ABSTRACT
A incidência de infecções fúngicas invasivas tem aumentado, como consequência do contingente cada vez maior de pacientes com imunossupressão. O tratamento de infecções fúngicas com anfotericina B (AmB) está associado a efeitos adversos importantes, como nefrotoxicidade e toxicidade hematológica. Nesta revisão buscou-se abordar os estudos sobre AmB nas diferentes formulações, focando em suas características farmacológicas e toxicidade. Formulações lipídicas de AmB estão associadas a um risco menor de nefrotoxicidade, entretanto ainda há controvérsia sobre diferenças entre as duas formulações lipídicas de AmB disponíveis. Diferenças em relação ao perfil imunomodulatório e ligação a lipoproteínas podem explicar parte das diferenças clínicas existentes entre as formulações de AmB. A maioria dos estudos clínicos que avaliou a nefrotoxicidade associada à AmB em diferentes formulações não utilizou critérios validados para classificação do dano renal, o que dificulta sua comparação. A toxicidade hematológica relacionada ao uso de AmB é um fenômeno descrito desde os primórdios do seu uso clínico, entretanto poucos dados existem sobre sua frequência, fatores de risco e impacto nos desfechos clínicos. Dados precisos, e adequados ao contexto local, sobre a toxicidade de AmB nas suas diferentes formulações são necessários para uma adequada avaliação dos aspectos de farmacoeconomia e custo-efetividade...
Invasive fungal infections have emerged in recent years, as a consequence of increasing numbers of immunosuppressed patients. Treatment of these conditions with amphotericin B (AmB) has been associated with important side effects, such as nephrotoxicity and hematological toxicity. In this review we aimed to assess studies about different formulations of AmB, focusing on pharmacological properties and toxicity. Lipid formulations of AmB have been linked to a lower risk of nephrotoxicity; however, there is still controversy about differences between the two available lipid formulations. Differences in immunomodulatory profile and lipoprotein binding could partly explain clinical inequalities among AmB formulations. Most clinical trials that evaluated AmB-associated nephrotoxicity did not use validated criteria for renal injury classification, impairing comparability. Hematological toxicity associated with AmB treatments is an occurrence described since the beginning of its clinical use; nevertheless, few data exist about its frequency, risk factors, and clinical impact. Clear and more precise information, derived from local studies, is needed to an adequate evaluation about pharmacoeconomic aspects of AmB treatment and cost-effectiveness of lipid formulations...
Subject(s)
Humans , Amphotericin B/adverse effects , Amphotericin B/toxicity , Blood Chemical Analysis , Kidney Diseases/chemically inducedABSTRACT
Objective To investigate the change of expression of toll like receptor 4( TLR4)on peripheral blood monouclear cells( PBMC) and clinical significance of sepsis acute kidney injury( AKI) patients. Methods ICU admission diagnosis of sepsis patients from May 2012 to December 2013 in the Zhongxin Hospital of Handan were diagnosed AKI according to the KDIGO guidelines of 2012 and were divided into AKI group and non AKI. Meanwhile,patients with AKI were also divided into group Ⅰ(KDIGO Ⅰ period);group Ⅱ( KDIGO Ⅱ period)and group Ⅲ( KDIGO Ⅲ period)according to the AKI stages. Thirty cases health patients were elected as the control group. The expression levels of TLR4,human leucocyte antigen(HLA-DR)on PBMC with of sepsis patients were detected with the flow cytometry. The levels of interleukin-6(IL-6) and interleukin-10(IL-10)in serum were detected by enzyme linked immunosorbent assay(ELISA). The length of ICU stay,ICU mortality and the APACHE Ⅱ in 24 h were recorded. Results (1)The expression levels of TLR4 in sepsis AKI patients was(34. 45 ± 9. 54),higher than that in patients without AKI and control group ((26. 29 ± 6. 76,10. 72 ± 8. 82;F = 55. 351,P < 0. 01). The expression of TLR4 in sepsis AKI patients was higher than sepsis patients without AKI(P < 0. 05). There was significant difference among sub AKI groups in terms of TLR4(F = 13. 235,P < 0. 01),and it significantly lower in group Ⅲ among three groups.(P < 0. 05 or P < 0. 01).(2)The levels of IL-6,IL-10 in sepsis AKI group were(565. 81 ± 106. 27)ng/ L,(76. 78 ± 12. 33) ng/ L,higher than those in non AKI group and control group((321. 85 ± 76. 62)ng/ L,(38. 53 ± 9. 93)ng/ L;(84. 36 ± 36. 91)ng/ L,(17. 53 ± 6. 08)ng/ L;F = 264. 962,254. 398,P < 0. 01). While,the levels of IL-6,IL-10 in sepsis AKI group were higher than those in non AKI group(P < 0. 05). However,there was no significant difference among three sub AKI groups in terms of IL-6 levels. The IL-10 level in group Ⅲ was highest among three sub AKI groups(P < 0. 05).(3)ICU mortality in sepsis AKI group and non AKI group were 34. 8% and 14. 8%(χ2 = 3. 410,P = 0. 065). Meanwhile,ICU mortality in three sub-AKI groups were 20. 0% ,33. 3% , 57. 1% ,and there was no significant difference(P = 0. 120). The length of ICU stay in non ALI group was(4. 14 ± 1. 65)d,shorter than that in AKI group(10. 52 ± 3. 70)d;t = 8. 201,P = 0. 000). Meanwhile,The length of ICU stay in three sub-AKI groups were(8. 93 ± 1. 81)d,(10. 17 ± 2. 31)d,(14. 71. ± 2. 81)d,and the difference was significant(F = 19. 052,P = 0. 000). APACHE-Ⅱ in three sub-AKI groups Ⅰ,group Ⅱ,groupⅢ were 20. 20 ± 4. 07,21. 00 ± 3. 16,30. 57 ± 2. 44 respectively and the difference was significant(P < 0. 05 or P < 0. 01). Conclusion TLR4 mediated inflammation is involved in the sepsis AKI process. Because the damage degree of AKI is aggravating,immune factors also participate in the development of AKI. And with the decrease of HLA-DR,the probability of RRT increases.
ABSTRACT
Objective To compare the impact of conventional vs. zero-balanced ultrafiltration on serum pro-inflammatory factors,acute kidney injury and clinical prognosis after cardio-pulmonary bypass procedure. Methods Forty patients receiving cardiac surgery under cardio-pulmonary bypass procedures in Xiangyang Central Hospital during January 2013 to June 2013 were randomly divided into conventional ultrafiltration group(group A,n=20)and zero-balanced ultrafiltration group(group B,n=20). Blood and urine samples were collected on different time points( pre-operation,T0;pre-ultrafiltration,T1;immediately after ultrafiltration,T2;24 hours post-operation,T3;48 hours post-operation,T4;7 days post-operation, T5). TNF-α,IL-6,KIM-1,CysC,serum creatinine and urea nitrogen were detected and compared. Pre-and post-operative clinical data were also collected. Results There was no difference in baseline data or intra-operative data(p>0. 05). TNF-αand IL-6 started to increase when the operation began. Compared with conventional ultrafiltration,zero-balanced ultrafiltration alleviated the increase of TNF-α and IL-6,espe-cially on T2,T3,and T4(pgrade I)in group A and 2 patients experienced in group B(p<0. 01). There were significant differences of ventilation time,total complication incidence and ICU stay time be-tween two groups. There was no difference in other complications,post-operative days in hospital or death rate within 30 days. Conclusion Though there is a trend of more patients receving renal replacement therapy,no statistical difference has been achieved. In conclusion,zero-balanced ultrafiltration can effec-tively decrease the concentration of serum pro-inflammatory factors,alleviate acute kidney injury and improve the clinical prognosis after cardio-pulmonary bypass procedures. It is a safe and reliable method valuable for promotion.