Influence of extracorporeal dialysis on parathyroid hormone secretion in patients with acute renal failure.

Serum immunoreactive parathyroid hormone (iPTH) was estimated in 30 patients with renal failure before and after haemodialysis. All patients were anuric or oliguric at the time of the investigation. Pre-dialysis iPTH values were significantly elevated (3.4 ng/ml) as compared with normal subjects (less than 0.5 ng/ml). Simultaneously, a significant hypocalcaemia (4.15 mEq/litre) was confirmed which was negatively correlated with iPTH levels. After 7-8 h of haemodialysis using a calcium concentration of 4.0 mEq/litre in the dialysate, a significant drop of iPTH level to 1.8 ng/ml was noted.     

慢性肾衰患者血红蛋白浓度变化对血清细胞因子活性的影响作用

目的为了探讨贫血与慢性肾衰（ＣＲＦ）免疫功能状态的关系。方法检测了ＣＲＦ患者单纯输血及用红细胞生成素（ＥＰＯ）治疗前后细胞因子白细胞介素２（ＩＬ２）、可溶性白细胞介素２受体（ｓＩＬ２Ｒ）、肿瘤坏死因子（ＴＮＦ）及γ干扰素（γＩＦＮ）水平，并与肾功能正常肾小球肾炎患者（ＧＮ）组及对照组（Ｃ）进行比较分析。结果ＣＲＦ组血清ＩＬ２，ＴＮＦ和γＩＦＮ水平均显著低于ＧＮ组及Ｃ组（Ｐ＜００１），ｓＩＬ２Ｒ水平则较ＧＮ组及Ｃ组明显升高（Ｐ＜００１）。ＣＲＦ组血清ＩＬ２，ＴＮＦ和γＩＦＮ水平与血红蛋白浓度存在直线正相关，而ｓＩＬ２Ｒ水平与血红蛋白浓度呈负相关性，单纯输血或应用ＥＰＯ治疗能改变这些细胞因子活性水平。结论ＣＲＦ免疫功能低下与贫血有关，及时治疗和改善贫血状态可部分纠正这种免疫异常。     

Influence of renal replacement therapy on outcome of patients with acute renal failure

There are many controversial results about the influence of acute renal failure (ARF) and renal replacement therapy (RRT) on patient outcome in intensive care units. This retrospective study compared demographics. severity, course, and prognosis of ARF during 36 months (period 1, 1991 through 1993; 128 cases) and 18 months (period 2, 1994 through 1995; 141 cases). Compared with period 1, during period 2 there was a markedly increased incidence of ARF. There were no significant differences in patient demographics or etiology of renal failure, but the therapeutic approach to ARF was quite different. During period 2, RRT was started at earlier stages of renal insufficiency (that is, less elevated creatinine serum concentrations or reduced diuresis). Additionally, there was a significant increase in the numbers of continuous RRT (CRRT) replacing the discontinuous mode of dialysis treatment. Compared with period 1, mortality was reduced from 78.9 to 59.6% during period 2 (P < 0.001). There were no differences in mortality between the patients from internal and surgical wards. Mortality in patients treated with CRRT was in period 1 and in period 2 higher than mortality in patients treated with intermittent RRT, but these results are biased by a preferred use of CRRT in severely ill patients with an unstable circulatory system. These data suggest that the early onset of RRT reduces the mortality of intensive care unit patients with ARF independent of underlying diseases. An influence of the method of RRT, sex, and age on outcome of patients with ARF could not be proven.     

Detection of a metalloproteinase in patients with acute and chronic renal failure

The effect of different dialyzer membrane materials (cuprophan, cellulose hydrate, polyacrylonitrile, polymethylmethacrylate, ethylene-vinyl alcohol copolymer) on the ultrafiltrate proteinase activity was investigated in 26 patients with acute renal failure (ARF) and 40 patients undergoing regular hemodialysis treatment (RDT). Furthermore, the proteinase activity was characterized in vitro using azocasein and phosphorylase kinase as substrates in the absence and presence of different proteinase inhibitors. Proteinase activity of ultrafiltrates obtained from ARF patients was significantly enhanced with the dialyzer KF 101 (ethylene-vinyl alcohol copolymer). The digestion pattern of phosphorylase kinase revealed an identical type of proteinases in ultrafiltrates of ARF and RDT patients. The pH optimum of this proteinase was at alkaline pH. The proteinase activity could be inhibited in the presence of EDTA, whereas serine proteinase inhibitors were ineffective. Furthermore, the inactivated proteinase after Sephadex G-10 chromatography (in order to separate ultrafiltrate electrolytes and trace elements from protein) could be reactivated after the addition of Mg++ and/or Ca++. We conclude that a metalloproteinase can be found in ARF and RDT patients, and that KF 101 is more effectively eliminating the proteinase activity in ARF patients than other dialyzer membranes.     

Effects of naloxone administration on endocrine abnormalities in chronic renal failure

In 72 patients with end-stage renal failure and 70 healthy subjects, the influence of blockade of opioid receptors by naloxone on secretion of prolactin, lutropin (LH), follitropin (FSH), adrenocorticotropin (ACTH), somatotropin (HGH), insulin (IRI), glucagon (IR-G), parathyroid hormone (PTH) and calcitonin (CT) was studied. Administration of naloxone stimulated luliberin-induced LH and FSH secretion quantitatively equally in patients and controls. Blockade of opioid receptors was followed by a less marked suppression of chlorpromazine-induced prolactin secretion but by a higher response of hypoglycemia-induced ACTH secretion in uremic patients than in controls. In addition, a less marked suppressive effect of naloxone was noted on hypoglycemia-induced HGH secretion in chronic renal failure as compared with controls. Blockade of opioid receptors improved significantly glucose tolerance and glucose-induced insulin secretion in uremic patients and suppressed nearly completely glucagon secretion response during the second phase of a glucose tolerance test. Finally, administration of naloxone was followed by a blunted response of Ca-induced CT secretion and suppression of PTH. Data presented in this paper suggest the existence of hyperendorphinism in end-stage renal failure.     

The risk of acute renal failure in patients with chronic kidney disease

Few studies have defined how the risk of hospital-acquired acute renal failure varies with the level of estimated glomerular filtration rate (GFR). It is also not clear whether common factors such as diabetes mellitus, hypertension and proteinuria increase the risk of nosocomial acute renal failure independent of GFR. To determine this we compared 1,746 hospitalized adult members of Kaiser Permanente Northern California who developed dialysis-requiring acute renal failure with 600,820 hospitalized members who did not. Patient GFR was estimated from the most recent outpatient serum creatinine measurement prior to admission. The adjusted odds ratios were significantly and progressively elevated from 1.95 to 40.07 for stage 3 through stage 5 patients (not yet on maintenance dialysis) compared to patients with estimated GFR in the stage 1 and 2 range. Similar associations were seen after controlling for inpatient risk factors. Pre-admission baseline diabetes mellitus, diagnosed hypertension and known proteinuria were also independent risk factors for acute kidney failure. Our study shows that the propensity to develop in-hospital acute kidney failure is another complication of chronic kidney disease whose risk markedly increases even in the upper half of stage 3 estimated GFR. Several common risk factors for chronic kidney disease also increase the peril of nosocomial acute kidney failure.     

Influence of ACE inhibition on glucose tolerance in patients with stable chronic renal failure

ACE inhibitors improve glucose tolerance and insulin sensitivityin hypertensive patients with normal renal function. Hypertensivepatients with renal failure are a high-risk group who are particularlyglucose intolerant and insulin resistant. We have thereforestudied whether ACE inhibition improve glucose tolerance inthis group as well. In a double-blind placebo-controlled crossover study 10 patientswith stable moderate chronic renal failure (mean endogenouscreatinine clearance 40±16 ml/ min/1.73 m² were examined.Patients were randomly allocated to receive either placebo orthe ACE inhibitor perindopril (2 mg/day per os) for 14 days.After 7 days of wash-out they received the alternative medicationsin random order for another 14 days. Before and after each ofthe two treatment periods (day 1 and day 15) an intravenousglucose tolerance test (i.v. GTT) with concomitant determinationof insulin levels was performed. The glucose disappearance rate(K value) was calculated to express changes in glucose tolerance.An i.v. GTT was also performed in a group of healthy volunteers. The mean K value was significantly (P<0.05) lower, i.e. glucosetolerance was impaired, in patients compared with healthy controls.In addition, baseline and peak insulin levels after the i.v.GTT were significantly higher (P<0.05) in patients than inhealthy subjects. The K values in patients before and afterplacebo treatment (1.33±0.31 and 1.41±0.45 respectively)were not significantly different from the values with perindopriltreatment (1.35±0.37 and 1.41±0.48 respectively).Furthermore, no significant differences between placebo andperindopril treatment were found with respect to the insulinresponse to the glucose load. The peak (5 min) insulin concentrationsafter the i.v. glucose load were 49.0±19.2 µU/ml(day 1) and 50.0±24.9 (day 15) with placebo and 49.2±19.3(day 1) and 46.8±17.9 (day 15) with perindopril. Finally,no significant differences between the two treatment periodswere observed with respect to serum lipid, HbA_1C, glucagon,potassium, and creatinine levels, whereas systolic blood pressuredecreased significantly with perindopril treatment. In contrast to hypertensive patients with normal renal function,ACE inhibition does not cause a demonstrable change of glucosetolerance in patients with moderate chronic renal failure.     

慢性肾功能衰竭患者的高同型半胱氨酸血症

目的 研究慢性肾功能衰竭（ＣＲＦ）患者血浆同型半胱氨酸（Ｈｃｙ）水平、影响因素以及与心、脑血管疾病的关系。方法 采用荧光偏振免疫分析法测定１６０例ＣＲＦ患者血浆总同型半胱氨酸（ｔＨｃｙ）水平，以３１例冠心病患者和４５例正常人为对照。结果 以正常组血浆ｔＨｃｙｘ±２ｓ为９５％可信度上限，ＣＲＦ患者高同型半胱氨酸血症的发生率为８２．５０％，明显高于冠心病组（２２．５８％）（Ｐ＜０．０１）；血液透析（ＨＤ）组血浆ｔＨｅｙ水平［（２４．１３±１２．６８）μｍｏｌ／Ｌ，ｎ＝７３］明显高于持续性非卧床腹膜透析（ＣＡＰＤ）组［（１６．４３ ±５．５８）μｍｏｌ／Ｌ，ｎ＝１９］、冠心病组［（１１．１３±４．９７）μｍｏｌ／Ｌ，ｎ＝３１］以及正常组（７．９７±２．６５）μｍｏｌ／Ｌ，ｎ＝４５，Ｐ均＜０．０１。９２例透析治疗的ＣＲＦ患者中有明确心、脑血管病者的血浆ｔＨｃｙ水平［（２７．１２±１５．９４）μｍｏｌ／Ｌ，ｎ＝３０］明显高于无此类病史的患者［（２０．１７±８．７１）μｍｏｌ／Ｌ，ｎ＝６２］。未经透析的 ＣＲＦ患者血浆 ｔＨｃｙ水平与内生肌酐清除率呈负相关（ｒ＝－０．３７４，Ｐ＜０．０１），与患者年龄、血葡萄糖、血脂及血浆白     

Zinc in patients with chronic renal failure

In order to assess zinc status in patients with chronic renal failure (CRF) plasma and erythrocyte zinc levels were determined in 13 patients undergoing regular haemodialysis. Additional determinations of plasma copper, plasma and erythrocyte magnesium and potassium were also performed. The mean plasma zinc level was slightly less than normal, but the difference was not statistically significant. The erythrocyte zinc content, however, as well as erythrocyte magnesium and potassium levels were significantly increased (p<0.001). This increase may be partly related to haemolysis in uraemia. Plasma copper concentration in CRF patients did not differ significantly from the control level. The almost normal plasma zinc concentration, elevated erythrocyte zinc, and normocupraemia do not indicate zinc deficiency in CRF patients.     

Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction

We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future.     

Pharmacokinetics and acute effect on the renin-angiotensin system of delapril in patients with chronic renal failure

The acute effect on the renin-angiotensin system and the pharmacokinetic properties of delapril, a new angiotensin converting enzyme inhibitor and its active diacid metabolites (delapril diacid and 5-hydroxy delapril diacid) arising from delapril in vivo were investigated in 4 hypertensive patients with chronic renal failure (CRF: 4 males, average age 49.5 (37-64) years, mean Ccr 22.2 ml/min/1.73 m2) and 9 patients with essential hypertension (EH: 6 males, 3 females, average age 42.8 (28-61) years, mean Ccr 79.3 ml/min/1.73 m2). In CRF, following a single dose of delapril hydrochloride (30 mg), the biological half lives (t1/2) of delapril diacid and 5-OH-delapril diacid were 4.69, 12.88 hours, the maximum serum concentration (Cmax) and the area under the plasma concentration-time curve ([AUC]24(0)) of delapril and its diacid metabolites were 414, 797 and 435 ng/ml, and 658, 6400 and 5068 ng X h/ml, respectively. In EH, the t1/2 of delapril diacid and 5-OH-delapril diacid were 1.21, 1.40 hours and the Cmax and [AUC]24(0) of delapril and its diacid metabolites were 489, 635 and 229 ng/ml, and 572, 1859 and 948 ng X h/ml, respectively. The [AUC]24(0) in CRF were significantly increased as compared with those in EH. The cumulative urinary excretions were significantly lower in CRF than in EH. The serum angiotensin converting enzyme (ACE) was markedly inhibited in both groups up to 24 hours. The plasma concentration of angiotensin II decreased in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiologic acid-base and electrolyte changes in acute and chronic renal failure patients

Patients with acute and chronic renal failure are vulnerable to a wide variety of acid-base and electrolyte disturbances. The variety is related not only to predictable disturbances that arise as a consequence of impaired urinary excretion, but also to associated factors, such as intercurrent disease processes, chronic medications, and renal replacement therapy. This article emphasizes the pathogenesis, diagnosis, and treatment of common problems, including metabolic acidosis, hyponatremia, hypernatremia, hyperkalemia, hyperphosphatemia, and hypocalcemia.     

Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis

In order to investigate the possible interaction between oral aspirin and antacids in uremic patients on chronic hemodialysis, we administered to 5 uremic patients: (1) aspirin alone; (2) aluminum-magnesium hydroxide with aspirin; (3) aluminum-magnesium hydroxide followed (two hours) by aspirin; (4) calcium carbonate simultaneously with aspirin; and (5) calcium carbonate followed (two hours) by aspirin. In all the occasions, aspirin was given two hours after a standard lunch. Both antacid preparations induced comparable changes in aspirin mean peak plasma concentration (Cmax), if given simultaneously with aspirin, whereas no difference was found in other pharmacokinetic parameters. When antacids were followed (two hours) by aspirin, both Cmax and time of maximum concentration (Tmax) were significantly altered in respect to the value with aspirin alone. No changes in the time course of post aspirin serum thromboxane B2 were detected when aspirin and antacids were administered simultaneously, but the inhibition of serum thromboxane B2 was delayed when antacids were followed (two hours) by aspirin. These results indicate that the administration of antacids to uremic patients interferes with absorption of oral aspirin. This interference can be minimized if aspirin and antacids are given simultaneously.     

Hip arthroplasty in patients with chronic renal failure

Patients with chronic renal failure who underwent total hip arthroplasty were retrospectively evaluated. Thirty hips in patients with renal transplants and 16 hips in patients on chronic renal dialysis were reviewed. The average follow-up period was 54 months. The renal transplant patients exhibited generally satisfactory results. Their postoperative course was comparable to that of patients with avascular necrosis undergoing hip reconstruction without underlying renal disease. However, patients undergoing hip arthroplasty while on chronic renal dialysis had poor results (81%), including a deep infection rate of 19%. It was concluded that total hip arthroplasty be reserved for patients who are expecting a renal transplant or preferably for those who have already received a successful transplant.     

Calcitriol metabolism in patients with chronic renal failure

We studied calcitriol metabolism in white patients with chronic renal failure and in age- and sex-matched normal subjects. The plasma levels of calcitriol (21.9 +/- 1.6 pg/mL, n = 7, v control, 37.4 +/- 2.9 pg/mL, P less than 0.001), metabolic clearance rate (MCR) of calcitriol (0.45 +/- .01 mL/min/kg v control, 0.58 +/- .02 mL/min/kg, P less than 0.001), and production rate (PR) of calcitriol (14.2 +/- 1.0 ng/kg/d v control, 31.8 +/- 3.2 ng/kg/d, P less than 0.001) were significantly lower in patients with moderate renal failure (average creatinine clearance, 0.59 +/- 0.01 mL/s [35.1 +/- 6.1 mL/min]) when compared with the respective values of normal control subjects. The MCR of calcitriol was determined again in patients with renal failure after they received calcitriol, 1 microgram/d, for 1 week. The MCR remained unchanged (0.46 +/- .04 mL/min/kg, n = 7) and plasma levels of calcitriol were increased to 34.6 +/- 2.77 pg/mL. The mechanism by which the MCR of calcitriol decreases in renal failure is partly due to the presence of inhibitory factors of degradation enzymes in uremic plasma. When the ultrafiltrates of uremic plasma obtained from hemodialysis patients were infused to normal Sprague-Dawley rats, the MCRs of calcitriol (0.20 +/- .01 mL/min/kg, n = 6) were markedly suppressed in comparison to those of rats infused with the ultrafiltrates of normal plasma (0.37 +/- .01 mL/min/kg, n = 6, P less than 0.001). The uremic plasma also contained factors that inhibit the synthesis of calcitriol. We conclude that metabolic degradation of calcitriol is decreased in patients with renal failure, and uremic plasma contains inhibitory factors that suppress the synthesis and degradation of calcitriol.