一系列肾小球滤过率计算公式适用性评估

目的评估基于血浆胱抑素C（Cystatin C,Cys-C）和血浆肌酐（Creatinine,Cr）含量建立的肾小球滤过率（Glomerular Filtration Rate,GFR）计算公式在中国健康人群中的适用性。方法从我院健康体检人群中根据体检报告筛选500例健康成人,测定其血浆Cys-C及Cr,并通过以Cys-C为基础的7个公式（Hoek,Orebro,Le Brican,Filler,Larsson,Grubb,Rule）与以Cr为基础的基于我国人口学资料改良的简化MDRD公式,Cockcroft-Gault公式,简化MDRD公式以及基于Cr和Cys-C的我国eGFR课题协作组公式计算得出的GFR进行比较。结果 Hoek、Orebro、Le Brican、Filler、Lars-son、Grubb、Rule、中国课题协作组、C-G、简化MDRD、改良后简化MDRD等公式计算的出的eGFR分别为96.1±15.1、132.6±23.31、01±14.6、117.9±19.9、102.7±19.4、124.7±31.4、99.4±17.3、126±17.5、116.6±20.4、116.9±18.4、126.9±23.2（ml/min/1.73 m^2）。以eGFR 90-160 ml/min/1.73 m^2为正常参考范围,上述公式的符合率分别为63.4%、83%、76%、91.8%、71.4%、73.4%、69.4%、89.2%、89%、88.6%、92.6%。结论目前发表的一系列GFR计算公式的结果存在明显差别,有必要进行更深入的研究来建立一个准确和适用的计算公式。     

Detailed glomerular ultrastructure in Japanese type 2 diabetic patients by the quick-freezing and deep-etching method

Mesangial expansion and glomerular basement membrane (GBM) thickening did not correlate with urinary albumin excretion (UAE) in type 2 diabetic patients in our previous studies; therefore, it was necessary to elucidate more detailed ultrastructural changes in the early stages of diabetic nephropathy (DN) in type 2 diabetic patients. The quick-freezing and deep-etching (QF–DE) method allows us to examine three-dimensional ultrastructures of human renal glomeruli in vivo at high resolution. The QF–DE method was applied to six type 2 diabetic patients without definable renal diseases other than DN. Four patients were normoalbuminuric (NA) and the other two were microalbuminuria (MA). Three control specimens were the normal parts from nephrectomies due to renal cell carcinomas. Electron microscopic morphometric analyses provided quantitative glomerular structural changes. Replica membranes were prepared by the QF–DE method, and diameters of mesh structures at the GBM and mesangial matrix (MM) were measured on electron micrographs as previously described. By the QF–DE method, both the GBM middle layer and MM were composed of polygonal meshwork structures. The mesh pores of the GBM and MM were more enlarged and irregular in shape in NA diabetic patients than those of the controls, and these ultrastructural changes became more obvious in MA patients. The mesh diameters of the GBM and MM in the diabetic patients were also larger than those of the controls. Such a mesh diameter of the GBM was well correlated with the amount of UAE, while the mesh diameter of MM showed a slight correlation with UAE. Although there were small number of subjects in the present study, the detailed ultrastructural changes in NA and MA type 2 diabetic patients, which had not been disclosed by conventional electron microscopy, were revealed by the QF–DE method. Increased mesh diameters of GBM might be related with the increase of UAE.     

Serum creatinine concentration and renal interstitial volume

Summary Renal biopsies of 44 patients with endocapillary acute glomerulonephritis (gn) and 64 patients with moderately severe mesangioproliferative gn were investigated morphometrically (point-counting-method, tubulometry).In both gn's statistically significant positive correlations between relative interstitial volume and the concentration of serum creatinine at the time of biopsy were found.Despite severe glomerular lesions the serum creatinine concentration is not increased in most cases of endocapillary acute gn, providing the relative interstitial volume is not increased by more than 15%.Increased serum creatinine concentration without a markedly enlarged interstitium was found in 11 cases of endocapillary acute gn with clinically and morphologically proven acute renal failure. In these cases the glomerular function is probably impaired by the Thurau-mechanism.In all other patients, especially in those with moderately severe mesangioproliferative gn, the serum creatinine concentration rises with an enlargement of relative interstitial volume. This reduction of renal function may be explained by a decrease to the total cross-sectional area of postglomerular vessels, caused by interstitial fibrosis. That may possibly lead to diminished renal blood flow and glomerular filtration with an increase of the serum creatinine concentration.Supported by the Deutsche Forschungsgemeinschaft     

Long-term renal and cardiovascular effects of antihypertensive treatment regimens based upon isradipine, perindopril and thiazide

The aim of this study was to describe the renal function (renal hemodynamics, water and sodium handling) and its relation to cardiovascular structural changes in a population of essential hypertensive patients before and after antihypertensive treatment. Glomerular filtration rate and renal plasma flow were measured by a constant infusion technique. The reference substances used were [¹³¹I]iodohippurate (Hippuran) and [¹²⁵I]iothalamate. The lithium clearance method was used for measuring renal water and sodium handling. Microalbuminuria was measured. A subcutaneous gluteal biopsy was taken and the media thickness to lumen diameter ratio of small resistance vessels was determined. Left ventricular mass index was determined by echocardiography. Thirty-seven patients with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with regimens based upon either isradipine, perindopril or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. Investigations were performed before and after 9 months of normalization of blood pressure. Renal function in untreated hypertensive patients was characterized by increased renal vascular resistance, decreased renal blood flow, normal glomerular filtration fraction and normal serum creatinine. No association was found between peripheral resistance vessel structure in subcutaneous vessels and renal hemodynamic parameters. Patients with severe left ventricular hypertrophy (left ventricular mass >360 g) had lower glomerular filtration fraction, greater renal vascular resistance, lower renal blood flow and increased microalbuminuria in comparison with patients with less pronounced cardiac changes. After 1 year of treatment, which had a profound effect on heart and vessel structure, renal hemodynamics were unchanged in patients receiving antihypertensive treatment regimens based on the ACE inhibitor perindopril or the Ca-antagonist isradipine, whereas renal plasma flow was reduced, glomerular filtration rate preserved and filtration fraction significantly increased in those treated with a regimen based on diuretics. The serum creatinine concentration was decreased in the former group, whereas it was unchanged in the latter two. Significantly detrimental effect on uric acid homeostasis was only found in patients treated with a regimen based on diuretics.     

Serum and urinary nitric oxide in Type 2 diabetes with or without microalbuminuria: relation to glomerular hyperfiltration

BACKGROUND: Glomerular hyperfiltration is considered as one of the pathophysiological mechanisms for the development of diabetic nephropathy. Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly, nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We investigated the relationship between hyperfiltration and NO system, and malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria. METHODS: In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and 32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin, nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR) values, calculated according to the Cockcroft and Gault formula, were recorded. RESULTS: Serum and urine NO levels were higher in both microalbuminurics and normoalbuminurics than controls. There were no significant differences in EGFR between groups. However, hyperfiltration was determined in 31% of normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were higher in patients with hyperfiltration. Plasma MDA levels were significantly elevated in both microalbuminurics and normoalbuminurics when compared with controls. Serum glucose and microalbuminuria were positively correlated in microalbuminuric diabetics. Serum NO levels were also positively correlated with EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were positively correlated with both urinary albumin excretion and plasma MDA levels in normoalbuminuric diabetics. CONCLUSIONS: Hyperglycemia is associated with an increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an increase in urinary albumin excretion and thus causes progression of nephropathy in early Type 2 diabetes.     

非糖尿病性终末期肾病患者透析时机的变化-2001年和2006年的比较

目的 评估目前终末期肾病(end stage renal disease,ESRD)患者的透析时机,并与5年前比较,探讨过晚透析可能的影响冈素及进一步的改进措施.方法 以2000年1月1日～2001年12月31日(A组)和2005年9月1日～2006年8月31日(B组)于北京大学第一医院透析中心开始透析治疗的所有非精尿病性ESRD患者为研究对象,收集患者开始透析时的肾功能(以简化MDRD公式计算估测的肾小球滤过率,eGFR)、尿毒症并发症以及急诊透析的情况.分析过晚透析的影响因素.结果 ①B组患者的透析时机较A组有一定改善,表现在开始透析时eGFR水平呈明显升高趋势,代谢性酸中毒状况改善. 但血白蛋白水平、尿毒症相关的心脑血管并发症和急诊透析的比例差异没有显著性;②过晚透析患者的贫血更严重,低血钙、高血磷更明显,急诊透析的比例增加,住院时间延长,花费增多;③与A组患者相比,B组患者过晚透析的比例明显下降(P＜0.05),但两组患者过晚透析的原因差异没有显著性,仍然以不知自己患有肾脏病或肾衰竭占首位(73.92%).结论 慢性肾脏病和肾衰竭发现过晚仍是过晚透析的主要影响因素,加强公众宣传、肾脏病筛查以及对肾脏专科医师的继续教育有望使更多的患者能适时开始透析.     

Chronic kidney disease prevalence and rate of diagnosis

Background

Chronic kidney disease is a major public health problem. However, no study to date has estimated the prevalence of chronic kidney disease based on the clinical guidelines established by the National Kidney Foundation and few studies have explored the rate of diagnoses by primary care providers.

Subjects and Methods

Cross-sectional study of ambulatory patients in Rochester, NY. The purpose of this study was to estimate the prevalence of chronic kidney disease and the rate of primary caregiver diagnosis in ambulatory patients with chronic kidney disease.

Results

Among the 24,492 outpatients that had at least 2 glomerular filtration rate estimates ≥3 months apart, 6895 had an estimated glomerular filtration rate <60 mL/min/1.73 m², indicating a 28.2% period prevalence of chronic kidney disease. The rate of clinical diagnosis among those with chronic kidney disease was 26.5% (95% confidence interval, 17.9 to 35.1), suggesting that 74% of patients with chronic kidney disease are undiagnosed.

Conclusions

We demonstrate that the prevalence of chronic kidney disease is substantially higher in health-seeking individuals than in the general population. Moreover, we demonstrate that laboratory reporting of estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation alone does not result in an optimal rate of clinical diagnosis.     

2型糖尿病患者血清同型半胱氨酸浓度变化分析

Objective To study the relationship between serum level of homocysteic acid(Hcy)and type 2 diabetic mellitus(T2DM),and to explore the influencing factors serum for Hey level in T2DM patients.Methods Totally T2DM 122 patients(T2DM group),67 patients with chronic kidney diease(CKD group)and 50 healthy controls(CON group)were enrolled in the investigation.The variation of serum Hcy of all groups was observed,and the correlation of serum Hcy level with estimated glomerular filtration rate(eGFR),fasting serum glucose,HbA1C,Urea and creatinine was analyzed.Serum Hcy was measured by enzymatic cycling assay;HbA1C was measured by high-pressure liquid chromatography assay;and eGFR was calculated by using the Levey-modified Modification of Diet in Renal Disease formula.Results There was no significant difference in serum level of Hcy between T2DM group and CON group(P＞0.05).The serum concentration of Hey was significantly higher in CKD group than that of T2DM group and CON group(P＜0.01).There was only 8.20% exceeding the upper limit of 95% of CON group in T2DM group,while 64.18% exceeding the upper limit of 95% of CON group in CKD group.There was no significant difference of Hcy level between patients with eGFR≥90 mL·(min·1.73 m2)-1 in T2DM group and healthy controls(P＞0.05),but the Hey level was significantly higher in patients with eGFR＜90 mL·(min·1.73 m2)-1 than that of healthy controls(P＜0.05).In T2DM group and CKD group,serum Hey level was negatively correlative to eGFR(P＜0.01).positively correlative to Urea and creatinine(P＜0.01);but serum Hcy level did not correlate with fasting serum glucose,HbA1C,total cholesterol and triglyceride(P＞0.05).Conclusion Renal function is an independent risk factor for serum homocysteine level in type 2 diabetes rather than diabetes itself.     

肾小球滤过率与血清VEGF、胆红素水平在糖尿病肾病中的关系研究

目的 研究糖尿病肾病(DKD)患者肾小球滤过率(eGFR)与血清血管内皮生长因子(VEGF)、胆红素水平的关系.方法 选取2016年1月至2017年2月我院收治的DKD患者90例为研究对象(DKD组),按照eGFR水平分为A1组:＜60mL/[min·(1.73m2)],A2组60mL/[min·(1.73m2)]≤eGFR＜ 90mL/[min·(1.73m2)],A3组:eGFR≥90mL/[min·(1.73m2)],另选取单纯糖尿病(DM)及健康志愿者各50例,分别纳入DM组和健康组,比较DKD组、DM组、健康组eGFR、血清白蛋白(ALB)、尿酸(UA)、血肌酐(SCr)、总胆红素(TBIL)、直接胆红素(DBIL)、VEGF及总胆固醇(TC)、甘油三酯(TG)水平,同时对比A1、A2、A3组病程及上述指标,分析eGFR与其他生化指标的相关性,评价eGFR、VEGF、胆红素诊断DKD的效能,并分析DKD患者中影响eGFR水平的独立危险因素.结果 DKD组血清eGFR(70.18±20.56) mL/[min· (1.73m2)]、ALB(35.29±10.67) g/L、TBIL(9.18±2.65) μmol/L、DBIL(2.17±0.45) μmol/L较DM组及健康组低,DKD组UA(401.23±10.09)μmol/L、SCr(1.29±0.67) mg/dL、VEGF(55.29±1.25) pg/mL、TC(6.30-±2.12) mmol/L、TG(2.79±1.36) mmol/L显著高于DM组及健康组(P ＜0.05);A1组病程长于A2、A3组,A1组血清ALB、SCr、TBIL、DBIL低于A2、A3组,A1组UA、VEGF、TC、TG较A2、A3组高(P＜0.05);相关分析显示DKD患者eGFR与TBIL、DBIL呈正相关(P＜0.05),与SCr、VEGF、TC、TG呈负相关(P ＜0.05);eGFR、VEGF、胆红素联合诊断DKD的灵敏度、准确度、特异性高于单项指标诊断;Logistic回归分析显示病程、血清VGEGF、TG、TBIL是影响DKD患者eGFR的独立危险因素(P＜0.05).结论 糖尿病肾病患者eGFR与其血清VEGF、胆红素水平密切相关,临床可综合上述指标进行诊断.     

Glomerular Capillary Hemorrhage Induced in Rats by Diagnostic Ultrasound with Gas–Body Contrast Agent Produces Intratubular Obstruction

Glomerular capillary hemorrhage (GCH) induced by ultrasonic cavitation during diagnostic imaging represents a unique contrast agent–related nephron injury. Consequences of GCH during 1.5-MHz diagnostic ultrasound with contrast agent were examined by histologic methods in rats. Definity was infused at 10 μl/kg/min for 5 min at the start of 8 min of intermittent image-exposure, with 2.3 MPa in situ peak rarefactional pressure amplitude. Kidney samples were taken for histology at 5 min, 30 min, 4 h, 2 d, 1 week and 4 weeks post exposure. In addition, samples were taken at 4 h from groups treated with heparin or aminocaproic acid. GCH was found in 61% of glomeruli in the center of the scan plane 5 min after exposure, which declined (p < 0.05) to 36.3% after 4 h. The width of Bowman's space was significantly increased for glomeruli with GCH relative to glomeruli without GCH (p < 0.05), consistent with tubular obstruction. Antibody staining revealed fibrin clotting in Bowman's space in 4-h samples and this persisted in the 2-d samples. Heparin reduced and aminocaproic acid increased the GCH seen in 4-h samples. Tubular dilation was evident with injury to the epithelium after 2 d. After one week, areas of inflammatory cell infiltration were present. After four weeks, areas of interstitial fibrosis were revealed by Masson's trichrome stain. The consequences of GCH induced by diagnostic ultrasound with contrast agents include rupture of glomerular capillaries, procoagulant activity resulting in intratubular obstruction, and the potential for progression of the resulting tubular injury toward interstitial fibrosis. (E-mail: douglm@umich.edu)