença , Adulto Jovem
8.
Int Urol Nephrol ; 53(11): 2349-2358, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33682051

RESUMO

PURPOSE: We aimed to investigate the prevalence of thyroid hormone abnormalities and the relationship between free triiodothyronine (fT3), thyroid stimulating hormone (TSH) and free thyroxine (fT4) serum levels with kidney function and proteinuria in 4108 subsequent patients admitted to a Nephrology Clinic at a tertiary Medical Centre. METHODS: All patients were categorized based on their estimated glomerular filtration rate (eGFR) as follows: normal-eGFR ≥ 60 ml/min, mild kidney impairment-30 ≤ eGFR < 60 ml/min, and severe kidney impairment-eGFR < 30 ml/min. RESULTS: Subjects with normal eGFR presented a laboratory constellation of hypothyroidism in 3.38% and "low-T3 syndrome" in 8.28%, while subjects with severe kidney impairment were diagnosed with hypothyroidism in 2.82% and "low-T3 syndrome" in 22.9%. Multivariate regression analysis showed that eGFR was a strong independent predictor of serum fT3 levels in patients with eGFR < 60 ml/min. Impaired kidney function was associated with low fT4 and fT3 but not TSH. Our findings showed an inverse correlation of fT3 and fT4 levels and proteinuria range. FT4 inversely correlated with the extent of proteinuria in all subgroups of patients. In contrast, the inverse correlation of fT3 serum levels and proteinuria disappeared in patients with eGFR < 60 ml/min. CONCLUSION: In a large cohort of inpatients, the prevalence of low-T3 syndrome was 2.5 times higher in patients with advanced kidney disease, compared to those with normal kidney function. In advanced CKD, both eGFR and proteinuria were strongly correlated with thyroid hormones. Therefore, close screening of the "thyroid profile" in patients with any stage of CKD, especially to those with proteinuria, might be warranted.


Assuntos
Taxa de Filtração Glomerular , Rim/fisiopatologia , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes de Função Tireóidea
9.
Int Urol Nephrol ; 53(5): 973-983, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33420892

RESUMO

INTRODUCTION: Evidence on vitamin D and parathyroid hormone (PTH) status in patients with early kidney impairment is limited. We aimed to determine the associations among kidney function, vitamin D, and PTH status in community-dwelling elderly patients with mild-to-moderate kidney impairment. METHODS: Community-dwelling elderly patients were enrolled in this Institutional Review Board approved cross-sectional study. The eligibility criteria were as follows: age > 60 years, no recent hospitalization within the past 12 months, no conditions that affect vitamin D status including vitamin D supplementation, and eGFR > 30 mL/min/1.73 m2. Serum 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels were assessed. RESULTS: A total of 226 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 26.61 ± 10.44 ng/mL and the mean serum PTH was 50.67 ± 22.67 pg/mL. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] and secondary hyperparathyroidism [PTH > 65 pg/mL] were 25.3% and 18.1%, respectively. Patients with eGFR 30- < 60 mL/min/1.73m2 had significantly higher prevalence of 25(OH)D < 20 ng/mL (33.7% versus 19.4%, p < 0.05) than patients with eGFR ≥ 60 mL/min/1.73 m2. Multiple regression analysis showed independent negative association of serum PTH level with eGFR (mL/min/1.73 m2, ß: - 0.261, 95% CI [- 0.408, - 0.114]) and serum 25(OH)D (ng/mL, ß: - 0.499, 95% CI [- 0.775, - 0.223], adjusted for possible confounders). CONCLUSIONS: The prevalence of vitamin D deficiency was higher in patients with eGFR 30 - < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. Both decreased serum 25(OH)D levels and decreased eGFR were independently associated with increased serum PTH levels among these patients.


Assuntos
Hormônio Paratireóideo/sangue , Insuficiência Renal/sangue , Vitamina D/sangue , Idoso , Estudos Transversais , Feminino , Humanos , Vida Independente , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/fisiopatologia , Índice de Gravidade de Doença
10.
J Vasc Interv Radiol ; 32(3): 459-465, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33386206

RESUMO

PURPOSE: To analyze the effect of a patient's renal failure status on acute outcomes after lower extremity endovascular interventions for peripheral artery disease. MATERIALS AND METHODS: A retrospective analysis of the American College of Surgery National Surgical Quality Improvement Program database from 2014 to 2017 was conducted. Patients were included based on current procedural terminology codes. They were divided into renal failure cohorts. Six thousand seven hundred and sixty-five patients were included in the analysis, 11.0% of whom had renal failure. A univariate analysis was performed using chi-squared test or Fischer's exact test as appropriate. Multivariate logistic regression models were constructed, while controlling for relevant patient factors, to identify the effect of renal failure on several outcomes of interest after the intervention. A sensitivity analysis was performed with a propensity score-matched cohort. RESULTS: Patients with renal failure were more likely to have infrapopliteal interventions (38.0% vs 20.9%), critical limb ischemia with tissue loss (73.5% vs 38.9%), diabetes (70.9% vs 52.3%), preoperative wound infection (59.2% vs 30.7%), mortality (5.1% vs 1.3%), prolonged hospital stay (68.5% vs 46.5%), transfusion after the intervention (13.3% vs 9.1%), reoperation (18.3% vs 9.5%), and readmission (24.9% vs 12.6%), compared to patients without renal failure. The multivariate analysis found renal failure to be significant for mortality (odds ratio [OR] = 4.11, 95% confidence interval [CI] = 2.71-6.24), any complication (OR = 2.03, 95% CI = 1.72-2.39), extended length of stay (OR = 1.53, 95% CI = 1.28-1.83), sepsis (OR = 2.37, 95% CI = 1.60-3.51), readmission (OR = 1.89, 95% CI = 1.57-2.29), reoperation (OR = 1.84, 95% CI = 1.48-2.27), major adverse cardiovascular event (OR = 3.50, 95% CI = 2.54-4.84), and major adverse limb event (OR = 1.97, 95% CI = 1.55-2.51). P value was <.001 unless otherwise noted. CONCLUSIONS: Renal failure before the intervention places patients at a significantly elevated risk of morbidity and mortality following endovascular revascularization procedures for peripheral artery disease.


Assuntos
Procedimentos Endovasculares , Rim/fisiopatologia , Doença Arterial Periférica/terapia , Insuficiência Renal/fisiopatologia , Idoso , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/mortalidade , Retratamento , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
11.
Cancer Chemother Pharmacol ; 87(2): 241-250, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33388951

RESUMO

PURPOSE: Glasdegib is being developed for indications in myeloid malignancies. The effect of renal impairment on the pharmacokinetics (PK) of a single, oral, 100-mg glasdegib dose under fasted conditions was assessed. METHODS: Open-label, parallel-group study (NCT03596567). Participants of good general health were selected and categorized, based on their estimated glomerular filtration rate, into normal (≥ 90 mL/min), moderate (≥ 30 to < 60 mL/min), or severe (< 30 mL/min) renal impairment groups. Blood samples were collected up to 120 h post-dose. PK exposure parameters were calculated using non-compartmental analysis. RESULTS: All 18 participants completed the study. Respectively, ratios of adjusted geometric means (90% confidence interval) for glasdegib area under the curve from time 0 to infinity and peak plasma concentration versus normal participants were 205% (142-295%) and 137% (97-193%) in the moderate group, and 202% (146-281%) and 120% (77-188%) in the severe group. Glasdegib median time to peak plasma concentration was 2.0 h in both impairment groups and 1.5 h in the normal group. Mean oral clearance was decreased by approximately 50% in both renal impairment groups compared with the normal group. The plasma-free fraction of glasdegib was not altered by renal impairment. Five all-causality adverse events were reported in three participants; two were considered treatment-related. CONCLUSION: The similar changes in exposure observed for participants with renal impairment, coupled with the known safety data from clinical experience, suggest that a lower starting dose of glasdegib may not be required for moderate or severe renal impairment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03596567 (started May 17, 2018).


Assuntos
Antineoplásicos/farmacocinética , Benzimidazóis/farmacocinética , Compostos de Fenilureia/farmacocinética , Insuficiência Renal/fisiopatologia , Administração Oral , Idoso , Antineoplásicos/efeitos adversos , Área Sob a Curva , Benzimidazóis/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Índice de Gravidade de Doença
12.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462030

RESUMO

This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced by Bacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential of B. cereus It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.


Assuntos
Bacillus cereus/genética , Exotoxinas/genética , Doenças Transmitidas por Alimentos/diagnóstico , Acetilcisteína/uso terapêutico , Acidose/fisiopatologia , Acidose/terapia , Adulto , Antiarrítmicos/uso terapêutico , Antibacterianos/uso terapêutico , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Bacillus cereus/isolamento & purificação , Transtornos da Coagulação Sanguínea/fisiopatologia , Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue , Encefalopatias , Terapia de Substituição Renal Contínua , Evolução Fatal , Feminino , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/fisiopatologia , Doenças Transmitidas por Alimentos/terapia , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Imunocompetência , Falência Hepática/fisiopatologia , Falência Hepática/terapia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Plasmaferese , Insuficiência Renal/fisiopatologia , Insuficiência Renal/terapia , Rabdomiólise/fisiopatologia , Rabdomiólise/terapia , Sepse/fisiopatologia , Sepse/terapia , Choque/fisiopatologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sequenciamento Completo do Genoma
13.
Oncol Rep ; 45(2): 413-426, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416184

RESUMO

In recent years, a number of tyrosine kinase inhibitors (TKIs) have been approved for the treatment of non­small cell lung cancer. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. TKIs are administered orally, which has the advantages of improved flexibility and convenience for the patients. However, challenges have arisen in the use of these novel agents. Prescribing drugs for patients with hepatic or renal function impairment poses a challenge for clinicians due to the large pharmacokinetic variability in each individual patient. Moreover, several TKIs have been shown to cause laboratory test abnormalities normally associated with hepatic or renal injury. The aim of the present review was to discuss the effects of hepatic and renal function impairment on the pharmacokinetic variability of 17 TKIs and their potential hepatotoxicity and nephrotoxicity, and to recommend dose adjustment for patients with hepatic or renal impairment.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Falência Hepática/fisiopatologia , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Insuficiência Renal/fisiopatologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Variação Biológica da População , Carcinoma Pulmonar de Células não Pequenas/complicações , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Eliminação Hepatobiliar/fisiologia , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Falência Hepática/complicações , Neoplasias Pulmonares/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Eliminação Renal/fisiologia , Insuficiência Renal/complicações
14.
Am J Kidney Dis ; 77(2): 255-263, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32771648

RESUMO

The omission of outcomes that are of relevance to patients, clinicians, and regulators across trials in autosomal dominant polycystic kidney disease (ADPKD) limits shared decision making. The Standardized Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) Initiative convened an international consensus workshop on October 25, 2018, to discuss the identification and implementation of a potential core outcome set for all ADPKD trials. This article summarizes the discussion from the workshops and the SONG-PKD core outcome set. Key stakeholders including 11 patients/caregivers and 47 health professionals (nephrologists, policy makers, industry, and researchers) attended the workshop. Four themes emerged: "Relevance of trajectory and impact of kidney function" included concerns about a patient's prognosis and uncertainty of when they may need to commence kidney replacement therapy and the lack of an early prognostic marker to inform long-term decisions; "Discerning and defining pain specific to ADPKD" highlighted the challenges in determining the origin of pain, adapting to the chronicity and repeated episodes of pain, the need to place emphasis on pain management, and to have a validated measure for pain; "Highlighting ADPKD consequences" encompassed cyst-related complications and reflected patient's knowledge because of family history and the hereditary nature of ADPKD; and "Risk for life-threatening but rare consequences" such as cerebral aneurysm meant considering both frequency and severity of the outcome. Kidney function, mortality, cardiovascular disease, and pain were established as the core outcomes for ADPKD.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Mortalidade , Dor/fisiopatologia , Rim Policístico Autossômico Dominante/fisiopatologia , Insuficiência Renal/fisiopatologia , Atividades Cotidianas , Pessoal Administrativo , Doenças Cardiovasculares/etiologia , Cuidadores , Técnica Delphi , Progressão da Doença , Humanos , Nefrologistas , Avaliação de Resultados em Cuidados de Saúde , Dor/etiologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/terapia , Insuficiência Renal/etiologia , Participação dos Interessados
15.
BJU Int ; 127(3): 311-317, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32772468

RESUMO

OBJECTIVE: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes. RESULTS: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001). CONCLUSIONS: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Insuficiência Renal/sangue , Fatores Etários , Idoso , Biomarcadores/sangue , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Nefrectomia/efeitos adversos , Tratamentos com Preservação do Órgão , Seleção de Pacientes , Período Pré-Operatório , Prognóstico , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Estudos Retrospectivos , Fatores de Risco
16.
CEN Case Rep ; 10(1): 139-144, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32951174

RESUMO

The severity of the poststreptococcal acute glomerulonephritis is considered to be modulated by the immune response of each individual, although there had been few reports regarding specific factors. Renal cell carcinoma is a cancer frequently associated with paraneoplastic syndrome, characterized by fever, leukocytosis, elevated cytokines, and elevated hormone levels. All of these symptoms resolve after tumor resection. A girl with renal cell carcinoma developed renal failure rapidly, which resolved promptly right after nephrectomy for the carcinoma. She was diagnosed as having poststreptococcal acute glomerulonephritis according to the results of pathological and serological examinations. In addition, elevated serum interleukin-6 level before the surgery was detected. Six and a half years after the diagnosis, the patient's renal function was within normal range and she was tumor free. Because of the quick resolution of her renal dysfunction after the nephrectomy, paraneoplastic syndrome induced by renal cell carcinoma seemed to play a key role in the accentuation of poststreptococcal acute glomerulonephritis.


Assuntos
Carcinoma de Células Renais/complicações , Glomerulonefrite/complicações , Nefrectomia/efeitos adversos , Síndromes Paraneoplásicas/complicações , Doença Aguda , Adolescente , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/microbiologia , Humanos , Neoplasias Renais/patologia , Nefrectomia/métodos , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/metabolismo , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Índice de Gravidade de Doença , Infecções Estreptocócicas/complicações , Resultado do Tratamento
17.
Ann Vasc Surg ; 70: 568.e13-568.e17, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32890641

RESUMO

BACKGROUND: Renal dysfunction, requiring renal replacement therapy (RRT) is commonly encountered in patients with left ventricular assist devices (LVADs). Continuous flow LVAD (CFLVAD) is the most widely used device. Nonpulsatile blood flow begets special hemodynamic changes. This poses a unique challenge in choosing a long-term dialysis access for patients with CFLVAD where life expectancy is limited. METHODS: A 61-year-old man with an implanted CFLVAD and renal dysfunction receiving intermittent RRT through a nontunneled dialysis catheter had progressed to dialysis-dependent renal failure. He was referred to us for a permanent hemodialysis access. RESULTS: The patient underwent a right brachio-brachial arterio-venous graft (AVG) placement. The graft was successfully cannulated for hemodialysis on postoperative day 15. On regular follow-up at 18 months, the graft was still functional. CONCLUSIONS: Dialysis access for patients on LVAD is an exceptional management problem owing to both altered physiology and guarded overall prognosis. We recommend the use of AVG as a convenient and durable option-facilitating early cannulation and expediting freedom from indwelling catheters that may lead to catastrophic consequences. This should limit the need for secondary interventions, hospitalization, and cost, thus improving quality of life.


Assuntos
Braço/irrigação sanguínea , Derivação Arteriovenosa Cirúrgica , Artéria Braquial/cirurgia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Diálise Renal , Insuficiência Renal/terapia , Veias/cirurgia , Função Ventricular Esquerda , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/complicações , Insuficiência Renal/diagnóstico , Insuficiência Renal/fisiopatologia , Resultado do Tratamento , Grau de Desobstrução Vascular , Veias/diagnóstico por imagem , Veias/fisiopatologia
18.
Surg Today ; 51(1): 165-171, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32862341

RESUMO

PURPOSE: Recent large-scale clinical studies have shown that preoperative renal insufficiency is associated with an increased risk of postoperative complications after esophagectomy; however, it remains unclear whether asymptomatic renal dysfunction affects the postoperative course after esophagectomy. METHODS: The subjects of this retrospective study were 177 patients who underwent esophagectomy between May, 2009 and December, 2018. Renal function was evaluated based on the pretreatment estimated glomerular filtration rate (eGFR). Patients were divided into two groups according to the eGFR cut-off value of 55 ml/min per 1.73 m2. RESULTS: There were 17 patients in the low eGFR group and 160 patients in the normal group eGFR group. The rate of severe complications was significantly higher in the low eGFR than in the normal eGFR group. A low eGFR was the only significant complication risk factor identified; however, there were no marked differences in mortality or survival between the low and normal eGFR groups. CONCLUSION: Our findings demonstrate that pretreatment asymptomatic renal dysfunction may be a significant risk factor for severe morbidity after esophagectomy.


Assuntos
Doenças Assintomáticas , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Insuficiência Renal/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Insuficiência Renal/epidemiologia , Insuficiência Renal/fisiopatologia , Estudos Retrospectivos , Risco , Fatores de Risco
19.
Leukemia ; 35(2): 562-572, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32444867

RESUMO

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ≥2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ≥60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Insuficiência Renal/fisiopatologia , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivados
20.
J Vasc Surg ; 73(1): 92-98, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32416308

RESUMO

BACKGROUND: Conflicting evidence exists regarding the comparative effects of endovascular aneurysm repair (EVAR) with and without suprarenal fixation. We compare outcomes in patients treated by EVAR with baseline normal kidney function and moderate and severe chronic kidney disease. METHODS: Patients with normal kidney function (glomerular filtration rate [GFR] ≥60 mL/min/1.73 m2) or moderate (GFR = 30-59 mL/min/1.73 m2) or severe (GFR <30 mL/min/1.73 m2) kidney disease who underwent EVAR (N = 5534) were identified from the American College of Surgeons National Surgical Quality Improvement Program targeted database (2011-2015). Groups were determined by the presence (Cook Zenith [Cook Medical, Bloomington, Ind] or Medtronic Endurant [Medtronic, Minneapolis, Minn]) or absence (Gore Excluder [W. L. Gore & Associates, Flagstaff, Ariz]) of a suprarenal fixation system. Postoperative renal complications, defined as rise in creatinine concentration of >2 mg/dL without dialysis or new dialysis requirements, were analyzed within the first 30 days with results stratified by degree of kidney disease. RESULTS: A total of 5534 patients underwent EVAR, with 3225 (58.3%) receiving a device using a suprarenal fixation system. Suprarenal fixation systems were less commonly used for symptomatic patients (11.0% vs 13.7%; P = .002) and patients with ruptured abdominal aortic aneurysm (4.5% vs 6.3%; P = .01). There was no difference in baseline kidney function between groups. EVAR with suprarenal fixation was associated with more renal complications (1.40% vs 0.65%; P = .008). In subgroup analysis, patients with moderate kidney dysfunction (n = 1780) had more renal complications (2.2% vs 0.8%; P = .02) with suprarenal fixation systems. No differences were seen in patients with normal kidney function (0.4% vs 0.2%; P = .32; n = 3597) or severe kidney dysfunction (14.3% vs 10.2%; P = .45; n = 157). This difference was driven mostly by postoperative elevation of creatinine concentration (0.6% vs 0.2%; P = .03) without requirements for new dialysis (0.8% vs 0.4%; P = .08). After adjustments with multivariate logistic regression models, EVAR with suprarenal fixation was associated with more renal complications (odds ratio, 2.65; 95% confidence interval, 1.32-5.34). CONCLUSIONS: In our study, EVAR with suprarenal fixation devices was associated with more perioperative renal complications in patients with moderate kidney dysfunction. Long-term evaluation of these patients undergoing EVAR should be considered.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular , Procedimentos Endovasculares/métodos , Taxa de Filtração Glomerular/fisiologia , Rim/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Insuficiência Renal/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
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