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1.
J Intern Med ; 291(3): 364-370, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34761839

RESUMO

BACKGROUND: Kidney failure is the major cause of morbidity and mortality in familial lecithin:cholesterol acyltransferase deficiency (FLD), a rare inherited lipid disorder with no cure. Lipoprotein X (LpX), an abnormal lipoprotein, is primarily accountable for nephrotoxicity. METHODS: CER-001 was tested in an FLD patient with dramatic kidney disease for 12 weeks. RESULTS: Infusions of CER-001 normalized the lipoprotein profile, with a disappearance of the abnormal LpX in favour of normal-sized LDL. The worsening of kidney function was slowed by the treatment, and kidney biopsy showed a slight reduction of lipid deposits and a stabilization of the disease. In vitro experiments demonstrate that CER-001 progressively reverts lipid accumulation in podocytes by a dual effect: remodelling plasma lipoproteins and removing LpX-induced lipid deposit. CONCLUSION: This study demonstrates that CER-001 may represent a therapeutic option in FLD patients. It also has the potential to be beneficial in other renal diseases characterized by kidney lipid deposits.


Assuntos
Deficiência da Lecitina Colesterol Aciltransferase , Apolipoproteína A-I/uso terapêutico , Humanos , Rim/patologia , Deficiência da Lecitina Colesterol Aciltransferase/tratamento farmacológico , Deficiência da Lecitina Colesterol Aciltransferase/patologia , Lipoproteínas , Fosfatidilcolina-Esterol O-Aciltransferase/farmacologia , Fosfatidilcolina-Esterol O-Aciltransferase/uso terapêutico , Fosfolipídeos , Proteínas Recombinantes
2.
Rev Endocr Metab Disord ; 18(3): 323-334, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28281103

RESUMO

Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.


Assuntos
Falência Renal Crônica/terapia , Transplante de Rim/efeitos adversos , Deficiência de Vitamina D/etiologia , Calcitriol/metabolismo , Suplementos Nutricionais , Humanos , Rim/metabolismo , Falência Renal Crônica/sangue , Falência Renal Crônica/metabolismo , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/prevenção & controle
3.
Eur J Clin Invest ; 46(7): 651-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27240092

RESUMO

BACKGROUND: Tacrolimus (TCR) is an immunosuppressive drug used by oral administration. Intravenous (IV) TCR administration is required under conditions of gastrointestinal diseases or abdominal surgery at the onset of paralytic ileus. The infusion formulation needs a large dilution and therefore a careful technical management during continuous infusion by 24 h and may determine anaphylaxis, cardiac arrhythmia, QT prolongation and torsades de pointes. Sublingual (SL) TCR administration was suggested as an alternative route. DESIGN: The aim of this study was to compare in the same kidney transplanted patients the TCR pharmacokinetic profiles by both the routes coupled with the pharmacoeconomic analysis. The study enrolled eight subjects undergoing renal transplantation and treated with TCR and methylprednisolone. TCR was administered by oral route at the scheduled dosage while the 50% of oral dosage was used by SL route, taking into account the absence of liver first pass. RESULTS: Except for AUC, which resulted significantly increased after oral administration, all exposure parameters were not significantly different between the two routes of administration. Analysis of dose-adjusted exposure parameters showed significant increases in AUC and Cmin after SL administration confirming a better bioavailability of the SL route compared with oral route. Cost saving was obtained using the SL rather than the IV route of TCR delivery. CONCLUSION: When oral administration of TCR is not advised, SL delivery represents an attractive option to IV administration.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim , Tacrolimo/administração & dosagem , Administração Oral , Administração Sublingual , Adulto , Área Sob a Curva , Disponibilidade Biológica , Cálculos da Dosagem de Medicamento , Farmacoeconomia , Feminino , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Infusões Intravenosas/economia , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Tacrolimo/sangue
4.
J Clin Pharmacol ; 50(5): 576-80, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20089827

RESUMO

This study investigates the potential pharmacokinetic interactions between an antimicrobial agent, moxifloxacin, and 2 immunosuppressant drugs, cyclosporine and tacrolimus, in kidney transplant recipients. Twenty-two kidney transplant patients needing antibiotic therapy for urinary tract infections are enrolled. Eleven patients are under cyclosporine treatment and the other 11 patients are under tacrolimus treatment. Because the urinary tract infections are caused by gram-negative aerobes sensitive to moxifloxacin, this antibiotic is administered by oral route at a dose of 400 mg/d for 1 week; in each patient pharmacokinetic studies are carried out before and at the seventh day of therapy. For both immunosuppressors, none of the pharmacokinetic parameters investigated show statistically significant differences between values obtained before and during treatment with moxifloxacin. In fact, the concentration-time profiles of monoclonal cyclosporine, polyclonal cyclosporine, and tacrolimus are not significantly different before and during the antimicrobial therapy. The results of the present study rule out interference of moxifloxacin with both cyclosporine and tacrolimus kinetics and indicate that the concomitant administration of the fluoroquinolone and cyclosporine or tacrolimus does not require modifications of the dosages of 2 immunosuppressant drugs.


Assuntos
Compostos Aza/farmacologia , Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Quinolinas/farmacologia , Tacrolimo/farmacocinética , Administração Oral , Adulto , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Compostos Aza/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Fluoroquinolonas , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Quinolinas/uso terapêutico , Tacrolimo/uso terapêutico , Fatores de Tempo , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
5.
J Nephrol ; 21 Suppl 13: S97-101, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18446740

RESUMO

Renal transplantation is associated with better survival and improved quality of life compared to maintenance dialysis. Although many sleep disorders improve or even disappear after a successful transplantation, sleep quality remains low, and the prevalence of sleep complaints, although lower than in dialysis patients, is much higher than in the general population. Few studies have dealt with sleep problems of renal transplant patients: despite reporting obvious differences in the prevalence of the single sleep disorders, all underline the importance of psychological problems in conditioning sleep. In the diagnosis of sleep disorders, the nephrologist must learn to distinguish medical risk factors (pain, pruritus, tremors, drugs) and psychological aspects (depression, anxiety, fear), since they are potentially modifiable with the appropriate treatment.


Assuntos
Nefropatias/terapia , Transplante de Rim/efeitos adversos , Qualidade de Vida , Diálise Renal/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/etiologia , Humanos , Nefropatias/cirurgia , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/psicologia
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