Digoxin-like immunoreactive substance in chronic hemodialysis patients: effect on digitoxin radioimmunoassay

Digoxin-like immunoreactive substance(s) (DLIS) in the sera of patients with renal insufficiency may confound attempts to monitor serum digoxin levels. We investigated whether DLIS would affect the radioimmunoassay (RIA) for digitoxin. DLIS was detected by RIA in 9 of 38 chronic hemodialysis patients and in none of 25 healthy controls. Digitoxin levels were not elevated in either the control or dialysis group, and false-positive results for digitoxin by RIA were not obtained in any patient with DLIS. It is concluded that DLIS does not interfere with the digitoxin RIA, nor are digitoxin levels spuriously elevated in chronic hemodialysis patients. Digitoxin may be a preferable preparation for digitalis-dependent dialysis patients with DLIS.     

Factors causing malnutrition in patients with chronic uremia

There is abundant evidence that patients with chronic renal failure (CRF), including those treated by hemodialysis or peritoneal dialysis, have evidence of malnutrition with decreased body weight and subnormal values of serum proteins (suggesting a loss of visceral protein stores). Potential causes of an abnormal nutritional status that have been identified include an inadequate intake of protein or calories, an inability to activate the metabolic responses that are needed to achieve nitrogen and protein balance, or the presence of a disease that prevents activation of these metabolic responses or acts to stimulate the breakdown of body protein stores. Three critical metabolic responses to a limited protein intake have been identified: a reduction in the irreversible degradation of amino acids and the degradation of protein breakdown and an increase in protein synthesis in response to a meal. Metabolic acidosis blocks the first two responses and hence contributes to malnutrition in patients with chronic uremia. Other factors that could contribute to malnutrition include an inadequate intake because of anorexia or hormonal imbalances that impair protein turnover. In evaluating CRF patients with malnutrition, the first task is to ensure an adequate intake and to eliminate factors that impair the ability to achieve nitrogen balance.     

Plasma fibronectin levels in patients with chronic uremia

Plasma fibronectin (FN) concentration was measured in patients with idiopathic glomerulonephritis (GN) with or without impaired renal function, in uremic patients undergoing periodic hemodialysis and in renal transplant patients before and after an acute rejection crisis. Results show normal FN levels in idiopathic GN and in renal transplant patients with normal renal function, while significantly lower levels were found in GN with severe renal damage, in uremia before and after dialysis, and in renal transplant patients during acute and chronic graft rejection. Significant correlations between high serum creatinine values and low plasma FN levels were found in renal transplant patients. These findings suggest that the kidney may influence FN levels in the blood since acute (rejection crisis) and chronic renal failure (uremia) cause low concentrations of this protein, while levels tend to return to normal values in patients with uremia after renal transplantation. We hypothesize that the normal kidney removes or perhaps degrades some substances or hormones that may control the release or synthesis of FN. These substances are not dialyzed by cellophane membranes since low plasma FN levels persist after periodic hemodialysis. Only the renal graft provokes an increase of FN in the blood stream.     

The beneficial effect of ketoacids on serum phosphate and parathyroid hormone in patients with chronic uremia

Hyperphosphatemia and secondary hyperparathyroidism are regular complications in patients suffering from advanced renal failure. As aluminum-containing drugs carry the well-known risk of aluminum intoxication, we were interested in testing in a prospective study a mixture of ketoanalogues and amino acids which have been shown to lower the serum phosphate and parathyroid hormone in uremic patients. For 3 months, in addition to their diet, 17 uremic patients and 12 hemodialysis patients received a daily supplement of this mixture. Although no additional phosphate binders were administered, serum phosphate decreased significantly in the former group and was slightly lower in the latter. The serum parathyroid hormone level was consistently lowered when the initial concentration was not higher than 20 times normal.     

Oral manifestations in chronic uremia patients

The incidence of chronic renal failure (CRF) is approximately 200 cases per million people in different Western countries. Recent data indicate that the incidences of these pathologies are increasing. Ninety percent of patients with CRF report oral signs and symptoms that affect both the bone and soft tissues. A broad range of lesions may be observed in chronic uratemia patients, including the following: gingival hyperplasia, enamel hypoplasia, petechiae, gingival bleeding, and others lesions. These patients require various types of treatment ranging from dietary and lifestyle changes to dialysis and kidney transplantation. CRF often leads to multiple oral manifestations that are difficult for dentists to manage. The present study examined the characteristics of this disease, the existing therapeutic options and the relevant considerations for dental professionals.     

Mepacrine-labeled platelet dense-body number in patients with chronic uremia

Dense bodies are platelet organelles that store adenosine diphosphate. We have estimated the number of platelet dense bodies in patients with chronic uremia treated conservatively, by peritoneal dialysis and by hemodialysis. All groups of patients and control subjects were found to have similar mean numbers of platelet dense granules. Analysis of platelet distribution according to number of dense bodies has shown that patients undergoing hemodialysis have a decreased percent of platelets with a greater number of granules.     

Prolidase and prolinase activities in the erythrocytes of patients with chronic uremia

To elucidate the nature of the iminoacidopathy in uremia, the prolidase and prolinase activities in erythrocytes from 36 normal subjects, 28 patients with chronic uremia, and 21 patients on maintenance hemodialysis were determined. A statistically significant decrease in the activities of both prolidase and prolinase was found in the uremic patients and the hemodialysis group. No difference has been observed in the enzyme activities in the pre- and postdialysis samples of the hemodialysis patients. It is suggested that decreased activities of prolidase and prolinase may contribute to the iminoacidopathy in uremia, including high contents of serum iminoacid containing peptides.     

Lecithin-cholesterol acyltransferase (LCAT) activity in chronic uremia.

High plasma concentrations of triglycerides and low plasma concentrations of esterified cholesterol and lysolecithin, with an impaired rate of VLDL and LDL catabolism, have been reported in chronic uremic patients. An important contribution to these abnormalitites might be an impaired activity of the (LCAT). Serum LCAT activity and cholesteryl ester clearance were determined in 11 patients with chronic renal failure and in 10 controls. LCAT activity was determined by using the serum of each patient both as a source of enzyme and as a substrate ("intrinsic" activity) and was compared with the activity determined on a standard substrate ("extrinsic activity), so as to ascertain the presence of inhibitory factors in the patients' sera. Both activityes have been found to be significantly (P less than 0.01) lower in chronic uremic patients than in controls. The cholesteryl ester clearance apparently did not respond to the stimulatory effect of hypertriglyceridemia, as observed in other cases of dislipoproteinemias. The parallel decrease of both enzyme activities makes it unlikely that it is due to the presence of "uremic toxins" inhibiting the enzyme activity. LCAT synthesis in the liver is probably reduced in chronic uremia. These results suggest that in chronic uremia the VLDL fail to cooperate in their own catabolism.     

尿毒症患者血浆蛋白酶体与内皮功能损伤的相关性

目的 探讨尿毒症患者血浆蛋白酶体与动脉内皮损伤的相关性。方法 选择新诊断未透析的尿毒症患者（A组，45例）和已行血液透析6~12个月的尿毒症患者（透析充分为B组，44例；透析不充分为C组，31例）为对象。正常健康人15例为健康对照组（D组）。应用多普勒超声检测左前臂桡动脉内-中膜厚度和内皮舒张功能。酶联免疫法（ELISA）检测各组血浆20S蛋白酶体、肿瘤坏死因子α（TNF-α）、C-反应蛋白（CRP）和转化生长因子β1（TGF-β1）的含量。分光光度法检测血浆20S蛋白酶体的活性。 结果 D组血浆20S蛋白酶体含量和活性均极低。与D组比较，A组、B组和C组患者血浆20S蛋白酶体含量和活性，以及TNF-α、CRP和TGF-β1的含量均显著升高。与A组比较，B组血浆20S蛋白酶体含量和活性均显著降低，而C组明显升高；TNF-α、CRP和TGF-β1也存在相似的变化。与D组比较，A组、B组和C组患者桡动脉内皮依赖性舒张功能（EDD）和非依赖性舒张功能（EID）均显著下降；切面内膜中膜面积（IMA）均显著增加；C组患者桡动脉内-中膜厚度（IMT）明显增厚，腔内径明显变小。与A、B组比较，C组患者EDD进一步显著降低。与D组血清比较，A、B、C组血清刺激内皮细胞释放蛋白酶体和TNF-α均显著升高，尤以C组升高最明显。在A组和C组，血浆20S蛋白酶体含量和活性、炎性细胞因子与内皮舒张功能EDD均呈负相关；血浆20S蛋白酶体含量和活性与TNF-α、CRP和TGF-β1均呈正相关。 结论 尿毒症患者血浆20S蛋白酶体含量和活性的显著升高与动脉内皮功能损伤密切相关。     

Echocardiographic assessment of left ventricular function in patients with chronic uremia

Cardiac function was determined non-invasively in 7 patients (average age 24 years) with chronic uremia. Each was on maintenance hemodialysis. Echocardiograms and carotid pulse tracings were recorded 30 minutes prior to dialysis, and again 30 minutes, 24 and 48 hours following hemodialysis. End-diastolic and end-systolic diameters averaged 5.4 +/- 0.2 and 3.4 +/- 0.1 cm, respectively before and 5.0 +/- 0.2 and 3.2 +/- 0.1 cm immediately after hemodialysis (P less than 0.05 for both). Calculated stroke volume fell from 92.1 +/- 8.8 to 76.7 +/- 10.5 ml (P less than 0.025). Heart rate increased minimally, and average cardiac output was not significantly increased. Following dialysis, body weight and systolic and diastolic blood pressures fell significantly. Thus preload as well as afterload declined. Because of the fall in both stroke volume and end-diastolic volume, a shift along the ventricular function curve downwards and to the left occurred implying diminished cardiac pumping function. Nonetheless the indices of myocardial contractility were normal and showed no change from pre-dialysis value. During the 48 hour interval following hemodialysis all measured and calculated values returned to pre-dialysis levels. Thus organic heart disease as evaluated by non-invasive techniques does not appear to be a necessary sequel to kidney failure, at least in young patients in a hemodialysis program. Gross abnormalities of myocardial function may be absent for at least seven years after the onset of chronic uremia.     

Partial pericardiectomy for pericardial tamponade in patients with chronic uremia under dialysis]

Two dialyzed uraemic patients were subjected to partial pericardiectomy because of haemorrhagic pericarditis and pericardial tamponade. Seventeen and nine months, respectively, after the operation the patients have still been under intermittent home haemodialysis.     

Platelets and platelet function in patients with chronic uremia on maintenance hemodialysis.

In 20 chronic uremic patients on maintenance hemodialysis, who were not taking any medication known to affect platelet function, the following investigations were carried out: platelet count, fibrin/fibrinogen degradation products, fibrinogen and plasminogen concentration, platelet adhesiveness, clot retraction and platelet aggregation induced by ADP, ristocetin, fibrinogen, collagen and epinephrine. The only significant abnormal result was a decreased clot retraction. We consider many cases of so-called uremic bleeding to be caused by the medication taken and conclude that on well-controlled hemodialysis treatment, bleeding tendency should not be a major problem.     

Protein metabolism in patients with chronic renal failure: role of uremia and dialysis

Individuals with chronic renal failure (CRF) have a high prevalence of protein-energy malnutrition. There are many causes for this condition, chief among which is probably reduced nutrient intake from anorexia. In nondialyzed patients with CRF, energy intake is often below the recommended amounts; in maintenance dialysis patients, both dietary protein and energy intake are often below their needs. Although a number of studies indicate that rats with CRF have increased protein catabolism in comparison to control animals, more recent evidence suggests that increased catabolism in CRF rats is largely if not entirely due to acidemia, particularly if these animals are compared to pair-fed control rats. Studies in humans with advanced CRF also indicate that acidemia can cause protein catabolism. Indeed, nitrogen balance studies and amino acid uptake and release and isotopic kinetic studies indicate that in nondialyzed individuals with CRF, who are not acidemic, both their ability to conserve body protein when they ingest low protein diets and their dietary protein requirements appear to be normal. For patients undergoing maintenance hemodialysis or chronic peritoneal dialysis, dietary protein requirements appear to be increased. The increased need for protein is due, in part, to the losses into dialysate of such biologically valuable nitrogenous compounds as amino acids, peptides, and proteins. However, the sum of the dietary protein needs for CRF patients (of about 0.60 g/kg/day) and the dialysis losses of amino acids, peptides and proteins do not equal the apparent dietary protein requirements for most maintenance dialysis patients. This discrepancy may be due to a chronic state of catabolism in the clinically stable maintenance dialysis patient that is not present in the clinically stable nondialyzed individual who has advanced CRF. Possible causes for such a low grade catabolic state include resistance to anabolic hormones (for example, insulin, IGF-1) and a chronic inflammatory state associated with increased levels of pro-inflammatory cytokines.     

慢性肾炎及尿毒症患者性激素及性激素受体改变的研究

目的 探讨性激素及其受体改变与慢性肾炎及尿毒症病因及发病机理的联系。 方法 应用放射配体结合法检测慢性肾炎６３例及尿毒症１０１例患者外周血白细胞雄激素受体（ＡＲ）及雌激素受体（ＥＲ）。 结果 （１）慢性肾炎患者白细胞ＡＲ测定结果显示男性、育龄女性及绝经女性３组与对照组比无显著性差异。（２）慢性肾炎患者白细胞ＥＲ测定结果显示上述３组明显高于对照组（Ｐ〈０．０１）。（３）尿毒症患者白细胞ＡＲ测定结果显     

Effects of uremia and inflammation on growth hormone resistance in patients with chronic kidney diseases

Resistance to the anabolic action of growth hormone may contribute to the loss of strength and muscle mass in adult patients with chronic kidney disease. We tested this hypothesis by infusing growth hormone in patients to levels necessary to saturate hormone receptors. This led to a significant decrease of plasma potassium and amino acid levels in control and hyperkalemic patients with chronic kidney disease. These effects were completely or partially blunted in patients with elevated C-reactive protein levels. In forearm perfusion studies, growth hormone caused a further decrease in the negative potassium and protein balance of hemodialysis patients without inflammation but no effect was seen in patients with inflammation. Only IL-6 levels and age were found to be independent correlates in these growth hormone-induced variations in plasma potassium and blood amino acids. This shows that although a resistance to pharmacologic doses of growth hormone is not a general feature of patients with chronic kidney disease, there is a subgroup characterized by blunted growth hormone action. Our results support the hypothesis that uremia with inflammation, but not uremia per se, inhibits downstream growth hormone signaling contributing to muscle atrophy.