检测肾病综合征患者尿中足细胞的临床意义

目的:探讨尿中肾小球上皮细胞(足细胞)检测在人局灶节段性肾小球硬化症(focal segmental glomerulosclerosis,FSGS)诊断中的意义.方法:病例选自我科经肾活检病理证实的FSGS患者12例,微小病变性肾小球病(minimal change disease,MCD)20例,8例健康人作对照.取晨尿离心,沉渣甩片,间接免疫荧光法检测尿中足细胞特异蛋白Podocalyxin(PCX)阳性染色细胞.采用免疫荧光法检测肾小球足细胞PCX的表达.结果:FSGS组尿中足细胞阳性8例(阳性率66.67%),MCD组和正常对照组中尿足细胞均为阴性.FSGS患者中,尿足细胞阳性者临床上呈肾病综合征表现.FSGS患者肾活检标本中,肾小球内均可见足细胞特异标记蛋白PCX表达呈节段性缺失,并与肾小球节段硬化部位一致;而MCD患者肾活检标本的肾小球中,上述标记蛋白表达完整.结论:在肾病综合征中,尿足细胞检测可作为FSGS与MCD鉴别的一项可靠、方便、无创性的辅助手段.     

Kidney biopsies can be used for estimations of glomerular number and volume: a pig study

In this study, we wanted to evaluate the use of kidney biopsies for estimation of N(glom) and V(glom) in both healthy and chronically diseased kidneys. Danish Landrace pigs with mean weight of 29 kg (range: 25–35 kg) were either subjected to unilateral ureteral obstruction (UUO) or non-obstruction (healthy). N(glom) and V(glom) was estimated by design-based methods using biopsies, N(glom)^biopsy and V(glom)^biopsy. From each kidney, six biopsies were withdrawn at six topographically different sites. All estimates were done following stereological principles and reference methods estimated number with the physical fractionator, N(glom)^PF, and volume with test point system, V(glom)^TPS. N(glom)^PF was for UUO kidneys and for healthy kidneys. N(glom)^biopsy was (p > 0.05) for UUO and (p = 0.04) for healthy kidneys. When UUO and healthy kidneys were grouped, N(glom)^PF was , and N(glom)^biopsy was (p > 0.05). V(glom)^TPS was 1,079 ± 126 mm³ for UUO and 1,707 ± 263 mm³ for healthy kidneys. V(glom)^biopsy was 1,048 ± 291 mm³ for UUO (p > 0.05) and 1,373 ± 393 mm³ for healthy kidneys (p > 0.05). When UUO and healthy kidneys were grouped, V(glom)^TPS was 1,180 ± 229 mm³ and V(glom)^biopsy 1,129 ± 334 mm³ (p > 0.05). Biopsy sites were tested for any systematic differences between site- and mean values, and no significant difference was found (p > 0.05). This study showed that biopsies can be used for estimating N(glom) and V(glom) by design-based methods, but more precise determination of biopsy volume is needed.     

8例高血压急症相关性肾损害的临床病理分析

目的探讨高血压急症相关肾损害的临床、病理特点和预后。方法回顾性分析2003年1月至2014年1月我院明确诊断的8例高血压急症相关性肾损害患者,所有患者均行肾活检病理检查,及相关实验室及影像学检查。结果患者初始平均收缩压/舒张压（232±30/140±13）mm Hg,平均血肌酐值（452±172）μmol/L（190-922）μmol/L。光镜检查显示：所有的肾活检标本均有小动脉洋葱皮样增厚,及肾小球毛细血管袢缺血皱缩,然而未见到小动脉纤维素样坏死。降血压治疗对所有患者有效,并明显改善患者肾功能。结论高血压急症相关肾损害最常见的病理表现是小动脉洋葱皮样增厚和肾小球毛细血管袢缺血性皱缩;严格控制血压可显著改善高血压急症相关肾损害的预后。     

Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte Injury

Open in a separate window     

IgG Fc membrane receptor on normal human glomerular visceral epithelial cells

Summary This study demonstrates that human glomerular epithelial cells are able to bind heat aggregated immunoglobulins and antigen-antibody complexes. This has been observed on kidney cryostat sections, on whole glomeruli and on cultured visceral epithelial cells. Binding depends on the presence of the Fc portion of IgG and occurs in the absence of complement, showing that the IgG Fc receptor is different from the C3b receptor. The use of heat aggregated anti-peroxidase IgG and of peroxidase anti-peroxidase complexes allowed us to demonstrate, at the ultrastructural level, that the binding of the reagents at the plasma membrane was followed by their internalization within coated pits of vesicles. These observations strongly suggest that glomerular visceral epithelial cells are capable of receptor mediated endocytosis. The role of this process in glomerular diseases remains to be established.     

RhoA和ROCK蛋白在高脂饮食幼鼠肾小球中的表达及其意义

目的：探讨RhoA和ROCK蛋白在高脂饮食（HFD） C57BL/6J幼鼠肾小球中的表达,阐明RhoA/ROCK通路是否与HFD诱导的肾小球损伤有关。方法：36只雄性C57BL/6J幼鼠随机分为正常对照组和HFD组,每组18只,正常对照组幼鼠给予标准饲料,HFD组幼鼠给予高脂饲料,分别饲养12周。检测幼鼠体质量和血清总胆固醇（TC）及甘油三酯（TG）水平。HE染色、PAS染色和Masson染色观察2组幼鼠肾组织病理形态表现、肾小球系膜和基底膜相对面积以及肾间质纤维组织相对面积,免疫组织化学法检测2组幼鼠肾小球中RhoA和ROCK蛋白表达水平,免疫蛋白印迹法检测2组幼鼠肾小球中RhoA、ROCK和Vimentin蛋白的表达水平。结果：与正常对照组比较,HFD组小鼠体质量、血清TC和TG水平明显升高（P<0.01）。HE染色,HFD组小鼠肾小球内出现明显脂肪变性;PAS染色,HFD组小鼠出现肾小球系膜基质轻度增生;Masson染色,HFD组小鼠肾小球内蓝色胶原纤维染色物质比正常对照组增多;与正常对照组比较,HFD组小鼠肾小球系膜和基底膜相对面积明显增加（P<0.05）,肾间质纤维组织相对面积增加（P<0.05）;免疫组织化学检测,与正常对照组比较,HFD组幼鼠肾小球中RhoA的ROCK蛋白表达水平升高（P<0.05）;免疫蛋白印迹法检测,与正常对照组比较,HFD组幼鼠肾小球中RhoA、ROCK和Vimentin蛋白表达水平升高（P<0.05）。结论：给予HFD的C57BL/6J小鼠肾小球中RhoA和ROCK蛋白高表达可能是诱发肾小球损伤的原因之一。     

More expression,less function: cleaved dynamin in glomerular kidney disease

The role of dynamin in regulation of kidney filtration barrier is well documented. Dynamin binds to and produces filamentous actin, which is a key component of healthy podocyte foot processes (FPs). Destruction of dynamin, for example by cathepsin L, leads to loss of a functional actin network and uncoordinated membrane signaling, a situation that allows for effacement of FPs and proteinuria. Now, Khalil et al have examined the dynamin expression in kidneys of proteinuric animal models as well as in kidney patients and produced data that further clarifies the role of dynamin in glomerular and tubular proteinuria and may aid in pinpointing patients who are affected by loss of dynamin function and may benefit from appropriate therapeutic approaches. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria

Abstract Aims/hypothesis. The predictive value of glomerular structure on progression of renal disease was examined in patients with Type II (non-insulin-dependent) diabetes and microalbuminuria (urinary albumin-to-creatinine ratio = 30–299 mg/g). Methods. Kidney biopsy specimens were obtained from 16 diabetic Pima Indians (6 men, 10 women). Progression of renal disease was assessed by measuring urinary albumin excretion 4 years after the biopsy (UAE_{4 years}) and by computing the change in urinary albumin excretion during the study (Δ UAE). Results. At baseline, the duration of diabetes averaged 13.3 years (range = 4.0–23.8 years) and the mean glomerular filtration rate was 159 ml · min^–1· 1.73m^–2 (range = 98 – 239 ml · min^–1· 1.73m^–2). Median urinary albumin excretion was 67 mg/g (range = 25–136 mg/g) and it increased to 625 mg/g (range = 9–13471 mg/g) after 4 years; 10 subjects (63 %; 4 men, 6 women) developed macroalbuminuria (urinary albumin-to-creatinine ratio ≥ 300 mg/g). Neither mean arterial pressure nor HbA_{1 c} changed substantially during follow-up. Among the glomerular morphologic characteristics, the number of visceral epithelial cells, or podocytes, per glomerulus was the strongest predictor of renal disease progression (UAE_{4 years}, r = –0.49, p = 0.05; ΔUAE, r = –0.57, p = 0.02), with fewer cells predicting more rapid progression. Glomerular basement membrane thickness did not predict progression (UAE_{4 years}, r = 0.11, p = 0.67; ΔUAE, r = 0.09, p = 0.73) and mesangial volume fraction had only a modest effect (UAE_{4 years,} r = 0.42, p = 0.11; ΔUAE, r = 0.48, p = 0.06). Conclusion/interpretation. Whether lower epithelial cell number per glomerulus among those that progressed was due to cellular destruction, a reduced complement of epithelial cells, or both is uncertain. Nevertheless, these findings suggest that podocytes play an important part in the development and progression of diabetic renal disease. [Diabetologia (1999) 42: 1341–1344] Received: 29 March 1999 and in final revised form: 16 July 1999     

Tuft-to-capsule adhesions and their precursors: differences between the vascular and tubular poles of the human glomerulus

Human glomerular capillary tufts were removed by microdissection and scanning electron microscopy was used to examine the surface of the capillary tuft and the interior of its Bowman's capsule in order to identify connections between the tuft and capsule. Glomeruli were examined in histologically normal renal cortex from 12 kidneys removed for tumour and 12 renal allografts removed for end-stage rejection. In normal kidney, the glomerular tuft was connected to Bowman's capsule by single podocytes and their processes. At the vascular pole, these were predominantly associated with parietal podocytes which lined Bowman's capsule. At the tubular pole, occasional podocytic processes derived from the capillary tuft bridged Bowman's space and connected to Bowman's capsule where there were no parietal podocytes. These podocytic connections were also found in all rejected transplants, but in addition adhesions were identified which consisted of thicker connections between the tuft and capsule. At the vascular pole, tuft-to-capsule adhesions were found in all 12 kidneys; these were always associated with parietal podocytes. Tubular pole adhesions were identified in ten of the 12 transplants. They were associated with abnormal squamous cells, but not with parietal podocytes. When the capillary tuft herniated into the proximal tubule, the tuft sometimes formed an adhesion with the origin of the proximal tubule. These observations suggest that podocyte connections between the glomerular tuft and Bowman's capsule may be precursors of glomerular adhesions at the vascular pole. Since tuft-to-capsule adhesions at the vascular pole differ morphologically from those at the tubular pole, this may reflect different pathogenetic mechanisms at the opposite poles of the glomerulus. © 1998 John Wiley & Sons, Ltd.     

Postnatal development of olfactory receptor cell axonal arbors

The mechanisms that subserve the distribution of the terminal arbors of olfactory receptor cell axons remain unknown. Elsewhere in the central nervous system, a common theme is early axonal exuberance followed by activity-dependent pruning to achieve the mature distribution. This led to the hypothesis that the orderly morphology of afferent axons in the olfactory glomerulus may follow a similar developmental scheme of exuberance followed by pruning. To test this hypothesis, we studied morphological features of olfactory receptor neuron (ORN) axonal arbors on postnatal days 0, 3, 6, 9, 12, and 21. The olfactory bulbs from Sprague-Dawley rats were processed using a Golgi technique that impregnated ORN axons. Axons from each age group were reconstructed by using camera lucida at ×100, oil immersion, and morphometrically characterized. In the adult, the percent glomerular area occupied by a single ORN axon was 14%, whereas the mean length of branches was 169.67 μm, the sum of branches and varicosities was 27, and the distance to first branch point in glomeruli was 21.98 μm. The values from the younger age groups were not statistically different from those in the adult. Because there was no evidence of early exuberance, our data suggest that ORN axons must innervate single glomeruli and arborize in a highly specific manner to achieve the adult pattern. Because our data suggest that ORN axons do not follow the hypothesized scheme, it is plausible to suggest that as ORN axons innervate a glomerulus during development they arborize to their adult levels but not beyond. This argues strongly that specific cell surface and trophic factors are used by the ORN axon to guide glomerular targeting and innervation. J. Comp. Neurol. 390:256–267, 1998. © 1998 Wiley-Liss, Inc.