血糖水平对糖尿病患者肾小球滤过率估算公式的影响

目的 评价糖尿病患者血糖水平对肾小球滤过率（GFR）公式估算结果的影响;比较不同血糖水平Cockcroft-Gault（CG）公式和MDRD公式法估算GFR对诊断肾功能不全的差异。 方法 选取1210例糖尿病患者,同步检测99mTc-GFR（iGFR）、Scr和糖化血红蛋白（HbA1c）。运用CG和MDRD公式计算GFR估计值（eGFRCG、 eGFRMDRD）。依据肾脏病透析预后质量指南（K/DOQI）的建议将糖尿病患者分为iGFR正常组589例[NGFR组,iGFR≥90 ml&#8226;min-1&#8226;(1.73 m2)-1],iGFR轻度下降组[GGFR组,60≤iGFR<90 ml&#8226;min-1&#8226;(1.73 m2)-1]470例,iGFR中度下降组[MGFR组,30≤iGFR<60 ml&#8226;min-1&#8226;(1.73 m2)-1]151例。根据HbA1c的四分位点（7.1%,10.5%）分为4组（<7.1%、7.1%~8.6%、8.7%~10.4%、≥10.5%）,其中HbA1c<7.1%者定义为血糖控制较好组,HbA1c≥10.5%定义为血糖控制差组。采用Spearman相关分析、t检验、Bland-Altman分析、受试者工作特征（ROC）曲线等评估方程的偏离度、准确度,以及血糖对估算结果的影响。 结果 eGFRMDRD在各GFR亚组中均高估GFR;eGFRCG在NGFR组中低估GFR,差异有统计学意义。Bland-Altman分析结果显示,血糖控制较差组的eGFRMDRD的偏差高于血糖控制较好组的eGFRMDRD;血糖控制较差组的eGFRMDRD15%和30%准确性低于血糖控制较好组的eGFRMDRD,差异有统计学意义。血糖控制较差组和较好组间eGFRCG偏差及准确性差异均无统计学意义;而eGFRCG的偏差高于eGFRMDRD,差异有统计学意义。血糖控制良好组CG公式和MDRD公式在诊断肾功能不全患者的ROC曲线下面积差异无统计学意义。血糖控制较差组eGFRMDRD ROC曲线下面积显著大于eGFRCG曲线下面积,差异有统计学意义。 结论 糖尿病患者采用MDRD和CG公式法可导致GFR估计差误。MDRD公式的eGFR估计值受到血糖的影响较大,MDRD公式法高估GFR。MDRD公式在血糖控制较差的患者对肾功能不全患者的估算效应要优于CG公式。     

三种肾小球滤过率评估方程对早期糖尿病肾病的诊断价值比较

Objective To investigate the value of CysC-based CFR in comparison with creatinine-based GFR (CG-GFR and MDRD-GFR) as an accurate serum marker in the prediction of early diabetic nephropathy. Methods A tatal of 133 type 2 diabetic patients (74 males and 59 females, aged 58.1 ±12.3) were enrolled. The level of diabetic nephropathy (normoalbuminuric, microalbuminuric and macroalbuminuric) was staged and estimated GFR based on serum creatinine and cystatin C(CysC) was calculated. The plasma clearance of Tc-DTPA, serum CysC, creatinine, BMI, HbA1c, serum lipid and blood pressure were measured. Results 99mTc-DTPA-GFR was used as golden standard. At 90 and 75 ml· min-1· (1.73 m2)-1 cut-points, diagnostic efficiencies of CysC-GFR (89% and 92%) were better than those of CG-GFR (79%=86%, P=0.004, 0.04) and MDRD-GFR (80%-86%, P=0.02, 0.04). At 60 ml · min-1 · (1.73 m2)-1 cut-point, diagnostic efficiencies of CysC-GFR,CG-GFR and MDRD-GFR were 92%, 90% and 92% respectively (P= 0.49, P=0.71). The Logistic regression analyses showed that retinopathy, HbA1c, CysC, diabetic duration, and CysC-GFR were indicators to predict the development of microalbuminuria. Conclusion CysC-GFR is more valuable than CG-GFR and MDRD-GFR in the prediction of early diabetic nephropathy and should be applied clinically.     

三种肾小球滤过率评估方程对早期糖尿病肾病的诊断价值比较

Objective To investigate the value of CysC-based CFR in comparison with creatinine-based GFR (CG-GFR and MDRD-GFR) as an accurate serum marker in the prediction of early diabetic nephropathy. Methods A tatal of 133 type 2 diabetic patients (74 males and 59 females, aged 58.1 ±12.3) were enrolled. The level of diabetic nephropathy (normoalbuminuric, microalbuminuric and macroalbuminuric) was staged and estimated GFR based on serum creatinine and cystatin C(CysC) was calculated. The plasma clearance of Tc-DTPA, serum CysC, creatinine, BMI, HbA1c, serum lipid and blood pressure were measured. Results 99mTc-DTPA-GFR was used as golden standard. At 90 and 75 ml· min-1· (1.73 m2)-1 cut-points, diagnostic efficiencies of CysC-GFR (89% and 92%) were better than those of CG-GFR (79%=86%, P=0.004, 0.04) and MDRD-GFR (80%-86%, P=0.02, 0.04). At 60 ml · min-1 · (1.73 m2)-1 cut-point, diagnostic efficiencies of CysC-GFR,CG-GFR and MDRD-GFR were 92%, 90% and 92% respectively (P= 0.49, P=0.71). The Logistic regression analyses showed that retinopathy, HbA1c, CysC, diabetic duration, and CysC-GFR were indicators to predict the development of microalbuminuria. Conclusion CysC-GFR is more valuable than CG-GFR and MDRD-GFR in the prediction of early diabetic nephropathy and should be applied clinically.     

Gitelman综合征的表型特点及性别因素对表型的影响

目的 探讨中国人Gitelman 综合征（GS）的表型特点以及性别因素对GS表型的影响。 方法 分析了28例GS患者的临床表现以及血、尿电解质、血pH、血管紧张素、血醛固酮、血压等水平，比较男性、女性GS患者两组之间的差异。临床表现症状通过问卷调查获得，肾小球滤过率（GFR）通过简化MDRD公式（成人）、Schwartz公式（18岁以下青少年）或同位素法评估。 结果 男性患者中夜尿增多的比例显著高于女性患者（P < 0.05），但发病年龄、四肢乏力、软瘫、手足抽搐等症状的发生差异无统计学意义。男性患者血肌酐明显高于女性患者[（82.7±43.3） μmol/L比（58.7±12.7） μmol/L]，但经体表面积校正后的肾小球滤过率差异并无统计学意义[（143.0±48.4） ml&#8226;min-1&#8226;（1.73 m2）-1比（138.0±38.9） ml&#8226;min-1&#8226;（1.73 m2）-1]。男性GS患者尿钾排泄分数和尿氯排泄分数显著高于女性患者(33.0%±22.9%比17.0%±4.7%；2.30%±1.59%比1.23%±0.39%，均P < 0.05），但两组间血钾、血氯、血镁、血碳酸氢根离子、血管紧张素、血醛固酮、尿pH、24 h尿钾、尿氯离子排泄总量差异均无统计学意义。3例肾功能受损的患者均为男性。 结论 男性GS患者的夜尿发生要多于女性患者，男性GS患者的肾功能可能更易受损，性别因素对表型的影响可能与雌激素影响钠氯共转子在远端小管的密度有关。     

中晚期慢性肾脏病患者肾功能进展危险因素——单中心慢性肾脏病专业门诊队列研究

目的 探讨在慢性肾脏病（CKD）专业门诊管理下CKD 3~5期未透析患者肾功能进展相关危险因素。 方法 采取前瞻性队列研究设计,收集北京大学第一医院CKD专业门诊规律随访的CKD 3~5期未透析患者的血压、血红蛋白、钙磷代谢及蛋白尿等指标控制及肾功能的变化情况,进行肾功能进展的多因素分析。肾功能进展定义为每年估计的肾小球滤过率（eGFR）下降大于4 ml&#8226;min-1&#8226;(1.73 m2)-1、开始肾脏替代治疗和（或）肾脏病相关的死亡。 结果 共纳入138例患者,其中CKD 3期84例,4期36例,5期18例。进入队列时基线年龄为（56.5±16.7）岁,基线eGFR为（32.3±13.4） ml&#8226;min-1&#8226;(1.73 m2)-1,平均随访（27.1±12.1）个月。随访过程中患者平均血压（126.5±12.4）/（76.4±7.9） mm Hg;平均血红蛋白（123.4±17.6）g/L;平均钙磷乘积（45.2±7.7） mg2/dl2。分别有70例（50.7%）血压控制达标;102例（73.9%）血红蛋白控制达标;123例（89.1%）患者钙磷乘积控制达标;62例（44.9%）患者肾功能进展。多因素分析显示,随访过程中蛋白尿和血红蛋白水平与肾功能进展独立相关。 结论 通过CKD专业门诊的一体化治疗,能够有效控制中晚期CKD患者的各种并发症。控制蛋白尿和（或）改善贫血有利于延缓中晚期CKD患者肾功能进展。     

抗体芯片在慢性肾脏病患者尿中多种细胞因子同步检测中的初步应用

目的 应用抗体芯片技术检测慢性肾脏病(CKD)患者尿液中细胞因子的水平，并探讨其临床意义。方法 研究对象共10例，7例为CKD患者，全部符合 K/DOQI指南中CKD的诊断标准，并且有肾脏病理诊断。依据GFR水平以及CKD分期，将7例患者分为两组:Ⅰ组:GFR≥80 ml&#8226;min-1&#8226;(1.73 m2)-1(CKD1~2期)共4例； Ⅱ组:GFR≤40 ml&#8226;min-1&#8226;(1.73 m2)-1(CKD3~5期)共3例。另选取3例性别、年龄相匹配的健康人作为正常对照。应用Raybiotech人类细胞因子抗体芯片，同时检测各组尿液中20种细胞因子水平的变化。结果 与正常对照组相比，CKD患者共有15种因子的水平发生了显著变化。单核细胞趋化蛋白(MCP)-1、RENTES、金属蛋白酶组织抑制物(TIMP)-1、肿瘤坏死因子(TNF)-α、血管内皮生长因子(VEGF)、E-选择素(seletin)、Fas、细胞间黏附分子(ICAM)-1、白细胞介素(IL)-2、基质金属蛋白酶(MMP)-2、转化生长因子(TGF)-β和血小板源生长因子(PDGF)-BB的水平同正常对照组相比升高了2~5倍，其中尿MCP-1， RANTES， TIMP-1， TNF-α和 VEGF的水平随着GFR的下降而进一步升高。VCAM-1 和PDGF-BB的水平同正常对照组相比有所下降。在芯片所包含的20种细胞因子中，MMP-9的水平变化尤其显著，同正常对照组相比，CKDⅠ组是正常对照组的492.8倍，CKDⅡ组是正常对照组的198.7倍。结论 首次应用抗体芯片技术，证实CKD患者尿液中细胞因子表达水平同正常对照组有明显差异，并且与疾病所处阶段有一定的关系。     

内蒙古呼伦贝尔地区成人慢性肾脏病流行病学调查

目的 探讨我国内蒙古自治区呼伦贝尔少数民族聚居区成年人群中慢性肾脏病（CKD）患病率及其危险因素。 方法 对该地区20岁以上常住居民进行CKD抽样调查,被调查者均检测了尿白蛋白/肌酐比率、血尿（离心后尿沉渣显微镜检查）及估计肾小球滤过率（eGFR,检验血清肌酐后用国人校正的简化MDRD公式计算）;并同时调查了CKD的相关危险因素。 结果 符合入选条件的被调查者共4522例,白蛋白尿阳性率为7.11%;血尿阳性率为2.64%;eGFR低于60 ml&#8226;min-1&#8226;(1.73 m2)-1者为2.75%;去除白蛋白尿、血尿及eGFR下降共同存在造成的重复,该地区CKD患病率为12.95%。高血压患病率38.90%,糖代谢异常6.61%,脂代谢异常34.60%,腰围增大24.79%,代谢综合征15.02%。多因素Logistic回归分析及分层分析显示,年龄增加、腰围增大、收缩压升高、空腹血糖升高、血清三酰甘油增高及患代谢综合征与白蛋白尿发生相关;年龄增加、收缩压升高及空腹血糖升高与肾功能下降相关;年龄增加与血尿发生相关。 结论 内蒙古自治区呼伦贝尔地区CKD患病率为12.95%。相关危险因素包括年龄增加、腰围增大、高血压、血糖或血脂异常、及代谢综合征。     

2型糖尿病肾病患者血清淀粉样蛋白A水平

目的：探讨2型糖尿病肾病患者的血清淀粉样蛋白A（SAA）水平。方法：2型糖尿病患者144例,依据尿白蛋白排泄率（UAER）结果分为单纯糖尿病组（SDM组）：UAER〈30mg/24h;糖尿病肾病组（DN组）：UAER≥30mg/24h。DN组依据肾小球滤过率（GFR）水平分为两组,DN早中期组（EDN组）：GFR〉30ml·min^-1·1.73m^-2;DN中晚期非透析组（LDN组）：GFR≤30ml·min^-1·1.73m^-2。同时入选正常对照组（NC组）30例。测定血清SAA水平,进行多因素分析。结果：DN组SAA水平较SDM组显著升高（P〈0.05）;SDM组SAA水平较NC组显著升高（P〈0.05）;LDN组SAA水平较NC组、SDM组、EDN组显著升高（均P〈0.01）。SAA水平与尿白蛋白、腰臀比呈正相关。结论：2型糖尿病肾病患者血清SAA水平明显升高,并与DN严重程度密切相关。     

替米沙坦对糖尿病大鼠肾小球表达整合素α3β1的影响

目的 观察整合素α3β1在糖尿病大鼠肾小球的表达以及替米沙坦对其影响&#65377;方法 制备糖尿病大鼠模型,随机将动物分为糖尿病组&#65380;治疗组, 另设对照组&#65377;治疗组给予替米沙坦3 mg·kg^-1·d^-1&#65377;6周后,检测各组24 h尿白蛋白定量&#65380;肌酐清除率&#65380;血糖&#65380;血胰岛素&#65380;血压&#65380;肾重/体重;免疫组化法检测肾小球整合素α3β1表达部位及表达水平&#65377;分离肾小球,Western印迹法检测肾小球整合素α3β1蛋白表达水平&#65377; RT-PCR 检测肾小球TGF-β1mRNA 的表达&#65377;光镜下观察肾组织病理改变;电镜下观察肾组织超微结构变化&#65377;结果 免疫组化结果显示,正常大鼠整合素α3β1主要沿肾小球血管袢呈线性表达,系膜区有少量表达&#65377;糖尿病组肾小球整合素α3β1表达比正常对照组明显减弱;替米沙坦治疗组整合素α3β1表达较糖尿病组明显增加,24 h尿白蛋白定量及其它肾功能指标以及病理改变明显改善,血压无明显变化, 肾小球TGF-β1mRNA表达比糖尿病组显著下降&#65377;结论 替米沙坦可以减少糖尿病肾病大鼠早期的尿蛋白,改善病理变化,保护肾功能,其作用机制可能部分通过减少TGF-β1表达,上调整合素α3β1表达而实现&#65377;     

小剂量环孢素A联合小剂量泼尼松治疗特发性膜性肾病的初步观察

目的 非随机前瞻性观察小剂量环孢素A（CsA）联合小剂量泼尼松在我国特发性膜性肾病治疗中的疗效及不良反应,比较其与环磷酰胺（CTX）联合足量泼尼松的异同。 方法 31例经肾活检病理证实为特发性膜性肾病（Ⅰ~Ⅲ期）的肾功能正常的大量蛋白尿患者纳入本研究。CTX组20例,100 mg/d, 累积量约8 g;口服泼尼松0.6~1.0 mg&#8226;kg-1&#8226;d-1,2～3个月后逐渐减量。CsA 组19例（包括CTX组中治疗无效或复发的8例）,起始量1.0~1.5 mg&#8226;kg-1&#8226;d-1,2～3个月无效者,逐渐加量,最大剂量≤2.5 mg&#8226;kg-1&#8226;d-1;口服泼尼松0.15~0.50 mg&#8226;kg-1&#8226;d-1,3月个后逐渐减量。观察两组治疗前后的尿蛋白、血白蛋白和血肌酐等疗效指标及不良反应。 结果 CTX组随访（48±22）周,13例有效(65%,7例部分缓解,6例完全缓解),7例无效(35%)。CsA组随访（44±15）周,其中2例因不良反应而退出,余17例中,12例有效(70%,6例部分缓解,6例完全缓解),5例无效(30%)。两组缓解比例的差异无统计学意义。CTX组的不良反应有肝功能损伤等。CsA组的不良反应有血肌酐上升（3例）、高血压（12例）等,停药后或用药可控制。 结论 小剂量CsA联合小剂量泼尼松与CTX联合足量泼尼松治疗特发膜性肾病的缓解比例相近,对于CTX治疗无效或复发的患者,仍可能有效,虽然不良反应较多,但易于监测和控制。     

Estimating the glomerular filtration rate using serum cystatin C levels in patients with spinal cord injuries

Study design:Prospective cohort study.Objectives:To investigate the relationship between (51)chromium-ethylene-diamine-tetra-acetate ((51)Cr-EDTA) clearance, serum cystatin C (CysC), serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR(MDRD), MDRD stands for modification of diet in renal disease) based on the serum creatinine in patients with complete or incomplete spinal cord injury (SCI) and to develop and evaluate a GFR-estimating equation using serum CysC.Settings:Spinal Cord Injury Unit, Viborg Regional Hospital, Viborg, Denmark.Methods:Ninety-eight men and 47 women with SCI were included in the study. Serum CysC levels were measured by an automated particle-enhanced nephelometric immunoassay, serum and urine creatinine levels were measured by an enzymatic method traceable to the IDMS creatinine reference method, and (51)Cr-EDTA clearance was measured by a multiple plasma sample method.Results:The area under the curves (AUCs) in the non-parametric receiver operating characteristics (ROC) plots for serum CysC were compared with serum creatinine and to eGFR(MDRD) and revealed a significant difference (P-value<0.05) for all SCI patients. There was no significant difference between the AUC for serum CysC compared with the AUC for creatinine clearance. GFR (ml?min(-1) per 1.73?m(2)) can be calculated from serum CysC values (mg?l(-1)) using the equation eGFR(CysC)=212·exp(0.914·CysC). The model accurately predicted the GFR of 88% of patients within ±30% of the measured GFR, and it was able to predict the GFR of 50% of patients within ±10% of the measured GFR.Conclusion:In patients with SCI, GFR can be estimated independent of age, sex and muscle mass by a newly developed equation based on a single serum CysC value.     

Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients

BACKGROUND: Glomerular filtration rate (GFR) is the best overall index of renal function in health and disease. Inulin and 51Cr-EDTA plasma clearances are considered the gold standard methods for estimating GFR. Unfortunately, these methods require specialized technical personnel over a period of several hours and high costs. In clinical practice, serum creatinine is the most widely used index for the noninvasive assessment of GFR. Despite its specificity, serum creatinine demonstrates an inadequate sensitivity, particularly in the early stages of renal impairment. Recently, cystatin C, a low molecular mass plasma protein freely filtered through the glomerulus and almost completely reabsorbed and catabolized by tubular cells, has been proposed as a new and very sensitive serum marker of changes in GFR. This study was designed to test whether serum cystatin C can replace serum creatinine for the early assessment of nephropathy in patients with type 2 diabetes. METHODS: The study was performed on 52 Caucasian type 2 diabetic patients. Patients with an abnormal albumin excretion rate (AER) were carefully examined to rule out non-diabetic renal diseases by ultrasonography, urine bacteriology, microscopic urine analysis, and kidney biopsy. Serum creatinine, serum cystatin C, AER, serum lipids, and glycosylated hemoglobin (HbA1c) were measured. GFR was estimated by the plasma clearance of 51Cr-EDTA. In addition the Cockcroft and Gault formula (Cockcroft and Gault estimated GFR) was calculated. RESULTS: Cystatin C serum concentration progressively increased as GFR decreased. The overall relationship between the reciprocal cystatin C and GFR was significantly stronger (r = 0.84) than those between serum creatinine and GFR (r = 0.65) and between Cockcroft and Gault estimated GFR and GFR (r = 0.70). As GFR decreased from 120 to 20 mL/min/1.73 m2, cystatin C increased more significantly that serum creatinine, giving a stronger signal in comparison to that of creatinine over the range of the measured GFR. The maximum diagnostic accuracy of serum cystatin C (90%) was significantly better than those of serum creatinine (77%) and Cockcroft and Gault estimated GFR (85%) in discriminating between type 2 diabetic patients with normal GFR (>80 mL/min per 1.73 m2) and those with reduced GFR (<80 mL/min/1.73 m2). In particular, the cystatin C cut-off limit of 0.93 mg/L corresponded to a false-positive rate of 7.7% and to a false-negative rate of 1.9%; the serum creatinine cut-off limit of 87.5 micromol/L corresponded to a false-positive rate of 5.8% and to a false-negative rate of 17.0%. CONCLUSIONS: Cystatin C may be considered as an alternative and more accurate serum marker than serum creatinine or the Cockcroft and Gault estimated GFR in discriminating type 2 diabetic patients with reduced GFR from those with normal GFR.     

血清中CysC、RBP、Hcy、CRP水平与糖尿病肾病分期相关性研究

目的探讨血清中胱抑素C(CysC)、视黄醇结合蛋白(RBP)、同型半胱氨酸(Hcy)、C反应蛋白(CRP)水平与糖尿病肾病分期的相关性。方法选取2016年7月至2018年8月阜阳市人民医院468例糖尿病肾病患者作为研究对象,使用简化的MDRD公式计算肾小球滤过率(GFR),根据K/DOQI慢性肾脏病临床实践指南将患者分为Ⅰ~Ⅴ期,利用西门子2400全自动生化仪测定患者血清中CysC、RBP、Hcy、CRP水平,利用Graphpad 5.0统计学软件进行数据处理并作回顾性分析比较。结果对468例糖尿病肾病患者根据血肌酐估算肾小球滤过率并利用其进行肾损伤分期,其中I期233例,II期70例,III期95例,IV期37例,V期33例。随后分别对肾损伤分期与CysC、RBP、Hcy、CRP相关性进行分析,结果显示,糖尿病肾病患者肾损伤程度与四个指标均具有相关性。其中肾损伤程度与CysC相关系数为0.5264(P<0.001);其与RBP和Hcy的相关系数分别为0.3355和0.2877(P<0.001);而肾损伤程度与CRP相关系数为0.0122(P=0.0168)。结论联合检测患者血清中CysC、RBP、Hcy、CRP水平与糖尿病肾病分期均有一定的临床价值,而CysC更能贴切的反应糖尿病肾损伤程度。     

The early natural history of nephropathy in Type 1 Diabetes: III. Predictors of 5-year urinary albumin excretion rate patterns in initially normoalbuminuric patients

Predictors of albumin excretion rate (AER) abnormalities could provide earlier indicators of diabetic nephropathy risk. Data from the Natural History Study, a prospective 5-year observation of renal structure and function in young type 1 diabetic patients, were examined for predictors of AER patterns in normoalbuminuric type 1 diabetic patients. Included were 170 patients (96 females) (aged 16.7 +/- 5.9 years, duration of diabetes 8.0 +/- 4.3 years) with normal blood pressure, normoalbuminuria (AER <20 microg/min), and eight or more follow-up visits over 5 years. AER, blood pressure, and HbA1c (A1C) were determined quarterly and glomerular filtration rate (GFR) annually. Persistent microalbuminuria (PMA) was defined as 20-200 microg/min in two of three consecutive values within 6-12 months. Four different AER patterns were identified. Group 1 (n = 99): all values <20 microg/min. Group 2 (n = 49): intermittent levels >20 microg/min but not meeting microalbuminuria criteria. Group 3 (n = 14): PMA during follow-up but normoalbuminuria at study exit. Group 4 (n = 8): microalbuminuria at study exit. Group 4 (497 +/- 95 nm, P < 0.01) and group 3 (464 +/- 113 nm, P = 0.03) patients had greater baseline glomerular basement membrane (GBM) width versus group 1 (418 +/- 67 nm). Baseline GFR in group 4 (163 +/- 37 ml.min(-1). 1.73 m(-2)) was higher than group 1 (143 +/- 28 ml.min(-1) . 1.73 m(-2), P = 0.04). A1C was higher in group 2 (9.0 +/- 1.2%) than group 1 (8.4 +/- 1.1%, P = 0.008). Thus, greater increases in GBM width and GFR were predictors of PMA. Since 64% of the patients that developed microalbuminuria reverted to normoalbuminuria, the risk of diabetic nephropathy as defined by current microalbuminuria criteria is unclear.     

The relationship between microalbuminuria and glomerular filtration rate in young type 1 diabetic subjects: The Oxford Regional Prospective Study

BACKGROUND: The purpose of this study was to examine the relationship between glomerular filtration rate (GFR) measured at 5 years' diabetes duration and annual urine albumin excretion in a prospective cohort of children with type 1 diabetes (T1DM). METHODS: Three hundred and eight children were followed from diagnosis of T1DM [aged 9.8 years (range 0.4-15.9) for a median duration of 10.9 years (6.0-17.8) with annual assessments comprising measurement of HbA1(c) and 3 urine samples for albumin:creatinine ratio (ACR). GFR was measured in all children at 5 years' diabetes duration. RESULTS: Two hundred forty-three (78.8%) subjects were normoalbuminuric (MA-) for the duration of the study. At 5 years: 35 (11.4%) subjects had MA (MA+) and 30 (9.7%) subjects were normoalbuminuric but developed MA during subsequent follow-up annual assessments (future MA+). In the future MA+ group compared to the MA+ and MA- groups; GFR was higher (167 vs. 134 vs. 139 mL/min/1.73 m(2), P < 0.002); the prevalence of hyperfiltration (GFR >125 mL/min/1.73 m(2)) was greater (97 vs. 57 vs. 64%, P= 0.006) and HbA1c levels were higher (11.4 vs. 10.8 vs. 9.7%, P < 0.001). The probability (Cox Model) of having hyperfiltration at 5 years' duration was related to puberty (a 1.7-fold increased risk with puberty onset) and poor glycemic control (a 10% increased risk for a 1% increase in HbA1c). Comparing subjects with and without hyperfiltration, prior to the first GFR measurement no difference in ACR levels existed; however, after this time median ACR levels were significantly greater [1.2 (0.1-86.4) vs. 0.9 (0.1-71.6) mg/mmol, P= 0.003], independent of age and HbA1c levels. The probability of developing MA between 5 and 10 years' duration was associated with poor glycemic control (a 30% increased risk for a 1% increase in HbA1c) and higher GFR at 5 years (22% increased risk for a 10 mL/min/1.73 m(2) rise in GFR). CONCLUSION: Glomerular hyperfiltration is associated with puberty and increasing ACR levels and is predictive of MA independent of HbA1c. This suggests that factors other than poor glycemic control may be involved in the pathogenesis of early diabetic nephropathy and early intervention with medical therapy to reduce GFR may be beneficial even before onset of MA.     

Change of glomerular filtration rate in healthy adults with aging

Aim:   In order to determine the relationship between glomerular filtration rate (GFR) and age, the associated factors, and the accurate method of GFR in healthy adults, we conducted a cross-sectional study in community-dwelling adults in Beijing.
Methods:   Renal function of 201 clinically healthy subjects was determined using technetium-99 m-labelled diethylene triamine pentacetic acid (^99mTc-DTPA). Estimated GFR was calculated with the Cockcroft–Gault (CG) equation, abbreviated Modification of Diet in Renal Disease (MDRD) equation, and plasma clearance of creatinine (Ccr). Serum cystatin C, biomarkers of inflammatory and endothelial cells were analyzed as well. Protein intake, carotid artery intima-media thickness and plaque formation were assayed as well.
Results:   Glomerular filtration rate was negatively associated with age and the correlation coefficient for ^99mTc-GFR, CG-GFR, MDRD-GFR, Ccr were −0.643, −0.736, −0.55 and −0.619, respectively ( P  < 0.001), while the correlation coefficient between cystatin C and age was 0.681 ( P  < 0.001). Estimated GFR were associated with measured GFR, and the correlation coefficient for Ccr, CG-GFR and MDRD-GFR were 0.813, 0.582 and 0.418, respectively ( P  < 0.001). The area under the receiver–operator curve of Ccr was larger, CG was smaller while MDRD was the smallest, and the difference was significant ( P  < 0.001). So a predicted equation was presented by cystatin C and C-reactive protein for the elderly.
Conclusion:   In the clinically healthy adults, GFR declined with age. MDRD and CG equation are not suitable to estimate GFR in healthy adults. The predicted equation established by cystatin C and C-reactive protein may be more accurate.     

Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease

Limited data suggest that HMG-CoA reductase inhibitors (statins) may slow loss of renal function in individuals with chronic renal insufficiency. This study was conducted to determine whether pravastatin reduced rates of loss of renal function in people with moderate chronic renal insufficiency. This was a post hoc subgroup analysis of a randomized double-blind placebo controlled trial. Data were analyzed from the CARE study (a randomized trial of pravastatin versus placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol < 240 mg/dl). Participants with estimated GFR (MDRD-GFR) < 60 ml/min per 1.73 m(2) body surface area at baseline were considered to have moderate chronic renal insufficiency. Multivariate regression was used to calculate rates of decline in MDRD-GFR for individuals receiving pravastatin and placebo, controlling for prospectively determined covariates that might influence rates of renal function loss. Change in renal function could be calculated in 3384 individuals, of whom 690 (20.4%) had MDRD-GFR < 60 ml/min per 1.73 m(2) and were eligible for inclusion. Among all individuals with MDRD-GFR < 60 ml/min per 1.73 m(2)), the MDRD-GFR decline in the pravastatin group was not significantly different from that in the placebo group (0.1 ml/min per 1.73 m(2)/yr slower; 95% CI, -0.2 to 0.4; P = 0.49). However, there was a significant stepwise inverse relation between MDRD-GFR before treatment and slowing of renal function loss with pravastatin use, with more benefit in those with lower MDRD-GFR at baseline (P = 0.04). Rate of change in MDRD-GFR in the pravastatin group was 0.6 ml/min per 1.73 m(2)/yr slower than placebo (95% CI, -0.1 to 1.2; P = 0.07) in those with MDRD-GFR < 50 ml/min, and 2.5 ml/min per 1.73 m(2)/yr slower (95% CI, 1.4 to 3.6 slower; P = 0.0001) in those with MDRD-GFR < 40 ml/min per 1.73 m(2)/yr. Pravastatin also reduced rates of renal loss to a greater extent in participants with than without proteinuria at baseline (P = 0.006). It is concluded that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. These findings require confirmation by a large randomized trial conducted specifically in people with chronic renal insufficiency.     

Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease

The performance of the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault (CG) equations as compared with measured (125)I-iothalamate GFR (iGFR) was analyzed in patients with chronic kidney disease (CKD) and in potential kidney donors. All outpatients (n = 1285) who underwent an iGFR between 1996 and 2003 were considered for analysis. Of these, 828 patients had CKD and 457 were potential kidney donors. Special emphasis was put on the calibration of the serum creatinine measurements. In CKD patients with GFR <60 ml/min per 1.73 m(2), the MDRD equation performed better than the CG formula with respect to bias (-0.5 versus 3.5 ml/min per 1.73 m(2), respectively) and accuracy within 30% (71 versus 60%, respectively) and 50% (89 versus 77%, respectively). Similar results are reported for 249 CKD patients with diabetes. In the kidney donor group, the MDRD equation significantly underestimated the measured GFR when compared with the CG formula, with a bias of -9.0 versus 1.9 ml/min per 1.73 m(2), respectively (P < 0.01), and both the MDRD and CG equations overestimated the strength of the association of GFR with measured serum creatinine. The present data add further validation of the MDRD equation in outpatients with moderate to advanced kidney disease as well as in those with diabetic nephropathy but suggest that its use is problematic in healthy individuals. This study also emphasizes the complexity of laboratory calibration of serum creatinine measurements, a determining factor when estimating GFR in both healthy individuals and CKD patients with preserved GFR.     

Is the Chronic Kidney Disease Epidemiology Collaboration four‐level race equation better than the cystatin C equation?

Aim: To evaluate the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) four‐level race equation in the assessment of glomerular filtration rate (GFR) in Chinese people with chronic kidney disease (CKD), which was published in 2011, compared with the cystatin C‐based GFR estimation equation (CysC GFR) and the combination of CysC and serum creatinine equation (CysC‐Scr GFR). Methods: The CKD‐EPI four‐level race equation estimated GFR (CKD‐EPI GFR) was compared with the CysC GFR and CysC‐Scr GFR. Three equations were compared with body surface area (BSA) standardized GFR (sGFR), which was measured by ^99mTc‐DTPA renal dynamic imaging method in 111 CKD cases. Results: A statistically significant correlation was found between sGFR and CKD‐EPI GFR, CysC GFR and CysC‐Scr GFR. Three estimated GFR (eGFR) equations of 30% accuracy were 58.6%, 56.8% and 63.5%, respectively. Average deviations of eGFR from sGFR were 2.34, 1.19, and 1.32 (mL/min per 1.73 m²) (P > 0.05), respectively. There was no significant deviation in the CKD from stages 1 to 5 in CKD‐EPI GFR and CysC‐Scr GFR. However, when estimated by CysC GFR, the deviation was increased, with the value of 12.41 mL/min per 1.73 m² (P= 0.002) in CKD stage 5. Conclusion: Our results showed that in a Chinese population with CKD, CKD‐EPI GFR, CysC GFR and CysC‐Scr GFR of bias and overall accuracy of 30% were very similar. There was little advantage in adding Asian coefficient to modifying the CKD‐EPI equation. CysC GFR overestimated GFR in patients with CKD stages 4 and 5.     

Pregnancy in Patients with Diabetic Nephropathy

Background and Aim  To determine the influence of pregnancy on renal functions in patients with diabetic nephropathy and influence of diabetic nephropathy on pregnancy outcome. Methods  A prospective cohort study was carried out on 15 patients with diabetic nephropathy with pregnancy (group 1), 15 diabetic patients with diabetic nephropathy without pregnancy (group 2) and 15 pregnant diabetic patients without nephropathy (group 3). Patients with diabetic nephropathy with serum creatinine less than 3 mg% were involved. Renal function tests were done every 3 months for 18 months. Pregnancy outcome and complications were recorded. Results  Comparing group 1 and group 2 shows significant difference as regards percent increase in serum creatinine, percent change in GFR and percent increase in urinary proteins. Comparing group 1 and group 3 shows significant difference as regards rate of toxemia of pregnancy, preterm delivery and small for age babies. Mean blood pressure, GFR deterioration and mean HbA1c are the main determinant of most complications. Conclusions  Pregnancy leads to deterioration in renal functions in patients with diabetic nephropathy with elevated serum creatinine; also the presence of diabetic nephropathy increases pregnancy unfavorable outcomes. Special care should be given to blood pressure control, blood sugar control and control of renal condition.