Renal prostaglandins, effective renal plasma flow and glomerular filtration rate in healthy elderly subjects.

This study tests the hypothesis that the age-associated reduction in glomerular filtration rate (GFR) and the presence of glomerulosclerosis renders effective renal plasma flow (ERPF) prostaglandin dependent. Ten healthy elderly volunteers were studied in a single-blind placebo-controlled manner using indomethacin to suppress the renal prostaglandins. There was no significant difference in ERPF or GFR following indomethacin when compared with placebo. These results suggest that blocking renal prostaglandins does not significantly alter ERPF or GFR in healthy elderly people.     

老年肾功能不全患者血浆同型半胱氨酸水平及其影响因素

目的研究老年肾功能不全（CRF）患者血浆同型半胱氨酸（Hcy）水平及其影响因素。方法采用快速高压液相层析法测定82例老年CRF患者和40例正常人的Hcy水平,同时用离子夺获分析法和微离子酶免疫分析法分别检测血浆叶酸（FA）和维生素B12（VitB12）水平。结果CRF患者高Hcy血症（HHcy）发生率高达86.6%,为正常对照组的34.6倍（P〈0.01）;且血浆Hcy的浓度随着血肌酐浓度的升高或内生肌酐清除率（Ccr）的降低而升高,有明显的相关性（P〈0.01）。CRF患者的血浆FA和VitB12与正常对照组均无明显差别,血浆tHcy水平与血浆FA浓度均呈负相关关系。血液透析后血浆Hcy水平较血液透析前下降约36%,但仍显著高于正常对照组（P〈0.01）。透析后20 h回复到透析前水平的76.6%～87.3%,在采用血仿膜和聚砜膜透析的患者之间,血浆tHcy水平无明显差异。结论老年CRF患者普遍存在HHcy血症,并且肾功能损害的程度与Hcy浓度明显相关,但没有明显的FA和VitB12缺乏,CRF时肾脏损害削弱了对Hcy的代谢或清除能力,可能是CRF患者血浆tHcy水平增高的主要原因。     

Urinary prostaglandin E2 and dopamine responses to water loading in young and elderly humans

Background: Human aging is associated with a number of unexplained changes in renal function, including a diminished capacity to excrete water and sodium loads and an increased susceptibility to acute renal failure. PGE2 and dopamine are intrarenal autocrine factors important in diuresis, natriuresis and also serve to protect against ischemic renal injury. Responses of these autocoids to provocative maneuvers such as water loading have not previously been studied in the elderly. Methods: Five healthy young (25±1 yrs) and five healthy elderly (70±1 yrs) women underwent a 20 ml/kg oral water load in the Clinical Research Center. Results: Urinary PGE2 and dopamine excretion were lower in the elderly. Urinary PGE2 and dopamine rose significantly during water diuresis only in the young subjects but remained essentially unchanged in the elderly (p<0.05, ANOVA). Minimum urine osmolality was lower in young than old (61±3 vs 83±9 mOsm/L, p<0.05). Old had less brisk diuresis and a greater decline in serum sodium than young (p<0.05, ANOVA). Conclusion: The defect in PGE2 and dopamine excretion in the elderly demonstrated here during water diuresis may have more general implications, relating to the susceptibility of the aged to hyponatremia and acute renal failure.     

Plasma thrombomodulin values and hepatorenal function in the elderly

To define the clinical significance of plasma thrombomodulin (TM) values in elderly, we examined plasma TM in healthy young subjects, healthy elderly subjects and patients with cerebral infarction sequelae. We also studied the relationship with effective renal plasma flow (ERPF) and with the liver's protein-production ability. The TM values of healthy elderly subjects were higher than those of healthy young subjects. There existed an inverse correlation between TM values and ERPF. Accordingly, high TM values might significantly influence renal arteriosclerosis. From the inverse correlation identified between TM and serum cholinesterase, it was estimated that high TM might appear in conjunction with the liver's protein production ability. Patients with cerebral infarction showed higher plasma TM values. It is thought that angiopathy has been maintained in patients as the anamnesis of cerebral infarction even though it occurred in the past. The TM values of patients with diabetes mellitus (DM) were higher than those without it. Moreover, the TM values of patients with DM complicated by retinopathy were higher than those uncomplicated by retinopathy. It is therefore estimated that increased TM might occur with angiopathy resulting from DM. A possibility thus exists that plasma TM could be utilized as one of the markers for endothelial injury.     

Renal net acid excretion capacity is comparable in prepubescence, adolescence, and young adulthood but falls with aging

OBJECTIVES: To evaluate whether renal net acid excretion capacity (NAEC) varies across different age groups and, specifically, whether it falls in elderly people. DESIGN: Cross‐sectional observational study. SETTING: Community‐based. PARTICIPANTS: Young participants were from the DOrtmund Nutritional and Anthropometric Longitudinally Designed Study, Dortmund, Germany; elderly participants were from Gothenburg, Sweden. MEASUREMENTS: Twenty‐four‐hour urine pH, net acid excretion (NAE), urinary phosphorus, total nitrogen excretion, and anthropometric data were measured in healthy elderly people (aged 55–75; n=85), young adults (aged 18–22; n=117), adolescents (aged 13–14; n=112), and prepubescent children (aged 6–7; n=217). NAEC was determined as 24‐hour NAE adjusted for urine pH using the residual method. RESULTS: In elderly participants 24‐hour urinary pH (5.9±0.53) was lower (P<.05) and NAE (60±27 mEq/d) higher (P<.05) than in the three other groups. In a regression model adjusted for age, sex, and body surface area, NAEC showed a clear decrease with age, with highest values in prepubescents and lowest in elderly participants. However, NAEC remained significantly lower only in elderly participants (P<.001) after the inclusion of total nitrogen excretion, a protein intake index, which was included because protein intake is known to modulate renal function. NAEC was approximately 8 mEq/d lower in healthy elderly participants than in young adults. CONCLUSION: The capacity to excrete net endogenous acid does not vary markedly from childhood to young adulthood but falls significantly with age, implying that elderly people may require higher daily alkalizing mineral intake to compensate for renal function losses.     

A case of chronic renal dysfunction following treatment with oral acyclovir

Nephrotoxicity is a well-known side effect of intravenous acyclovir treatment but occurs rarely by oral treatment. A 76-y-old healthy male, with normal baseline renal functions (blood creatinine 0.6 mg%), received oral acyclovir at a dose of 800 mg five times daily for 10 days for treatment of herpes zoster ophthalmicus. He developed renal failure with blood creatinine levels of 3 mg% and his renal function failed to improve within eight months of end of treatment. Affection of renal function has to be considered also in relation to oral acyclovir treatment, especially in elderly subjects.     

Pharmacokinetics of sulfisoxazole in young and elderly subjects

The pharmacokinetics of sulfisoxazole was studied in 6 elderly (age 63-75 years) and 7 young (age 22-37 years) healthy nonsmoking volunteers following the oral administration of 2 g of Gantrisin. The plasma levels of sulfisoxazole obtained in the postabsorption phase were higher in the elderly subjects. There was no significant variation between the two groups of volunteers in the absorption rate constant, Cmax, bioavailability, the fraction of the dose of sulfisoxazole excreted unchanged, the area under the plasma curve of the N4-acetyl conjugate formed, and in the apparent volume of distribution of the drug. The tmax value and plasma half-life of sulfisoxazole were significantly longer, and the total body and renal clearances of the drug decreased in the elderly subjects. Diminished renal function as estimated by the creatinine clearance and urinary flow may explain the slower elimination of sulfisoxazole in the elderly subjects. Therefore, advancing age should be considered as a factor in the adjustment of sulfisoxazole dosage.     

Laboratory blood parameters in a group of centenarians

Several laboratory blood parameters in a group of healthy centenarians (7 males and 15 females) living in Eastern Sicily were studied and compared with those recorded in a group of healthy elderly subjects (5 males and 12 females) from 80 to 87 years of age. Almost all the laboratory test parameters analyzed were within the range considered to be normal for adult subjects. The exceptions were some renal function markers such as azotemia and creatinine, which were higher in the centenarians, and total cholesterol levels, which were significantly lower in the male centenarians as compared to the elderly male subjects. The conclusion is drawn, therefore, that laboratory tests reflect the health conditions rather than the age of an individual.     

Passive and active carbohydrate absorption by the ageing gut

We investigated the effects of advanced age, hospitalization and poor nutrition on passive and active carbohydrate absorption using the probe molecules lactulose and mannitol (passive absorption), and 3-O-methylglucose (active absorption). We studied five groups of subjects; healthy controls aged 20-30 years, 40-50 years and over 65 years, respectively, together with long-stay patients and elderly in-patients being investigated for malnutrition. Each subject undertook two separate studies ingesting a drink containing 5 g lactulose, 2 g mannitol and 2.5 mg 3-O-methylglucose (3-O-MG), on one occasion in isotonic solution and in the second study in hypertonic solution, following overnight fast. Urinary recovery of all three probe molecules declined significantly with age (P less than 0.02) and was reduced in malnourished elderly subjects compared to healthy elderly controls (P less than 0.05). Correction of urinary recoveries for renal function on the basis of creatinine clearance abolished significant differences between groups. Thus passive absorption of carbohydrate is not impaired with advanced age in healthy elderly subjects or long-stay hospital patients. The ratio of the percentage recovery of 3-O-MG to the percentage recovery of mannitol was significantly reduced in the healthy elderly subjects compared to middle-aged and young controls in the hypertonic study; similar changes did not occur in the long-stay and malnourished elderly patients, interpretation of this finding is thus difficult. If confirmed, this impairment would suggest a possible defect in active sugar transport in the elderly.     

老年高血压患者心率变异与靶器官损害的相关性研究

目的探讨老年高血压患者心率变异（HRV）与靶器官损害的关系。方法选取老年高血压患者210例,其中单纯高血压组4l例,高血压伴左室肥厚（LVH）患者65例、伴肾功损害者53例、伴颈动脉IMT增厚患者51例;选择健康者50名作为对照组,进行心率变异性时域分析。对人选者做以下检查：心电图、超声心动图、24h动态心电图、颈动脉内膜-中层厚度（IMT）、血肌酐。结果老年高血压患者HRV各项指标低于对照组（P〈0．05）;高血压伴LVH组HRV与单纯高血压组比较,差异有统计学意义（P〈0．01）.高血压伴肾功损害及IMT增厚者HRV与单纯高血压组比较,差异有统计学意岁。’P〈0．05）。结论老年高血压靶器官损害患者的HRV减低,即自主神经对心脏的调节能力减弱;可通过自主神经功能受损程度来评估靶器官受损的程度和判断预后。     

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.     

老年慢性肾衰患者瘦素水平与营养状况的关系

目的　探讨瘦素与老年慢性肾功能衰竭患者营养状况的关系。方法　检测 2 6例老年慢性肾功能衰竭患者和 2 8例正常老年人的生化指标、血浆瘦素及胰岛素水平 ,同时应用生物电阻抗方法测量身体脂肪容量和体重指数 (BMI)。结果　两组年龄与BMI相匹配。老年慢性肾衰组平均血浆瘦素水平显著高于对照组 (P <0 .0 1 ) ,两组女性的平均血浆瘦素水平均显著高于男性的平均血浆瘦素水平 (P <0 .0 5)。肾衰组男性的平均血浆瘦素水平稍高于对照组男性的平均血浆瘦素水平 ,而二者的平均身体脂肪容量和leptin/fat比值有统计学意义。两组的血浆瘦素水平均与身体脂肪容量、BMI、胰岛素浓度呈显著的正相关 ;而未发现与白蛋白、前白蛋白、血肌酐、尿素氮和肌酐清除率有相关关系。结论　瘦素可以作为评价老年CRF患者营养状况的灵敏指标之一     

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.     

Advancing age and acute infection influence the kinetics of ceftazidime

The pharmacokinetics of ceftazidime were studied after single intravenous injections of 2 g in 10 healthy, elderly male volunteers (63-76 years old). None of the subjects were on concurrent drug treatment and all had normal age-correlated glomerular filtration rate. Mean values for major pharmacokinetic variables were: terminal half-life 2.63 h, area under the serum concentration curve 417.6 h mg/l, total clearance 74.6 ml/(min 1.73 m2), renal clearance 53.6 ml/(min 1.73 m2), urinary recovery/12 h 71.7% of dose and apparent volume of distribution (Vss) 15.0 l/1.73 m2. Data were compared with our earlier findings in studies of young male volunteers and elderly, acutely ill male patients. Advanced age was accompanied by a reduction in clearance of ceftazidime, while no significant age-related changes in distribution were noted. Acute infection was associated with increased Vss and enhanced renal clearance; alterations possibly caused by fever-induced changes in vascular permeability and renal blood-flow.     

Single-dose pharmacokinetics of dicloxacillin in healthy subjects of young and old age

Dicloxacillin was administered as 2 g single intravenous doses to healthy young and old subjects of both sexes aged 19-32 years and 65-76 years, respectively, and the pharmacokinetics were studied. Peak serum concentrations were higher in young than in elderly subjects and in each age group in females than in males. The elimination rate was similar in all groups and the only striking pharmacokinetic differences observed were that the urinary recovery of active dicloxacillin was higher in young subjects and that the non-renal clearance was higher in elderly volunteers. The findings were interpreted to be due to a systemic metabolism of dicloxacillin, compensating for a reduced renal elimination in the elderly subjects. In all subjects dicloxacillin was well tolerated. No increases of serum creatinine were observed.     

Serum vitamin D2 and vitamin D3 metabolite concentrations and absorption of vitamin D2 in elderly subjects

The serum vitamin D2 and vitamin D3 metabolite concentrations and intestinal absorption of vitamin D2 were determined in healthy ambulatory and chronically institutionalized elderly subjects with normal renal function. The 25-hydroxyvitamin D (25OHD) concentrations were normal in all subjects (range, 8-43 ng/ml), although institutionalized subjects had a significantly lower mean value [19.2 +/- 2 (+/- SEM) ng/ml; P less than 0.01] compared with ambulatory subjects (25.3 +/- 2 ng/ml). All but one ambulatory subject had 25OHD3 as the major circulating form, whereas 25OHD2 was the major circulating metabolite in one third of the institutionalized subjects. The mean 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in both groups was normal, but nine subjects had levels at or below the lower limit of normal despite normal 25OHD concentrations. Separate assay of 1,25-(OH)2D2 and 1,25(OH)2D3 revealed proportional distributions similar to those for 25OHD2 and 25OHD3. To study the effect of age on the intestinal absorption of vitamin D, we compared serum vitamin D2 concentrations after oral administration of 50,000 IU vitamin D2 in both healthy vitamin D-sufficient elderly subjects and young adults. We found no evidence of malabsorption of vitamin D in the elderly subjects. In summary, elderly subjects in New York, whether institutionalized or not, have normal serum 25OHD concentrations. However, while most elderly subjects have normal serum 1,25-(OH)2D levels, a significant proportion fail to produce normal concentrations of 1,25-(OH)2D, possibly due to age-related disturbances in renal synthesis of the hormone.     

Osteomalacia Due to Unusual Causes Presenting in Adults

Summary: Severe osteomalacia due to causes other than malabsorption and, where renal function was impaired, disproportionate to the degree of renal failure, is described in 15 adults. Only one was younger than 46 years, the median age being 59 years. The diagnosis was not made for months in most patients. After investigation, the patients were grouped as follows: nutritional three cases, "renal" six cases, hypophosphataemia three cases, neurofibromatosis and primary hyperparathyroidism one each. The last patient was poorly nourished and had taken anticonvulsants and analgesics. Most patients responded well to treatment with calciferol.
These cases indicate the need to be aware that osteomalacia may occur in previously healthy middle-aged or elderly subjects.     

Physiological and pathological aging and electrolyte metabolism

The extracellular and intracellular concentrations of electrolyte were maintained by various systems including kidney and endocrine system. Although concentrations of electrolyte in the extracellular fluid were maintained in normal ranges in healthy elderly subjects, the reserve ability for the maintenance of electrolyte balance decreases with physiological aging. Occurrence of abnormality in electrolyte concentrations in extracellular fluid is thought to be related to pathological aging. The frequency of subjects with abnormal circulating concentrations of electrolytes, as well as abnormal rates of severe such abnormalities increase with age. Clinical characterization and differentiation of physiological and pathological aging are not always easy. On the other hand, the kidney is the central organ for maintenance of electrolyte homeostasis. Decrease in renal ability to retain electrolytes sometimes affect the features of disorders such as hypertension and osteoporosis of elderly subjects. Intravenous infusion of physiological saline at a dose of 20 ml/kg over 2 hr evoked excessive excretion of sodium, calcium and inorganic phosphate in the urine in hypertensive elderly patients and in some patients with senile osteoporosis. These subjects showed decreased levels of plasma renin activity and increased serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. These features indicate that abnormal renal metabolization of electrolytes involving abnormality of endocrine system may be a cause of, and modulate the clinical features of, some disorders of elderly subjects.     

成都城市社区80岁以上人群肾功能下降的流行病学研究

目的：探讨成都城市社区≥80岁人群肾功能下降的流行状况及危险因素。方法采取分层整群抽样的方法,于2012年至2013年在成都城市社区抽取≥80岁人口826人,进行肾功能下降及相关危险因素的问卷调查、体格检查和实验室检查。结果成都城市社区≥80岁人群肾功能下降的患病率19.6%,随年龄增加患病率进一步增高。在肾功能下降人群中,知晓率24.1%、治疗率11.1%。多因素logistic回归提示糖尿病、年龄、高血压、超重或肥胖为≥80岁人群肾功能下降的独立危险因素。结论成都城市社区≥80岁人群中肾功能下降较为普遍,在高龄人群中需加强肾功能监测。≥80岁人群肾功能下降知晓率、治疗率较低,形势严峻。在该人群中,积极防治糖尿病、高血压,控制超重或肥胖,对于干预肾功能下降的发生发展有着重要意义。