Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

Workshop on Late Renal Allograft Dysfunction

Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation.     

Mycophenolate Mofetil Is Associated with Altered Expression of Chronic Renal Transplant Histology

Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking. We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry. MMF reduced acute rejection and OKT3 use (p < 0.05) compared with AZA. MMF therapy was associated with limited chronic interstitial fibrosis, striped fibrosis and periglomerular fibrosis (p < 0.05-0.001), mesangial matrix accumulation (p < 0.01), chronic glomerulopathy scores (p < 0.05) and glomerulosclerosis (p < 0.05). MMF was associated with delayed expression of CSA nephrotoxicity, reduced arteriolar hyalinosis, striped fibrosis and tubular microcalcification (p < 0.05-0.001). The beneficial effects of MMF remained in recipients without acute rejection. Retrospective analysis shows that MMF therapy was associated with substantially reduced fibrosis in the glomerular, microvascular and interstitial compartments, and a delayed expression of CSA nephrotoxicity. These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis.     

低铁与低热量饮食延缓糖尿病肾病的进展

目的探讨低铁与低热量饮食是否能延缓糖尿病肾病的进展。方法以168例Ⅱ型糖尿病肾病患者为研究对象,随机分为两组,对照组予以常规治疗,治疗组在进行同样常规治疗的同时,予低铁、低热量饮食。结果平均随访37±22个月,治疗组患者血清铁水平显著降低,与对照组比较,有显著差异(P<0.01);治疗组血清肌酐189±78μmmol/L,对照组257±115μmmol/L,两组比较,有显著差异(P<0.01)。治疗组有6例患者达到终止随访目标,血红蛋白低于80g/L和或红细胞压积<33%,需进行促红素治疗,占17.6%;对照组有10例达到终止目标,占35.7%,两组比较,有显著差异(P<0.01)。结论低铁饮食治疗能显著降低糖尿病肾病患者铁负荷,配合低热量饮食治疗,能明显延缓糖尿病肾病的进展。     

刺五加注射液及抗凝剂对糖尿病足的早期干预治疗

目的观察刺五加注射液及抗凝剂(潘生丁、肠溶阿斯匹林)对糖尿病足早期干预治疗的影响。方法将符合1999年WHO诊断标准的100例糖尿病合并早期足病变的患者分为两组:干预治疗组50例,对照组50例。在控制血糖、血压、糖尿病教育的基础上,干预组予以静滴刺五加注射液及口服抗凝剂(潘生丁、肠溶阿斯匹林)治疗,对照组为口服VitB1、VitB6、复方丹参片治疗。观察治疗前后两组患者足背动脉搏动、皮肤颜色、温度,痛、温、触觉等相关指征,血糖、HbA1c、血TG、TC、HDL-C,及血流变学、眼底病变、心脑血管事件发生率等。结果干预组糖尿病足病变治疗好转率高,恶化发展率低,心脑血管事件发生率少。血脂、血流变学、下肢血管多普勒彩超及眼底病变等好转改善明显,与对照组比较差异有统计学意义(P<0.05或P<0.01)。结论刺五加注射液及抗凝剂(潘生丁、肠溶阿斯匹林)对糖尿病足病变的早期干预治疗疗效显著,有重要的临床意义。     

原发性高尿酸血症肾病的中西医治疗探讨

既往认为高尿酸血症肾病是西方国家的一种常见病,在中国少见。近年来,由于经济情况好转,饮食结构的变化,蛋白质及富含嘌呤成分的食物摄入量增加,中国发病率有增高的趋势。因此文章旨在通过探讨原发性高尿酸血症肾病的诊断及其中西医治疗方法,希望能够对临床及时正确的诊断和恰当周全的治疗该病提供一定的指导。     

灌注液对糖尿病玻璃体切割手术中角膜内皮的影响

目的 评价不同灌注液对糖尿病玻璃体切割手术中角膜内皮细胞的影响。方法 对30例术中应用BSS或BSSPlus的糖尿病玻璃体切割手术眼的角膜内皮细胞密度和细胞面积变异系数进行前瞻性研究．结果 无囊膜组中应用BSSPlus的玻切手术眼角膜内皮细胞密度、细胞面积变异系数与应用BSS的手术眼之间存在明显差异，在有囊膜组中二者之间无明显差异。结论 对于囊膜不完整的糖尿病患者玻切手术中使用BSSPlus可减轻手术对角膜内皮细胞的损害。     

Fiberglass or silica exposure and increased nephritis or ESRD (end-stage renal disease)

The U.S. multiplant cohort mortality study of workers producing manufactured mineral fibers is finding increasing mortality from nephritis and/or nephrosis. We examine other data sets to see if similar effects can be identified. In a case-referent study among Michigan patients with end-stage renal disease (ESRD), men with exposures to silica have elevated odds ratio for ESRD. In a California occupational mortality study based on 1979–81 data, a number of the construction trades, farmers, and farm laborers show excess mortality for renal disease. The highest mortality ratio is found in the category including insulation workers. This ratio remains significantly elevated when adjusted for estimated exposures to smoking, alcohol, and for socio-economic status. California mortality data from 20 years earlier (1959–61) fail to show much excess renal disease in construction workers, but do for farmers. In Singapore, granite workers with a long-term exposure to silica have excess excretion of albumin and similar compounds compared to less exposed controls, leading to the presumption that silica exposure can lead to silica nephrotoxicity. Balkan nephropathy has been associated with consumption of well water high in silica. In the Negev of Israel, dust storms are a vehicle for increasing respiratory uptake of silica. The Beduin, thought to be a population with maximal exposures, have higher rates of ESRD than do Jews in the age groups over 60 years. Although high blood concentrations of silica are found in persons with renal failure, the close association with elevated creatinine has been interpreted as evidence that the buildup of silica is due to renal failure, rather than vice-versa. The evidence is consistent with, but not yet compelling, that exposure to silica, which can be readily absorbed (or dissolved) from the lung, may increase the long-term risk of renal disease including renal failure. © 1993 Wiley-Liss, Inc.     

Idiopathic membranous glomerulonephritis in Brazil

Summary: A survey of the medical records and renal biopsy reports of 41 patients with a diagnosis of membranous glomerulonephritis seen at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo was undertaken between 1961 and April 1992. Twenty-three of these patients were found to have idiopathic membranous glomerulonephritis (IMG) and 22 of them were treated with corticosteroids and/or immunosuppressants. Data for these 22 patients showed that the age at clinical presentation was 36.3± 17.5 years, white skin colour predominated (14 patients), and 15 were males; nephrotic syndrome was the clinical presentation in 20 patients and proteinuria was accidentally discovered in two patients. On the first hospital visit 11 patients presented proteinuria of up to 3 g/24 h and 16 presented serum creatinine below 1.5 mg/dL, and 14 developed renal hypertension during follow up. Clinicalmorphological correlation permitted us to conclude (in agreement with the literature) that advanced patient age, intensity of proteinuria, serum creatinine levels above 1.5 mg/dL on the occasion of the first hospital visit, and arterial hypertension are clinical-laboratory factors indicating a poor prognosis for IMG. More advanced staging of glomerular damage, presence of segmental mesangial sclerosis and tubulointerstitial involvement are microscopic factors indicating a poor prognosis for IMG.