Lipo-PGE1对局灶节段性肾小球硬化患者血管内皮生长因子生成影响研究

目的 :观察前列腺素E1脂微球载体制剂 (Lipo PGE1)对原发性肾病综合征局灶节段性肾小球硬化 (FS GS)患者血管内皮生长因子 (VEGF)生成的影响。方法 :39例肾活检确诊为FSGS患者随机分为治疗组 2 0例 ,未治疗组 19例 ,另选性别、年龄相匹配的健康查体者 2 0例作为对照组。治疗组用Lipo PGE110 μg ,未治疗组用ATP 2 0mg ,两组药物均溶于 10 0ml生理盐水中静脉滴注 ,1次 /d ,2周为 1疗程。 1疗程完成后采用ELISA方法测定三组血、尿VEGF水平 ,同时测定三组内生肌酐清除率和 2 4h尿蛋白定量。结果 :FSGS组血、尿VEGF及 2 4h尿蛋白定量与对照组相比明显增高 ,内生肌酐清除率较低 ;治疗组血、尿VEGF浓度显著下降 ,2 4h尿蛋白定量明显降低 ,内生肌酐清除率上升。两两比较P <0 .0 5 ,差异有统计学意义。结论 :Lipo PGE1治疗FSGS可以有效减轻蛋白尿 ,改善肾功能 ,对早期防治慢性肾衰竭有重要意义 ,VEGF的表达生成与治疗作用有一定的关系。     

Rho-GTPase Activating Protein myosin MYO9A identified as a novel candidate gene for monogenic focal segmental glomerulosclerosis

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Recurrence of focal segmental glomerulosclerosis in renal allograft: An in‐depth review

Vinai M, Waber P, Seikaly MG. Recurrence of focal segmental glomerulosclerosis in renal allograft: An in‐depth review.
Pediatr Transplantation 2010: 14: 314–325. © 2010 John Wiley & Sons A/S. Abstract: Focal segmental glomerulosclerosis is a major cause of chronic kidney disease requiring transplantation in children. Recurrence rate in the renal allograft transplantation is as high as 50%. Recurrence of FSGS is associated with renal dysfunction and early graft loss. To date, there is no established therapy for recurrent FSGS after renal transplant. We have reviewed the current English literature in order to summarize current practices with emphasis on graft outcome. We conclude that despite multiple approaches to the post transplant management of recurrent FSGS, none have been shown to be consistently beneficial. Currently, pheresis combined with high dose anti‐calcineurin with or without rituximab seems to be the most promising. Further controlled studies are needed to define the optimal therapeutic regimens to treat recurrent of FSGS.     

Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD

Apolipoprotein L1 gene (APOL1) G1 and G2 variants are strongly associated with progressive nondiabetic nephropathy in populations with recent African ancestry. Selection for these variants occurred as a result of protection from human African trypanosomiasis (HAT). Resequencing of this region in 10 genetically and geographically distinct African populations residing in HAT endemic regions identified eight single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium and comprising a novel G3 haplotype. To determine whether the APOL1 G3 haplotype was associated with nephropathy, G1, G2, and G3 SNPs and 70 ancestry informative markers spanning the genome were genotyped in 937 African Americans with nondiabetic ESRD, 965 African Americans with type 2 diabetes–associated ESRD, and 1029 non-nephropathy controls. In analyses adjusting for age, sex, APOL1 G1/G2 risk (recessive), and global African ancestry, the G3 haplotype was not significantly associated with ESRD (P=0.05 for nondiabetic ESRD, P=0.57 for diabetes-associated ESRD, and P=0.27 for all-cause ESRD). We conclude that variation in APOL1 G3 makes a nominal, if any, contribution to ESRD in African Americans; G1 and G2 variants explain the vast majority of nondiabetic nephropathy susceptibility.     

Clinical Features and Histology of Apolipoprotein L1-Associated Nephropathy in the FSGS Clinical Trial

Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone.     

儿童原发性局灶节段性肾小球硬化的临床与病理特点

目的 探讨原发性局灶节段性肾小球硬化(FSGS)的病理诊断和病理特点,提高对本病的诊断水平.方法 对2005年6月至2013年6月病理确诊的72例原发性FSGS患儿的临床资料进行回顾性分析.依据2004年原发性FSGS组织病理学分型标准,分为非特异型、顶部型、细胞型、门部型、塌陷型5个亚型,比较不同病理分型的病理和临床特点.结果 72例原发性FSGS患儿中,非特殊型占56.9％,顶端型占22.2％,细胞型占16.7％,门部型占2.8％,塌陷型占1.4％.本病临床表现以肾病综合征为主,顶部型以单纯型肾病综合征为主(87.5％),非特殊型以肾炎型肾病综合征为主(78.0％).结论 FSGS临床及病理表现不均一,不同病理类型之间存在差异.顶部型FSGS诊断的确立依赖标本中肾小球的数目,细胞型FSGS诊断不依赖标本中肾小球的数目.电镜下足细胞空泡变性易见于非特殊型局灶节段性肾小球硬化患儿.全面评价各型FSGS临床病理特征,有助于提高诊断的准确性.