Plasma cystatin C determinations in a healthy elderly population

Plasma cystatin C measurement has been previously shown to be a better indicator of changes in glomerular filtration rate (GFR) than plasma creatinine. The available literature on reference intervals for cystatin C concentration encompasses only paediatric and adult populations up to 60 years of age, therefore we set out to determine an elderly reference range. Blood was taken from 401 subjects (65-101 years) and cystatin C and creatinine concentrations measured using commercially available methodologies. The availability of height and weight measurements allowed the additional calculation of predicted creatinine clearances using the Cockcroft and Gault formulae. Whilst no notable gender difference in cystatin C values was observed (female, 1.48 mg/l; male, 1.53 mg/l), concentrations rose with increasing age (60-79 years, 1.39 mg/l; >80 years, 1.70 mg/l). Conversely, there was a significant (P<0.0001) gender difference in creatinine values (female, 99 micromol/l; male, 120 micromol/l) but none between age groups (60-79 years, 105 micromol/l; >80 years, 113 micromol/l). Calculated GFR determinations resulted in a predicted creatinine clearance range of 21-81 ml/min per 1.73 m2 (n=361). There was no significant difference between gender (male, 18-88 ml/min per 1.73 m2; female, 24-69 ml/min per 1.73 m2), but a very significant 20% decrease in predicted GFR per decade. Sex-related reference intervals for creatinine were established (female, 66-149 micromol/l; male, 71-204 micromol/l); whilst age-related reference intervals were established for both cystatin C (60-79 years, 0.93-2.68 mg/l; >80 years, 1.07-3.35 mg/l) and predicted creatinine clearance (60-79 years, 27-89 ml/min per 1.73 m2; >80 years=18-55 ml/min per 1.73 m2). Plasma cystatin C measurement offers a simple, more sensitive screening assay for early changes in GFR and reflects the decreasing GFR that occurs with increasing age.     

Effect of naproxen on renal haemodynamics in elderly patients with arthritis

The effects of naproxen on renal haemodynamics were observed in ten elderly arthritic patients who were otherwise healthy and without clinical evidence of renal disease. Glomerular filtration rate (GFR,51Cr-EDTA clearance) and effective renal plasma flow (ERPF, 125I-iodohippurate clearance) were measured after 2 weeks' treatment with naproxen 500 mg twice daily and again after 2 weeks off the drug, in random order. Baseline values for GFR and ERPF were within normal limits (mean 72 ml/min/1.73 m2, 110% predicted and 326 ml/min/1.73 m2, 111% predicted, respectively). On naproxen, ERPF and renal blood flow decreased by 10% and 9%, respectively (-32 ml/min/1.73 m2; p = 0.05 and -49 ml/min/1.73 m2; p less than 0.01). These events produced no untoward clinical effects. Nevertheless, this response might impair the kidney's ability to preserve GFR if a further stress were to supervene. Consequently, temporary withdrawal of non-steroidal anti-inflammatory drugs from elderly patients should be considered in response to intercurrent illness or drug therapy likely to compromise renal blood flow.     

老年男性高血压患者血压变异性与肾功能的相关性分析

目的了解血压控制良好的老年及高龄老年男性高血压患者血压变异性与肾功能的相关性。方法选择老年男性高血压患者413例,根据年龄分为老年组196例(年龄<80岁)和高龄组217例(年龄≥80岁)。给予24h动态血压监测及血液指标检测。血压变异性指标用24h收缩压和舒张压血压标准差表示,肾功能指标由估算的肾小球滤过率(eGFR)表示。将研究人群按照eGFR≥90ml/(min.1.73m2)、60～89ml/(min.1.73m2)、<60ml/(min.1.73m2)分为eGFR 1组89例、eGFR 2组179例和eGFR 3组145例。结果与老年组比较,高龄组年龄、糖尿病和冠心病患病、尿酸、夜间收缩压、24h收缩压负荷水平明显增高,TC、LDL-C、eGFR、24h舒张压、夜间收缩压下降、夜间舒张压下降明显降低(P<0.05,P<0.01)。多因素分析显示,24h收缩压标准差是血压控制良好的老年及高龄老年患者肾功能下降的独立危险因素。结论在血压控制良好的老年男性高血压患者中,只有24h收缩压标准差是肾功能下降的独立危险因素,改善血压变异性是延缓肾功能下降的重要治疗内容。     

老年心房颤动患者慢性肾功能受损对血栓栓塞事件的影响

目的探讨老年心房颤动(房颤)患者慢性肾功能受损对血栓栓塞事件的影响。方法选择无抗凝治疗的老年房颤患者265例,根据慢性肾脏疾病分级分为估算肾小球滤过率(eGFR)≥60ml/(min·1.73m2)152例、eGFR45⁵9ml/(min·1.73m2)69例、eGFR<45ml/(min·1.73m2)44例,通过eGFR和尿蛋白的评估,观察其随访期间是否出现血栓栓塞事件。结果房颤血栓栓塞的发生与eGFR下降(RR=4.183,95%CI:2.57159ml/(min·1.73m2)69例、eGFR<45ml/(min·1.73m2)44例,通过eGFR和尿蛋白的评估,观察其随访期间是否出现血栓栓塞事件。结果房颤血栓栓塞的发生与eGFR下降(RR=4.183,95%CI:2.571⁶.805,P<0.01)和尿蛋白(RR=3.692,95%CI:2.7316.805,P<0.01)和尿蛋白(RR=3.692,95%CI:2.731⁵.105,P<0.01)相关。多因素分析显示,尿蛋白使血栓栓塞的危险性增加46.2%(HR=1.462,95%CI:1.2155.105,P<0.01)相关。多因素分析显示,尿蛋白使血栓栓塞的危险性增加46.2%(HR=1.462,95%CI:1.215¹.904,P<0.01);将eGFR≥60ml/(min·1.73m2)作为参照,eGFR在451.904,P<0.01);将eGFR≥60ml/(min·1.73m2)作为参照,eGFR在45⁵9ml/(min·1.73m2)出现血栓栓塞事件增加17.2%(HR=1.172,95%CI:0.91559ml/(min·1.73m2)出现血栓栓塞事件增加17.2%(HR=1.172,95%CI:0.915¹.402,P<0.01),eGFR<45ml/(min·1.73m2)则增加42.1%(HR=1.421,95%CI:1.2111.402,P<0.01),eGFR<45ml/(min·1.73m2)则增加42.1%(HR=1.421,95%CI:1.211¹.816,P<0.01)。结论慢性肾功能受损增加了不用抗凝药物的老年房颤患者血栓栓塞的危险性。     

Validity of creatinine clearance from serum creatinine in subjects over 80 years old

In clinical practice, the Cockcroft and Gault formula (CG) is used to evaluate creatinine clearance from serum creatinine in the elderly. Its validity in a very old nondebilitated population over 80 years of age has not been investigated. In our study, we compared the calculated creatinine clearance with the glomerular filtration rate (GFR) measured using the clearance of 99m-diethyleenetriamine pentaacetic acid (99m Tc TDPA), isotopic method which avoids urinary collection in 25 patients over 80 years old. The CG clearance largely underestimates the isotopic GFR: mean calculated creatinine clearance is 37.6 ± 9.8 ml/min/1.73 m2 and the mean isotope GFR is 57.8 ± 15 ml/min/1.73 m2. The mean underestimation is the same in the subgroup of 11 patients with plasma creatininemia below 100 μmol/l and in the subgroup of 14 patients with creatininemia over 100 μmol/1.     

Reduced quinidine clearance in elderly persons.

The influence of age on quinidine pharmacokinetics was assessed in 22 healthy male and female volunteers; 14 of the subjects were young (aged 23 to 34 years) and 8 elderly (aged 60 to 69 years). All subjects received 180 to 300 mg of quinidine base by constant rate intravenous infusion over 10 to 15 minutes. The concentration of total and unbound quinidine in multiple serum samples and in urine collected within 48 hours after the administration of quinidine qas determined with spectrophotofluorometric assay. Mean kinetic values for total quinidine in the young subjects were: elimination half-life (t 1/2 beta), 7.3 hours; total volume of distribution (Vd), 2.39 liters/kg; total clearance, 4.04 ml/min per kg; renal clearance 1.43 ml/min per kg; and percent unbound, 24.6 In the elderly subjects, the values for Vd (2.18 liters/kg) and percent unbound (28.2) did not differ significantly from these values in the young subjects. However, in the elderly subjects t 1/2 beta was significantly longer (9.7 hours, P less than 0.05) and total quinidine clearance significantly less (2.64 ml/min per kg, P less than 0.005) than in the young subjects. Renal clearance of quinidine in the elderly was also significantly less (0.99 ml/min per kg, P less than 0.05) than in the young and was associated with lower rates of creatinine clearance in the elderly (r = 0.66). Reduced clearance of quinidine and prolongation of its elimination half-life could predispose to toxicity in the elderly unless the dose were appropriately adjusted.     

Effect of oral cyclosporin on renal function in Crohn's disease

Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0,6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m²; at six weeks: 100.9 ml/min/1.73 m²; mean ERPF at baseline: 497.3 ml/min/1.73 m²; at six weeks: 398.5 ml/min/1.73 m²). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m²), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m²). Serum creatinine rose significantly (median pretreatment 72 mol/liter; median at four weeks 86 mol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction.     

Pharmacokinetics of Famotidine after Intravenous Administration in Liver Disease

The pharmacokinetics of famotidine were studied after the administration of a single intravenous dose of 20-mg to seven normal volunteers, six patients with chronic hepatitis, 14 patients with compensated cirrhosis, and seven patients with decompensated cirrhosis. The plasma terminal elimination half-life of famotidine was significantly prolonged and famotidine total body clearance was significantly reduced in patients with decompensated cirrhosis, whose creatinine clearance was 57.2 +/- 6.7 ml/min/1.48 m2, but these changes were not significant in patients with chronic hepatitis (creatinine clearance: 109.2 +/- 10.5 ml/min/1.48 m2) or in patients with compensated cirrhosis (creatinine clearance: 72.2 +/- 26.5 ml/min/1.48 m2 in comparison with normal volunteers. The total volume of distribution at steady state was not significantly different between the normal volunteers and the three groups of patients. Famotidine total body clearance showed a weak but significant correlation with the creatinine clearance (r = 0.66, p less than 0.001), serum albumin level (r = 0.51, p less than 0.01), and serum total bilirubin level (r = 0.36, p less than 0.05), which suggested that the reduction in clearance was due in part to the concomitant renal impairment, as well as hepatic dysfunction in these patients. In conclusion, famotidine total body clearance was reduced in decompensated cirrhosis, indicating that the dose schedule requires modification in patients with this condition.     

Pharmacokinetics of ceftazidime in elderly patients and young volunteers

When given 2 g ceftazidime intravenously a group of 13 acutely ill but renally healthy, elderly patients demonstrated prolonged terminal half-life, increased area under the curve and reduced total and renal clearance compared to 9 young, healthy, male volunteers. The volume of distribution was enlarged in elderly males. Ceftazidime elimination correlated to renal function. Dosage twice daily for one week did not result in any clinically significant accumulation.     

Preservation of glomerular filtration rate in human heart failure by activation of the renin-angiotensin system

When renal perfusion pressure is reduced in experimentally induced low-output states, glomerular filtration rate is preserved by angiotensin II-mediated efferent arteriolar vasoconstriction, but available evidence in man suggests that angiotensin II supports renal function only to the extent that it preserves systemic blood pressure. We performed simultaneous assessments of cardiac and renal function in 56 patients with severe chronic heart failure before and after 1 to 3 months of converting-enzyme inhibition. Among the 29 patients with a pretreatment renal perfusion pressure under 70 mm Hg, patients with preserved renal function (creatinine clearance greater than 50 ml/min/1.73 m2) had markedly elevated values for plasma renin activity (11.8 +/- 3.8 ng/ml/hr) and showed a significant decline in creatinine clearance after converting-enzyme inhibition (61.1 +/- 3.0 to 45.9 +/- 5.3 ml/min/1.73 m2; p less than .05). In contrast, although similar with respect to all pretreatment demographic, hemodynamic, and clinical variables, patients with a creatinine clearance under 50 ml/min/1.73 m2 had low values for plasma renin activity (3.4 +/- 0.8 ng/ml/hr) and, despite similar drug-induced decreases in systemic blood pressure, showed no change in creatinine clearance after therapy with captopril or enalapril (32.6 +/- 2.5 to 41.4 +/- 3.8 ml/min/1.73 m2). Changes in creatinine clearance varied linearly and inversely with pretreatment values for plasma renin activity (r = - .64, p less than .001); converting-enzyme inhibition effectively abolished the pretreatment difference in renal function seen in the high- and low-renin subgroups. In the 27 patients with a renal perfusion pressure of 70 mm Hg or greater, creatinine clearance did not vary significantly with plasma renin activity and was not altered by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sodium-lithium countertransport and cardiorenal abnormalities in essential hypertension

The rate of red blood cell sodium-lithium countertransport is elevated only in a subgroup of patients with essential hypertension. We have therefore compared renal and cardiac function and morphology in two groups of hypertensive patients with high (n = 23) or normal (n = 22) sodium-lithium countertransport (mean +/- SEM: 0.61 +/- 0.10 versus 0.29 +/- 0.07 mmol/l red blood cells.hr). The two groups were similar in age, sex distribution, body mass index, smoking habit, duration of hypertension, and actual levels of untreated blood pressure. Hypertensive patients with elevated sodium-lithium countertransport activity showed elevated glomerular filtration rate (118 +/- 2 versus 109 +/- 2 ml/min.1.73 m2; p less than 0.001), albumin excretion rate (23 +/- 3 versus 14 +/- 2 micrograms/min; p less than 0.001), larger kidney volume (250 +/- 15 versus 203 +/- 13 ml.1.73 m2; p less than 0.01), lower lithium clearance rate (26.7 +/- 0.3 versus 28.9 +/- 0.3 ml/min.1.73 m2; p less than 0.01), and higher total body exchangeable sodium (2,716 +/- 33 versus 2,485 +/- 41 mmol.1.73 m2; p less than 0.01). Left ventricular mass index (139 +/- 6 versus 119 +/- 6 g/m2; p less than 0.05), relative wall thickness (0.39 +/- 0.05 versus 0.29 +/- 0.04 cm; p less than 0.001), and left posterior wall plus intraventricular septum thickness (2.02 +/- 0.04 versus 1.76 +/- 0.03 cm; p less than 0.05) were also higher in patients with high sodium-lithium countertransport. Hypertensive patients with normal sodium-lithium countertransport had renal and cardiac parameters similar to those of a normotensive control group (n = 21) except for a higher glomerular filtration rate and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered water excretion in healthy elderly men

The renal and vasopressin (AVP) response to a standard oral water load (20 ml/kg) was examined in a group of water-replete healthy elderly men (n = 6). Two groups, respectively, of water-replete and water-deprived young healthy volunteers acted as controls. After 2 h, the old group had excreted 41 +/- 2.4% (mean +/- SEM) of the water load compared to 100.7 +/- 8.8% in the water-replete young group and 70 +/- 3.8% in the water-deprived young group (P less than 0.01). Similarly, peak diuresis (7.01 +/- 0.48 ml/kg) and peak free-water clearance (5.7 +/- 0.48 ml/min) as determined from hourly sampling in the old group were delayed and significantly less than both young groups (P less than 0.01) (peak diuresis, young water-replete, 10.86 +/- 0.56 ml/kg, young water-deprived, 10.2 +/- 0.64 ml/kg, peak free-water clearance, young water-replete 8.4 +/- 0.72 ml/min, young water-deprived 9.5 +/- 0.88 ml/min). When these indices were adjusted for reduced creatinine clearance (Ccr) in the elderly, there was no significant difference between the young and old groups. Plasma AVP decreased similarly in all three groups following ingestion of water but there was no significant difference in mean plasma AVP between the young and old subjects throughout the study period. We therefore conclude that ability to excrete excess water promptly is impaired in healthy elderly men. This defect is due, at least in part, to an age-related reduction in glomerular filtration rate.     

难治性高血压肾功能损害与左心室肥厚的关系

目的研究难治性高血压(RH)患者肾功能损害与左心室肥厚(LVH)的关系,并探讨影响RH患者LVH的相关危险因素。方法回顾性分析2007-10-2010-07北京安贞医院高血压科住院患者215例(RH患者120例,非RH患者95例)的临床资料,通过"肾脏病膳食改良试验(MDRD)"公式评估肾功能;进行24h动态血压监测;行超声心动图检查,计算左心室质量指数(LVMI),LVMI>125(男性),>110g/m2(女性)作为LVH的诊断。结果与非RH患者比较,RH患者估算的肾小球滤过率(eGFR)[(72.3±22.1)比(83.1±19.5)mL/(min·1.73m2)]较低,eGFR<60mL/(min·1.73m2)检出率(29.2%比10.5%)、LVH检出率(32.5%比16.8%)、继发性高血压检出率(31.7%比5.3%)、左心室质量指数[(108.0±27.1)比(95.3±22.9)g/m2]较高(均P<0.01)。经Logistic回归分析,LVH的影响因素为eGFR<60mL/(min·1.73m2)[OR4.5(95%CI1.82～11.07),P=0.001]和合并高胆固醇血症[OR3.6(95%CI1.36～9.58),P=0.010]。结论 RH患者有明显的肾功能损害和LVH,不同肾功能水平对LVH影响不同,eGFR<60mL/(min·1.73m2)是LVH的危险因素。     

老年人肾功能、贫血和促红细胞生成素的相关性

目的 通过分析老年人肾小球滤过率（ GFR）和血清促红细胞生成素（EPO）水平对老年贫血患病率的影响,探讨老年贫血发生的相关因素及其与老年人肾功能水平的关系.方法 选取200例年龄≥60岁的老年患者作为观察对象,既往无慢性疾病的健康体检者30人作为正常对照组.采用Cockcroft-Gault方程计算eGFR;根据eGFR分为A组[eGFR＞ 50ml/（ min·1.73m2）,62例]、B组[30ml/（ min· 1.73m2）≤eGFR≤50ml/（ min·1.73m2）,114例]和C组[eGFR＜ 30ml/（ min· 1.73m2）,24例];66例老年贫血患者再根据GFR估算值（eGFR）分为AA组、AB组和AC组（分组标准同上）.测定血红蛋白（Hb）、血肌酐（Scr）、EPO水平.结果 伴随着肾功能水平的降低,老年人贫血患病率呈升高趋势,并且A,B,C3组之间比较均有显著性差异（P＜0.05）;正常对照组Log EPO与Hb呈负相关（r2=0.219,P=0.009）;A组Log EPO与Hb成负相关（r2=0.065,P=0.045）,B组Log EPO与Hb之间无相关关系,C组Log EPO与Hb为正相关（r2=0.294,P=0.006）;老年贫血患者随着肾功能水平的降低,EPO呈现下降趋势,AA组和AC组比较有显著性差异（P=0.042）.结论 老年人肾功能水平中度减退时贫血患病率即显著增加;随着年龄的增长,老年人EPO的分泌代偿性增加,但随着eGFR的不断下降,这种代偿机制逐渐减弱;当肾功能水平严重降低时,EPO分泌的减少是老年贫血发生的主要原因.     

Cardiovascular and renal profile of acute peripheral dopamine1-receptor agonism with fenoldopam

Whether the dopaminergic system may be involved in essential hypertension is of pathogenetic as well as therapeutic interest. Therefore, we investigated in eight hypertensive and 12 normal subjects cardiovascular, endocrine, and renal responses to fenoldopam, which has been characterized experimentally as an agonist of peripheral postsynaptic dopamine1 receptors. A single oral dose of fenoldopam, 100 mg, changed blood pressure (BP) in hypertensive subjects (from 163/103 to 147/76 mm Hg; p less than 0.01 for systolic and p less than 0.001 for diastolic BP) and normal subjects (from 121/81 to 123/65 mm Hg; p less than 0.001 for diastolic BP); percentage decreases in diastolic BP averaged -20 +/- 6 and -16 +/- 7%, respectively. Fenoldopam-induced effects on other variables were similar in the two groups. Heart rate rose (p less than 0.001) on average from 69 to 92 beats/min in hypertensive and from 64 to 84 beats/min in normal subjects. Effective renal plasma flow increased (from 552 to 765 and 634 to 937 ml/min/1.73 m2; p less than 0.01), while glomerular filtration rate tended to decrease (from 121 to 99 ml/min/1.73 m2 in the hypertensive and from 119 to 97 ml/min/1.73 m2; p less than 0.001 in the normal group). Fractional sodium clearance was elevated (from 2.8 to 5.2 and 1.7 to 3.8%; p less than 0.01), as was free water clearance (from -1.7 to 0.6 and -1.7 to 0.1 ml/min/1.73 m2; p less than 0.01). Potassium clearance was largely unchanged. Plasma renin activity increased about twofold (p less than 0.01 in normal subjects), and plasma aldosterone by 40% (NS). Plasma norepinephrine levels increased twofold to 2.5-fold (p less than 0.001), and urinary norepinephrine excretion fivefold to 10-fold (p less than 0.01). Fenoldopam-induced changes were not significantly modified by intravenous and/or oral pretreatment with the dopamine-receptor antagonist metoclopramide or the cyclooxygenase inhibitor indomethacin. These findings suggest that in humans, fenoldopam may acutely override the dopaminergic antagonism of metoclopramide given in clinical dosage and that its cardiovascular and renal effects are not prostaglandin-mediated. Although acute sympathetic stimulation may be partially antagonistic, the concomitant BP-lowering, renal vasodilating, and natriuretic actions of fenoldopam represent a desirable profile of a potential antihypertensive agent.     

Pharmacokinetics of methicillin in patients with cystic fibrosis.

The disposition of methicillin in normal subjects and in subjects with cystic fibrosis (CF) was studied after administration of single intravenous doses of 15 mg/kg. The area under the serum concentration vs. time curve for CF patients was, on the average, only 75% of that found for normal subjects. The low concentrations in serum were caused by more rapid urinary excretion of the antibiotic, with rates of renal clearance averaging 425 ml/min per 1.73 m2 in the patients with CF and 362 ml/min per 1.73 m2 in the normal subjects. No differences were found in volumes of distribution and metabolic clearance rates of methicillin or in rates of creatinine clearance between the two groups of subjects. These data support previous findings with dicloxacillin which show that patients with CF exhibit unusually rapid, active tubular secretion of certain penicillins that may necessitate use of larger doses of these drugs in treatment of infections.     

经皮肾动脉介入治疗肾动脉狭窄的远期临床疗效

目的观察肾动脉狭窄患者经皮肾动脉介入治疗对血压及肾功能的远期疗效。方法选取1998年1月至2006年6月在沈阳军区总医院心内科住院诊治的肾动脉狭窄患者120例为研究对象,观察术后72h及随访5年的血压及肾功能的变化,评价肾动脉介入治疗对肾性高血压、肾功能不全的影响。结果120例行经皮肾动脉介入治疗的患者肾动脉病变狭窄程度76．1％±19．4％,支架直径（5．8±1．2）mm,支架长（17．1±4．2）mm,支架残余狭窄2．1％±0．5％,介人手术成功率达100％。术前血压（178．7±28．4／100．2±17．6mm）Hg,术后72h血压（128．1±14．5／75．1±10．1）mmHg,随访5年时血压（140．2±18．7／84．4±13．2）mmHg;术后72h及5年随访血压值较术前显著下降,差异均有统计学意义（P〈0．05）。术后人均服用降压药物比术前明显减少,差异有统计学意义[（2．7±1．0）种m（3．5±1．0）种,P〈O．05]。术前估算肾小球率过滤（estimated glomerular filtration rate,eGFR）（65．50±24．41）mL／（min·1．73m^2）,术后72heGFR（61．16±23．36）mL／（min·1．73m^2）,术后5年eGFR（64．12±23．30）mL／（min·1．73m^2）;术后72h及术后5年与术前eGFR比较,均差异无统计学意义（P〉O．05）。27例肾动脉狭窄合并肾功能异常的患者术前eGFR（35．43±11．66）mL／（min·1．73m^2）,术后72heGFR（33．86±12．51）mL／（min．1．73m^2）,术后5年eGFR（39．10±12．69）mL／（min·1．73mz）;术后5年eGFR较术前呈上升趋势,但与术前比较,差异无统计学意义（P〉0．05）。结论肾动脉介入治疗可显著降低肾性高血压患者术后血压,减少应用降压药物种类．对术前肾功能正常者无影响;5年随访观察经皮肾动脉介入治疗对术前肾功能异常者无明显改善。     

Pharmacokinetics of a new angiotensin-converting enzyme inhibitor, benazepril hydrochloride, in special populations

To investigate the pharmacokinetics of benazepril hydrochloride in special populations, single or multiple doses between 5 and 20 mg of the new drug were given, and the pharmacokinetics of unchanged benazepril and its pharmacologically active metabolite benazeprilat were compared with those in healthy male volunteers. In elderly subjects and patients with mild and moderate renal insufficiency, there was little change in the kinetics of benazepril or benazeprilat. In patients with severe renal impairment (creatinine clearance less than 30 ml/min), benazeprilat elimination was slowed, which resulted in greater accumulation after repeated dosing. In patients with hepatic cirrhosis, the kinetics and bioavailability of benazeprilat were not affected. Therefore dose adjustment is unnecessary because of the patient's age, mild or moderate renal impairment, or hepatic cirrhosis. Dose reduction is necessary in patients with creatinine clearance less than 30 ml/min.     

Establishing pragmatic estimated GFR thresholds to guide metformin prescribing.

AIMS: Renal impairment is a contraindication to metformin treatment because of the perceived increased risk of lactic acidosis. Current guidelines define renal impairment according to the serum creatinine of the individual, but this measure is being supplanted by the use of estimated glomerular filtration rate (eGFR) as it gives a closer estimate to true GFR. This study aimed to establish pragmatic eGFR limits for use in patients being considered for metformin treatment. METHODS: Estimated GFR measurements corresponding to currently used metformin creatinine limits of 130 and 150 micromol/l were derived and then applied to 12 482 patients with diabetes in Hull and East Yorkshire. RESULTS: Few patients with a serum creatinine of 130 or 150 micromol/l have an eGFR of < 30 ml/min/1.73 m(2)[chronic kidney disease (CKD) stage 4 or greater], while most are between 30 and 59 ml/min/1.73 m(2) (CKD stage 3). When applied to the 12 482 patients (median age 67 years, interquartile range 56-75), males predominated when using creatinine cut-offs (13.6% of males and 8.3% of females had creatinine > 130 micromol/l; 8.2% males and 5.2% females > 150 micromol/l), but not using eGFR CKD thresholds (3.3% males and 4.7% females < 30 ml/min/1.73 m(2); 20.8% males and 28.1% females eGFR 30-59 ml/min/1.73 m(2)). Similar proportions of patients as currently would have metformin withheld if using eGFR cut-offs between 30 and 49 ml/min/1.73 m(2). CONCLUSIONS: We have proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment. CKD stage 4 or greater should be an absolute contraindication to metformin, while CKD stage 3 should alert clinicians to consider other risk factors before initiating or continuing treatment.