2型糖尿病患者尿蛋白排泄率与肌酐清除率关系分析

目的观察2型糖尿病患者尿白蛋白排泄率与肌酐清除率的关系。方法收集550例2型糖尿病患者的晨尿,测定即时尿标本白蛋白／肌酐比值（ACR）,同时测定血肌酐并计算肌酐清除率（Ccr）。结果在550例患者中Ccr〈60ml／min者106例,ACR增高者130例,约20％的患者ACR与Ccr不一致,且偏差较大,两者相关系数｜r｜为0．54,呈非高度相关。结论在筛查糖尿病肾病时既要测定尿白蛋白量,同时还应该计算肌酐清除率。     

血清尿酸水平与糖代谢状况及肌酐清除率的关系

目的探讨糖尿病（DM）高危人群在糖耐量正常（NGT）、糖调节受损（IGR）和新诊断DM状态下血尿酸（SUA）水平及其与肌酐清除率（Ccr）的关系，验证在DM人群中SUA水平下降与肾小球滤过率（GFR）升高相关的科学假设。方法对822例行糖耐量筛查患者按照糖代谢状态分成7组，比较SUA和Ccr的变化；用线性回归分析SUA和Ccr的变化趋势。结果（1）性别、BMI、TG、HbA1C和Ccr是影响SUA的独立因素。（2）IGR患者的SUA较NGT者高，DM患者的SUA较IGR患者低（P＜0．01），且低于NGT。而DM组的Ccr高于IGR组和NGT组（P＜0．01）。（3）当FPG＜7.0mmol／L时，SUA水平与FPG的升高不相关，当FPG≥7．0mmol／L时，随着FPG的升高，SUA明显下降（P＜0.01）；而Ccr在FPG≥6.0mmol／L时显著升高，在一定的范围内与FPG正相关（P＜0.01）。结论本研究肯定了先前报道的在中国新诊断T2DM人群中SUA降低的现象，并提示GFR的增高可能是导致该人群SUA降低的原因之一。     

2型糖尿病患者内生肌酐清除率与胰岛β细胞功能相关

目的 探讨2型糖尿病患者的胰岛β细胞分泌功能及胰岛素敏感性与内生肌酐清除率(creatinine clearance rate,Ccr,ml·min-1·1.73-1 m-2)的相关性.方法 432例2型糖尿病患者按Ccr水平分为4组:肾功能正常组(90≤Ccr＜130,123例)、肾小球高滤过组(Ccr≥130,80例),肾功能轻度下降组(60≤Ccr＜90,145例)和肾功能中重度下降组(Ccr＜60,84例).进行口服葡萄糖耐量试验及胰岛素释放试验,用稳态模型评估的胰岛素抵抗指数(HOMA-IR)、胰岛素曲线下面积(AUCI)和葡萄糖曲线下面积(AUCG)的比值(AUCI/AUCG)来评价胰岛素抵抗;用胰岛素敏感指数(ISI)及Matsuda ISI来反映胰岛素敏感性;以稳态模型评估的β细胞功能指数(HOMA-β)、早期胰岛素分泌功能指数(△I30/△G30)、第二时相胰岛素分泌功能指数(胰岛素曲线下面积)及葡萄糖处置指数(disposal index,DI)评价胰岛β细胞分泌功能;比较各组间各指标的差异,并对Ccr与胰岛素抵抗相关指标进行相关性分析.结果 (1)与肾功能正常组相比,肾功能轻度下降、肾功能中重度下降组HOMA-IR明显升高,ISI、Matsuda ISI明显下降(P＜0.01);肾功能中重度下降组AUCI/AUCG明显高于其他3组(P＜0.05).(2)肾功能中重度下降组AUCI明显高于其他3组(P＜0.05);肾功能轻度下降、肾功能中重度下降组DI明显低于肾功能正常组(P＜0.05).(3)Ccr与糖尿病病程、收缩压、舒张压、AUCI、HOMA-IR、AUCI/AUCG呈负相关(P＜0.05),与ISI、Matsuda ISI呈正相关(P＜0.01);多元逐步回归分析结果显示Ccr与收缩压、病程、AUCI/AUCG呈负相关(P＜0.05).结论 在2型糖尿病中,Ccr与胰岛素抵抗负相关,随着Ccr的下降,胰岛素抵抗逐渐加重,胰岛素抵抗可能是肾功能下降的独立危险因素.     

瘦体重法推算内生肌酐清除率的临床应用

目的探讨瘦体重法推算肌酐清除率(LBWCcr)在评估肾功能中的意义.方法肾脏病人81例分为两组,第1组51例用于计算24h尿肌酐与瘦体重的比值;第2组30例同时测定其99mTc-DTPA清除率(DTPAGFR)、LBWCcr、4hCcr.以DTPA-GFR作为标准方法,LBWCcr、4hCcr与其进行比较,以验证LBWCcr检测肾小球滤过率的可行性及4hCcr的准确性.结果①LBWCcr、4hCcr、DTPA-GFR三种方法进行方差分析P=0.56,无显著性差异.②LBWCcr、4hCcr与DTPA-GFR进行相关分析,相关系数分别为0.89、0.86,显示LBWCcr与DTPA-GFR显著相关,且好于4hCcr.③在肥胖组及肾功能不全组取得了相似的结果.结论LBWCcr能准确反映肾功能,而且是一种简便、快速推算Ccr的方法.     

ST段抬高型心肌梗死患者肌酐清除率的变化及临床意义

目的探讨肌酐清除率（Ccr）对ST段抬高型心肌梗死（STEMI）患者急性期并发症发生的预测意义，并进一步探讨多种临床变量对Ccr的影响。方法154例STEMI住院病例分为Ccr正常组（Ccr≥70ml／min）和Ccr降低组（Ccr〈70ml／min），比较两组患者在STEMI发生7d内各种并发症的发生率及病死率；进一步用多因素logistic回归分析统计多种因素对Ccr的影响。结果Ccr降低组患者在STEMI发生7d内并发症的发生率较Ccr正常组高（P〈0．05）；多因素logistic回归分析显示年龄〉75岁及多支冠脉病变是Ccr降低的独立危险因素，它们的比值比分别是4．848和4．002，95％可信区间分别为1．644-14．297和2．310～6．934，P值分别为0．0042和0．0001。结论STEMI患者早期肌酐清除率的下降预示并发症发生率、病死率高；多支冠脉病变、年龄〉75岁可影响STEMI患者急性期肌酐清除率。     

2型糖尿病患者预估肾小球滤过率与血清胆红素的相关性

目的 研究2型糖尿病患者预估肾小球滤过率（eGFR）与血清总胆红素（TBIL）、直接胆红素（DBIL）、间接胆红素（IBIL）的相关性.方法 选取2011年11月至2012年9月于天津医科大学代谢病医院糖尿病肾病科住院治疗的2型糖尿病患者523例为研究对象,按eGFR分为肾小球高滤过组（133例）、肾功能正常组（194例）、肾功能轻度下降组（125例）、肾功能中重度下降组（71例）.比较各组TBIL、DBIL、IBIL水平,并行相关因素分析,多组计量资料间比较采用方差分析.结果 肾小球高滤过组各胆红素水平较肾功能正常组水平均明显下降[分别为TBIL：（10.9±4.0）比（12.5 ±4.5）μmol/L、DBIL：（3.8±1.6）比（4.4±1.7） μmol/L、IBIL：（7.1 ±2.8）比（8.0±3.1）μmol/L,均P＜0.05].肾功能中重度下降组TBIL、DBIL、IBIL水平较其他3组均明显下降（F=15.296、15.024、11.609,均P＜0.05）.在eGFR＜ 130 ml/min的人群中,eGFR的相关分析结果提示：eGFR与年龄、病程、总胆固醇、低密度脂蛋白胆固醇呈负相关（r=-0.307、-0.203、-0.149、-0.111,均P＜0.05）,与TBIL、DBIL、IBIL呈正相关（r=0.291、0.275、0.254,均P＜0.05）.结论 2型糖尿病患者血清胆红素水平与肾小球滤过率相关.     

2型糖尿病患者肾小球滤过率与尿白蛋白的关系

目的探讨2型糖尿病患者慢性肾脏病(CKD)的患病率及肾小球滤过率与尿白蛋白排泄间的关系。方法收集自2008年1月至2009年12月在江苏省省级机关医院就诊的2型糖尿病患者资料,采用MDRD公式评估肾小球滤过率(eGFR),CKD定义为存在白蛋白尿或者eGFR60 ml/(min·1.73 m2)。白蛋白尿定义为尿白蛋白/肌酐比值(ACR)≥30 mg/g。采用多项式回归及曲线拟合分析eGFR与尿ACR之间的关系。结果研究纳入1521例2型糖尿病患者,平均年龄(63.9±12.0)岁,CKD及白蛋白尿的患病率分别为31.0%和28.9%。eGFR≥90、60~89、30~59、15~29 ml/(min·1.73 m2)患者白蛋白尿的患病率分别为19.9%、34.5%、65.6%和100%。在正常蛋白尿、微量白蛋白尿及大量白蛋白尿患者中,肾功能不全的比率分别为3.0%、9.3%和40.4%。多项式回归分析显示当患者尿ACR90 mg/g时,eGFR下降缓慢且稳定保持在90 ml/(min·1.73 m2)以上,而当尿ACR≥90 mg/g时,eGFR则迅速下降。结论 2型糖尿病患者CKD及白蛋白尿发生率高,对2型糖尿病人群进行CKD的筛查应该同时检测尿白蛋白与eGFR,为了延缓CKD的进展,应尽早对白蛋白尿进行干预治疗。     

Ketone bodies increase glomerular filtration rate in normal man and in patients with Type 1 (insulin-dependent) diabetes mellitus

Summary The purpose of this study was to investigate whether the administration of acetoacetic and hydrochloric acids in a group of control and Type 1 (insulin-dependent) diabetic patients influenced renal haemodynamics. Renal plasma flow increased from 657±88 to 762±81 ml·min^–1. 1.73 m^–2 in diabetic patients (p<0.01) and from 590±71 to 691±135 in control subjects (p<0.01). Glomerular filtration rate increased from 135±9 to 180±8 ml·min^–1·1.73 m^–2 in diabetic patients (p< 0.001) and from 117±8 to 145±7 in control subjects (p<0.01). Similar effects on renal haemodynamics, even if less pronounced, were observed with low dose acetoacetic but not with hydrochloric acid infusion. Total protein, 2-microglobulin but not albumin excretion rates were increased by acetoacetic acid. We conclude that an acute increase in blood concentration of ketone bodies within the range found in diabetic patients with poor metabolic control (1) increases renal plasma flow and glomerular filtration rate both in control subjects and diabetic patients and (2) causes a tubular proteinuria.     

Long-term glycaemic control directly correlates with glomerular filtration rate in early Type 1 diabetes mellitus before the onset of microalbuminuria

Hyperfiltration occurs early in diabetes mellitus and has been implicated in the development of microalbuminuria. Our aim was to re-examine the controversial relationship between glycaemic control and glomerular filtration (GFR) in normoalbuminuric, normotensive, non-obese patients with short duration Type 1 diabetes mellitus (DM). We studied 75 Type 1 DM patients, 35 male, aged 18–42 years, with a duration of diabetes of 4–8 years. GFR was determined by inulin clearance; hyperfiltration was defined as above 145 ml min⁻¹ 1.73 m⁻² (equivalent to 2 SD above mean for a control population). Analysis was by paired Student’s t-testing and linear regression. GFR correlated significantly with HbA_1c (r = 0.47, p < 0.0001) and fructosamine (r = 0.24, p = 0.035). Mean HbA_1c and fructosamine in the 13 patients with hyperfiltration was significantly higher than in the rest of the group (HbA_1c: 9.2 % (95 % C.I. 7.9–10.4 %) vs 7.6 % (7.2–7.9), p = 0.002; fructosamine: 479 μmol l⁻¹ (450–507) vs 410 μmol l⁻¹ (388–432), p = 0.009. This significant difference persisted even when the two highest values of HbA_1c or fructosamine were removed from analysis. Effective renal plasma flow, assessed by PAH clearance, also correlated in all patients with HbA_1c (r = 0.31, p = 0.039). We conclude that poor glycaemic control directly correlates with hyperfiltration and renal hyperperfusion in early Type 1 DM. Copyright © 1998 John Wiley & Sons, Ltd.     

核苷和核苷酸类药物对慢性乙型肝炎患者肾小球滤过率和血肌酐水平的影响

目的研究核苷和核苷酸类药物(NAs)对慢性乙型肝炎(CHB)患者肾小球滤过率(e GFR)和血肌酐(Scr)的影响。方法收集2010年9月-2014年9月在大连医科大学附属第二医院感染科门诊及住院的CHB患者184例,根据应用NAs的不同将其分为3组,分别为阿德福韦酯(ADV)组(n=58)、替比夫定(LDT)组(n=62)和恩替卡韦(ETV)组(n=64),疗程均为104周。比较治疗前后各组e GFR、Scr水平的变化。计量资料组内治疗前后比较采用Wilcoxon秩和检验,多组间比较采用Kruskal-Wallis H秩和检验,计数资料组间比较采用χ2检验。结果 ETV组治疗52、104周后Scr、e GFR变化均不明显,与基线相比差异无统计学意义(P值均0.05);与基线水平相比,ADV组治疗52、104周的Scr水平升高,e GFR水平降低,差异均有统计学意义(Z值分别为-3.020、-3.456、-4.623、-4.831,P值分别为0.018、0.008、0.004、0.001);LDT组治疗52、104周的Scr水平较基线降低,e GFR较基线升高,差异均有统计学意义(Z值分别为-5.596、-5.687、-5.335、-5.162,P值分别为0.007、0.003、0.002、0.001)。治疗104周后ADV组与LDT组e GFR水平的分布比较差异有统计学意义(χ2=21.039,P0.001),其中LDT组中有77.78%(7/9)的患者e GFR水平转为≥90 ml·min-1·1.73 m-2,ADV组中有23.81%(10/42)的患者e GFR水平转为90 ml·min-1·1.73 m-2。结论在治疗过程中观察到LDT治疗能提高e GFR,显著改善肾功能,而ADV治疗会导致e GFR降低,有潜在的肾毒性,且在NAs治疗CHB患者过程中e GFR比Scr更能早期反映出肾损伤。有关LDT提高e GFR保护肾功能的作用机制有待进一步研究。     

A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy

Summary Glomerular filtration rate (GFR, single bolus ⁵¹Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (> 0.5 g/day) secondary to diabetic nephropathy. Twelve of the 14 patients had normal serum creatinine levels. None of the patients received antihypertensive treatment. During the mean observation period of 26 months (range 23 to 33 months) GFR decreased from 107 to 87 ml/min/1.73 m² (p< 0.001), serum creatinine remained unchanged: 107 and 112/gmmol/l (NS), proteinuria increased from 1.8 to 3.3 g/day (p<0.001) and arterial blood pressure rose from 132/88 to 153/101 mmHg (p<0.001). Glomerular filtration rate decreased linearly with time (slope=–0.75, r=0.99, p<0.001) by a mean of 0.75 ml/min/month (range 0.1 to 1.5 ml/ min/month). The decrease in GFR did not correlate with sex, age at onset, duration of diabetes, arterial blood pressure, proteinuria, insulin requirement, postprandial blood glucose or the initial GFR, but numbers were small. The decline in GFR in each individual was constant, but varied considerably between patients. Increase in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy in young insulin-dependent diabetics.     

Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes

AimThe role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking.MethodsRenal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD).ResultsAfter the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6 ± 3.8 mL/min/1.73 m⁻² BSA to 86.9 ± 6.1 mL/min/1.73 m⁻² BSA (P = 0.026) and from 979 ± 107 μmol/min¹/m² BSA to 1205 ± 94 μmol/min¹/m² BSA (P = 0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r = 0.625, P = 0.017).ConclusionOur observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function.     

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy

Summary Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mmHg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 g/min (geometric mean 688 g/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml·min^–1· (1.73 m²)^–1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open+occluded) was estimated by combined light- and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r=0.77, p<10^–4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r=-0.78, p<10^–5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects.Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.     

Increased kidney size,glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics

Summary Glomerular filtration rate (GFR), renal plasma flow (RPF) and kidney volume were measured in thirteen male subjects (mean age 30 years) with short-term insulin-dependent diabetes (mean duration of disease 2.4 years) and fourteen normal male subjects (mean age 29 years). GFR and RPF were measured by constant infusion technique using I¹²⁵-iothalamate and ¹³¹I-hippuran. Kidney size was determined by means of ultrasound. GFR, RPF and kidney volume were increased in the diabetic patients compared to the normal controls, 144 versus 113 ml/ min×1.73m² (p<0.0005), 627 versus 523 ml/ min×1.73 m² (p<0.0025) and 278 versus 224 ml/ 1.73 m² (p<0.0005) respectively. Combining results from diabetic patients and controls revealed a positive correlation between kidney size and GFR (r= 0.70, p<0.001) and between kidney size and RPF (r=0.61, p<0.001). Within the groups kidney size and RPF correlated significantly in the diabetics (p< 0.01) and the same was found for kidney size and GFR (0.025< p<0.05), while no correlations were found in the normal group. GFR and RPF correlated in the diabetics when evaluated separately (r=0.81, p<0.001) and in the controls (r=0.73, p<0.001). The previous and present data suggest that the mechanisms of the elevated GFR in insulin-dependent diabetics are enhanced RPF, increased transglomerular hydrostatic pressure gradient and increased glomerular ultrafiltration coefficient. The increased kidney size is probably the main cause of the above alterations in the GFR determinants.     

Estimating glomerular filtration rate preoperatively for patients undergoing hepatectomy

AIM： To compare creatinine clearance （Ccr） with estimated glomerular filtration rate （eGFR） in preoperative renal function tests in patients undergoing hepatectomy.METHODS： The records of 197 patients undergoing hepatectomy between August 2006 and August 2008 were studied, and preoperative Ccr, a three-variable equation for eGFR （eGFR3） and a five-variable equation for eGFR （eGFR5） were calculated. Abnormal values were defined as Ccr 〈 50 mL/min, eGFR3 and eGFR5 〈 60 mL/min per 1.73 m2. The maximum increases in the postoperative serum creatinine （post Cr） level and postoperative rate of increase in the serum Cr level （post Cr rate） were compared.RESULTS： There were 37 patients （18.8%） with abnormal Ccr, 31 （15.7%） with abnormal eGFR3, and 40 （20.3%） with abnormal eGFR5. Although there were no significant differences in the post Cr rate between patients with normal and abnormal Ccr, eGFR3 and eGFR5 values, the post Cr level was significantly higher in patients with eGFR3 and eGFR5 abnormality than in normal patients （P 〈 0.0001）. Post Cr level tended to be higher in patients with Ccr abnormality （P = 0.0936 and P = 0.0875, respectively）.CONCLUSION： eGFR5 and the simpler eGFR3, rather than Ccr, are recommended as a preoperative renal function test in patients undergoing hepatectomy.