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1.
Transpl Int ; 33(4): 376-390, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31705694

RESUMO

Among factors determining long-term kidney allograft outcome, pretransplant renal replacement therapy (RRT) is the most easily modifiable. Previous studies analysing RRT modality impact on patient and graft survival are conflicting. Studies on allograft function are scarce, lack sufficient size and follow-up. We retrospectively studied patient and allograft survival together with allograft function and its decline in 2277 allograft recipients during 2000-2014. Pretransplant RRT modality ≥60 days as grouped into "no RRT" (n = 136), "haemodialysis (HD)" (n = 1847), "peritoneal dialysis (PD)" (n = 159), and "HD + PD" (n = 135) was evaluated. Kaplan-Meier analysis demonstrated superior 5-/10-/15-year patient (93.0/81.8/73.1% vs. 86.2/71.6/49.8%), death-censored graft (90.8/85.4/71.5% vs. 84.4/75.2/63.2%), and 1-year rejection-free graft survival (73.8% vs. 63.8%) in PD versus HD patients. Adjusted Cox regression revealed 34.5% [1.5-56.5%] lower hazards of death, whereas death-censored graft loss was similar [HR = 0.707 (0.469-1.064)], and rejection was less frequent [HR = 0.700 (0.508-0.965)]. Allografts showed higher 1-/3-/5-year estimated glomerular filtration rate (eGFR) in "PD" versus "HD" groups. Living donation benefit for allograft function was most pronounced in groups "no RRT" and "PD". Functional allograft decline (eGFR slope) was lowest for "PD". Allograft recipients on pretransplant PD versus HD demonstrated superior all-cause patient and rejection-free graft survival along with better allograft function (eGFR).


Assuntos
Falência Renal Crônica , Transplante de Rim , Aloenxertos , Estudos de Coortes , Sobrevivência de Enxerto , Humanos , Rim , Falência Renal Crônica/cirurgia , Diálise Renal , Estudos Retrospectivos , Resultado do Tratamento
2.
Amino Acids ; 51(3): 529-547, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30604095

RESUMO

We developed and validated gas chromatography-mass spectrometry (GC-MS) methods for the simultaneous measurement of amino acids and their metabolites in 10-µL aliquots of human plasma and urine. De novo synthesized trideutero-methyl esters were used as internal standards. Plasma proteins were precipitated by acidified methanol and removed by centrifugation. Supernatants and native urine were evaporated to dryness. Amino acids were first esterified using 2 M HCl in methanol and then amidated using pentafluoropropionic anhydride for electron-capture negative-ion chemical ionization. Time programmes were used for the gas chromatograph oven and the selected-ion monitoring of specific anions. The GC-MS methods were applied in clinical studies on the HELLP syndrome and pediatric kidney transplantation (KTx) focusing on L-arginine-related pathways. We found lower sarcosine (N-methylglycine) and higher asymmetric dimethylarginine (ADMA) plasma concentrations in HELLP syndrome women (n = 7) compared to healthy pregnant women (n = 5) indicating altered methylation. In plasma of pediatric KTx patients, lower guanidinoacetate and homoarginine concentrations were found in plasma but not in urine samples of patients treated with standard mycophenolate mofetil-based immunosuppression (MMF; n = 22) in comparison to matched patients treated with MMF-free immunosuppression (n = 22). On average, the global arginine bioavailability ratio was by about 40% lower in the MMF group compared to the EVR group (P = 0.004). Mycophenolate, the major pharmacologically active metabolite of MMF, is likely to inhibit the arginine:glycine amidinotransferase (AGAT), and to enhance arginase activity in leukocytes and other types of cell of MMF-treated children.


Assuntos
Amidinas/metabolismo , Aminoácidos/sangue , Aminoácidos/urina , Arginase/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Síndrome HELLP/metabolismo , Nefropatias/metabolismo , Transplante de Rim/métodos , Adolescente , Adulto , Arginina/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Imunossupressores/farmacologia , Nefropatias/tratamento farmacológico , Nefropatias/cirurgia , Metilação , Projetos Piloto , Gravidez
3.
Kidney Blood Press Res ; 43(3): 793-806, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29807363

RESUMO

BACKGROUND/AIMS: Whether the immunosuppressive regimen is associated with micro- and macro-vascular status in pediatric kidney transplant recipients (KTx) is unknown. METHODS: We performed a cross-sectional, case-control study in 44 pediatric KTx patients on either everolimus (EVR) plus calcineurin inhibitor or standard treatment, i.e. mycophenolate mofetil plus calcineurin inhibitor. Measurement of carotid intima-media thickness (cIMT) via ultrasound, central pulse wave velocity (PWV) by a cuff-based oscillometric technique, and skin microvascular blood flow during local heating via laser-Doppler-fluximetry (LDF) served as marker of subclinical vascular disease. Serum concentrations of angiopoietin-1 and -2, fibroblast-growth factor 23 (FGF23) and soluble klotho were measured. RESULTS: EVR-treated patients exhibited a similar degree of hypertension, increased cIMT, elevated pro-inflammatory angiopoietin-2, and diminished endothelial survival factor angiopoietin-1 compared to healthy children but presented with a twofold more reduced skin micro-vascular function compared to standard treatment (each p< 0.001). By contrast, PWV and soluble klotho levels were normal in both groups. CONCLUSION: Endothelial dysfunction seems more frequent in KTx patients on EVR-based immunosuppressive regimen compared to standard immunosuppression.


Assuntos
Imunossupressores/farmacologia , Transplante de Rim/efeitos adversos , Microcirculação/efeitos dos fármacos , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Endotélio/fisiopatologia , Everolimo/farmacologia , Everolimo/uso terapêutico , Fator de Crescimento de Fibroblastos 23 , Humanos , Imunossupressores/uso terapêutico , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Doenças Vasculares/diagnóstico
4.
Pediatr Nephrol ; 32(6): 1005-1011, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28180952

RESUMO

BACKGROUND: Shiga-toxin-producing Escherichia coli (STEC)-associated hemolytic-uremic syndrome (HUS) is a major cause of acute kidney injury (AKI), especially in children. Its long-term outcome with respect to endothelial damage remains largely elusive. METHODS: This was a cross-sectional study in 26 children who had suffered from STEC-HUS in the past and achieved a complete recovery of renal function (eGFR >90 ml/min/1.73 m2). Skin microcirculation after local heating was assessed by laser Doppler fluximetry, carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (cIMT), 24-h ambulatory blood pressure, and angiopoietin (Ang) 1 and 2 serum levels after a median follow-up period of 6.1 years. The results were compared to those of healthy controls. RESULTS: All patients were normotensive, mean eGFR was 102 (range 91-154) ml/min/1.73 m2, and 13 of the 26 patients showed albuminuria. Endothelial dysfunction was present in 13 patients, and the mean serum Ang2/Ang1 ratio was increased compared to healthy children (each p < 0.05). In contrast, mean values for PWV and cIMT in the patients did not differ from those of the controls. Endothelial dysfunction was significantly associated with younger age at STEC-HUS manifestation, time after HUS, and presence of albuminuria. CONCLUSION: The results of this study highlight the need for long-term follow-up of STEC-HUS patients even after complete recovery of eGFR and lack of hypertension with respect to microvascular damage.


Assuntos
Endotélio Vascular/patologia , Infecções por Escherichia coli/patologia , Síndrome Hemolítico-Urêmica/patologia , Microvasos/patologia , Escherichia coli Shiga Toxigênica/isolamento & purificação , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Adolescente , Fatores Etários , Albuminúria/sangue , Angiopoietina-1/sangue , Angiopoietina-2/sangue , Monitorização Ambulatorial da Pressão Arterial , Espessura Intima-Media Carotídea , Criança , Pré-Escolar , Estudos Transversais , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/microbiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/microbiologia , Síndrome Hemolítico-Urêmica/terapia , Humanos , Hipertensão/diagnóstico , Lactente , Masculino , Análise de Onda de Pulso , Diálise Renal , Pele/irrigação sanguínea , Fatores de Tempo
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