Hemodialysis and continuous ambulatory peritoneal dialysis effects on erythropoiesis in renal failure

Parameters of erythropoiesis were studied in patients with endstage renal disease established on continuous ambulatory peritoneal dialysis (CAPD) and regular hemodialysis treatment (RDT). Serum erythropoietin was measured by radioimmunoassay, and erythroid progenitor cell (CFU-E) formation was assayed in fetal mouse liver cultures. Serum erythropoietin concentrations in both CAPD (35.3 +/- 4.0 mU/ml) and RDT (31.9 +/- 1.9 mU/ml) patients were significantly higher (P less than 0.01) than normal values (23.1 +/- 1.0 mU/ml). The serum erythropoietin concentration did not correlate with either hematocrit or inhibition of CFU-E formation in either group of dialysis patients. In both CAPD and RDT patients the hematocrit correlated significantly (P less than 0.001) with the degree of serum inhibition of CFU-E formation. CFU-E formation decreased from 74.5 +/- 2.5 to 62.5 +/- 3.5% of control with increasing concentrations of uremic serum in cell cultures from 5 to 20%. In RDT patients a single hemodialysis produced a decrease in the mean serum erythropoietin concentration from 31.8 +/- 2.1 to 27.4 +/- 1.8 mU/ml (P less than 0.01) but no significant change in CFU-E formation. In conclusion, although serum immunoreactive erythropoietin levels are elevated above the normal range in dialysis patients, the response remains inadequate for the severity of the anemia, and it is the degree of serum inhibition of erythropoiesis in both CAPD and RDT patients which correlates with and possibly determines the degree of anemia.     

Insulin-like growth factor I: a modulator of erythropoiesis in uraemic patients?

Anaemia is a feature almost invariably complicating chronic renal failure. Its pathophysiology is multifactorial but the most important cause is erythropoietin (Epo) deficiency. However, either no relation or even a weakly positive relation generally exists between serum immunoreactive (i) Epo and haematocrit values in uraemic anaemia, whereas in anaemias of non-renal origin the correlation is most often strongly negative. Recent evidence indicates that growth hormone also stimulates erythropoiesis. Moreover, late erythroid progenitor cells (CFU-E) require insulin and/or insulin-like growth factor I (IGF-I) for development in vitro. IGF-I has been shown to have a synergistic action with Epo. We have measured serum iEpo and IGF-I levels in 17 haemodialysis patients with severe hyperparathyroidism (mean +/- SEM serum iPTH, 988 +/- 88 pg/ml). Mean age and duration of dialysis treatment were 46.1 +/- 3.4 and 8.8 +/- 1.0 years respectively. Mean haematocrit and haemoglobin values wer 28.1 +/- 1.7% and 9.39 +/- 0.54 g/dl respectively. Mean serum iEpo and IGF-I levels were 20.3 +/- 4.7 mU/ml and 320 +/- 20 ng/ml respectively (normal values for serum iEpo and IGF-I, 17.9 +/- 6 mU/ml and 91 +/- 23 ng/ml respectively). We found that serum IGF-I concentrations were well correlated with haematocrit values (r = 0.68, n = 15, P less than 0.004) whereas serum iEpo values were not (r = 0.41, n = 12, P = 0.18). IGF-I could therefore be an important factor regulating erythropoiesis in uraemic patients, at least when associated with severe hyperparathyroidism.     

Erythropoietin deficiency in acute renal failure

Erythropoietin (Epo) was sequentially measured by radioimmunoassay in 11 patients with acute renal failure (ARF) of varied aetiology. Epo rapidly decreased to a level inappropriately low for the haemoglobin, the reduced Epo value persisting throughout the oliguric phase and for up to 2 weeks after the restoration of apparently normal renal function. Epo values found in ARF were: at referral 18.2 +/- 9.5, mid-oliguria 14.4 +/- 6.8, diuresis 15.6 +/- 5.8, and recovery 25.1 +/- 15.8 mU/ml. Results are compared with 34 patients with end-stage chronic renal failure, 42 with non-renal anaemia, and 96 normal subjects. Epo deficiency alone is an inadequate explanation of the rapid reduction in haemoglobin at the onset of ARF, but would appear to be an important factor in the maintenance of anaemia in prolonged ARF and accounts for the slow increase in haemoglobin following recovery.     

Erythropoietin in patients with acute renal failure and continuous veno-venous haemofiltration

Erythropoietin (Epo) is a glycoprotein hormone produced in the kidney in response to hypoxia or anaemia. In acute renal failure (ARF) anaemia also occurs and current opinion is that Epo production is depressed with inappropriately low plasma levels throughout the uraemic phase. Our study was designed to determine the excretion of Epo in patients with ARF. Fifty-nine ventilated patients were studied, 39 with ARF and continuous veno-venous haemofiltration therapy (group 1) and 13 patients with normal renal function who served as a control group (group 2). All patients with ARF were anaemic and needed a mean transfusion of 0.6 units/day. Values for vitamin B12, folic acid, serum iron and ferritin were normal. While patients with normal renal function had Epo values within the normal range, patients with ARF had significantly higher values at the onset of haemofiltration therapy. Mean Epo (mean±SEM) values on days 0–2 were 92.6±11.7 mU/ml in group 1 and 16.5±6.4 mU/ml in group 2 (p<0.0002). Epo levels declined in group 1 to 49±10.5 mU/ml on days 9 and 10 compared to 23±9.1 mU/ml in group 2 (ns). These values were maintained until the end of the observation period. No differences were seen between oliguric and non-oliguric patients. Our data show that patients with ARF have increased Epo levels at the beginning of the disease with a strong tendency to decrease, suggesting that there might be inadequate Epo levels during the course of acute renal failure.     

Elevation of serum erythropoietin after subtotal parathyroidectomy in chronic haemodialysis patients.

After successful subtotal parathyroidectomy (PTX) in 10 chronic haemodialysis patients, significant elevation of Epo was observed, from 48.4 +/- 17.8 mU/ml(M +/- SEM) at preoperative state to 103.3 +/- 34.7 mU/ml at 6 h and 163.4 +/- 50.2 mU/ml at 12 h after PTX. Significant reductions in both PTH-m and ionized calcium (iCa) were confirmed. Since Epo did not increase in the cases with an inadequate PTX and ovariectomy, an abrupt reduction in PTH with a decrease in iCa may play some role in the elevation of Epo.     

Role of erythropoietin in the reversal of anemia of renal failure with continuous ambulatory peritoneal dialysis

We report serum erythropoietin levels in a patient who showed significant improvement in hematocrit when switched from hemodialysis to continuous ambulatory peritoneal dialysis (CAPD) treatment. This 22-year-old woman had severe anemia and low serum immunoreactive erythropoietin levels (8.0 +/- 1.2 mU/ml; n = 5) while on hemodialysis for 7 years. Serum erythropoietin levels were 80 and 177 mU/ml, 2 and 3 weeks, respectively, after starting CAPD. This was followed by an increase in reticulocyte count from 3.9 to 22% and hematocrit from 19 to 48%. The serum erythropoietin concentration obtained on CAPD treatment (62.7 +/- 15.2 mU/ml; n = 9) was significantly higher than that obtained on hemodialysis. Our findings indicate that CAPD facilitates increased erythropoietin production compared to hemodialysis and that the anemia of uremia may reverse if sufficient erythropoietin is available.     

Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency

The relative importance of erythropoietin (Ep) and inhibition of erythropoiesis in the anemia of chronic renal insufficiency has been investigated. Sixty patients with varying degrees of renal insufficiency, 40 normal subjects and 40 patients with anemia and normal renal function, were studied. Erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell colony formation were assayed in fetal mouse liver and human bone marrow cultures, respectively. Erythropoietin was measured by radioimmunoassay. Hematocrit and plasma creatinine concentration correlated with the degree of serum inhibition of CFU-E formation (r = 0.69, P less than 0.001, and r = 0.62, P less than 0.001, respectively). Serum erythropoietin levels in patients with renal insufficiency (34.4 +/- 6.7 mU/ml) were slightly higher than normal values (23.1 +/- 0.98 mU/ml), but showed no relationship to plasma creatinine, hematocrit, or inhibition of CFU-E formation. In contrast, serum erythropoietin concentrations increased exponentially as the hematocrit decreased below 32% (r = 0.61, P less than 0.001), and CFU-E formation was stimulated by serum in anemia patients with normal renal function. Studies of granulopoiesis showed uremic sera supported in vitro CFU-GM growth more efficiently than sera from normal subjects. These results suggest that inhibition of erythroid, but not granulocytic, progenitor cell formation, in addition to a relative erythropoietin deficiency, are the primary factors responsible for the anemia of chronic renal failure.     

Insulin-mediated glucose uptake in nondialyzed and dialyzed uremic insulin-dependent diabetic subjects

A three-step euglycemic insulin clamp was performed in six matched groups: nine healthy subjects, 10 insulin-dependent diabetic (IDD) subjects with normal kidney function, 10 nondiabetic uremic subjects, six nondialyzed uremic IDD subjects, seven uremic IDD subjects on chronic hemodialysis (HD), and six uremic IDD subjects on chronic ambulatory peritoneal dialysis (CAPD). Insulin was infused sequentially at rates of 0.5 (step 1), 2.0 (step 2), and 4.0 (step 3) mU X kg-1 X min-1. Each dose was given for 120 min; however, in the IDD subjects with fasting hyperglycemia, step 1 of the clamp was slightly extended. Average serum free insulin levels at steady state ranged from 22 to 342 microU/ml and were comparable in all groups. Step 3 glucose infusion rate (GIR), the last 30 min of the infusion period, was extremely suppressed in nondialyzed uremic IDD subjects, amounting to 53% of that in healthy subjects (7.7 +/- 0.7 versus 14.4 +/- 0.9 mg X kg-1 X min-1, P less than 0.001) indicating severe insulin resistance in peripheral tissues. As expected, step 3 glucose disposal was also reduced in IDD subjects with normal kidney function (12.4 +/- 0.6 mg X kg-1 X min-1) and nondiabetic uremic subjects (9.2 +/- 0.6 mg X kg-1 X min-1) as compared with healthy subjects (P = 0.06 and P less than 0.001, respectively). The pronounced impairment of insulin responsiveness in nondialyzed uremic IDD subjects was almost equal to the sum of the defects in nondiabetic uremic and IDD subjects with normal kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Binding of hippurate in normal plasma and in uremic plasma pre- and postdialysis

The protein binding of 14C-hippurate has been measured by conventional ultrafiltration techniques in the plasma of normal subjects and in uremic subjects pre- and postdialysis. In addition, the clearance of 14C-hippurate was determined in vitro in both isotonic saline and plasma to assess binding limitations on hippurate removal during dialysis. Binding levels of hippurate in normal subjects of 68+/-1.8% (n = 5) were significantly higher than either postdialysis (48.3+/-15.4%; n = 7) or predialysis (36.6+/-11.7%; n = 7) levels in the same uremic subjects. Actual levels of plasma hippurate were, however, considerably greater in uremics (24.7+/-11.2 mg/dl' n = 7) than in normal subjects (congruent to 0.5 mg%). The difference in hippurate binding between pre- and postdialysis samples in uremics was significantly different from zero (p less than 0.01, t = 5.36), indicating depletion of competitive site-binding species during dialysis. The saline clearance of hippuric acid (99.1 +/-0.5 ml/min; n = 6) under standard conditions in a capillary dialyzer (CDAK-4) was consistent with the expected clearance of a solute of its molecular weight. Hippurate clearance in citrated plasma, where binding was determined as 50+/-3%, was 65+/-0.7 ml/min (n = 6), in good agreement with a theoretically predicted clearance of 60 ml/min for this level of binding. High serum levels of hippurate and its derivatives, may depress effective function of various organs. In addition to the normal dietary intake of hippurate and its precursors, patients on dialysis receive a further burden of hippurate precursor in the form of benzyl alcohol, the common preservative in heparin solutions. The large body burdens of hippurate in dialysis patients, coupled with its impaired removal on dialysis due to binding, point to the necessity for a through investigation of the potential toxicity of this compound.     

Intraperitoneal production of erythropoietin with continuous ambulatory peritoneal dialysis

Higher hematocrit and serum erythropoietin (EPO) levels have previously been shown in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD) compared with hemodialysis. We investigated whether EPO was produced intraperitoneally in CAPD patients. EPO concentration was 3.5±0.3 mU/ml by radioimmunoassay in 26 samples of peritoneal dialysis effluent obtained from 15 CAPD patients. EPO was not detectable in the fresh unused dialysate. No correlation was observed between EPO levels in the serum and dialysis effluent. Peritoneal macrophages were isolated from the dialysis effluent of 9 CAPD patients after an overnight dwell. The culture supernatant obtained after 24 h of in vitro culture of a million cells yielded EPO of 3.5±0.3 mU/ml. Our study demonstrated that peritoneal macrophages from CAPD patients produce EPO on in vitro stimulation, and EPO is present in the dialysis effluent of CAPD patients.     

Elimination and serum protein binding of phenylbutazone in patients with renal insufficiency.

In uremic patients the serum protein binding of phenylbutazone was significantly decreased. The concentration of the dialyzable drug estimated by equilibrium dialysis was increased by 117-1100% (mean +/-SD = 502 +/- 236%). No correlation exists between the serum protein binding of phenylbutazone and the concentration of serum albumin, urea and creatinine. The serum protein binding of glymidine was also decreased in the uremic patients (dialyzable fraction increased by 214%). The apparent plasma levels of phenylbutazone immediately after its ingestion (600 mg per os) were decreased in uremic patients (44.5 +/- 11 mug/ml) in comparison with healthy subjects (66.3 +/- 17.3 mug/ml). The half life of phenylbutazone was decreased in the uremic patients (41.7 +/- 12.4 hr) in comparison with healthy volunteers (58.9 +/- 14.9 hr). It is suggested that the accelerated elimination of phenylbutazone in uremic patients is caused by an altered distribution of the drug caused by its decreased serum protein binding.     

Increased erythropoietin response to venesection in erythrocytosic renal transplant patients

Anaemia of end-stage chronic renal failure improves following successful kidney transplantation. However, erythrocytosis occurs in 6.8–17.3% of transplanted patients. Mechanism of post-transplant erythrocytosis (PTE) and its erythropoietin (Epo) dependence are still controversial. Firstly, we compared basal serum Epo levels of 10 PTE patients, 14 non-erythrocytosic renal transplant (non-PTE) patients and 12 healthy blood donors. Then we performed venesection in PTE patients and healthy blood donors and compared their Epo response to venesection 5 hours later. The mean basal serum Epo of 24.3 mU/ml was significantly higher in the PTE group than the 10.8 mU/ml in the non-PTE and 8.6 mU/ml in the healthy blood donor group (p<0.01). Epo levels in the non-PTE group did not differ significantly from those of healthy blood donors (p>0.05). Following venesection the mean serum Epo levels increased significantly in both groups, from 24.3 mU/ml to 67.7 mU/ml (p<0.001) in the PTE group and from 8.6 to 12.1 mU/ml (p<0.01) in the healthy blood donor group, but the increment in the PTE group was more marked. We conclude that PTE patients have elevated basal serum Epo levels and there is a feedback regulation of Epo secretion in these patients like in healthy blood donors, but in an exaggerated way.     

Effects of erythropoietin-gene electrotransfer in rats with adenine-induced renal failure

BACKGROUND: We previously demonstrated that erythropoietin (Epo) expression increases in five-sixths nephrectomized rats, after muscle-targeted gene transfer by in vivo electroporation, using plasmid DNA expressing rat Epo (pCAGGS-Epo). Here, we apply this method to a rat model with severe anemia associated with chronic renal failure; these rats have hematocrit levels in the 30-35% range, similar to those in humans with end-stage renal disease. METHODS: Wistar rats were treated to produce adenine-induced uremia. The uremic rats were then treated with muscle-targeted gene transfer using pCAGGS-Epo. Some uremic rats died from chronic renal failure; one of these was dissected, and the kidneys were histologically examined. For the remaining rats, we measured body weight and blood pressure, and obtained blood samples regularly. RESULTS: The uremic rats showed severe anemia, with hematocrit levels at 32.6 +/- 3.3%. Epo-gene transfer increased Epo expression and serum Epo levels, and also increased the hematocrit levels to 64.5 +/- 4.8%. The dose of pCAGGS-Epo used in this study did not induce severe hypertension. CONCLUSIONS: Continuous Epo-gene expression improves the anemia associated with chronic renal failure, and without severe side effects. Our results support the potential use of gene electrotransfer for human gene therapy applications.     

Serum levels of advanced glycosylation end products in diabetic nephropathy

BACKGROUND/AIMS: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. METHODS: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. RESULTS: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 +/- 0.73 mU/ml; 15-24%, 4.01 +/- 0.71 mU/ml; 25% or more, 5.12 +/- 0.64 mU/ml). CONCLUSIONS: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.     

Relationship between erythropoietin and chronic heart failure in patients on chronic hemodialysis.

In the present study, the relationship between the blood erythropoietin level and cardiac function was investigated in 15 patients on chronic hemodialysis who developed chronic heart failure. Another 45 patients without cardiac dysfunction were selected as a control group that was matched for gender, age, and the duration of dialysis. The erythropoietin level was 256.3 +/- 481.8 mU/ml in the heart failure group, which was significantly higher than that in the control group (17.0 +/- 10.0 mU/ml, P < 0.01). Eight of the 15 patients in the heart failure group maintained a hematocrit of more than 30% without receiving recombinant human erythropoietin therapy, whereas 29 of the 45 patients in the control group required erythropoietin. In the heart failure group, the erythropoietin level was significantly correlated with the levels of atrial natriuretic peptide and brain natriuretic peptide (P < 0.01). These results suggest that heart failure can increase the erythropoietin level in proportion to the severity of cardiac dysfunction, even in patients on long-term dialysis.     

Procalcitonin: a new marker of inflammation in haemodialysis patients?

BACKGROUND: Although procalcitonin (PCT) has been described as a new marker of infection and inflammation, it has not been extensively studied in dialysis patients. METHODS: We measured plasma PCT levels in 62 patients on maintenance haemodialysis (30 M/32 F, age 61.8+/-17.1 years, on dialysis for 75+/-93 months, 12 h/week, with a Kt/V of 1.53+/-0.31, high-flux membrane being used in 25 patients and low-flux in 37 patients, without reuse). PCT levels were compared with other markers of inflammation and nutritional status, including C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), leukocytes, urea, creatinine, albumin, prealbumin, normalized protein catabolic rate (nPCR), haemoglobin (Hb), and epoetin (Epo) doses. Patients were divided into different groups according to their infectious and vascular status. RESULTS: PCT plasma levels before dialysis were 0.69+/-0.81 ng/ml. Fifty-seven per cent of PCT values were higher than the upper normal limit of 0.5 ng/ml. CRP and PCT concentrations were high in patients with a current infection, while IL-6 values were elevated in all patients regardless of infection status. Plasma CRP concentrations before dialysis were 21.2+/-31.4 mg/l, and 70% of these values were higher than the upper normal limit. CRP, PCT, IL-6, and fibrinogen were positively correlated with each other and were all negatively correlated with albumin. Prealbumin was negatively correlated with CRP and IL-6. In the 43 patients treated with Epo, haemoglobin was negatively correlated with IL-6 and Epo doses, while Epo doses were positively correlated with IL-6 but not with CRP or PCT. The 23 patients with both elevated PCT and CRP plasma levels had the lowest Hb, albumin, and prealbumin concentrations, and the highest fibrinogen concentrations and Epo doses. CONCLUSION: PCT in haemodialysis patients is positively correlated with currently used markers of inflammation such as CRP and fibrinogen, and negatively correlated with markers of nutritional status such as albumin. The concomitant elevations in PCT and CRP could be more sensitive in the evaluation of inflammation than each marker separately.     

Study on the assay of uremic protein-binding inhibitors: furan compound and hippuric acid]

Plasma levels of 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (FA) and hippuric acid (HA) were studied in healthy subjects, uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). Analysis of FA and HA in the plasma were performed by gas chromatography with capillary column. The mean value of FA in HD patients (16.7 +/- 6.1 micrograms/ml) was significantly higher than these in healthy subjects (3.6 +/- 1.0 micrograms/ml) and in patients on CAPD (4.1 +/- 3.7 micrograms/ml) (p less than 0.01). HA levels in CAPD and HD groups were higher than those in healthy controls (2.4 +/- 0.8 micrograms/ml). In addition, the values in HD patients (46.7 +/- 53.5 micrograms/ml) were more increased than those in CAPD (18.5 +/- 16.5 micrograms/ml) (p less than 0.05). Approximately 95% of total FA and 25% of HA were bound to the plasma protein. However, the plasma level of HA was significantly reduced by HD therapy, whereas that of FA was not altered. In the previous study, it was described that no effect of HD on the percent of the binding of acid drugs to the plasma protein in the uremic plasma was observed. Therefore it is supposed that FA is more involved in the binding of drugs to the plasma protein in comparison with HA. The peritoneal losses of FA and HA in CAPD were 2.3 +/- 1.3 mg/day and 276 +/- 40 mg/day, respectively. As the duration of HD became longer, plasma concentrations of FA in HD patients were more increased. In general, they were maintained to be comparatively low in patients on CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced superoxide dismutase activity in erythrocytes of dialysis patients: a possible factor in the etiology of uremic anemia

Superoxide dismutase (SOD) plays a major part in the destruction of oxygen-free radicals in the body. SOD activity is impaired by several trace elements including aluminium and silicon which are found in increased levels in plasma and tissues of uremic man. SOD activity was investigated in the erythrocytes of normal controls and of dialysis patients to determine if lack of SOD-protective activity could be a contributory cause to the increased hemolysis of uremia. It was found that SOD levels in red cell hemolysate were significantly lower in dialysis patients (41.4 +/- 9.1 units/100 ml) compared to control (49.3 +/- 7.2 units/100 ml) (U = 7.3; p less than 0.005). When expressed per 100 ml of whole blood SOD levels were 3.25 +/- 0.93 units/100 ml in dialysis patients and 6.46 +/- 0.99 units/100 ml in controls (U = 96; p less than 0.001). It is concluded that inhibition of SOD activity in the erythrocytes of dialysis patients may contribute to their anemia.     

Abnormalities of thirst regulation in patients with chronic renal failure on hemodialysis.

To determine whether thirst mechanisms are altered in nondiabetic patients with chronic renal failure on hemodialysis, 4 patients with an average weight gain between dialysis sessions of more than 5% of dry body weight (group I), 5 patients with less than 3% weight gain (group II), and a group of 6 healthy subjects (group III) were submitted to infusion of hypertonic saline. After infusion the subjects had free access to water. Thirst was evaluated by visual analogue rating scales. Despite similar increments of effective plasma osmolality during saline infusion, patients of group I were thirstier than groups II and III (p less than 0.005 and p less than 0.01, respectively). Changes in thirst ratings were similar in groups II and III. Osmotic thresholds for thirst onset were similar in groups II and III (288.9 +/- 8.5 and 289.8 +/- 3.4 mosm/kg, respectively), but lower in group I (277.6 +/- 7.6 mosm/kg). Nevertheless, great variations were observed in the latter group. Thus, 2 patients showed thresholds for thirst within the normal range, whereas the others had low osmolar thresholds for thirst and baseline plasma osmolalities and high basal thirst scores. During the drinking period, the patients of group I drank more (14.2 +/- 2.8 ml/kg) than those of groups II (5.3 +/- 1.6 ml/kg; p less than 0.02) and III (10.2 +/- 1.6 ml/kg; n.s.) The plasma levels of angiotensin II in uremic patients were higher than in healthy subjects, although there were no differences between groups I and II and no correlation between basal angiotensin II levels and the interdialytic weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostate-specific antigen in hemodialysis patients and the influence of dialysis in its levels

The determination of prostate-specific antigen (PSA) is a useful tool in the diagnosis and follow-up of prostate cancer in males, but its diagnostic validity is uncertain in hemodialysis patients. We prospectively evaluated PSA in male hemodialysis patients as well as the influence of a single dialytic session on its levels. We measured pre- and postdialysis total PSA (tPSA) in 63 hemodialysis patients (mean age 68.44 +/- 11.16 years, range 33-86 years) who had received dialysis with low flux membranes as well as in 729 normal subjects (mean age 63.22 +/- 16.85 years, range 28-92 years). We also measured pre- and postdialysis hematocrit (Hct) in patients in order to estimate the degree of hemoconcentration after the dialysis session. If any of the examined patients or subjects had abnormal tPSA levels then free PSA (fPSA) and the f/tPSA ratio were additionally measured. Patients had lower levels of tPSA compared with those of the subjects (2.41 +/- 4.06 vs. 3.76 +/- 7.16 ng/ml, p < 0.05) while both of the two groups had near equal prevalence of individuals with abnormal values of tPSA or f/tPSA ratio (patients 12.69 and 7.93%, subjects 11.01 and 7.11%, respectively; nonsignificant. Dialysis resulted in a 9.48% increase in mean tPSA levels (2.41 +/- 4.06 vs. 2.69 +/- 4.06 ng/ml, nonsignificant) and in a 10.09% increase in mean Hct; the correlation between these increases was significant (r = 0.79, p < 0.001). In conclusion, our male hemodialysis patients had lower PSA levels compared with the general population, while both groups of individuals had a similar prevalence of abnormal values of tPSA and f/tPSA ratio. Dialysis with low flux membranes does not eliminate PSA and its postdialysis increase is due to hemoconcentration.