Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells.

We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes.     

Mechanisms of proteinuria in nephrotic humans

The glomerular capillary wall imposes a remarkably efficient barrier to the passage of proteins the size of albumin and larger. The development of heavy proteinuria signifies impairment of the function of this barrier. Because endogenous proteins of graded size are heterogeneous with respect to their molecular charge and undergo extensive tubular reabsorption, they are not useful for quantifying the extent of barrier dysfunction. An alternative approach is to determine the fractional clearance of uncharged and non-reabsorbable polymers of graded size. When combined with a hydrodynamic theory of solute transport through a heteroporous membrane, the intrinsic properties of healthy and diseased glomerular capillary walls can be inferred. This approach reveals the nephrotic range proteinuria that attends minimal change nephropathy to be associated with impairment of both the size- and charge-selective properties of glomerular capillary walls.     

伊那普利治疗糖尿病肾病的临床研究

目的评估伊那普利治疗糖尿病肾病(DN)的临床疗效 ,并探讨其作用机制。方法40例持续微量蛋白尿的非胰岛素依赖型糖尿病(NIDDM)患者随机分为常规治疗组(n=19)和伊那普利治疗组(n=21)。利用 131I -邻碘马尿酸钠测定有效肾血浆流量(ERPF) ;肾小球滤过率(GFR)以内生肌酐清除率表示 ;通过ELISA法测定尿微量蛋白 ,包括白蛋白(ALB)、转铁蛋白(TF)、视黄醇结合蛋白(RBP)和N -乙酰 - β氨基葡萄糖苷酶(NAG)。结果伊那普利治疗组增高的尿ALB、TF、RBP和NAG均显著下降 ;ERPF显著增加 ;增加的滤过分数(FF)显著减低。而常规治疗组这些参数无显著变化。结论伊那普利具有改善DN患者的肾小球血流动力学 ,保护肾小球和肾小管功能的作用     

Leukocytosis and low serum IgA in workers exposed to the epoxy compound,t-methyl-3-phenylglycidate

Summary Forty-nine out of 54 male workers engaged in the production of an epoxy compound, t-methyl-3-phenylglycidate, showed skin symptoms in varing degrees that may be due to the skin-irritative effect of the compound. The exposed workers were also shown to have subjective symptoms which may be related to the irritative property of the compound on surface tissue. Laboratory examinations on the blood obtained from the exposed workers showed significantly higher values of leukocyte concentration as compared with the non-exposed controls. This was chiefly caused by the increase of neutrophilic granulocytes and T-cell lymphocytes. Serum IgA levels of the exposed workers were shown to be significantly lower than those of the control group. Hemoglobin concentration, hematocrit value and red cell count of the exposed workers remained at the same level as those of the control subjects. Liver or kidney damage was not found in biochemical analyses on the sera of exposed workers.     

N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis.

The objectives of this study was to assess the overall effect of N-acetylcysteine (NAC) in preventing radiocontrast-induced nephropathy (RCIN) using all available data in the literature. RCIN is associated with increased morbidity and mortality. Existing randomized trials of NAC are small and show inconsistent results. Prior meta-analyses do not include data from the most current studies. We used standard search protocols to identify all published articles and abstracts of prospective trials using NAC with fluid hydration compared to hydration alone in patients with chronic renal insufficiency undergoing contrast procedures. A rise in serum creatinine by 0.5 mg/dl or 25% above baseline at 48-72 hr after contrast exposure was used as the primary outcome. We identified 14 trials of NAC with 1,584 patients published as full-text articles. Using a random-effects model, the use of oral NAC resulted in a significant reduction in the risk for developing RCIN (RR = 0.57; 95% CI = 0.37-0.84; P = 0.01). This finding did not significantly change in a fixed-effect model (RR = 0.55; 95% CI = 0.42-0.73) or when the data were reanalyzed using only randomized trials in all forms (i.e., articles and abstracts; RR = 0.67; 95% CI = 0.47-0.95). We identified only one important difference between the positive and the negative studies: the cumulative exposure to contrast media (174 vs. 152 ml). Metaregression did not show a significant relationship between contrast volume and the RR of developing RCIN (P > 0.10). In the trials showing benefit for NAC, the treated patients' postprocedure creatinine unexpectedly decreased by 0.21 mg/dl (95% CI = 0.33-0.08). Prophylaxis with NAC significantly reduces the risk for RCIN. The reasons for improvement in serum creatinine in patients treated with NAC are unclear, but may include improved renal blood flow due to NAC and/or vigorous hydration.     

P_(27)、PCNA与IgA肾病中医证型及病理类型的关系

目的 :运用免疫组化方法研究原发性IgA肾病患者肾组织中细胞周期调控蛋白P2 7(P2 7)、增殖细胞核抗原PCNA(PCNA)的表达 ,探讨两者与IgA肾病病理分级及其与中医证型之间的关系。 方法 :选择行肾穿刺活检的IgA肾病住院患者 5 2例 ,并按照中医辨证分型标准将其分为肺肾气虚证、脾肾阳虚证、肝肾阴虚证、气阴两虚证、血瘀证、湿热证六型。系膜增生的病理组织学分为 4级。运用免疫组化方法检测P2 7、PCNA的表达。结果 :(1)IgA肾病各个病理分级P2 7、PCNA的表达两两比较有统计学意义。显示随着系膜细胞增生的病理分级程度增高 ,PCNA的表达增高 ,而P2 7的表达则按相反方向进行。病理分级和P2 7、PCNA表达的等级相关性检验 (Spearman法 )显示 :P2 7的表达与病理类型呈非常显著负相关 ,而PCNA的表达与病理类型呈显著正相关。 (2 )IgA肾病三个中医证型的病理分级之间有统计学意义 ,其中气阴两虚证的病理分级比湿热证、肝肾阴虚证高 ,湿热证与肝肾阴虚证的病理分级之间无统计学意义。 (3)随着湿热→肝肾阴虚→气阴两虚的进展 ,P2 7的表达呈现出逐渐减少的趋势 ,而PCNA的表达呈现出逐渐增加的趋势。结论 :(1)P2 7、PCNA作为判断IgA肾病肾脏组织学损伤程度和预后的指标值得深入研究。 (2 )IgA肾病中医证型之间病理分     

大豆异黄酮对大鼠慢性移植肾肾病的防治作用

目的通过对肾移植大鼠的饮食营养干预，观察大豆异黄酮对慢性移植肾肾病的防治作用。方法选择近交系雄性Fisher（F344）大鼠作为供者，雄性Lewis（Lew）大鼠作为受者，采用显微外科技术制作肾移植模型。将受者随机分为三组，分别给予高异黄酮大豆蛋白饲料（HIS组）、低异黄酮大豆蛋白饲料（LIS组）或酪蛋白饲料（CAS组）。移植前和移植后第4、12和24周时检测血压，并收集受者的血和尿样，检测尿蛋白和血肌酐含量。24周时处死大鼠获取移植肾，行组织学和免疫组织化学检查。结果在移植后4周时，HIS组受者的尾动脉收缩压、24h尿蛋白含量和血肌酐浓度即低于LIS组和CAS组，但差异无统计学意义（P〉0．05）；移植后12周和24周时，HIS组的受者尾动脉收缩压、24h尿蛋白含量和血肌酐浓度均较LIS组和CAS组显著降低（P〈0．05）；移植后24周时，HIS组移植肾组织的间质纤维化和炎症、血管硬化、肾小球硬化和肾小管萎缩等慢性病变均较LIS组和CAS组为轻（P〈0．05）；HIS组移植肾组织中转化生长因子-β1（TGF-β1）的表达和分泌均较LIS组和CAS组为少（P〈0．05）。结论大豆异黄酮对移植肾功能和结构有保护作用，可作为一种防治慢性移植肾肾病的新方法。     

Long-term follow-up study of 268 diabetic patients undergoing haemodialysis, with special attention to visual acuity and heterogeneity

We studied the long-term outcome of 268 patients suffering fromdiabetic end-stage renal disease (DM-ESRD) treated with long-termhaemodialysis between 1978 and 1991, with special emphasis onvisual acuity as well as the heterogeneity of DM-ESRD The 50%patient survival on haemodialysis was 60 months. Visual disturbanceswere found in 73.1% (392/536) of eyes at the start of haemodialysis.Chronological assess ment of visual acuity demonstrated thestabilization of visual acuity and 87.1% (364/418) of eyes werestable, 4.8% (20/418) were improved, and 8.1% (34/418) wereaggravated in the long term respectively. The change of visualacuity was frequently seen in the short term, and rapid shiftsof body fluid to correct overhydration induced abrupt changesof glycaemic control as well as retraction of macular oedema.Hence it might be one of the factors affecting rapid changeof visual acuity in the short term. Meanwhile, long-term deterioration of visual acuity resulted from either hyperten sionunresponsive to medical treatment or poor glycaemic control.Some DM-ESRD patients had only background retinopathy at thestart of haemodialysis and these were likely to have the nephroscleroticglomerular lesion. They were old, not nephrotic and had a milddegree of diabetes during the predialysis stage. Thus, DM-ESRDpatients seem to have some heterogeneity in their clinical characteristics,and old DM-ESRD patients with only background retinopathy havethe appearance of diabetic macroangiopathy rather than microangiopathy.     

Angiotensinogen gene M235T polymorphism is not associated with diabetic nephropathy

BACKGROUND.: There is agreement that a family history of hypertension (HT),is a predictor for the risk of diabetic nephropathy (DN) inpatients with type 2 diabetes, and possibly also type 1 diabetes.It follows that genes related to the risk of hypertension mustalso be considered candidate genes for DN. The 235T allele ofthe angiotensinogen gene was found to be related to primaryHT. METHODS.: To examine whether it is predictive for DN as well, we examinedthe angiotensinogen gene polymorphism in 230 healthy local controls,423 patients with type 1 diabetes (n=180 with DN; n=243 withoutDN) and 663 patients with type 2 diabetes (n=310 with DN; n=353without DN). The angiotensinogen gene M235T polymorphism wasdetermined using PCR amplification. RESULTS.: The following results were obtained (i) no significant differenceof genotype distribution (type 1: MM/MT/TT(%) 27.6/57.2/15.2vs. 27.2/56.1/16.7 (P=0.92); type 2: MM/MT/TT (%) 31.7/48.2/20.1vs. 32.9/46.8/20.3 (P=0.93)) or allele frequencies (type 1:M 0.56 vs. 0.55 (P=0.795); type 2: M 0.56 vs. 0.56 (P=0.86))was found, between diabetic patients with or without DN, (ii)no difference was found between normotensive and hypertensivediabetic patients. CONCLUSION.: The data argue against a role of the angiotensinogen gene M235Tpolymorphism in the manifestation of diabetic nephropathy orhypertension in diabetic patients.     

糖尿病肾病患者血清TRPM7、Sirtuin-1与钙磷代谢、颈动脉钙化的相关性

目的 探讨糖尿病肾病（DN）患者血清瞬时受体电位通道7(TRPM7)、沉默调节蛋白-1(Sirtuin-1)与钙磷代谢、颈动脉钙化的相关性。方法 选取2020年12月—2022年11月成都大学附属医院收治的97例DN患者作为DN组,另取同期在该院就诊的120例2型糖尿病患者作为对照组。采用实时荧光定量聚合酶链反应检测血清TRPM7的表达,酶联免疫吸附试验检测血清Sirtuin-1水平。采用Pearson法分析DN患者血清TRPM7、Sirtuin-1水平与钙磷代谢的相关性,并通过多因素Logistic逐步回归模型分析DN患者颈动脉钙化的危险因素。结果 DN组血肌酐、尿素氮、血清TRPM7、血磷、颈动脉钙化率高于对照组（P <0.05）。DN组Sirtuin-1、血钙低于对照组（P <0.05）。Pearson相关性分析结果显示,DN患者血清TRPM7与血钙呈负相关（r=-0.247,P=0.000）,与血磷呈正相关（r=0.415,P=0.000）;DN患者血清Sirtuin-1与血钙呈正相关（r=0.367,P=0.000）,与血磷呈负相关（r=-0.505,P=0.00...