Response of serum angiotensin converting enzyme,plasma renin activity and plasma aldosterone to conventional dialysis in patients on chronic haemodialysis

The aim of this study was to examine serum angiotensin converting enzyme (SACE) activity and the renin-angiotensin-aldosterone system in patients on chronic haemodialysis during one routine dialysis session. Fourteen patients (8 men and 6 women; mean age 51.9±17 years) with end stage renal disease, receiving regular haemodialysis treatment for an average of 6 months, were studied. The patients were dialysed for 4 hours three times a week using cellulose membranes (cuprophan). After an overnight fast blood samples were taken from the patients before and after the haemodialysis session. Serum and plasma were separated and stored at −20°C until assayed for SACE, plasma renin activity (PRA) and plasma aldosterone (PA). For comparison, SACE, PRA and PA were also measured in 8 patients after renal allotransplantation and on treatment with cyclosporin A (5 men, 3 women; mean age 38.9±12.3 years) and in 19 healthy subjects (13 men, 6 women; mean age 38.9±12.3 years). SACE levels in patients with chronic renal failure and on haemodialysis (17.55±9.03 nmol/ml/min) and in patients with renal transplantation (18.12±3.92) were significantly higher than those of the healthy subjects (9.27±1.67) (p<0.0001, respectively). At the end of the dialysis session SACE levels in patients with chronic renal failure (14.9±7.19) did not increase in respect to pre-dialysis levels (17.55±9.03; p=0.132). PRA and PA values increased after the dialysis session (p<0.026 and p<0.044, respectively). Correlation of SACE with PRA and PA was not demonstrated before or after the dialysis session. In patients with chronic renal failure and on haemodialysis our findings suggest that a disarrangement exists between the circulatory components of the renin-angiotensin-aldosterone system before and after the dialysis session.     

Comparison of body fluid distribution between chronic haemodialysis and peritoneal dialysis patients as assessed by biophysical and biochemical methods.

BACKGROUND: The control of extracellular volume is a key parameter for reducing hypertension and the incidence of cardiovascular mortality in dialysis patients. In recent years bioimpedance measurement (BIA) has been proven as a non-invasive and accurate method for measuring intracellular and extracellular fluid spaces in man. In addition, plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphatase (cGMP) concentrations have been shown to reflect central venous filling. Using these methods, we compared body fluid status between stable patients on haemodialysis and peritoneal dialysis. METHODS: Thirty-nine chronic haemodialysis patients, 43 chronic peritoneal dialysis patients and 22 healthy controls were included in the study. Multifrequency BIA was performed using the Xitron BIS4000B device (frequencies from 5 to 500 kHz were scanned and fitted) in patients before and after haemodialysis. Peritoneal dialysis patients were measured after drainage of the dialysate. Plasma ANP and cGMP levels were measured in plasma using a (125)I solid phase RIA. Serum albumin concentrations and serum osmolality were measured in all patients. The body fluid data were analysed in relation with the clinical findings. RESULTS: Total body water (TBW) was 0.471+/-0.066 l/kg before haemodialysis and 0.466+/-0.054 l/kg after haemodialysis. Peritoneal dialysis patients had a TBW (0.498+/-0.063 l/kg) that was greater than the before and after dialysis values of haemodialysis patients. The extracellular body fluid (V(ecf)) was increased pre-haemodialysis. It was even greater in peritoneal dialysis patients compared with patients both pre- and post-haemodialysis (pre 0.276+/-0.037 l/kg; post 0.254+/-0.034 l/kg; peritoneal dialysis 0.293+/-0.042 l/kg, P<0.05). However, plasma ANP concentrations (representing intravascular filling) in peritoneal dialysis patients were comparable with post-haemodialysis values (284+/-191 pg/ml vs 286+/-144 pg/ml). The correlation coefficient between sysRR and V(ecf) was r=0.257 in haemodialysis (P=0.057) and r=0.258 in peritoneal dialysis (P<0.05). A significant negative correlation was found between serum albumin and V(ecf)/TBW in peritoneal dialysis patients (r= -0.624). CONCLUSION: Body fluid analysis by BIA demonstrated that TBW and V(ecf) were increased in peritoneal dialysis patients, and were comparable or even greater than values found before haemodialysis. However, plasma ANP levels indicated that intravascular filling was not increased in peritoneal dialysis. The ratio of V(ecf) to TBW was correlated to systolic pressure and negatively to serum albumin in peritoneal dialysis patients.     

Assessment of dry body-weight in haemodialysis patients by the biochemical marker cGMP

We investigated whether cGMP might be a suitable marker of ideal weight in chronic haemodialysis patients. In 20 patients on chronic haemodialysis (10 males, 10 females, mean age 55.5 +/- 7.4 years; mean interdialytic weight gain 2.4 +/- 1.1 kg) we determined plasma ANP and cGMP values before and after several haemodialysis treatments. ANP and cGMP before haemodialysis were markedly elevated (ANP 255 +/- 190 pg/ml; cGMP 28.6 +/- 16.2 pmol/ml). A significant decrease was found after haemodialysis (ANP 169 +/- 88 pg/ml; cGMP 13.5 +/- 7.4 pmol/ml). These values were still well above normal. There was a significant positive correlation between excessive body-weight delta P (difference between actual weight and estimated ideal weight), indicating fluid overload and ANP before (r = 0.57; P less than 0.001) and after haemodialysis (r = 0.47; P less than 0.001) as well as cGMP before (r = 0.42; P less than 0.01) and after haemodialysis (r = 0.85; P less than 0.0001). With cGMP and delta P after haemodialysis, the correlation appeared to be close enough for clinical application. All patients with a cGMP value of 18 pmol/ml or more after haemodialysis had an excessive body-weight of at least 0.5 kg. We conclude from these data that the plasma cGMP value determined immediately after haemodialysis is a sensitive marker for hyperhydration in patients with end-stage renal disease.     

Increased Plasma Levels of Atrial Natriuretic Peptide in Patients with Chronic Renal Failure: Effect of Noradrenaline Infusion

Basal plasma atrial natriuretic peptide (ANP) and blood pressurewere measured in 11 patients with chronic renal failure beforerequirement of dialysis, 13 patients on chronic dialysis, and28 control subjects (Study 1). Changes in ANP during noradrenalineinfusion were determined in eight patients with chronic renalfailure before dialysis, 12 patients on chronic dialysis, and17 control subjects (Study 2). ANP was also measured in 14 healthycontrol subjects during angiotensin II infusion (Study 3). Study1 showed a significantly greater ANP in patients before thestage of dialysis (median 23 pg/ml) and in dialysis patients(34 pg/ml) than in control subjects (19 pg/ml) p 0.01 for both.In Study 2, noradrenaline induced an increase in ANP in thenon-dialysed patients (P<0.05) and in the control subjects(P<0.01), but not in the dialysis patients. According toStudy 3, ANP was unchanged during angiotensin II infusion. Bloodpressure was increased in all groups during noradrenaline andangiotensin II infusions. It can be concluded that ANP is increasedboth in patients with chronic renal failure before requirementof dialysis and in patients on maintenance dialysis. It is suggestedthat noradrenaline stimulates ANP release.     

Atrial natriuretic peptide and cyclic 3′5′-guanosine monophosphate as indicators of fluid volume overload in children with chronic renal failure

Plasma atrial natriuretic peptide (ANP) and cyclic 35-guanosine monophosphate (cGMP) were investigated as indicators of fluid volume overload in children and adolescents with chronic renal failure. Plasma ANP and cGMP were measured in both paediatric patients with chronic renal failure (n=17, mean serum creatinine 371±242 mol/l) and those with end-stage renal disease on haemodialysis (n=18). cGMP was higher in children with chronic renal failure than in 45 healthy controls (1.0±0.4 vs 2.1±0.8 nmol/l,P<0.01), whereas plasma ANP was similar (26.9±9.7 vs 34.0±12.3 pmol/l). Both ANP and cGMP were markedly elevated in children with end-stage renal disease before haemodialysis and fell significantly during dialysis. During dialysis body weight decreased by 1.6±0.7 kg, corresponding to 4.5±2.1% of body weight. Plasma ANP correlated positively with plasma cGMP in haemodialysed patients (r=0.43,P<0.05). Reduction in body weight and in mean arterial pressure correlated more closely with plasma ANP than with cGMP. Therefore, elevation of plasma ANP appears to indicate volume overload in children undergoing haemodialysis, but whether it can be used also in children with chronic renal failure requires further investigation     

Adrenal Responsiveness During and After Intermittent Haemodialysis

ACTH and cortisol were measured by radioimmunoassay in 15 patients undergoing long term haemodialysis. Also a basal ACTH stimulation test was done by administration of 250μg of Synachten (Synthetic ACTH, CIBA foundation) and the results compared with those of normal controls and end-stage chronic renal failure patients (CRF). All 15 had been receiving intermittent haemodialysis three times weekly for 5 hours on a twin coil dialyser. The duration of dialysis was from 6 to 20 months and the mean value of pre - dialysis serum creatinine was 1093±182 umol/1. Both hormones had significantly risen in the middle and at the end of dialysis (p<0.005), While they had fallen back to normal mean levels 24 hours after dialysis. The Synachten stimulation test showed that adrenal response was within normal limits in both groups of patients, but dialysis patients responded significantly better (p<0.05) than patients with end stage CRF. We concluded that the adrenal responsiveness is within normal limits during and after regular haemodialysis and our likely explanation is a fall in plasma volume produced by the extracorporeal circulation and the increased turnover of cortisol during haemodialysis.     

Renal and hemodialysis clearances of endogenous natriuretic peptide. A clinical and experimental study

The purpose of the present study was to assess the plasma levels of atrial natriuretic peptide (ANP) in chronically uremic patients not submitted to dialysis and to determine the predialysis plasma concentration of ANP, the effect of ultrafiltration on plasma levels of ANP (hemodialysis, (HD), and the HD clearance of ANP in a population of adult patients treated with maintenance HD. The mean plasma ANP concentration (pg/ml) in HD was 370.2 +/- 35.5 pg/ml (mean +/- SEM) before HD and decreased to 165.3 +/- 15.2 after HD (p less than 0.01). Both values were significantly higher than in controls (28 +/- 2; n = 39). The changes in plasma ANP levels correlated inversely with those in plasma protein concentration (r = -0.53; p less than 0.03; y = 48.6 +/- 0.8 x). ANP clearance across the cuprophan membrane averaged 13 +/- 6.4 ml/mn. Resting plasma ANP values in the 16 uremic patients ranged between 16 and 277 pg/ml (124 +/- 11 pg/ml). These levels were significantly higher than those observed in controls (p less than 0.01). In these patients there was a highly significant correlation between serum creatinine and plasma ANP concentrations (p less than 0.01; r = 0.75; y = 0.2x + 3). Furthermore we report the results of the determination of the renal clearance of ANP in normal dogs. In all dogs a fall in plasma ANP concentration was recorded between the aorta (28.6 +/- 4.5 pg/ml) and the renal vein (14.2 +/- 2.7 pg/ml). The renal extraction ratio averaged 51.3 +/- 3.7%. Mean ANP renal clearance was 38.2 +/- 5.2 ml/mn.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum chromogranin A concentration and intradialytic hypotension in chronic haemodialysis patients

Aim The aim of this study was to investigate the influence of haemodialysis on plasma chromogranin A (CgA) concentration and to assess the relationship between CgA, blood pressure, occurrence of intradialytic hypotension episodes and residual renal function, respectively. Methods The study included 38 chronic haemodialysis patients (24 M, 14 F; mean age 56.2 ± 13.6 years). Plasma CgA and blood pressure were measured before and after a mid-week dialysis. Control group included 10 age- and sex-matched healthy subjects. Results Plasma CgA levels were on average 50-fold higher in HD patients than in the controls (699 ± 138 vs. 14 ± 6 U/L). In HD patients plasma CgA corrected for ultrafiltration rates significantly increased (to 836 ± 214 U/L, P < 0.001) at the end of dialysis procedure. In patients with (n = 8) and without frequent symptomatic intradialytic hypotension episodes predialysis values of CgA were similar (701 ± 169 vs. 698 ± 132 U/L) but post-dialysis were significantly lower in the former group (746 ± 312 vs. 860 ± 177 U/L; P = 0.03) despite a similar rate of ultrafiltration (2675 ± 1009 and 2583 ± 1311 ml, respectively). Accordingly, in patients with intradialytic hypotension an increase of plasma CgA during dialysis was also much lower than in patients without hypotension (45 ± 81 vs. 163 ± 144 U/L; P = 0.001). Conclusions CgA undergoes marked accumulation in renal failure. The increase of plasma CgA during dialysis is impaired in subjects with intradialytic hypotension episodes, which confirms the role of autonomic dysfunction in the pathogenesis of this complication.     

Treatment of Hypertension in Dialysis and Essential Hypertension Patients with Nifedipine

The immediate antihypertensive effect of 10mg nifedipine sublingually (nifedipine test), was measured in 19 chronic renal failure hypertensive patients on dialysis and 34 essential hypertensive patients with normal kidney function. The blood pressure decreased significantly in both groups. The minimal values were observed between 30 and 60 minutes after the sublingual administration of nifedipine. The blood pressure decreased from 178±3.3 / 104.0±3.9 to 136.0±4.7 / 87.0±5.1 mm Hg (p<0.001) in dialysis patients and from 176.8±4.5 /107.1±2.4 to 133.0±3.0 / 81.7±2.2 mm Hg in essential hypertension patients (p<0.001). The decrease in blood pressure during the test had a significant positive correlation with the pre-test values.

Thirteen hypertensive patients on dialysis and 20 essential hypertensive patients completed 2 weeks of daily oral nifedipine therapy, with a dose of 30 to 40 mg per day. The mean blood pressure at the end of the 2 weeks of treatment decreased from 179.5±4.5 / 108.5±5.3 mm Hg to 154.4±6.3 / 82.3±2.6 mm Hg (p<0.001) in dialysis patients, and from 176.8±5.8 / 110.3±2.9 to 151.3±5.3 / 93.5±2.6 mm Hg (p<0.001) in essential hypertension patients.

The present results reveal that nifedipine has a powerful immediate as well as a long-term antihypertensive action in dialysis patients with high blood pressure. This effect is similar to that obtained in essential hypertensive patients.     

Odour perception in chronic renal disease

Background: The sense of smell plays an important role in the quality of life. Many studies have shown a declining odour perception in the elderly, as well as in subjects in poor health or nutritional state. Considering the high prevalence of poor nutritional state in renal disease and the importance of odour perception in nutrition and health, the relationship between renal function, nutritional state, and odour perception is explored in this study. Method: A total of 101 patients with chronic renal failure participated in the study. Thirty-eight haemodialysis patients (mean age=64.3 years) were evaluated both before and after dialysis. Sixteen patients on peritoneal dialysis treatment (mean age=64.0 years), 28 transplanted patients (mean age=53.5 years, mean creatinine clearance=64.0 ml/min) and 19 patients with varying degrees of renal insufficiency were also included (mean age=63.7 years, mean creatinine clearance=29.5 ml/min). Patients with cognitive deficits or upper respiratory airway diseases were excluded. A validated objective procedure was used to measure odour perception, by determining the detection threshold for isoamyl acetate (banana odour) as the lowest detectable odour concentration. Results: Healthy control persons had significantly lower odour thresholds compared to patients on peritoneal (P=0.001) and haemodialysis (P=0.02). No significant difference was observed in odour perception between patients on peritoneal and haemodialysis (P=0.779) and for patients on haemodialysis before and after a dialysis session. Transplanted patients had significantly better odour perception compared to matched patients on dialysis (P <0.001). Odour perception of transplanted patients and matched healthy control persons was similar (P-0.81). In patients with varying degrees of renal insufficiency, including healthy controls and transplanted patients, a significant positive correlation was found between odour perception and creatinine clearance (P=0.02). A significant negative correlation was found between odour perception and serum concentration of urea (P <0.001), serum phosphorus (P=0.022) and protein catabolic rate (P <0.05). Other parameters measuring nutritional status (albumin, BMI) were not correlated with odour perception. Conclusion: Our results show that the ability to smell is severely impaired in patients with chronic renal failure and is related to the degree of renal impairment and the degree of accumulation of uraemic toxins. After renal transplantation, patients have a normal odour perception, indicating the capacity of the olfactory system to recover once the concentration of uraemic toxins remains below a critical threshold. Acute removal of uraemic toxins by dialysis does not correct olfactory disturbances, suggesting a long lasting effect of uraemia on olfactory function.     

Changes of manganese levels during haemodialysis

Manganese (Mn) transfer during haemodialysis and plasma Mn concentrations in haemodialysis patients were examined. Also, the correlation with plasma Mn levels and haematocrit levels and total plasma protein levels were studied. Fifteen volunteer outpatients undergoing haemodialysis showed significant increases in plasma Mn from 0.20±0.02 to 0.22±0.02 μg/dl after a 5-hour dialysis. The increase was mainly the result of haemoconcentration as evidenced by a significant increase in the haematocrit and total plasma protein during dialysis; however, diffusion was not found. There was a significant relationship between plasma Mn levels before dialysis and haematocrit values (r=0.95, p<0.01) and total plasma protein levels (r=0.92, p<0.01).     

Effect of treatment with simvastatin on serum cholestryl ester transfer in patients on dialysis

Background. Plasma cholesteryl ester transfer activity is increased in patients with chronic renal failure on dialysis who have elevated levels of apolipoprotein B (apoB)-containing lipoproteins. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, reduces levels of these lipoproteins but the effect of treatment on cholesteryl ester transfer activity in patients on dialysis remains to be determined. Methods. We measured serum newly synthesized cholesteryl ester transfer (NCET) activity, lecithin:cholesterol acyltransferase (LCAT) activity and serum lipid, lipoprotein and apolipoprotein concentrations before and immediately after 6 months of treatment with simvastatin (10 mg daily, n=24) or placebo (n=29) in 53 patients with chronic renal failure receiving haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Results. Simvastatin therapy significantly reduced serum cholesterol, LDL cholesterol, apoB concentrations, and both NCET (P=0.001) and LCAT (P=0.012) rates. The decrease in NCET activity was correlated significantly with the corresponding decrease in apoB concentration (r=0.715, P <0.001) during simvastatin therapy and was no longer significant when apoB concentration (P=0.14) or LCAT activity (P=0.07) were controlled. Conclusion. These data show that simvastatin therapy reduces serum NCET rates, and suggest that this may be linked to the concomitant decrease in levels of apoB-containing lipoproteins which are acceptors of transferred cholesteryl esters, and to the decrease in serum LCAT rates in patients with chronic renal failure with treatment.     

The Effect of Renal Transplantation on Plasma Protein Binding

The in vitro plasma protein binding was determined in nine maintenance hemodialysis patients who later underwent renal transplantation. The organic acid fluorescein (10 ug/ml) or the organic base quinidine (5 ug/ml) was added to the pre and post transplant serum of these patients. Drug concentrations were measured spectrophotofluorometrically after equilibrium dialysis. The results were compared with the plasma protein binding of eight normal volunteers. The patients on maintenance hemodialysis had lower plasma protein binding of fluorescein than normals (78 ± 5% vs 89 ± 4, p < 0.001). Plasma protein binding improved significantly after renal transplantation (85 ± 3, p < 0.01) but was still lower than in normals (p < 0.05). Plasma protein binding of quinidine was not significantly different than in normal volunteers (77 ± 8%) either prior to (72 ± 10%) or after (73 ± 12%) kidney transplantation. Plasma protein binding of quinidine remains unaffected by renal transplantation. However, the abnormal plasma protein binding of organic acids in chronic renal failure may be significantly improved by renal transplantation.     

Effects of atrial natriuretic peptide (99-126) in chronic renal disease in man

Plasma concentrations of human atrial natriuretic peptide (99-126) are elevated in patients with end-stage chronic renal failure and on haemodialysis. Plasma atrial natriuretic peptide (ANP) concentrations change with extracellular fluid volume, suggesting that ANP continues to have a role in chronic renal failure. We have studied the effects of an infusion (5 pmol/kg per min) in subjects with chronic renal failure (CCr) less than 30 ml/min per 1.73 m2). Glomerular filtration rate and effective renal plasma flow increased by 23% (P less than 0.01) and 27% (P less than 0.01) respectively and sodium excretion more than doubled. Systolic and diastolic blood pressures decreased by 14 (SD 1.6) and 6 (SD 0.8) mmHg respectively (P less than 0.001), and plasma renin activity declined (P less than 0.01). Plasma ANP concentrations were elevated compared to normal subjects and reached a peak of 224 (SD 87) pmol/l at the end of the infusion. Plasma half-life was 4.8 (SD 2.7) min. Plasma concentrations are elevated in chronic renal failure and ANP may play a physiological role in controlling extracellular fluid volume and blood pressure.     

Subclinical pulmonary oedema and intermittent haemodialysis

It has been postulated that patients with chronic renal failure,even in the absence of cardiopulmonary symptoms, accumulateinterstitial pulmonary fluid, which is removed by haemodialysis.To test this hypothesis we used the indocyanine green (ICG)-heavywater double indicator dilution method to measure lung water,cardiac output, and central blood volume in relation to haemodialysis.Ten uraemic patients, without cardiopulmonary symptoms, wereinvestigated at the beginning and end, and 2 h after, a regulardialysis session. A group of 18 surgical patients about to undergoelective abdominal surgery served as controls. Despite normalgas exchange, central blood volume, and cardiac output at thestart of dialysis the mean (SD) lung water was significantlyhigher than in the control group [4.8 (0.9) compared with 3.6(0.7) ml/kg, P<0.001]. There was no correlation between weightgain between sessions of dialysis and the magnitude of lungwater at the start of dialysis. Lung water decreased (P <0.001)to the level of the control group in response to dialysis. Therewas no correlation between weight loss and reduction in lungwater induced by dialysis. In conclusion, we have verified thepresence of subclinical pulmonary oedema which was removed bydialysis in a group of patients with established renal failure.The variations in lung water cannot be explained by hydrostaticmechanisms alone.     

Specific Pattern of Growth Factor Distribution in Chronic Subdural Hematoma (CSH): Evidence for an Angiogenic Disease

Summary. Summary. Background: The aim of this prospective study was to evaluate the significance of growth factors as determinants of the pathological degree of neovascularisation found in the parietal neomembrane of chronic subdural hematoma (CSH). Thus far the pathogenesis of the vascularisation has not been elucidated. Method: The concentrations of growth factors, i.e. vascular endothelial derived growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) were determined using ELISA technique in hematoma fluid and serum of 20 patients with uni- or bilateral CSH. For comparison, growth factor concentrations were determined in cerebrospinal fluid (CSF) of patients undergoing diagnostic myelography. Findings: Concentrations of VEGF and bFGF were significantly (p<0.001) increased in the hematoma fluid as compared with serum (VEGF_h=8,142 pg/ml, bFGF_h=8.7 pg/ml versus VEGF_s=368 pg/ml, bFGF_s=1.8 pg/ml). In contrast, PDGF concentration was significantly (p<0.001) lower in the hematoma (PDGF_h=3,456 pg/ml versus PDGF_s=31,937 pg/ml). The serum levels for VEGF, bFGF and PDGF in CSH patients lay within the range of normal volunteers. No growth factors were found in normal CSF. Interpretation: These results reveal a specific distribution pattern of growth factors in CSH patients. This pattern suggests that CSH may be considered a member of the angiogenic disease family.     

C REACTIVE PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASES

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53 ± 5.8 years with a mean creatinine clearance (C_Cr) of 52 ± 37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0 ± 4.6 mg/L and 5.8 ± 5.6 pg/mL, respectively and were not significantly correlated (r = 0.11, p = n.s.). CRP and IL-6 were however related with renal function (CRP versus C_Cr r = ?0.40 p < 0.001; IL-6 versus C_Cr r = ?0.45; p < 0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4 ± 6.3 mg/L in the group of patients with a C_Cr lower than 20 mL/min (n = 32) and 2.76 ± 4.35 in the group of patients with a C_Cr higher than 20mL/min (n = 70) (p < 0.0001). CRP and IL-6 were positively related with ESR (r = 0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2 ± 0.4 versus 3.0 ± 0.5 g/dL). CRP and serum albumin were not significantly related (r = 0.17). CRP and IL-6 correlated positively with ESR (r = 0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation – even in the predialysis phase of renal failure – of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.     

Plasma level of atrial natriuretic peptide as an indicator of increased cardiac load in uremic patients

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in 43 non-dialyzed uremic patients at rest and during maximal exercise to assess the possible relationship between plasma ANP levels and cardiac function, as judged by M-mode echocardiography and exercise tolerance. Patients with poor exercise capacity (exercise time less than 6 min) on dynamic exercise test had decreased left ventricular ejection fraction, increased left atrial diameter, and increased left ventricular mass index (LVMI), compared with patients with better exercise capacity (exercise time greater than 6 min). Plasma ANP was significantly higher in patients with poor exercise capacity and impaired cardiac function (202 pg/ml [95% confidence interval 119 to 284] at rest and 227 pg/ml [149 to 304] during exercise), compared with patients with better exercise capacity (75 pg/ml [50 to 102], p less than 0.005, and 123 pg/ml [80 to 167], p less than 0.05, respectively). Plasma ANP increased significantly (p less than 0.005) during exercise only in patients with better cardiac function. The best correlation among the variables studied was found between LVMI and plasma ANP concentration at rest (r = 0.56, p less than 0.001) and during exercise (r = 0.51, p less than 0.005), whereas neither blood pressure nor renal function showed any significant correlation with ANP levels. We conclude that plasma ANP levels are elevated in uremic patients with impaired cardiac function, correlating with increased LVMI. Plasma ANP determinations are useful in identifying increased cardiac load and consequent cardiac hypertrophy and dysfunction with known associations with increased cardiovascular mortality in patients with chronic renal failure.     

Endothelin in chronic renal failure.

The aims of the present study were to determine plasma endothelin (ET) in chronically uraemic patients, the renal clearance of endogenous ET in normal dog and man, and the effect of acute volaemic expansion on ET. The mean plasma ET concentration in haemodialysis patients was 57.5 +/- 5 pg/ml before haemodialysis and remained unchanged at 52.5 +/- 5 pg/ml after haemodialysis. They were thus significantly elevated both before and after haemodialysis (P less than 0.01) compared with plasma ET in normal subjects of 20.8 +/- 0.8 pg/ml. There was no evidence of ET clearance across the cuprophane membrane of the dialyser. Resting plasma ET values in the 15 non-dialysed uraemic patients ranged between 20 and 52.5 pg/ml (mean 38.2 +/- 2.3 pg/ml), significantly greater than those observed in controls (P less than 0.01). In CAPD patients, plasma ET was also significantly (P less than 0.01), elevated (63 +/- 10 pg/ml) when compared to controls, and similar to those observed in patients before haemodialysis. In dogs, mean ET did not diminish between the aorta and the renal vein (28.1 +/- 1 versus 28.4 +/- 2 pg/ml). In man mean ET did not significantly decline between the renal artery and the renal vein (17 +/- 3 to 13 +/- 0.8 pg/ml). In the seven healthy subjects who received 2000 ml of isotonic saline intravenously ET remained unchanged (24 +/- 2; 23 +/- 1 and 23 +/- 2 pg/ml before and 1 and 2 h after starting hydration respectively). We have thus shown that plasma ET is elevated in patients with chronic renal failure especially those on dialysis and CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters.

BACKGROUND: Malnutrition and chronic systemic inflammatory response syndrome not only coexist in uraemia, but may also have a bi-directional cause-and-effect relationship. To evaluate the role of dialysate-related cytokine induction in inflammatory response and nutritional status, we conducted a prospective comparison of two dialysis fluids differing in their microbiological quality. METHODS: Forty-eight early haemodialysis patients were assigned to either treatment with conventional (potentially microbiologically contaminated) or on-line produced ultrapure dialysis fluid. Study parameters were bacterial growth, markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6), and parameters of nutritional status (estimated dry weight, upper mid-arm muscle circumference, serum albumin concentration, insulin-like growth factor 1, leptin, and protein catabolic rate). Patients were followed for 12 months. RESULTS: There were no statistically significant differences in demographic and treatment characteristics, degree of bacterial contamination of the dialysate, markers of systemic inflammation, or parameters of nutritional status among the two treatment groups at recruitment. Changing from conventional to ultrapure dialysis fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases in estimated dry body weight, mid-arm muscle circumference, serum albumin concentration, levels of the humoral factors, and in protein catabolic rate after 12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml) was not associated with significant alterations in markers of inflammation (IL-6 21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of nutritional status at any time of the study. All differences in systemic inflammation and nutritional parameters observed during the study period (from recruitment to month 12) were significant between the two patient groups. CONCLUSIONS: Cytokine induction by microbiologically contaminated dialysis fluid has a negative impact on nutritional parameters of early haemodialysis patients. The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status in addition to known factors, such as dose of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but may improve the nutritional status in long-term haemodialysis patients.