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1.
N Engl J Med ; 382(7): e11, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053318
3.
J Immunother Cancer ; 7(1): 262, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623673

RESUMO

BACKGROUND: Immune checkpoint inhibitors have improved clinical outcomes including survival in several malignancies but have also been associated with a range of immune-related adverse events (irAEs). Neurological irAEs are rare compared to the more typical skin, gastrointestinal, and endocrine toxicities, and are often underrecognized and challenging to diagnose. Here, we report a case of seronegative autoimmune autonomic ganglionopathy (AAG) induced by dual immune checkpoint inhibitor therapy (ICI) in a patient with metastatic melanoma. CASE PRESENTATION: A patient with metastatic melanoma was treated with ipilimumab and nivolumab. He developed a constellation of new symptoms including nausea, fatigue, and severe orthostatic hypotension refractory to fluid resuscitation. An infectious, cardiac, neurologic, and endocrine workup were unrevealing. Cardiovascular autonomic testing revealed poor sympathetic nervous system responses. He was diagnosed with seronegative AAG and significantly improved with immunomodulatory therapies including IVIG and steroids as well as varying doses of midodrine and fludrocortisone. He was able to restart nivolumab without recurrence of his symptoms. However, the AAG reoccurred when he was re-challenged with ipilimumab and nivolumab due to disease progression. While the AAG was manageable with steroids at that time, unfortunately his melanoma became resistant to ICI. CONCLUSIONS: Immune checkpoint inhibitors can have a wide range of unusual, rare irAEs, including neurotoxicity such as AAG. Clinicians should maintain suspicion for this toxicity so that treatment can be rapidly provided to avoid disability.

6.
Kidney Int Rep ; 3(2): 412-416, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29725645

RESUMO

Introduction: As part of the precision medicine initiative, the National Institutes of Health/National Institute of Diabetes and Digestive Kidney Diseases has proposed collecting human kidney tissue to discover novel therapeutic targets from patients with kidney diseases. Patient attitudes on participating in kidney biopsy-based research are largely unknown. Methods: We evaluated attitudes toward donating kidney tissue to research among participants who had experienced a clinically indicated kidney biopsy, through a survey conducted 9 months (interquartile range, 5-13 months) after their biopsy. Results: Of the 177 participants contacted, 117 (66%) participated in the survey. A total of 85 participants (73%) reported that they would allow additional needle passes during a clinically indicated biopsy to donate kidney tissue for research. As reasons for participating in such a study, the participants reported the desire to help others and to contribute to science, and the lack of additional burden while participating in such a study. In a multivariable logistic model, older and African American participants had lower odds of allowing an additional pass for research (odds ratio: age ≥65 years [vs. ≤40], 0.15 [95% confidence interval, 0.03-0.73]; African Americans (vs. all others), 0.15 [95% confidence interval, 0.05-0.44]). However, participants' self-reported biopsy complications such as pain, anxiety, and hematuria did not affect their willingness to allow additional passes. A total of 23 participants (20%) stated that they would agree to undergo a biopsy for research even if it was not clinically indicated. Conclusion: Among patients who had experienced a kidney biopsy, a majority were amenable to additional needle passes to donate kidney tissue for research during a future, clinically indicated biopsy, whereas a minority would undergo a biopsy for research purpose only.

7.
Kidney Int ; 92(4): 816-823, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28938954

RESUMO

The association between blood pressure (BP) and mortality is unique in hemodialysis patients compared with that in the general population. This is because of an altered benefit-risk balance associated with BP reduction in these patients. An adequately designed study comparing BP targets in hemodialysis patients remains to be conducted. The current evidence available to guide dialysis providers regarding treatment strategies for managing hypertension in this population is limited to large observational studies and small randomized controlled trials. In this opinion article, we review these data and discuss the key points regarding BP management for hemodialysis patients. Our aim is to provide a practical opinion regarding BP targets that nephrologists can incorporate into clinical practice, with a focus on moving away from dialysis unit BPs and focusing on out-of-dialysis unit BPs.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/normas , Humanos , Hipertensão/etiologia , Hipertensão/mortalidade , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Nefrologistas/normas , Guias de Prática Clínica como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/normas , Fatores de Risco
8.
Adv Chronic Kidney Dis ; 23(4): 255-61, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27324679

RESUMO

Hypertension is present in ∼90% of patients in late-stage CKD. There are scarce data focusing on the transition period between CKD Stages 4 and 5 (end-stage kidney disease) as it relates to hypertension evaluation and management. Here, we propose that a combination of the principles used in the management of patients with CKD Stages 4 and 5 be applied to patients in this transition. These include the use of out-of-office blood pressure (BP) monitoring (eg, home BP), avoidance of excessively tight BP goals, emphasis of sodium restriction, preferential use of blockers of the renin-angiotensin system and diuretics, and consideration of the use of beta blockers.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Bloqueadores dos Canais de Cálcio/uso terapêutico , Dieta Hipossódica , Progressão da Doença , Diuréticos/uso terapêutico , Hipertensão/complicações , Hipertensão/dietoterapia , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/complicações
9.
Ann Intern Med ; 164(9): W42-7, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27136231
10.
Semin Dial ; 29(4): 323-5, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27113685

RESUMO

Hypertension is the most common complication of end-stage renal disease and chronic hemodialysis and yet, only a third of these patients have adequately controlled blood pressures. Pathogenesis of hypertension in this population is complex and multifactorial and therefore poses numerous treatment challenges. Furthermore, it is common practice among nephrologists to withhold antihypertensives prior to a hemodialysis procedure due to concerns for intradialytic hypotension (IDH). Intradialytic hypertension (ID-HTN) is an increasingly recognized phenomenon and although less common than IDH, portends poor cardiovascular prognosis as well as reflects higher hypertension burden in the dialysis population. Withholding antihypertensives prior to dialysis routinely in patients may worsen interdialytic blood pressure control as well as increase the prevalence of euvolemic ID-HTN. It may also increase the risk of cardiac arrhythmias and further compromise hemodynamic stability during dialysis. In such situations, predialysis administration of antihypertensive is appropriate and necessary and drug choice should be based on the patient's comorbidities, pharmacokinetics of the drug and its dialyzability.


Assuntos
Anti-Hipertensivos/administração & dosagem , Falência Renal Crônica/terapia , Nefrologia/métodos , Diálise Renal , Pressão Sanguínea , Humanos , Hipertensão/tratamento farmacológico , Hipotensão/prevenção & controle
11.
Methodist Debakey Cardiovasc J ; 11(4): 214-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27057289

RESUMO

Out-of-office blood pressure (BP) monitoring is becoming increasingly important in the diagnosis and management of hypertension. Home BP and ambulatory BP monitoring (ABPM) are the two forms of monitoring BP in the out-of-office environment. Home BP monitoring is easy to perform, inexpensive, and engages patients in the care of their hypertension. Although ABPM is expensive and not widely available, it remains the gold standard for diagnosing hypertension. Observational studies show that both home BP and ABPM are stronger predictors of hypertension-related outcomes than office BP monitoring. There are no clinical trials showing their superiority over office BP monitoring in guiding the treatment of hypertension, but the consistency of observational data make a compelling case for their preferential use in clinical practice.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão/diagnóstico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento
12.
Semin Nephrol ; 34(5): 492-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25416657

RESUMO

Patients with resistant hypertension belong to a very high cardiovascular risk group and have a high prevalence of target organ damage. Microalbuminuria and low estimated glomerular filtration rate are associated with resistant hypertension, and could be a cause and/or complication of hypertension. In this review, we explore the relationship between these 2 markers of kidney disease and the prevalence of resistant hypertension. We identified different phenotypes of resistant hypertension that associate with microalbuminuria and/or low estimated glomerular filtration rate. These phenotypes suggest that high sympathetic activity associated with fluid overload and endothelial dysfunction may contribute differently to the development of resistant hypertension.


Assuntos
Albuminúria/fisiopatologia , Resistência a Medicamentos/fisiologia , Taxa de Filtração Glomerular/fisiologia , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Vasoespasmo Coronário/fisiopatologia , Vasoespasmo Coronário/urina , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/fisiopatologia , Hipertensão/urina
13.
Clin J Am Soc Nephrol ; 9(11): 1857-67, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25183658

RESUMO

BACKGROUND AND OBJECTIVES: AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality. RESULTS: Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05-4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index. CONCLUSIONS: Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.


Assuntos
Lesão Renal Aguda/complicações , Lesão Renal Aguda/urina , Progressão da Doença , Cirrose Hepática/complicações , Lesão Renal Aguda/mortalidade , Proteínas da Fase Aguda/urina , Adulto , Idoso , Albuminúria/etiologia , Albuminúria/urina , Biomarcadores/urina , Proteínas de Ligação a Ácido Graxo/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A , Mortalidade Hospitalar , Humanos , Interleucina-18/urina , Lipocalina-2 , Lipocalinas/urina , Masculino , Glicoproteínas de Membrana/urina , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Proteínas Proto-Oncogênicas/urina , Receptores Virais , Sódio/urina
14.
Clin J Am Soc Nephrol ; 9(12): 2164-72, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25092599

RESUMO

The evaluation of causes of hypertension in young adults with a family history of hypertension needs to be methodical to identify potentially treatable causes. Renal- and renovascular imaging and measurement of plasma aldosterone and plasma renin activity are at the core of this evaluation in most patients. Pertinent aspects of hypertension in autosomal dominant polycystic kidney disease are discussed with a focus on the role of the endothelium in mediating early hypertension and a review of treatment strategies. Finally, the possibility that autosomal dominant polycystic kidney disease and primary aldosteronism are connected beyond coincidence is explored; evidence to support it is scant, although there is a likely role for aldosterone excess and the resultant hypokalemia in promoting cyst growth.


Assuntos
Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Rim Policístico Autossômico Dominante/complicações , Adulto , Anti-Hipertensivos/uso terapêutico , Progressão da Doença , Humanos , Hiperaldosteronismo/etiologia , Hipopotassemia/induzido quimicamente , Masculino , Anamnese , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
15.
Nephrol Dial Transplant ; 29(1): 22-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24137013

RESUMO

Renalase, a recently discovered flavoprotein, which is strongly expressed in the kidney and heart, effectively metabolizes catecholamines. It was discovered during the search to identify proteins secreted by the kidney that could help explain the high incidence of cardiovascular disease in patients with chronic kidney disease. Recent advances have led to more detailed knowledge of its biology, structure, enzymatic activity, mechanisms of action, associations with human disease states and potential therapeutic value. In this study, we review these advances with a focus on hypertension and kidney disease.


Assuntos
Hipertensão/enzimologia , Nefropatias/enzimologia , Monoaminoxidase/metabolismo , Animais , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Catecolaminas/metabolismo , Modelos Animais de Doenças , Genótipo , Humanos , Hipertensão/complicações , Rim/inervação , Rim/fisiopatologia , Nefropatias/complicações , Túbulos Renais/fisiologia , Monoaminoxidase/química , Monoaminoxidase/genética , Monoaminoxidase/urina , Polimorfismo de Nucleotídeo Único/genética , Insuficiência Renal Crônica/complicações , Acidente Vascular Cerebral/enzimologia , Sistema Nervoso Simpático/fisiologia
16.
Hepatology ; 60(2): 622-32, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24375576

RESUMO

UNLABELLED: Acute kidney injury (AKI) is common in patients with cirrhosis and associated with significant mortality. The most common etiologies of AKI in this setting are prerenal azotemia (PRA), acute tubular necrosis (ATN), and hepatorenal syndrome (HRS). Accurately distinguishing the etiology of AKI is critical, as treatments differ markedly. However, establishing an accurate differential diagnosis is extremely challenging. Urinary biomarkers of kidney injury distinguish structural from functional causes of AKI and may facilitate more accurate and rapid diagnoses. We conducted a multicenter, prospective cohort study of patients with cirrhosis and AKI assessing multiple biomarkers for differential diagnosis of clinically adjudicated AKI. Patients (n = 36) whose creatinine returned to within 25% of their baseline within 48 hours were diagnosed with PRA. In addition, 76 patients with progressive AKI were diagnosed by way of blinded retrospective adjudication. Of these progressors, 39 (53%) patients were diagnosed with ATN, 19 (26%) with PRA, and 16 (22%) with HRS. Median values for neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and albumin differed between etiologies and were significantly higher in patients adjudicated with ATN. The fractional excretion of sodium (FENa) was lowest in patients with HRS, 0.10%, but did not differ between those with PRA, 0.27%, or ATN, 0.31%, P = 0.54. The likelihood of being diagnosed with ATN increased step-wise with the number of biomarkers above optimal diagnostic cutoffs. CONCLUSION: Urinary biomarkers of kidney injury are elevated in patients with cirrhosis and AKI due to ATN. Incorporating biomarkers into clinical decision making has the potential to more accurately guide treatment by establishing which patients have structural injury underlying their AKI. Further research is required to document biomarkers specific to HRS.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/metabolismo , Proteínas da Fase Aguda/urina , Proteínas de Ligação a Ácido Graxo/urina , Interleucina-18/urina , Lipocalinas/urina , Glicoproteínas de Membrana/urina , Proteínas Proto-Oncogênicas/urina , Adulto , Idoso , Albuminúria/diagnóstico , Albuminúria/urina , Biomarcadores/urina , Creatinina/urina , Diagnóstico Diferencial , Feminino , Taxa de Filtração Glomerular/fisiologia , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Rim/metabolismo , Lipocalina-2 , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores Virais , Sódio/urina
18.
Am J Kidney Dis ; 61(5): 822-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23481366

RESUMO

Metabolic alkalosis, isolated or in combination with another abnormality, is the most common acid-base disorder in patients with congestive heart failure. In most cases, it is a result of diuretic therapy, which causes activation of the renin-angiotensin system, chloride depletion, increased distal sodium delivery, hypokalemia, and increased urine acidification, all of which contribute to bicarbonate retention. In addition, the disease state itself results in neurohormonal activation (renin-angiotensin system, sympathetic nervous system, and endothelin) that further amplifies the tendency toward alkalosis. Treatment of metabolic alkalosis is based on the elimination of generation and maintenance factors, chloride and potassium repletion, enhancement of renal bicarbonate excretion (such as acetazolamide), direct titration of the base excess (hydrochloric acid), or, if accompanied by kidney failure, low-bicarbonate dialysis. In congestive heart failure, appropriate management of circulatory failure and use of an aldosterone antagonist in the diuretic regimen are integral to treatment.


Assuntos
Alcalose/etiologia , Insuficiência Cardíaca/complicações , Equilíbrio Ácido-Base , Idoso , Alcalose/metabolismo , Alcalose/terapia , Seguimentos , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Diálise Renal
19.
J Am Soc Hypertens ; 7(2): 157-62, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23403215

RESUMO

To evaluate the spectrum of hemodynamic patterns in patients with isolated diastolic hypertension-predominantly diastolic hypertension, we re-analyzed a previously reported cohort of 189 non-medicated hypertensive individuals that were assessed by impedance cardiography. We selected 46 patients who were less than 50 years old and had pulse pressure less or equal than 45 mm Hg confirmed by ambulatory blood pressure monitoring. The selected cohort had a mean age of 39.7 years and was 47% men. Three distinct groups were identified: a high cardiac index (CI) "hyperdynamic" group, with normal to near normal systemic vascular resistance (SVR); an intermediate CI and SVR group; and a "vasotonic" group, with low CI and high SVR. Heart rate was similar among the three groups. Stroke volume index (SVI) was significantly higher in the hyperdynamic group (61.8, 49.7, and 39.7 mL/m(2) in the high, intermediate, and low CI groups, respectively). The hyperdynamic group had greater total arterial compliance index than the vasotonic group (1.3 ± 0.3 vs 0.92 ± 0.2 mL/m(2) mm Hg for high vs low CI, respectively; P < .001). In conclusion, isolated diastolic hypertension-predominantly diastolic hypertension patients can have diverse hemodynamic patterns that cannot be predicted based on peripherally measured blood pressure and heart rate alone. This hemodynamic complexity must be taken into account when considering the genetic and pathophysiologic mechanisms of hypertension.


Assuntos
Diástole , Hemodinâmica , Hipertensão/fisiopatologia , Adulto , Monitorização Ambulatorial da Pressão Arterial , Cardiografia de Impedância , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Volume Sistólico
20.
Curr Hypertens Rep ; 15(2): 89-94, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23344662

RESUMO

Hypertension complicates most cases of chronic kidney disease. While the prevalence and severity of hypertension increase as glomerular filtration rate falls, hypertension is often observed in patients with structural kidney disease while renal function is normal, in particular those with polycystic kidney disease or proteinuric glomerular diseases. On the other hand, even severe reductions in renal function may not result in hypertension, especially if there is effective control of extracellular fluid volume. Recent clinical and experimental data indicate that proteinuria may mediate sodium retention and hypertension via plasmin-mediated activation of the epithelial sodium channel. Current evidence supports the notion that chronic kidney disease is a cause of chronic hypertension, even in the absence of detectable changes in glomerular filtration rate.


Assuntos
Hipertensão/etiologia , Insuficiência Renal Crônica/complicações , Taxa de Filtração Glomerular , Humanos , Hipertensão Renal/etiologia , Rim/patologia , Rim/fisiopatologia
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