Plasma Renin Activity and Blood Pressure in 89 Patients Receiving Maintenance Haemodialysis Therapy

Blood pressure, plasma renin activity, plasma sodium concentration, plasma potassium concentration, dietary sodium intake, and duration of dialysis have been measured under standard conditions in 89 patients on maintenance haemodialysis. No significant relation was found between plasma renin activity and blood pressure. Statistically significant correlations were found between plasma renin activity and plasma sodium concentration and between plasma renin activity and dietary sodium intake.Only one patient was found to have uncontrollable hypertension associated with a markedly raised plasma renin activity. Reasons are given for not performing bilateral nephrectomy in this patient. We believe the low incidence of uncontrollable hypertension and hyperreninaemia in our patients to be due to their slow introduction to haemodialysis, thus preventing violent swings in body weight, blood pressure, and renin secretion.Although plasma renin activity did fall with duration of dialysis, all 15 patients who have been on maintenance dialysis for longer than five years have normal levels.     

Active Uptake of Copper and Zinc during Haemodialysis

The uptake of copper and zinc by patients undergoing regular haemodialysis has been assessed by measuring the dialysis fluid for copper and zinc concentration, and the blood entering and leaving the dialysis coil for red cell copper, plasma free copper, and plasma zinc levels during priming of the coil and subsequent haemodialysis, and by in-vitro studies.Red cells avidly removed copper from dialysis fluid when mixed with saline during priming, but did not take up copper during the haemodialysis. At both these stages plasma actively took up both copper and zinc from dialysis fluid, even against a concentration gradient, so that loss of these metals from plasma to dialysis fluid did not occur.In the dialysis systems investigated the sources of the copper in the dialysis fluid were the copper plumbing of the tap-water and the dialysis coil, and the major source of zinc was the zinc oxide of the adhesive plaster around the dialysis coil.     

Pharmacodynamics of Practolol in Chronic Renal Failure

Plasma levels of practolol were measured in advanced chronic renal failure. The plasma half life was found to be markedly prolonged. During haemodialysis considerable shortening of the half life occurred. Therapeutic blood levels of practolol can be achieved in maintenance haemodialysis patients by the administration of 200 mg of the drug by mouth at the beginning and end of each dialysis.     

Permanent Neurological Sequelae Despite Haemodialysis for Lithium Intoxication

Three patients with lithium toxicity are reported, two of whom were exposed to toxic lithium levels for a prolonged period: both survived with permanent damage to basal ganglia and cerebellar connexions despite effective lowering of lithium levels by haemodialysis. Data obtained during dialysis treatment show prolonged haemodialysis to be the treatment of choice. If facilities for haemodialysis are not available or the patient presents with toxic lithium levels and minimal symptoms peritoneal dialysis will effectively lower serum lithium levels, but more slowly than haemodialysis.     

Effect of Potassium Supplements on the Exchangeable Potassium in Chronic Heart Disease

A study of the effect of additional oral potassium on the low body potassium of seven patients with severe valvular heart disease showed that the potassium supplements were retained. After one month''s treatment the exchangeable potassium was significantly increased, but the predicted value was not reached in any of the patients. There was no significant change in plasma potassium. These results suggest that it is of benefit to increase the dose of oral potassium for at least one month preoperatively in patients undergoing cardiac surgery.     

Renal transplantation in patients treated with haemodialysis and short term and long term continuous ambulatory peritoneal dialysis.

Forty two adult patients who had been treated with continuous ambulatory peritoneal dialysis for one to 142 weeks (mean (SD) 38 (36)) received a total of 44 allografted kidneys. Twenty one had been treated with continuous ambulatory peritoneal dialysis for less than 26 weeks (mean 11 (8)) and the other 21 for longer than 26 weeks (mean 64 (35)). These two groups were compared with 55 patients who had been treated with haemodialysis and received a total of 63 grafts. In the group of patients treated with continuous ambulatory peritoneal dialysis azathioprine and low dose prednisolone were used as the immunosuppressive regimen for 20 transplantations in 18 patients, and 24 patients receiving 24 grafts were treated with cyclosporin A and low dose prednisolone. In the group of patients treated with haemodialysis 38 patients receiving 43 grafts were treated with azathioprine and low dose prednisolone, and 20 patients receiving 20 grafts were treated with cyclosporin A and low dose prednisolone. Actuarial survival of patients and grafts at two years was 95% and 72%, respectively, in the continuous ambulatory peritoneal dialysis group compared with 89% and 58%, respectively, in the haemodialysis group. No difference was found in graft survival between short term treatment with continuous ambulatory peritoneal dialysis (72% graft survival) and long term treatment (65% graft survival). In conclusion, continuous ambulatory peritoneal dialysis is suitable treatment for patients awaiting renal transplantation.     

In vivo intracellular cytokine production by leukocytes during haemodialysis

Several chronic inflammatory changes undergone during chronic haemodialysis are associated with increased pro-inflammatory cytokine production. Although generation of anaphylatoxins has been incriminated in the untoward effects of haemodialysis, it is still debated whether anaphylatoxins stimulate monocyte secretion of TNF-alpha and IL-1. We demonstrate that peripheral mononuclear cells isolated from healthy controls and cultured with complement-activated autologous serum or recombinant C5a induced high levels of IL-1, IL-1ra, IL-8 and MCP-1, low levels of TNFalpha and sTNFRII but no IL-10 and MIP-1alpha. Cytokine production by leukocytes was investigated by FACS analysis in six patients dialysed consecutively with three equivalent low permeability membranes known to activate the complement to different degrees: polysulfone (F6HPS), cellulose acetate (CA) and cuprophane (CP). Percentage of leukocytes expressing IL-1, IL-1ra, TNF-alpha and IL-8 is increased in patients dialysed with CP. Moreover, we show for the first time that haemodialysis is associated with the production of cytokines by circulating neutrophils. Predialysis plasma levels of MCP-1 and TNFRII did not increase during the dialysis session at the time when anaphylatoxin generation was highest. Dialysis with membranes that activate the complement to a high extent induce activation of leukocytes which may explain chronic complications associated with dialysing with CP.     

Significance of High Plasma Renin Activity in Patients on Maintenance Haemodialysis Therapy

Blood pressure and plasma renin activity were remeasured after an interval of 8 to 17 months in 16 patients on maintenance haemodialysis previously found to have high renin activity. Continuing intermittent haemodialysis changed the plasma renin activity and blood pressure but no consistent pattern was seen. This confirmed our previous finding that adequate dialysis can control blood pressure in the presence of high renin activity. We therefore conclude that bilateral nephrectomy should be approached with renewed caution.     

Potassium Balance and Acid-Base Changes in Patients Undergoing Regular Haemodialysis Therapy

Serial measurements of total body potassium in 21 patients with chronic renal failure being treated with three 10-hour periods of dialysis per week, against a dialysate fluid containing 1·5 mEq of potassium per litre, showed no evidence of potassium depletion. Mild hyperkalaemia was found in some patients before dialysis, correlated with the pre-dialysis hydrogen ion concentration. Hypokalaemia occurred during dialysis in almost half of the studies made; the plasma potassium concentration, however, rose to normal levels within two to four hours of stopping dialysis. A delay in the movement of potassium from the cells into the extracellular fluid is suggested as a cause for the observed hypokalaemia.In all but one patient the pre-dialysis blood pH was normal, but rose to alkalaemic levels during dialysis. A pronounced degree of hypocapnia was noted before dialysis, and this was not altered by a rising blood pH during dialysis. It is suggested that a stimulus to respiration other than the hydrogen ion gradient between the brain cells and cerebral spinal fluid may produce the observed hypocapnia.     

Regular short haemodialysis in end-stage renal failure.

A study was made of thrice weekly haemodialysis of 3-3 1/2 hours'' duration using a large surface area dialyser in patients with end-stage renal failure. Body water, potassium, and blood pressure control were satisfactory and comparable with the more widely used long dialysis schedules (6-9 hours thrice weekly). Patient rehabilitation was improved overall and the regimen enabled the dialysis unit to treat more patients despite a reduction in technical and nursing staff. The technique proved inadequate, however, in two patients with an intercurrent infection, and more intensive dialysis in recommended in such cases.     

Effect of dialysis on oxidative stress in uraemia

It has been postulated that dialysis of patients with chronic renal failure (CRF) is associated with increased lipid peroxidation which may contribute to vascular and other complications of the syndrome. In the present study, a specific and precise technique [ferrous oxidation in xylenol orange (FOX) assay] was used to measure plasma lipid hydroperoxides (ROOHs) in three groups of uraemic patients. Patients were either studied before starting dialysis (n = 12) or on continuous ambulatory peritoneal dialysis (CAPD, n = 12) or haemodialysis (HD, n = 36) and compared to healthy controls (n = 20). Plasma ROOHs were markedly elevated in HD patients compared with the controls (7.01 +/- 2.9 microM versus 4.25 +/- 2.05 microM; P < 0.005, Mann-Whitney test). Plasma ROOH concentrations in the CAPD patients were increased but not significantly higher than controls (5.36 +/- 3.56 microM versus 4.25 +/- 2.05 microM). By contrast, no differences in ROOH levels were found between controls and predialysis patients. There was no difference in plasma thiobarbituric acid reactive substances (TBARS) between control and the three CRF groups. Absolute and cholesterol standardised plasma alpha-tocopherol levels were lower in the patients (whether they were on dialysis or not) than in the controls (18.62 +/- 6.88 microM versus 22.73 +/- 5.33 microM; P < 0.01 and 1.99 +/- 1.88 microM/mM versus 5.25 +/- 1.0 microM/mM; P < 0.0005, respectively). This study provides direct evidence that enhanced oxidative stress in CRF patients is related to the dialysis treatment rather than the disease itself. Further studies will be necessary to establish the relationships between plasma measures of oxidative stress and cardiovascular complications in CRF patients under dialysis and whether treatment with antioxidants may reduce oxidative stress or reverse adverse effects associated with dialysis.     

Impacto de la modalidad de terapia de reemplazo renal en adultos mayores frágiles

IntroductionEnd-stage renal disease prevalence is increasing in older adults. Frailty is highly prevalent in older adults with end-stage renal disease. However, there are no prospective studies comparing the performance of the different modalities of renal replacement therapy (RRT) in frail older adults.ObjectiveTo compare clinically relevant outcomes (hospital admission, falls, hip fractures, and mortality) in prefrail and frail older adults according to the modality of RRT: peritoneal dialysis or haemodialysis.MethodsA prospective observational study in prefrail and frail older adults (according to FRAIL scale) on peritoneal dialysis and haemodialysis was carried out. An evaluation was made using baseline characteristics (age, Charlson, body mass index, time on RRT, compliance with Kt/V dose, haemoglobin, and albumin). The patients were followed-up over 12 months, recording mortality, days and number of hospital admissions, falls, and hip fractures.ResultsA total of 54/65 (83%) older adults on RRT met criteria for prefrailty or frailty, and signed informed consent (27 in each modality). Baseline characteristics were similar, except for serum albumin and time on RRT, both of which were significantly lower in the peritoneal dialysis group. The FRAIL score was similar in both groups. Baseline FRAIL correlated with higher comorbidity, lower albumin levels, and non-compliance of Kt/V dose, while it was independent of age, body mass index, and time on RRT. Days and number of hospital admissions at 12 months were similar in patients on peritoneal dialysis and haemodialysis. Survival on peritoneal dialysis and haemodialysis was similar. There were no differences in falls or hip fractures.ConclusionsPre-frail and frail older adults on peritoneal dialysis and haemodialysis have similar clinical outcomes.     

Comparison of Surgery and Prolonged Spironolactone Therapy in Patients with Hypertension,Aldosterone Excess,and Low Plasma Renin

The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin. In the series as a whole a highly significant reduction in both systolic and diastolic pressures was achieved, with no evidence of escape from control during therapy lasting several years in some cases. The drug was equally effective in controlling blood pressure in patients with and without adrenocortical adenomata. Occasional unresponsive patients were encountered in both groups; pretreatment blood urea levels in these were significantly higher than in the responsive patients. The hypotensive effect of spironolactone usually predicted the subsequent response to adrenal surgery.Spironolactone in all cases corrected plasma electrolyte abnormalities; significant increases in total exchangeable (or total body) potassium and significant reductions in total exchangeable sodium, total body water, extracellular fluid, and plasma volumes were seen. Plasma urea rose during treatment and there was a slight fall in mean body weight. Significant increases in peripheral venous plasma renin and angiotensin II concentrations occurred during treatment.In two patients no increase in aldosterone secretion rate was found during treatment, although plasma aldosterone rose in three of four subjects studied.Severe side effects were rare; in only two of the 67 patients did the drug have to be stopped.In addition to its routine preoperative use, spironolactone can now be advised as long-term therapy in selected patients.     

Continuous ambulatory peritoneal dialysis and renal transplantation: a five year experience.

Continuous ambulatory peritoneal dialysis is a new and increasingly popular method of routine dialysis, but its effect on renal transplantation is uncertain. A non-randomised comparison was made of the outcome of grafting in patients who had been treated before transplantation with continuous ambulatory peritoneal dialysis with that in patients treated with haemodialysis. During the five years, 1979-84, after continuous ambulatory peritoneal dialysis was introduced to Newcastle upon Tyne 220 patients have received transplants after either continuous ambulatory peritoneal dialysis (61 patients) or haemodialysis (159 patients). During follow up no significant differences occurred in survival of patients or grafts between the two treatment groups. One year after transplantation the percentages of survivors who had received continuous ambulatory peritoneal dialysis and haemodialysis were 88% and 91% respectively, and overall graft survival was 66% and 72%, respectively. A multiple regression model was used to allow for differences among patients--for example, duration of dialysis and number of preoperative transfusions--on the survival of grafts. When only first cadaver grafts were considered (in 152 patients) graft survival (non-immunological failures excluded) was not significantly different between the patients treated with continuous ambulatory peritoneal dialysis and haemodialysis. Continuous ambulatory peritoneal dialysis is not a risk factor in renal transplantation, and its continued use in treatment of potential renal graft recipients is recommended.     

Role of the kidney in regulating plasma immunoreactive beta-melanocyte-stimulating hormone.

An analysis of the factors that influence the increase in plasma immunoreactive beta-melanocyte-stimulating hormone (beta-MSH) concentration in chronic renal failure showed that: (a) the increase correlated with the increase in serum creatinine concentrations; (b) beta-MSH was not cleared from the plasma by haemodialysis; (c) beta-MSH concentrations increased with length of time on dialysis and increased further after bilateral nephrectomy but there was no further increase with time; (d) beta-MSH levels decreased to normal after renal transplantation; and (e) beta-MSH was excreted in urine only when plasma levels rose to well above those of chronic renal failure (in Nelson''s syndrome). These findings suggest that the kidney regulated plasma beta-MSH by a non-excretory mechanism and is the major site of beta-MSH metabolism.     

Spleen size in chronic renal failure.

To investigate the cause of clinically detectable splenomegaly, which is common in patients receiving regular haemodialysis, splenic volume was assessed by isotopic scanning using intravenously injected technetium-99m microspheres in 34 controls and 149 patients with chronic renal failure. Of the patients, 16 had never received dialysis, 10 were undergoing continuous peritoneal dialysis, 94 were undergoing regular haemodialysis, and 29 had undergone successful renal transplantation more than nine months previously. Mean splenic volume was increased only in the patients who were receiving haemodialysis. Splenic enlargement was probably not due to iron overload as it occurred in all patients who had received haemodialysis, 14 of whom had not received intravenous iron. No patient had had hepatitis. Splenic enlargement was probably related to the process of haemodialysis itself and may have been due either to red cell damage produced by haemodialysis or to an immunological reaction induced by a component of haemodialysis, possibly ethylene oxide.     

Transient and Persistent Hypercalcaemia in Patients Treated by Maintenance Haemodialysis

In a group of 32 patients with terminal renal failure the initial hypocalcaemia was corrected after two months'' adequate maintenance haemodialysis. In seven patients hypercalcaemia occurred with a peak incidence after about six months'' treatment. In six of these patients hypercalcaemia was transient and the plasma calcium became normal with haemodialysis alone. In one patient the hypercalcaemia was persistent and the plasma calcium reverted to normal only after subtotal parathyroidectomy. This patient had no radiological bone disease, a normal alkaline phosphatase, and no metastatic calcification of the soft tissues.It is concluded that in some patients with terminal renal failure treated with maintenance haemodialysis autonomy of the parathyroids becomes evident in the absence of bone disease or a raised plasma alkaline phosphatase, and that subsequently with continued dialysis there is a spontaneous involution towards normal parathyroid function.     

Paraproteins associated with low plasma sodium levels

The mechanism of the maintenance of low plasma sodium levels seen in certain multiple myeloma cases has been attributed to the cationic nature of pathological immunoglobulins (paraproteins). This hypothesis was tested with equilibrium dialysis and polyacrylamide gel electrophoresis techniques. Citrated plasma samples and affinity chromatography purified paraproteins of three multiple myeloma patients with abnormally low plasma sodium levels were dialysed against 140 mmol/L NaCl solution at pH 7.4 for 24 hours. The electrophoresis of paraproteins was conducted under non-denaturing conditions. Low plasma sodium concentrations observed under the dialysis of the patients' plasma samples were in good agreement with earlier reports. However, the isolated paraproteins did not show any sodium exclusion during the dialysis experiment. The electrophoretic mobility of the paraproteins at pH 7.4 indicated that the isoelectric point of these molecules was below 7.4, so they cannot behave as cations at the pH of the blood. From these data it appears that the maintenance of low plasma sodium levels in certain IgG type myeloma cases cannot be explained by the previously postulated cationic nature of the paraproteins.     

Factor VIII complex in uraemia and effects of haemodialysis.

Levels of the factor VIII complex were found to be raised in patients with chronic renal failure and further raised by regular dialysis. Increased fibrinogen concentrations were also found. These results suggest the existence of a prothrombotic state in uraemia that is exacerbated by haemodialysis. Ristocetin-induced platelet agglutination, however, was depressed in uraemia and worsened by dialysis. This defect may be transferred to normal platelets from dialysed uraemic plasma, suggesting the existence of an inhibitor of the interaction between factor VIII and platelet glycoprotein. These results may help to explain the anomaly of a prolonged bleeding time together with accelerated atherogenesis that is found in patients with uraemia receiving dialysis.     

Vitamin E-coated filter decreases levels of free 4-hydroxyl-2-nonenal during haemodialysis sessions

Uraemic subjects undergoing chronic haemodialysis show increased oxidative stress. The use of non-biocompatible filters and reduced antioxidative defences are important sources of reactive oxygen species (ROS) release. The highly oxidative environment accelerates the onset and progression of tissue damage and atherosclerotic cardiovascular disease. The aldehyde 4-hydroxyl-2-nonenal (HNE) is probably the best marker of oxidative stress. In this study, the concentration of plasma HNE was evaluated in eight uremic subjects during two sessions of haemodialysis: the first using a standard biocompatible filter and the second using a filter coated with vitamin E. Baseline plasma levels of HNE were elevated, and dropped during haemodialysis. At the end of the session, however, low levels were maintained only when the vitamin E-modified filter was used. By contrast, a marked increase in HNE was recorded at the end of the session in all subjects who underwent haemodialysis with the conventional filter. This study provides evidence that the vitamin E-coated filter plays a role in counteracting oxidative stress. The chronic use of vitamin E-modified filters in haemodialysed subjects might help to counterbalance oxidative attack and, consequently, contribute to preventing cardiovascular disease.