Atherosclerosis in uremia: a longitudinal study.

The ways by which uremia may lead to atherosclerosis are still unknown. Furthermore, whether atherosclerosis is accelerated with prolonged hemodialysis is still under debate. The results of a longitudinal study carried out in 47 selected patients who were treated first with dietary regimen followed by dialysis and then transplantation indicate: 1) The longer the duration of uremia on low protein diet, the worse are the clinical and metabolic problems of atherosclerosis. 2) In subsequent regular dialysis treatment 2 distinct clinical and metabolic pictures may emerge, slowly progressive or comparatively accelerated, according to whether dialysis is initiated early or late. 3) In subsequent transplantation the avoidance of risk factors largely depends on the time at which regular dialysis begins. 4) Early direct transplantation without dialysis proves similar to transplantation in patients treated with early dialysis as far as prevention of accelerated atherosclerosis is concerned.

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.

Cytomegaloviru; antibody in the urine of renal transplant patients.

Small amounts of cytomegalovirus (CMV) antibody were detected in the urine of renal transplant patients excreting the virus. The antibody was probably produced locally, as a result of active CMV infection of the urinary tract.

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.

Progression rate of residual renal function in conservative treatment and early dialysis.

A retrospective comparative study was carried out in patients with chronic renal failure on conservative treatment (26 cases) and early dialysis (23 cases). The two groups were well matched for age, sex, etiology of renal disease and residual Ccr. In contrast with other papers, patients on dialysis showed a gentler deterioration rate of residual renal function than those on conventional low protein diet regimen. Between the two groups statistically significant differences concerned the control of blood pressure, serum phosphate and uric acid.

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.

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.

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.

[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.

Effect of calcitonin on bone lesions in chronic dialysis patients.

The effects of synthetic salmon CT, administered subcutaneously and intermittently (1 MRC U/kg/day for 15 days/month over 6 months) were investigated in 15 uremic patients on regular dialysis treatment (RDT), all presenting various degrees of osteodystrophy. Clinically, osteoarticular pain disappeared in 8 out of 10 cases; 1 patient with rib fractures had a rapid calcification of the bone fracture repair tissue. No significant changes were found in serum calcium and PTH levels. Phosphotemia showed a significant decrease within the first 20 days. The varying individual hypophosphatemic response proved to be related to the initial level of phosphatemia. The alkaline phosphatase, when increased, showed a decrease to the normal range. A significant decrease in osteoclastic hyperactivity (active resorption surface, osteoclast index) and a slight increase in osteoblastic pool (active osteoid surface) were documented. No change was noted when osteomalacia predominated. Side effects included: anorexia, nausea, vomiting, face flushing. Our data suggest that salmon CT may be usefully employed in chronic uremic patients on RDT, when secondary hyperparathyroidism predominates.

Serum antibody profile against herpesviruses in renal transplant recipients.

Forty-eight renal allograft recipients who had received a kidney graft 2 months to 8 years previously, were followed for the presence of serum antibody against Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes simplex virus (HSV), and Varicella-Zoster virus (VZV). These investigations were performed over a 6 months period and in at least two serum samples from each patient, obtained at intervals of 2-3 months. The presence of serological signs of recent or active infection were observed in 31 patients for CMV, in 22 patients for EBV (18 patients were positive both for CMV and EBV) and only in 3 patients for HSV, while no patients showed serological signs of recent or active infection by VZV.

Effects of different dialysis membranes on lipid and lipoprotein serum profiles in hemodialysis patients.

We measured the serum concentrations of a variety of lipid constituents--total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoproteins A1 and B, and lipoprotein(a)--in well-matched uremic patients undergoing chronic hemodialysis with either cuprophane (n = 13) or polysulfone (n = 13) membranes. We found that the patients on polysulfone membrane dialysis had significantly higher mean HDL cholesterol and apolipoprotein A1 concentrations than the patients on cuprophane membrane dialysis. There were no significant differences in the other variables studied. Moreover, polysulfone membrane dialysis was associated with a lower prevalence of potentially atherogenic lipid abnormalities such as low HDL cholesterol levels and high total cholesterol/HDL cholesterol rations. We concluded that the use of more physiological dialysis procedure may improve, in the long term, lipid and lipoprotein profiles in hemodialysis patients, though the exact mechanism(s) remains unknown.

Nephrotic-range proteinuria in a patient with high renin hypertension: effect of treatment with an ACE-inhibitor.

A 65-year-old man presented proteinuria in the nephrotic range that occurs in the setting of high renin hypertension. Proteinuria persisted after normalizing blood pressure by nifedipine. In contrast, treatment with an ACE-inhibitor (enalapril) resulted in the prompt resolution of the proteinuria. Interestingly, proteinuria relapsed after removing the ACE-inhibition. These observations suggest a causal relation between the overactivity of the renin-angiotensin system in this patient and his proteinuria.

Evolution of serum prealbumin following hemodialysis: effect of different dialysis membranes.

The effects of hemodialysis on the levels of serum prealbumin (pA) were studied on a crossover basis in 17 uncomplicated patients. Bicarbonate dialysate was used exclusively, and two different membranes, cuprophane and polysulfone, were compared. We aimed to prove the induction of an acute-phase response during the procedure. Serum pA, corrected for hemoconcentration, decreased significantly 24 h after the start of cuprophane hemodialysis and returned to the initial value within 48 h. No such change was observed using polysulfone membranes. These results were seemingly correlated with the effects of the membranes on complement activation. It is concluded that cuprophane hemodialysis is indeed associated with an acute-phase response, probably due to interleukin-1 release during the treatment, and that the membrane composition has some role in inducing it. Thus, serum pA analysis may prove useful as an indicator of the biocompatibility of the dialysis procedure.

Serial histomorphometric and histochemical bone biopsy studies in dialysis and transplantation.

A serial bone biopsy longitudinal study has been undertaken to asses the effects of Dialysis and Transplantation on uremic osteodystrophy. The clinical material consists of: normal (24 cases, 61 biopsies), patients with moderate renal failure on free diet (50 c., 61 b.), patients on Low Protein Diet (146 c., 251 b.), patients on Regular Dialysis Treatment (114 c., 256 b.), patients submitted to Transplantation (50 c., 84 b.). A significant correlation has been documented between duration of low protein diet and bone changes. In long-term dialysis patients remarkable differences have been found in "late" dialysis starting time (mean value of creatinine clearance at the beginning of treatment 2.04 +/- 1.7) in respect to "early" starting-time (mean value 13.1 +/- 3.9). In late group bone histomorphometry showed quite evident signs of secondary hyperparathyroidism and hyperosteoidism which remarkably worsened 3-4 years after dialysis. The aminoacids composition of the bone showed an increase in the total amount of aminoacids during dialysis, expecially for proline, hydroxyproline and glycine. In early group both basic values and progression rate of bone lesions were less severe. In transplanted patients with good renal function (serum creatinine less than 1.4 mg%) bone histomorphometric analysis showed a rather rapid disappearance of uremic bone lesions. A significant correlation was found between serum PTH, renal function and bone histology. On some occasions signs of secondary hyperparathyroidism were documented even after 16 months. A good correlation between inactive bone surfaces and immunosuppressive regimen was found.