Analysis of the factors influencing bicarbonate balance during acetate-free biofiltration.

In acetate-free biofiltration (AFB), the physical separation between the base losses and the gains could facilitate the modeling of intradialytic bicarbonate (HCO3) balance. In order to verify this hypothesis, we analyzed in a multicenter study, 126 AFB sessions in which differing parameters were evaluated (dialysis time, blood flow, ultrafiltration, infused HCO3, pre- and post-dialytic HCO3, hematocrit and body wt). Statistical analysis performed with multiple linear regression showed that the post-dialysis HCO3 was significantly dependent (F = 21.68, d.f. 5.95, P < 0.001) directly on the amount of infused HCO3, the level of pre-dialysis HCO3 and the final body weight, and inversely on the dialysis time and the blood flow. HCO3 values predicted by the statistical model correlated well with the observed ones (r = 0.788, P < 0.0001) with a mean absolute difference of 2.138 mEq/liter. This modeling approach allowed us to predict, with a computer-aided procedure, the quantities of HCO3 to be infused to obtain a desired and personalized acidosis correction.

Effect of ibopamine on the progression of chronic renal failure.

Persistent changes in the slope of the reciprocal of serum creatinine concentration against time after medical intervention are likely to reflect the influence of therapy on progression of chronic renal failure. This observation allowed us to demonstrate the ability of ibopamine, a new orally active dopamine-related drug, to improve renal function or at least to slow its deterioration in 20 patients studied over a period of 6 months. We also noted that the therapeutic response to the drug varied considerably according to the nature of the underlying nephropathy, with maximal benefit being observed in nonglomerular diseases.

Osmotic fragility of erythrocytes, cell deformability and secondary hyperparathyroidism in uremic patients on maintenance hemodialysis.

The possible relationship between erythrocyte (RBC) function and secondary hyperparathyroidism (HPT) was examined in 35 uremic patients on maintenance hemodialysis. Mechanical tests (i.e., osmotic fragility and deformability) were used to assess RBC function. Secondary HPT was evaluated by means of serum biochemistry (parathyroid hormone, calcium, phosphorus, and alkaline phosphatase) and radiographic examinations (X-ray films of the hand skeleton). Sixteen sex and age-matched normal volunteers acted as controls. This study shows that the mechanical properties of RBC were indeed markedly altered in hemodialysis patients when compared with controls. No significant correlations between either the osmotic fragility or the deformability of RBC and the hematochemical changes associated with secondary HPT were found. No differences in RBC function tests were found as far as the activity (alkaline phosphatase) or the severity (X-ray findings) of secondary HPT are concerned. Effective treatment of secondary HPT by either pharmacological means (1,25-dihydroxycholecalciferol) or surgical removal was not associated with consequent improvement in RBC function. These findings clearly speak against secondary HPT as a major cause of RBC dysfunction in uremic patients on maintenance hemodialysis.

Serum CA 19-9 and CA 50 antigens in hemodialysis patients.

Serum concentrations of monoclonal antibody-defined tumor markers CA 19-9 and CA 50 were measured in 64 uncomplicated hemodialysis patients (Group 1) and in 8 hemodialysis patients with cancer (Group 2) in comparison with corresponding CEA determinations. From our results in Group 1 patients it appears that both CA 19-9 and CA 50 maintained an excellent specificity in these patients. As to the sensitivity of these tests, our findings in Group 2 patients are comparable with those reported in patients with cancer and normal renal function. It is concluded that, unlike CEA, these new tumor markers maintain their clinical value in chronic renal failure.

Elevated acute phase reactants in hemodialysis patients.

The incidence of elevated acute phase reactants, measured by nephelometry, was examined in 69 otherwise uncomplicated hemodialysis patients in comparison with 30 healthy subjects. Increased C-reactive protein was found in 40.6% of the patients (p less than 0.001 vs controls) and the degree of increase was correlated with the duration of hemodialysis. Haptoglobin was increased in 33.3% (p less than 0.01 vs controls). High levels of alpha-1-acid glycoprotein and alpha-1-proteinase inhibitor were present in 15.9% and 2.9%, respectively; these frequencies were not significantly different from controls. No differences between pre- and postdialysis values were observed. It is concluded that, unlike C-reactive protein, both alpha-1-acid glycoprotein and alpha-1-proteinase inhibitor maintain an excellent specificity in hemodialysis patients. Vice versa, haptoglobin may be unreliable as an acute phase reactant in these patients because of the unacceptably high false-positive rate.

Long-term treatment of chronic renal insufficiency with Ibopamine (SB 7505), a new orally active dopamine-related drug.

When administered orally Ibopamine, the diisobutyric ester of N-methyldopamine, has pharmacological properties similar to intravenous dopamine: in particular, both renal blood flow and the urinary excretion of sodium and water increase. The drug also enhances creatinine clearance, both in normal subjects and in patients with impaired renal function. Twenty-eight patients affected with chronic renal insufficiency were treated with oral Ibopamine (100 mg/day) for 4-56 weeks. They were divided into 2 groups according to whether the creatinine clearance was more or less than 15 ml/min: Group 1 contained 21 patients (mean clearance 29.09 ml/min) and Group 2 7 patients (mean clearance 8.42 ml/min). Ibopamine treatment was ineffective in Group 2, while in Group 1 patients there was a statistically significant increase in creatinine clearance (+23% after 3 months, +31% after 6 months). Drug tolerance was excellent from both clinical and laboratory points of view.

Effect of different dialyzer membranes on serum angiotensin-converting enzyme during hemodialysis.

The effects of different dialyzer membranes on serum concentration of angiotension-converting enzyme (ACE) and white blood cells during hemodialysis were examined on a cross-over basis in 20 chronically uremic patients. Hemodialysis with cuprophane membranes was associated with a significant (p less than 0.001) fall in the mean leukocyte count during the 1st hour of treatment. The use of polymethylmethacrylate membranes resulted in a more attenuated form of leukopenia and with polyacrylonitrile membranes no change was observed during hemodialysis. Hemodialysis with each membrane caused a comparable, significant (p less than 0.005) increase in serum ACE, independent of the degree of leukopenia but significantly (p less than 0.001) correlated with the increases in serum proteins. We conclude that this increase in serum ACE concentration after hemodialysis does not reflect acute damage of the pulmonary vascular endothelium during treatment and most probably is a result of hemoconcentration. Therefore, serum ACE analysis is not an indicator of dialyzer membrane biocompatibility.

Immune response to a recombinant hepatitis B vaccine in hemodialysis patients.

A 20-microgram dose of a recombinant hepatitis B vaccine was given at 0, 1, 2 and 6 months to 24 hemodialysis patients. From month 7 (i.e., 1 month after the fourth injection), 58.3% (14/24) of the patients had developed protective levels of antibodies against hepatitis B surface antigen (anti-HBs). In patients responding to vaccination, the fourth injection led to an abrupt rise of the anti-HBs titres which reached their maximum 2 months later, that is, in month 8. At that time, the geometric mean titre of anti-HBs was 145.79 mlU/ml. Eighteen months after the start of vaccination, 50% (12/24) of the patients were maintaining protective levels of anti-HBs antibodies. It is noteworthy that these results could be obtained with a considerably lower dosage than previously recommended.

Serum alpha-1-antitrypsin in hemodialysis patients with dialysis arthropathy.

Dialysis arthropathy is the most prominent dialysis-related amyloidosis feature. Alpha-1-antitrypsin (alpha-1-proteinase inhibitor) is the major circulating antiprotease. Twenty-three otherwise uncomplicated hemodialysis patients with well-documented dialysis arthropathy had a significantly (p < 0.05) lower serum mean concentration, 1,960 +/- 410.4 mg/l of alpha-1-antitrypsin than 47 patients with no joint symptoms who had a mean concentration of 2,256.6 +/- 424.5 mg/l. Decreased levels of the substance were detected in 13 (56.5%) of the 23 patients with dialysis arthropathy and in 13 (27.6%) of those 47 with no joint symptoms, the incidence in the former group being significantly (p < 0.05) higher than in the latter. In the dialysis arthropathy group, serum alpha-1-antitrypsin levels correlated inversely (r = -0.54, p < 0.01) with the dialysis duration and directly (r = 0.413, p < 0.05) with the corresponding beta-2-microglobulin determinations. We speculate that reduced antiprotease activity may play a role in amyloidogenesis in the setting of long-term hemodialysis.

Red blood cell volume distribution width (RDW) in uraemic patients on chronic haemodialysis.

Red blood cell volume distribution width (RDW) was obtained with the Coulter counter in 60 haemodialysis patients and 55 normal individuals. RDW tended to be higher in the former and the degree of increase was to some extent correlated with the underlying nephropathy. Although RDW failed to correlate with conventional tests of iron status, it was observed that iron administration could produce a decrease toward normal in RDW and a parallel increase in haemoglobin when the initial RDW was increased. In contrast, the response to iron was negligible in the patients with normal RDW basally. It was concluded that high RDW is an acceptable indicator of iron deficiency in haemodialysis patients.

Serum lipoprotein(a) and coronary artery disease in uremic patients on chronic hemodialysis.

There is convincing clinical and experimental evidence to support the notion that lipoprotein(a) [Lp(a)] is atherogenic. Patients undergoing chronic hemodialysis have an increased risk of atherosclerotic cardiovascular complications. In the present study, we investigated the possible relation between the alteration, if any, in serum Lp(a) and coronary artery disease in such patients. The mean serum concentration of Lp(a) tended to be higher in the 64 hemodialysis patients than in the 30 normal controls (15.1 +/- 15.2 vs. 9.7 +/- 10.4 mg/dl). However the difference did not reach statistical significance. The prevalence of levels above 30 mg/dl was 14% (9/64) and 10% (3/10), respectively, and the difference was also not statistically significant. Eleven hemodialysis patients with coronary artery disease had a significantly higher mean serum concentration of Lp(a) than the unaffected 53 (33.7 +/- 18.4 vs. 11.1 +/- 11.2 mg/dl, p < 0.001). Elevated levels were present in 63.6% (7/11) and 3.8% (2/53), respectively (p < 0.01). Other parameters of lipid metabolism were not different between the two groups. We observed statistically significant positive correlations of Lp(a) to total cholesterol, LDL cholesterol and apolipoprotein B in controls, in hemodialysis patients as a whole and in those without coronary artery disease. No such correlations were obtained when hemodialysis patients with coronary artery disease were analysed separately. It is concluded that firstly, high serum levels of Lp(a) in hemodialysis patients are strongly associated with coronary artery disease, as well as in the general population; and secondly, abnormalities in the metabolism of Lp(a) may underlie atherogenesis in these patients, independently of alterations in other lipid constituents.

Hemodialysis-associated platelet loss: study of the relative contribution of dialyzer membrane composition and geometry.

To evaluate the relative contribution that dialyzer membrane composition and geometry make to hemodialysis-associated platelet loss, the effect of a single dialysis with three different types of dialyzers on platelet count was examined on a cross-over basis in 19 uremic patients on maintenance hemodialysis. Also, the plasma levels of antithrombin-iii before and after dialysis were measured, but no significant variations were found regardless of which dialyzer was in use. Our patients suffered significant platelet loss during cuprophan dialysis, but not polyacrylonitrile dialysis. More than 99% of initial circulating platelets were recovered at the end of polyacrylonitrile dialysis, whereas cuprophan dialysis did leave a significantly lower percentage of circulating platelets (p less than 0.05). The internal comparison of results obtained with the two cuprophan dialyzers used shows no difference as to the dialyzer geometry (flat plate or hollow fiber). This indicates that the membrane composition is the major factor influencing hemodialysis-associated platelet loss. We suggest that patients with low platelet count and/or with risk of bleeding may benefit from polyacrylonitrile dialysis.

[Osteo-articular amyloidosis caused by dialysis. Clinical and radiologic aspects]. / Amiloidosi osteoarticolare da dialisi. Aspetti clinici e radiologici.

Twenty-nine patients who had received chronic hemodialysis for more than 5 years provided the material for the present study. In 12 of them (41%) there were radiological findings of dialysis related amyloidosis, mainly destructive spondyloarthropathy of the cervical spine (n = 11) and geodes of the shoulder (n = 5). When compared with negative patients, these patients were significantly older (p less than 0.001 and had been dialyzed for longer periods of time (p less than 0.01). Moreover, in such patients there was an higher incidence of carpal tunnel syndrome (p less than 0.025) and shoulder pain (p less than 0.001). Our results confirm that osteoarticular amyloidosis is a frequent long-term complication of chronic hemodialysis and underline the correlation between clinical and radiological findings.

[Pre-dialysis arteriovenous fistula results in better patency rate]. / Fistola artero venosa pre-dialisi = migliori risultati.

BACKGROUND: The timing of creation of the first permanent vascular access is crucial to the clinical history of haemodialysis patients. Our strategy is to create vascular access early enough to allow its maturation before the start of the treatment. METHODS: Aim of the study is to evaluate patency of primary A-V fistulas in patients treated between 1985 and 2000 in our dialysis unit. One hundred and thirty A-V fistulas created before haemodialysis treatment (range 10-540 days) and used at its beginning (pre-HD group) are compared with 74 A-V fistulas created and/or used after the start of the haemodialysis treatment (post-HD group). RESULTS: Pre-HD group fistulas resulted in higher patency rate than the post-HD group, immediately at the start of the treatment (94.6% vs. 86.5%, p<0.05), at 6 months (89.2% vs. 75.6%, p<0.025), at 12 months (84.5% vs. 64.6%, p< 0.005), at 24 months (77.2% vs. 54.8%, p< 0.005). CONCLUSIONS: A-V fistula is to be preferred in the choice of primary vascular access for chronic haemodialysis patients. It should be created early enough before the beginning of the treatment (when serum creatinine reaches 6 to 7 mg/dL). This planning avoids central venous catheter placement, preserves vessels and the choice of the best surgical option thus resulting in a better fistula survival.

[Significance of serum levels of beta-2-microglobulin in dialysis patients]. / Significato dei livelli sierici di beta-2-microglobulina nei pazienti in dialisi.

beta 2M has been shown to be a major constituent of the amyloid deposits developing in uremic patients undergoing long-term hemodialysis. In this study, serum levels of beta 2M were determined in 67 hemodialysis patients and a mean +/- SD concentration of 57.8 +/- 18.5 mg/L was obtained. There was no difference in the concentration of the substance between the patients with evidence of dialysis-related amyloidosis and those without it. Moreover, no correlation between beta 2M levels and duration of hemodialysis was found. Interestingly, the patients with residual diuresis had a significantly lower mean beta 2M concentration than the anuric patients (35.0 +/- 13.1 vs 62.8 +/- 15.8 mg/L, p less than 0.001). Not surprisingly, a significant decrease in the predialysis serum concentration of the substance was obtained after changing treatment from cuprophan hemodialysis to hemodialysis with high-permeable membranes (delta beta 2M = -16.1 +/- 14.4 mg/L at month 6, p less than 0.01). These results suggest the possible long-term use of these membranes to reduce risk of dialysis-related amyloidosis.

Lack of relation between secondary hyperparathyroidism and red blood cell osmotic fragility in chronic renal failure.

The possible relationship between red blood cell (RBC) osmotic fragility and secondary hyperparathyroidism (HPT) in chronic renal failure was examined in 23 uremic patients on conservative therapy and in 42 patients on maintenance hemodialysis. Secondary HPT was evaluated by means of serum biochemistry (parathyroid hormone, calcium, phosphorus, and alkaline phosphatase) and radiographic examinations (X-ray films of the hand skeleton). This study showed increased RBC osmotic fragility in uremic patients when compared with controls, with no difference between those on conservative therapy and those on maintenance hemodialysis. No correlation between RBC osmotic fragility and the hematochemical changes associated with secondary HPT was found. No difference in RBC osmotic fragility was observed with regard to the activity (alkaline phosphatase) and the severity (X-ray findings) of secondary HPT. Effective treatment of secondary HPT by either pharmacological means (1,25-dihydroxycholecalciferol) or surgical removal was not associated with consequent improvement in RBC osmotic fragility. It is concluded that secondary HPT is probably not a major factor influencing RBC osmotic fragility in chronic renal failure.

Successful declotting of arteriovenous grafts with local infusion of urokinase in hemodialyzed patients.

Local infusion of urokinase was used in 15 cases of thrombotic occlusion of polytetrafluoroethylene grafts in 10 hemodialyzed patients. The treatment was successful in all patients except one in whom recurring thrombosis occurred because of junctional stenosis at the venous anastomosis. No relevant side effects were observed. Follow-up data show that such treatment can significantly prolong the survival of arteriovenous grafts in hemodialyzed patients with otherwise difficult access to the circulation.

Therapeutic response of idiopathic edema to captopril.

Idiopathic edema is a condition characterized by diurnal weight gain and intermittent swelling, affecting adult females without evidence of any other condition known to cause sodium retention. It has been suggested that an alteration in the aldosterone response to upright posture plays a pathogenetic role in orthostatic sodium and water retention peculiar to this syndrome. To test this hypothesis, the effect of captopril was evaluated in 4 women with idiopathic edema. The therapeutic response was impressive in all. In summary, we noted a remarkable decrease in morning to evening weight difference, an increase in both diuresis and natriuresis, and a definite symptomatic improvement. It is therefore possible to speculate that captopril, by reversing the basic abnormality acting in idiopathic edema, may prove of benefit in most patients with this peculiar syndrome.