Clinical manifestations of APS-nephropathy in primary antiphospholipid syndrome

AIM: To elicit clinical features of nephropathy associated with antiphospholipid syndrome (APSN) in patients with primary antiphospholipid syndrome (PAPS). MATERIAL AND METHODS: The analysis of clinical characteristics and course of APSN has covered 24 patients with PAPS (16 females and 8 males, mean age 34.3 years). Renal damage was represented by arterial hypertension (AH), urinary syndrome, functional decline. All the patients were tested for anticardiolipin antibodies and/or lupus anticoagulant. Renal biopsy was made in 7 patients. RESULTS: PAPS patients developed renal affection in the onset of APS or within the first 5 years of its course. In the majority of patients APSN combined with abnormalities of CNS, heart and skin. Arterial/arteriolar thromboses prevailed. APSN manifested with: AH (n = 23, severe AH in 11), abnormal renal filtration (n = 17, creatinine rise in 8), urinary syndrome with proteinuria (n = 23, in 14 with hematuria). The following clinical variants of APSN were proposed: urinary syndrome with AH (n = 16; 67%), acute nephritic syndrome (n = 7; 29%), nephrotic syndrome (n = 1). Morphological studies of biopsies from APSN patients have revealed sclerotic changes, thrombotic microangiopathy, nonspecific alterations in the glomeruli. CONCLUSION: APSN is a variant of microvascular renal affection caused by thrombotic processes in intra-organ microcirculation. It is an early clinical marker of APS. Clinically, APSN manifests with vascular renal affection, the earliest symptom being inhibition of glomerular filtration. Clinical combinations of the symptoms allow to distinguish variant of APSN suggesting the existence of acute and chronic APSN. Combination of APSN with affection of the CNS, heart and skin points to a special PAPS subtype characterized by generalized ischemic damage to the organs as a result of intraorganic arterial and/or arteriolar thromboses.     

Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis

Focal segmental glomerular sclerosis (FSGS) is a primary kidney disease that is commonly associated with proteinuria and progressive loss of glomerular function, leading to development of chronic kidney disease (CKD). FSGS is characterized by podocyte injury and depletion and collapse of glomerular capillary segments. Progression of FSGS is associated with TGF-β activation in podocytes; however, it is not clear how TGF-β signaling promotes disease. Here, we determined that podocyte-specific activation of TGF-β signaling in transgenic mice and BALB/c mice with Adriamycin-induced glomerulosclerosis is associated with endothelin-1 (EDN1) release by podocytes, which mediates mitochondrial oxidative stress and dysfunction in adjacent endothelial cells via paracrine EDN1 receptor type A (EDNRA) activation. Endothelial dysfunction promoted podocyte apoptosis, and inhibition of EDNRA or scavenging of mitochondrial-targeted ROS prevented podocyte loss, albuminuria, glomerulosclerosis, and renal failure. We confirmed reciprocal crosstalk between podocytes and endothelial cells in a coculture system. Biopsies from patients with FSGS exhibited increased mitochondrial DNA damage, consistent with EDNRA-mediated glomerular endothelial mitochondrial oxidative stress. Our studies indicate that segmental glomerulosclerosis develops as a result of podocyte-endothelial crosstalk mediated by EDN1/EDNRA-dependent mitochondrial dysfunction and suggest that targeting the reciprocal interaction between podocytes and endothelia may provide opportunities for therapeutic intervention in FSGS.     

零点肾穿活检:对供者临床资料与组织学异常情况的相关性分析

背景:目前,活体肾脏捐赠的数量在全国乃至全世界范围内增长,因此,保障供者安全在亲体肾移植中占有重要地位.如何准确诊断移植供者可能存在的肾脏疾病,以指导供者手术后潜在肾脏病治疗和肾功能保护成为亲体肾移植后保障供者安全的重要课题.目的:建立一种对供者捐肾前的临床资料与组织学异常情况间相关性的评价方法.方法:对解放军南京军区福州总医院2008-02/2009-11所有亲属肾移植的相关数据做回顾件分析,于供肾血管离断并灌注完成后进行穿刺.用零点肾穿的方法评估下列病变:间质纤维化,小管萎缩,微小动脉透明变性,肾小球系膜增生和肾小球硬化.移植前的统计数据包括:体质量,体质量指数,收缩压,舒张压,血清肌酸酐,肾小球滤过率和蛋白尿.结果与结论:62例供者术前检查均未发现明显肾脏疾病征象,零点肾穿活检发现肾脏病理改变28例,其中间质纤维化与收缩压和肌酐清除率,肾小管萎缩与舒张压和尿蛋白,小动脉透明样变与肌酐和肾小球滤过率,肾小球系膜增生和体质量指数具有弱相关性,肾小球硬化与其他变量均无相关性.     

Proteinuria in atherosclerotic renovascular disease

Proteinuria is well described in atherosclerotic renovascular disease (ARVD), but the prevalence is unknown, and the pathogenesis may vary between patients. Substantial proteinuria (> 2 g/day) however, would be regarded by many as atypical of ARVD. We studied 94 patients (52 male) with ARVD, median age 67 years (range 49-87). Digital subtraction angiography was performed on all patients. Protein was assayed in 24-h urine samples and GFR derived using the Cockroft-Gault formula. Forty-nine patients (52%) had proteinuria < 0.5 g/24 h. Proteinuria increased with worsening renal function. Biopsies from seven non-diabetic patients with substantial proteinuria showed: minimal changes (1); glomerular sclerosis with marked ischaemic changes (3); focal glomerulosclerosis (2); and athero-emboli (1). Proteinuria, rather than being indicative of other pathology, is often a marker of severity of parenchymal disorder in atherosclerotic nephropathy, which itself is the major determinant of renal dysfunction in patients with ARVD.     

Contribution of irreversible morphological changes of different renal structures to development of anemia in immune glomerulopathies

AIM: To find out correlations between severity of sclerotic affection of the glomeruli, tubules, interstitium, vessels and development of anemia in patients with glomerulopathy. MATERIAL AND METHODS: Assay of global and segmentary sclerosis, semiquantitative morphometry of severity of atrophic tubular changes, diffuse interstitial fibrosis, vascular changes (arteriolohyalinosis, elastofibrosis and perivascular sclerosis) were made in parallel with analysis of clinical laboratory data in 276 cases of chronic primary glomerulopathy with morphologically verified diagnosis by vital renal biopsy. RESULTS: Hemoglobin concentration and advance of anemia correlate negatively with severity of diffuse interstitial fibrosis and atrophic tubular alterations. However, no correlation was found between onset of anemia, severity of global and segmental glomerular sclerosis, the presence of vascular changes in the form of arteriolar hyalynosis, elastofibrosis of small arteries and perivascular sclerosis. CONCLUSION: The findings suggest that development of anemia in patients with primary glomerulopathy may be the result of structural-functional disturbances in tubular epithelium and renal stroma.     

Methodology for assessment of renal function

A variety of methods for evaluation of renal function have been discovered, among which glomerular filtration rate (GFR) attracts much attention because of the major determinant of renal function. Recently, novel technique to evaluate glomerular filtration has been developed, including cystatin C, which reflects the changes in GFR at the earlier stage than serum creatinine. Furthermore, a progress has been made in evaluating tubular damage, with the discovery of N-acetyl glucosaminidase and liver-type fatty acid binding protein. More convenient and sensitive methods will be required to assess the changes in renal function in a clinical setting.     

Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the pathogenesis of focal segmental sclerosis, the vast majority of patients with this disease, even those with a familial linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of genetic heterozygosity (bigenic heterozygosity) that alone do not result in clinical kidney disease could function together to enhance susceptibility to glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage. These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1. This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that combined mutations in 2 or multiple podocyte genes may be a common etiology for glomerular disease.     

Effect of nifedipine on renal haemodynamics in an animal model of cyclosporin A nephrotoxicity

1. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in the spontaneously hypertensive rat. 2. Cyclosporin A, administered daily by subcutaneous injection at 25 mg/kg body weight for 14 days, induced a significant reduction in glomerular filtration rate (35.3%) and effective renal plasma flow (45.0%), and an increase in renal vascular resistance (219%). Using this regimen, tubular, glomerular or vascular morphological damage was not evident on light microscopy. 3. The administration of nifedipine simultaneously with cyclosporin A from day 1 prevented the characteristic decline in renal function and increase in renal vascular resistance. However, the administration of nifedipine to spontaneously hypertensive rats previously exposed to cyclosporin A for 7 days failed to improve renal haemodynamics. 4. This study suggests that the beneficial effect conferred by nifedipine on cyclosporin A nephrotoxicity is present only when treatment is initiated simultaneously with cyclosporin A.     

Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients

The effect of asthma pathogenesis on serum cystatin C, a potent inhibitor of cysteine proteinases and a newly proposed marker of the renal function, has not been yet determined. The objectives were to determine the 24-h pattern of cystatin C and creatinine concentrations in sera of asthmatic patients in order to test whether their concentrations might reflect circadian rhythms, the disease severity and the effect of therapy. Serum concentrations of cystatin C and creatinine were determined in steroid-independent and steroid-dependent asthmatics before and after 1 week of treatment with methylprednisolone and cyclosporin A, respectively. Samples were collected every 4 h during a 24-h period. Little or no significant effects of time on cystatin C and creatinine concentrations over a 24-h period were observed in healthy and asthmatic sera. However, significantly higher cystatin C concentrations were found in asthmatic patients compared to controls which suggests its role in the pathogenesis of asthma. Methylprednisolone increased and cyclosporin A decreased serum cystatin C concentrations after 1 week of therapy. Additionally these results support the need for the evaluation of cystatin C as a marker of glomerular filtration rate determination in asthma.     

CD2相关蛋白及Wilms肿瘤基因在原发性肾病综合征肾小球的表达及意义

目的 检测CD2相关蛋白(CD2 associated protein,CD2AP)、Wilms肿瘤基因(Wilms tumor gene,WT1)在成人原发性肾病综合征不同病理类型肾小球的表达,并分析二者与临床指标(如24小时尿蛋白定量、血肌酐、肾小球硬化率)的关系.方法 80例原发肾病综合征的患者,依据病理分型分为肾小球微小病变组(MCN组)20例,IgA肾病组(IgAN组)20例,膜性肾病组(MN组)20例及局灶节段性肾小球硬化组(PSGS组)20例,另选10例正常对照组,采用免疫组织化学方法检测肾小球CD2、WT1的表达和分布情况.结果 CD2AP在肾小球和部分肾小管上皮细胞刷状缘均有表达.在正常对照组CD2AP沿毛细血管壁呈均匀、线状分布.MCN组、MN组、FSGS组CD2AP沿毛细血管壁不均匀分布,呈细颗粒状,部分毛细血管壁表达缺失;IgAN组CD2AP表达不均呈断续不等颗粒状,在病变区域表达缺失.对照组、MCN组、IgAN组、MN组、FSGS组的CD2AP表达指数分别为14.35±3.29、11.69±3.36、11.84±4.37、7.67±3.06、8.71±3.06.MN组、FSGS组与正常对照组比较显著降低(P<0.05),而MCN组、IgAN组较正常对照组差异无统计学意义.MN组、FSGS组与MCN组、IgAN组比较CD2AP的表达也有显著降低(P<0.05).WT1在肾小球内沿毛细血管壁均匀分布.MCN组、IgAN组、FSGS组WT1表达强度减弱,IgAN组病变区域部分表达缺失.时照组、MCN组、IgAN组、MN组、FSGS组的CD2AP表达指数分别为3.51±0.51、2.54±0.85、2.45±0.57、3.71±1.08、1.93±0.31.MCN组、IgAN组、FSGS组与对照组比较表达明显降低,而MN与对照组差异无统计学意义.原发性肾病综合征患者肾小球CD2AP、WT1的表达水平与24小时尿蛋白定量呈负相关(r=-0.861,-0.304,P<0.05).结论 成人原发性肾病综合征不同病理类型肾小球CD2AP、WT1的表达和分布不同,二者与24小时尿蛋白定量呈负相关.     

Sera from patients with collapsing focal segmental glomerulosclerosis increase albumin permeability of isolated glomeruli

The collapsing variant of focal segment glomerulosclerosis (FSGS) is characterized by heavy proteinuria and rapid progression to renal failure. Its cause is not known. We have characterized a substance in the circulation of patients with classic FSGS that increases in vitro permeability of glomeruli to albumin (P(alb)) and causes proteinuria when injected into rats. Inclusion of normal serum prevents the increase in P(alb) caused by this FSGS factor. We investigated the effect of sera from patients with collapsing FSGS on P(alb), as well as the effect of inclusion of normal serum. Isolated glomeruli were incubated with serum from each of 11 patients with collapsing FSGS (1:50 dilution) or with patient serum and an equal volume of pooled normal serum. P(alb) was determined on the basis of changes in glomerular volume in response to an oncotic gradient. Sera from 10 of the 11 patients with collapsing FSGS increased P(alb) of isolated glomeruli to a value of 0.5 or greater. In each of the 5 cases tested, inclusion of normal serum abolished the increase in P(alb). Sera of patients with collapsing FSGS increased glomerular P(alb). Our finding that the increase in P(alb) is abolished by normal serum suggests that the substance and its mechanism of action are similar or identical to the FSGS factor we have isolated from the plasma of patients with recurrent FSGS. The presence of a circulating factor in collapsing FSGS has implications for prognosis and treatment in primary and recurrent collapsing FSGS.     

肝素防治局灶节段性肾小球硬化的实验研究

目的　观察肝素钙注射液防治局灶节段性肾小球硬化 (FSGS)的可能性。方法　 18只 Wistar大鼠随机分为正常对照组 (A组 )、肝素治疗组 (B组 )和模型组 (C组 )。采用小剂量分次阿霉素间羟胺高脂饲料法建立大鼠 FSGS模型 ,B组于实验第 2 9d予肝素钙注射液治疗。各组均测定 2 4 h尿蛋白、血生化指标及肾脏组织血流量 ,并在光镜和电镜下检查肾脏形态、肾小球硬化指数 (SI)及细胞外基质 (ECM)。结果　治疗后 2周 (实验 6周 )时肝素治疗组尿蛋白排泄量开始降低 ,实验 12周时肝素治疗组胆固醇升高的幅度低于模型组。肝素治疗组肾组织血流量明显增加。光镜检查显示 ,肝素治疗组 SI及 ECM/肾小球面积 (GA)均明显减低 ;电镜检查显示 ,肝素治疗组毛细血管腔通畅 ,基底膜改变及足突融合均较模型组明显减轻。结论　肝素对FSGS有一定的防治作用。     

Cystatin C对心脏手术患者肾功能的评估价值

目的 评价胱氨酸蛋白酶抑制荆C（Cystatin C）在心脏手术患者肾功能评估的应用价值。方法测定并统计心脏外科手术患者术前的Cystatin C、血清肌酐、手术后次晨的血清肌酐，并对部分患者手术前进行24h尿内生肌酐清除率的检查，分析Cystatin C、24h尿内生肌酐清除率及与手术前后血清肌酐变化之间的关系。结果Cystatin C对术后肌酐异常的敏感性为68．3％，特异性为16．6％，诊断符合率为68．9％。24h尿肌酐清除率的相关指标为62．5％、55．6％和66．7％。两者比较差异有显著性（P〈0．01）。两者联合应用，则相关指标分别为66．7％、77．8％和74．1％。结论Cystatin C是肾小球滤过率监测中的一个较敏感的指标。联合应用Cystatin C和24h尿内生肌酐清除率可以更准确地评估肾功能。     

Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome.

1. To elucidate the mechanisms by which cyclosporin A diminishes proteinuria, we studied 20 patients with severe nephrotic syndrome. Biopsy-established pathologies included minimal change disease (n = 5), membranous glomerulopathy (n = 6), membranoproliferative glomerulonephritis (n = 5) and focal segmental glomerulosclerosis (n = 4). Before, at the end of a 90 day course of cyclosporin A, and finally 1 month after stopping cyclosporin A we determined 24 h protein excretion. Measurements of glomerular filtration rate, effective renal plasma flow, fractional clearance rates of albumin and immunoglobulins with different charges and the transglomerular sieving of uncharged dextrans of broad size distribution were used to study the effects of cyclosporin A on renal perfusion and the glomerular filtration barrier. The findings were analysed with a theoretical model of solute transport. 2. Among the different forms of glomerulopathy the response to low-dose cyclosporin A (trough levels 32.0-36.9 ng/ml) varied markedly. In minimal change disease, proteinuria decreased from 9.5 +/- 3.1 to 1.3 +/- 0.2 g/24 h (mean +/- SEM, P less than 0.01). This response was due to restoration of the charge selectivity of the glomerular barrier. The depressed value of the glomerular permeability coefficient also returned to normal. Glomerular filtration rate, effective renal plasma flow and renal vascular resistance did not change. Proteinuria returned after stopping cyclosporin A, although it did not reach pretreatment levels. In membranous glomerulopathy, proteinuria fell from 9.9 +/- 1.5 to 1.8 +/- 0.3 g/24 h (P less than 0.01). Changes in protein excretion and dextran sieving were compatible with an increase in glomerular permselectivity and a decrease in filtrate flow through the 'shunt' pathway. Glomerular filtration rate was maintained, although effective renal plasma flow fell significantly. Proteinuria relapsed after stopping cyclosporin A. In membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis proteinuria did not respond to cyclosporin A, although cyclosporin A exerted important haemodynamic effects. 3. In minimal change disease and membranous glomerulopathy cyclosporin A exerts its beneficial effects on proteinuria through changes in the properties of the glomerular barrier, resulting in increased charge and size selectivity, respectively.     

A Longitudinal Assessment of Renal Function during Treatment with Lithium

Renal function was studied during lithium treatment in 28 patientson two occasions separated by a mean interval of 4.7 years.Glomerular filtration rate, assessed by creatinine clearanceand serum creatinine concentrations, showed no impairment. Albuminexcretion rate, a marker of glomerular permeability, showedno consistent change. In contrast, a decline in urine concentratingability (mean 140 mOsm/kg) was found in all patients, exceedingthe reduction to be expected from ageing in all but three. Theseresults support the view that treatment with lithium long-termdoes not damage renal glomerular function, but that progressiveimpairment of the distal tubular responsiveness to arginineisvasopressin is common.     

The renin-angiotensin system: renal actions and blood pressure regulation

The RAS is part of an extremely powerful feedback system for long-term control of blood pressure and volume homeostasis. Disturbances that tend to lower blood pressure, such as heart failure, cirrhosis, and peripheral vasodilation, cause sodium and water retention until blood pressure returns to normal due, in large part, to the combined actions of ANGII and reduced arterial pressure. In response to increased sodium intake, decreased ANGII formation greatly amplifies the effectiveness of pressure natriuresis, thereby preventing large increases in body fluid volumes and blood pressure. In circumstances in which the RAS is inappropriately activated, the sodium retaining effects of ANGII necessitate increased blood pressure to maintain sodium balance via pressure natriuresis. Because the RAS is so powerful in regulating blood pressure, blockade of the system with ACE inhibitors offers a powerful therapeutic tool in diseases such as hypertension and congestive heart failure. The control of sodium excretion and blood pressure by ANGII is exerted through multiple intrarenal as well as extrarenal effects, including stimulation of aldosterone secretion, which can influence renal excretion. Current evidence suggests that the intrarenal effects of ANGII are quantitatively more important than those mediated by aldosterone in controlling blood pressure and renal excretion. The most important intrarenal effects of ANGII include efferent arteriolar constriction as well as direct effects on sodium transport. The constrictor effect on efferent arterioles also is important in preventing reductions in GFR in circumstances associated with impaired renal perfusion. Therefore blockade of ANGII formation in circumstances such as renal artery stenosis may caused marked reductions in GFR. However, in many patients efferent arteriolar vasodilation caused by ANGII blockade may not lower GFR markedly because of other autoregulatory mechanisms that compensate by causing parallel reductions in afferent arteriolar resistance. In these individuals, chronic ACE inhibition may prove to be beneficial in slowing the progression of renal disease because a reduction in glomerular hydrostatic pressure may help to prevent glomerular damage.     

Effects of dopexamine on rat cardiorenal functions during lipopolysaccharide-induced experimental sepsis

We aimed to test the protective effect of dopexamine on renal function and systemic haemodynamics in rats with induced sepsis. Female Sprague-Dawley rats were randomized into three equal groups: group 1 (control, received 3% creatinine throughout the experiment); group 2 (sepsis, received 3% creatinine and Escherichia coli lipopolysaccharide [LPS] endotoxin [8 mg/kg per h]); and group 3 (sepsis plus dopexamine, received 3% creatinine, E. coli LPS and dopexamine [1 microgram/kg per min]). Time-adjusted heart rate, systolic, diastolic and mean arterial pressures, urine volume and glomerular filtration rate (from creatinine clearance) were recorded. After bacterial infusion heart rate increased and mean arterial pressure decreased; the fall in mean arterial pressure was less pronounced with dopexamine (group 3) than without (group 2). Dopexamine also induced significant and moderate increases in urine volume and heart rate, respectively. We concluded that dopexamine has some positive inotropic-chronotropic effects and induces favourable responses in renal function.     

Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion.

To evaluate the pathophysiologic importance of renal nerves in regulating the renal vasomotor tone, we measured several parameters of renal cortical microcirculation before and after acute renal denervation (DNx) in the following three groups of anesthetized Munich-Wistar rats: (group 1) congestive heart failure after surgically induced myocardial infarction (n = 10), (group 2) acute extracellular fluid volume depletion after deprivation of drinking water for 48 h (n = 8), and (group 3) sham or nontreated controls (n = 6). In the myocardial-infarcted rats, DNx led to a uniform increase in glomerular plasma flow rate of, on average, 36%. Single nephron glomerular filtration rate of myocardial-infarcted rats also increased despite a reduction in glomerular capillary hydraulic pressure. These changes were associated with a fall in arteriolar resistances, particularly in the efferent arteriole. The glomerular capillary ultrafiltration coefficient rose in all but one myocardial-infarcted animal. A similar hemodynamic pattern was seen after DNx in water-deprived animals. In every water-deprived animal, glomerular plasma flow rate and single nephron GFR increased on average by 28 and 14%, respectively. Again, afferent and efferent arteriolar resistances decreased significantly. Furthermore, the ultrafiltration coefficient increased uniformly and substantially with DNx. To ascertain the potential importance of the interaction between the renal nerves and angiotensin II in these circumstances, we compared the renal cortical hemodynamics in additional groups of water-deprived rats (group 4) after DNx (n = 15), (group 5) during inhibition of angiotensin II with saralasin (n = 15), and (group 6) during treatment with both saralasin and DNx (n = 15). No appreciable difference was detected between group 4 vs. 6. In contrast, substantial differences were noted between group 5 vs. 6: on average, the glomerular plasma flow rate was 26% higher and the afferent and efferent arteriolar resistances 25% and 27% lower, respectively, in group 6. These observations provide direct evidence to indicate pathophysiologic importance of renal nerves in the profound intrarenal circulatory adjustments in prerenal circulatory impairment. The vasoconstrictive effects of renal nerves appear to be mediated in part by their stimulatory influence on angiotensin II release and their direct constrictor actions on pre- and post-glomerular vessels as well.     

Mitochondrial dysfunction and focal segmental glomerular sclerosis

Focal segmental glomerular sclerosis (FSGS) is known as one of major renal complication of mitochondrial cytopathies. Glomerular epithelial cells are primary pathogenic sites in FSGS lesions. Glomerular epithelial cells are regarded as terminally differentiated cells and do not proliferate. This characteristic is the same for neuron cells and muscular cells, which are major sites of mitochondrial DNA mutations accumulation. Accumulation of mitochondrial DNA mutations might induce mitochondrial dysfunction and lead to FSGS lesion in glomeruli or these accumulations are only consequences of pathogenic stimuli to glomerular epithelial cells during the disease course of several glomerulopathies. Further investigations are needed to clarify pathogenic role of mitochondria and mitochondrial DNA mutations.     

肾活检68例临床与病理分析

目的:回顾性分析本科自1998年12月～2005年12月共68例因肾脏疾病行活检的病理资料,总结常熟地区肾脏疾病的临床病理类型特点。方法:参照WHO肾小球疾病组织学分型修订方案(1982年及1995年),对每1例患者均进行临床病理讨论,由病理医师和临床医师结合临床资料、实验室检查结果、免疫病理及超微结构改变特点,共同探讨明确病理诊断及拟定相应的治疗措施。结果:本组中原发性肾小球疾病占92.65%,继发性肾小球疾病占7.35%。原发性肾小球疾病以系膜增生性肾炎(MsPGN)居多(32.35%),其次分别为局灶节段增生性肾小球肾炎(FSGP)(26.47%)、微小病变(MCD)(19.12%)、膜性肾病(MN)(8.82%)、FSGS(5.88%)等。继发性肾脏病中以狼疮性肾炎(LN)多见(4.41%),其次是紫癜性肾炎(HSPN)(1.47%)等。临床表现为肾病综合征患者,以MN多见(31.25%),其次为MsPGN(25.0%)、FSGS(12.5%)等。临床表现为尿检异常患者,以MsPGN多见(40.0%),其次为FSGP(32.5%)、MCD(17.5%)、FSGS(5.0%)等。结论:常熟地区原发性肾小球肾炎仍是最常见的肾小球疾病,其中以系膜增生性肾小球肾炎和微小病变最常见,继发性肾脏病以狼疮性肾炎多见,女性占绝对优势。肾活检的适应证可以扩大。