Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients.

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. Objective: Analyze the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients’ records, in which the patient’s profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions ® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (±5.4) different medicines after the transplantation, and 7.4 (±4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs’ effects were related to, mainly, increase their immunosuppressant activity. Discussion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs’ effects to prevent and minimize side effects in transplanted recipients

Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients.

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. Objective: Analyze the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients’ records, in which the patient’s profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions ® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (±5.4) different medicines after the transplantation, and 7.4 (±4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs’ effects were related to, mainly, increase their immunosuppressant activity. Discussion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs’ effects to prevent and minimize side effects in transplanted recipients

Antithymocyte globulin and everolimus effects on T and B peripheral lymphocyte profile in the elderly, kidney-transplant recipients

Introdução: Apesar do número crescente de idosos transplantados renais, poucos estudos descrevem os efeitos de imunossupressores ou as alterações imunológicas desta população. Receptores idosos apresentam menor incidência de rejeição aguda, mas maior incidência de complicações infecciosas e neoplasias. Neste estudo avaliamos os efeitos da doença renal crônica e do envelhecimento no sistema imune de idosos candidatos a transplante, bem como efeitos da indução com globulina antitimócito (ATG) e da conversão precoce para everolimo após o transplante. Materiais e métodos: Na situação basal comparamos 4 grupos: a- voluntários adultos jovens sadios (AdS) (n=14, 26±2anos); b- voluntários idosos sadios (IdS) (n=15, 79±7anos); c- pacientes adultos jovens com doença renal crônica (AdDRC) (n=18, 36±7anos) e; dpacientes idosos com doença renal crônica (IdDRC) (n=31, 65±3anos) antes de transplante renal. Na avaliação após transplante, comparamos três grupos de pacientes transplantados: a- adultos jovens (n=20, 36±7anos) em uso de imunossupressão padrão (AdISP), (prednisona, tacrolimo e micofenolato sódico); b- idosos em uso de imunossupressão padrão (IdISP) (n=35, 65±3anos) ou c- Idosos em imunossupressão padrão convertidos precocemente para everolimo (IdCEv) (n=16, 65±3anos). Todos os pacientes transplantados receberam indução com dose única de ATG 2,0mg/Kg. Foram avaliadas as populações de linfócitos T e B periféricos de perfis naive, memória e regulador nas análises basais e nos grupos de transplante após 0d, 30d, 60d e 365d do transplante. Resultados: Envelhecimento e doença renal crônica apresentaram efeito aditivo em reduzir os números de linfócitos T [AdS=1737(1446-1933) vs. IdS=1172(934-1360) vs. AdDRC=1238(847-1599) vs. IdDRC= 718(484- 993)cels/mm3, DRC p 0,9999]. Os adultos jovens não apresentaram mudanças nos números de linfócitos totais nos períodos avaliados [2100(1630-2400) vs. 1960(1270-2970) vs. 1850(1590-2120)cels/mm3]. Tanto em idosos [8,2(5,3-12,9) vs. 6,7(4,4-11)%, p= 0,049] como em adultos jovens [6,2(3,8-10,8) vs. 5,3(2,5-7,3)%, p=0,036], os percentuais de linfócitos T de memória central apresentaram redução transitória no pós-transplante recente com recuperação após 1 ano. No transplante tardio, idosos em imunossupressão padrão apresentavam maiores percentuais de linfócitos T de memória central [21,2(10,9-28) vs. 8,6(5-13,5)%, p=0,048] e menores percentuais de linfócitos T com reexpressão de RA comparado [7,2 (5,5-11,4) vs. 15,7(9,1-30,2)%, p=0,048] a adultos jovens. Os linfócitos T reguladores apresentaram redução em seus valores percentuais tanto nos adultos jovens [1,29(0,45-1,85) vs. 0,84(0,18- 1,82)%, p=0,038] como nos idosos [2,1(1,23-3,51) vs. 1,69(0,8-2,66)%, p=0,028], entretanto, no transplante tardio nos idosos [IdISP=2,04(0,88-2,42)%, p=0,062 e IdCEv=0,83(0,41-1,09)%, p=0,19] houve recuperação dos valores basais, enquanto nos adultos jovens os percentuais permaneceram reduzidos [0,86(0,7-1,34)%, p=0,016]. Adultos jovens [8,33(5,56-11,2) vs. 14,1(9,37- 18,95)%, p=0,0008] e idosos [6,41(3,46-8,93) vs. 11,5(6,46-18,8)%, p 0,9999]. The young adults had no changes in lymphocyte counts [2100(1630-2400) vs. 1960(1270-2970) vs. 1850(1590-2120)cells/mm3]. Both, elderly [8,2(5,3-12,9) vs. 6,7(4,4-11)%, p= 0,049] and young adults [6,2(3,8- 10,8) vs. 5,3(2,5-7,3)%, p=0,036], presented decrease in central memory Tlymphocytes percentages early after transplantation, with return to baseline within 1 year. Elderly in standard immunosuppression presented higher percentages of central memory T-cells [21,2(10,9-28) vs. 8,6(5-13,5)%, p=0,048] and lower percentages of effector memory T-cells with RA reexpression [7,2 (5,5- 11,4) vs. 15,7(9,1-30,2)%, p=0,048] later after transplantation compared to adult recipients. In elderly [2,1(1,23-3,51) vs. 1,69(0,8-2,66)%, p=0,028] and young adults [1,29(0,45-1,85) vs. 0,84(0,18-1,82)%, p=0,038], regulatory T-cells percentages decreased in early transplantation, but while in elderly the percentages returned to baseline within one year [EldSI=2,04(0,88-2,42)%, p=0,062 e EldEC=0,83(0,41-1,09)%, p=0,19], in young adults the percentages remained lower than baseline late after transplantation[0,86(0,7-1,34)%, p=0,016]. Both, young adults [8,33(5,56-11,2) vs. 14,1(9,37-18,95)%, p=0,0008] and elderly [6,41(3,46-8,93) vs. 11,5(6,46-18,8)%, p < 0,0001] presented an elevation in B cells percentage within 30 days, with rise in counts [young adults - 43,98(22,57-52,21) vs. 97(37,99-123,2)cells/mm3, p=0,0003 and elderly - 21,35(9,56-30,34) vs. 25,93(16,51-45,72)cells/mm3, p=0,0129] and percentages [young adults - 28,2(19,25-34,88) vs. 31(22,85-37,85)%, p =< 0,0001 and elderly - 22,5(15,4-33,78) vs. 31,2(20,7-36,5)%, p=0,0002] of B memory lymphocytes and lowering of B regulatory percantages [young adults - 7,93(5,09-10,45) vs. 4,46(3,03-5,26)%, p < 0,0001 and elderly - 9,94(6,46-14,1) vs. 7,12(4,53-8,93)%, p < 0,0001]. Conclusions: Lower counts of lymphocyte populations and memory pattern in lymphocyte composition are observed for aging and CKD. Aging presented association with regulatory profile, with higher regulatory T-cells percentages, while CKD resulted in lower percentages of regulatory T-cells. Time to refilling of peripheral lymphocyte counts after thymoglobulin infusion in elderly suggests that ATG in standard dosing should be considered, in spite of immunosuppressive maintenance regimen. We could not observe favoring of ATG or everolimus conversion on regulatory profile, although ATG modified memory lymphocyte percentages. Aging favored regulatory T-cell occurrence in late transplantation in spite of the immunosuppressive regime

Glomeruloesclerose segmentar e focal (GESF) colapsante associada ao parvovírus B19: relato de caso

Objetivo: Descrever quadro cl&#237;nico-laboratorial de glomeruloesclerose segmentar e focal (GESF) subtipo colapsante em associa&#231;&#227;o com infec&#231;&#227;o por parvov&#237;rus B19 (PVB19). Relato do caso: Paciente feminino, 37 anos, parda, iniciou quadro de faringoalgia e febre aferida com melhora parcial ap&#243;s penicilina. Com uma semana, observou redu&#231;&#227;o de d&#233;bito urin&#225;rio e edema de membros inferiores. Tabagista, com hist&#243;rico familiar e pessoal negativos para hipertens&#227;o, diabetes ou nefropatias. &#192; admiss&#227;o, apresentava-se com oliguria, hipertens&#227;o e edema, associados &#224; anemia microc&#237;tica e hipocr&#244;mica hipoproliferativa, protein&#250;ria nefr&#243;tica, hemat&#250;ria microsc&#243;pica e altera&#231;&#227;o da fun&#231;&#227;o renal. A investiga&#231;&#227;o reumatol&#243;gica e sorologias para hepatites e HIV foram negativas. Ultrassonografia de rins e vias urin&#225;rias sem altera&#231;&#245;es. PCR foi positivo para PVB19 em aspirado de medula &#243;ssea e sangue. A bi&#243;psia renal conclusiva de GESF subtipo colapsante. Ocorreu remiss&#227;o espont&#226;nea com duas semanas do quadro. Em retorno ambulatorial, o PCR em sangue perif&#233;rico foi negativo para PVB19, sugerindo associa&#231;&#227;o de GESF colapsante a fase aguda ou reativa&#231;&#227;o da infec&#231;&#227;o viral. Conclus&#227;o : Este relato registra a associa&#231;&#227;o temporal entre GESF colapsante e viremia pelo PVB19, seja por infec&#231;&#227;o aguda ou reativa&#231;&#227;o de infec&#231;&#227;o latente. A associa&#231;&#227;o GESF colapsante e PVB19 &#233; descrita na literatura, com demonstra&#231;&#227;o da presen&#231;a do v&#237;rus em tecido renal, por&#233;m, a real rela&#231;&#227;o do v&#237;rus na patog&#234;nese dessa glomerulopatia permanece indefinida

Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients.

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. Objective: Analyze the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients’ records, in which the patient’s profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions ® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (±5.4) different medicines after the transplantation, and 7.4 (±4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs’ effects were related to, mainly, increase their immunosuppressant activity. Discussion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs’ effects to prevent and minimize side effects in transplanted recipients

Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients.

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. Objective: Analyze the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients’ records, in which the patient’s profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions ® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (±5.4) different medicines after the transplantation, and 7.4 (±4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs’ effects were related to, mainly, increase their immunosuppressant activity. Discussion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs’ effects to prevent and minimize side effects in transplanted recipients

Análise de registros eletrocardiográficos associados ao infarto agudo do miocárdio Analysis of electrocardiographic recordings associated with acute myocardial infarction

OBJETIVO: Avaliar correlações entre as variações do eletrocar­diograma (ECG) e o infarto agudo do miocárdio. MÉTODOS: Uso de software de baixo custo para digitalização de ECG impressos e/ou em formato "pdf". Cálculo de área do segmento ST e das amplitudes dos pontos J e Y RESULTADOS: A amplitude do ponto Y possui máxima correlação com a concentração da enzima troponina. O supradesnivelamento do segmento ST não se constitui bom indicador estatístico da gravidade do infarto. Existe uma forte correlação negativa entre a amplitude do ponto J e a quantidade de íons magnésio, mas nenhuma correlação estatística com os íons sódio ou cálcio. Os dois métodos de cálculo da área do segmento ST (contagem de pixels e interpolação) não mostraram diferenças significativas nos resultados. CONCLUSÃO: O software utilizado mostrou-se viável do ponto de vista econômico e funcional. A amplitude do ponto Y é um marcador sensível à ocorrência do infarto, tendo cálculo mais simples e menos sujeito a erros do que o cálculo da área de supradesnivelamento do segmento ST.<br>OBJECTIVE: Evaluate correlations between variations in eletrocardiogram (ECG) recordings and acute myocardial infarction. METHODS: Use of a low-cost software to digitalize printed and/or ".pdf" file format ECG recordings. Calculation of ST-segment area and amplitudes of the J and Y points. RESULTS: The amplitude of the Y point holds maximum correlation with troponin concentration. ST-segment elevation is not a good statistical indicator of myocardial infarction severity. There is a strong negative correlation between the amplitude of the J point and the amount of magnesium ions, but no statistical correlation with sodium or calcium ions. Neither method for calculating the ST-segment area (pixel counts and interpolation) indicated any significant differences in the results. CONCLUSION: The software used proved to be functional and cost-effective. Y point amplitude is a sensitive marker of myocardial infarction, and is also a calculation method both simpler to use and less subject to error than the calculation of the ST-segment elevation area