Online-haemodiafiltration vs. conventional haemodialysis: a cross-over study.

BACKGROUND: The main short-term advantages of haemodiafiltration (HDF) are supposedly better removal of Beta2-microglobulin (ß2-m) and phosphate, and better haemodynamic stability. The main disadvantage is higher costs. The aim of the study was to compare the clinical and biological parameters associated with HDF and high-flux haemodialysis (HD), using a cross-over design, while maintaining the same dialysis parameters. METHODS: All patients on a 3 × 4 hours schedule were observed during 3 identical 6-months periods: HDF1 - HD - HDF2. The mean values for the 2 last months of each period were compared. RESULTS: A total of 51 patients (76 % males, 45 % diabetic) with a mean age of 74 ± 15 years, and who had been on dialysis for 49 ± 60 months were included. The mean blood flow (329 ± 27 ml/min), dialysate flow (500 ml/min), and convection volumes (21.6 ± 3.2 L) were recorded. Patient medications were not changed. Predialysis blood pressure, phosphataemia, calcaemia, iPTH, Kt/V, nPNA and intradialytic events were similar throughout the 3 periods. Only serum albumin (34. 4 ± 3.6, 35.9 ± 3.4, 34.1 ± 4 g/L, p < 0. 0001) and ß2-m serum levels (26.1 ± 5.4, 28 ± 6, 26.5 ± 5 mg/L, p < 0.001, values shown for HDF1, HD, HDF2, respectively) were significantly lower during the HDF periods. Factor associated with higher delta serum albumin levels between HD and HDF periods was mainly a lower convection volume. CONCLUSION: Comparing HDF and HD, we did not observe any differences in haemodynamic stability or in serum phosphate levels. Only serum ß2-m (-6% vs. HD) and albumin (-5% vs. HD) levels changed. The long-term clinical consequences of these biochemical differences should be prospectively assessed.

Induction of rainbow trout MH class I and accessory proteins by viral haemorrhagic septicaemia virus.

Major histocompatibility (MH) class I receptors are glycoproteins which play a critical role during responses to intracellular pathogens by presenting endogenous peptides to cytotoxic T cell lymphocytes (CD8+). To date, little is known about MH class I regulation at the protein level during viral infections in fish. In this study, we characterised the MH class I pathway response to polyinosinic-polycytidylic acid (poly I:C) and upon infection with viral haemorrhagic septicemia virus (VHSV) genotype IVa using the rainbow trout monocyte/macrophage cell line RTS11. A 14-day challenge with VHSV IVa at 14°C demonstrated enhanced expression of the class I heavy chain, ß2 microglobulin (ß2M) and tapasin, while the expression of other accessory molecules ERp57 and calreticulin remained unchanged. However, when infection occurred at 2°C no change in expression levels of any of these molecules was observed. ß2M accumulated in the media of RTS11 over time, however the ß2M concentrations were 2 fold higher in cultures infected with VHSV 14 days post infection. Strikingly, when cells were maintained at 2°C the secretion of ß2M was significantly reduced in both infected and non-infected cultures. These results indicate that VHSV infection alters the kinetics of ß2M release as well as the expression of MH class I and suggests that cellular immunity against VHSV can be compromised at low temperatures which may increase host susceptibility to this virus during the winter.

Predicting survival in chronic lymphocytic leukemia.

There is increasing interest in the use of prognostic markers that may predict survival and guide management in patients diagnosed with the early stages of chronic lymphocytic leukemia (CLL). Currently, the most important traditional prognostic factors include clinical staging, lymphocyte doubling time and ß2-microglobulin/thymidine kinase; and the most important novel markers include karyotypic aberrations (typically assessed by FISH probes or CpG oligonucleotide karyotyping) and IgVH mutation status. Although each of these factors have individually shown significant correlations with survival, there is increasing appreciation that the most complete information may be obtained by using a combination of several factors in prognostic normograms or models. In this article, we review the current state-of-the-art with regards to CLL prognostic factors and discuss how they can be applied in the clinic.

Amyloidosis and its impact on patients with ESRD.

Patients, like those with ESRD, who have lost the ability to filter excess proteins from their bodies are at risk to develop beta-2-microglobin amyloidosis, also known as dialysis-related amyloidosis (DRA). When the kidneys do not work efficiently, a protein called beta-2-microglobulin can build up in the blood. Eventually, these molecules can form large deposits and potentially damage surrounding tissues. Currently, dialyzer membranes do not effectively remove these large molecules and, as the blood levels become elevated, deposits begin forming in bone, joints, and tendons resulting in pain and/or stiffness. Unfortunately, there is no known cure for DRA, although attempts are being made to develop dialyzer membranes that can more efficiently remove beta-2-microglobulin from the blood. Implications for practice include early diagnosis, patient teaching, optimal pain management and fall risk management.

Assessment of bone metabolism in cadmium-induced renal tubular dysfunction by measurements of biochemical markers.

Bone metabolism related to the severity of cadmium (Cd)-induced renal tubular dysfunction (RTD) was assessed by measuring several bone biochemical markers. Fifty-three female subjects with RTD aged 65-76 years (mean 70.0+/-3.3 years) and who lived in the Cd-polluted Jinzu River basin in Toyama, Japan were studied. Bone alkaline phosphatase (bone-ALP), intact bone Gla-protein (intact-BGP) and carboxy-terminal propeptide of type I collagen (PICP) in serum as bone formation markers and pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in urine as bone resorption markers were measured. All markers of bone turnover were increased and significantly correlated with each other, suggesting that bone formation and resorption were coupled and increased in Cd-induced RTD. Fractional excretion of beta(2)-microglobulin (beta(2)-m, FE(beta 2-m)) as an index of severity of Cd-induced RTD was extremely varied ranging from 0.45 to 53%. There were no significant correlations between FE(beta 2-m) and each of the five bone biochemical markers. The bone turnover in Cd-induced RTD appeared to be determined by the glomerular filtration rate (GFR): in subjects with GFRs above 50 ml/min, the levels of bone-ALP or intact-BGP tended to be inversely related to the GFRs, whereas in subjects with GFRs below 40 ml/min, those levels tended to decrease. These results suggest that the bone turnover, in particular the bone formation, was influenced by renal tubular function as assessed by the levels of GFR in Cd-induced RTD.

Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media.

To determine whether there are early renal function parameters (RFP) which can be monitored to rapidly detect nephrotoxicity induced by contrast media (CM), we observed RFP in 16 patients with normal renal function before and after administration of CM. Forty-eight hours after diatrizoate meglumine administration, blood urea nitrogen (BUN) and serum creatinine (SCr) increased (p < 0.05). In all patients, acute tubular damage was revealed by early urinary RFP. Increases in levels of serum angiotensin-I-converting enzyme (ACE), beta(2)-microglobulin (beta(2)M) and urinary albumin (Alb) were associated with alterations in glomerular function. The changes in early RFP occurred earlier than those of BUN and SCr. The present study demonstrates that serum ACE, beta(2)M, urinary Alb, gamma-glutamyl-transpeptidase and N-acetyl-beta-D-glucosidase are sensitive parameters for the early assessment of subclinical nephrotoxicity induced by CM.

Quantitative assessment of serum beta-2-microglobulin in liver transplant recipients and relationship to liver graft rejection.

OBJECTIVE: To investigate the usefulness of serum beta 2-microglobulin determination in the diagnosis of acute liver allograft rejection. DESIGN: Prospective study. SETTING: Liver transplant unit. PATIENTS: Twenty consecutive patients who underwent liver transplantation because of a non-virus-related end-stage liver disease. METHODS: Serum samples were collected before the transplant, at days 7, 30 and 90 and whenever a clinical complication developed after liver transplantation. beta 2-Microglobulin was quantified using a new quantitative automated microparticle enzyme immunoassay. RESULTS: Serum beta 2-microglobulin levels increased significantly (P < 0.05) during rejection episodes and correlated with the degree of hepatocyte injury as assessed using serum aspartate aminotransferase levels. Increased beta 2-microglobulin levels were also found in surgical or infectious post-transplant complications. A significant difference in beta 2-microglobulin values was recorded between patients with rejection and only those with bacterial sepsis. CONCLUSION: Although highly sensitive in recognizing damage to the graft, determination of beta 2-microglobulin was not sufficiently specific to differentiate between rejection and other post-transplantation complications.

Cross-sectional assessment of renal function in the inhabitants of a cadmium-polluted area.

To understand the development of cadmium (Cd)-induced renal tubular dysfunction, cross-sectional assessment of renal function in the inhabitants of the Cd-polluted Jinzu River basin in Toyama, Japan, was carried out. Sixty-seven men and 78 women, aged 56 to 71 years whose urinary beta 2-microglobulin (beta 2-m) exceeded 1,000 micrograms/g creatinine, were examined and divided into five groups according to their values of fractional excretion of beta 2-m (FE beta 2-m). Comparisons were made between six groups including the inhabitants of a non-polluted area as a reference group. Significantly increased values of fractional excretion of urate (FEUA), calcium (FECa), sodium (FENa), and chloride (FECl), serum creatinine and beta 2-m, and urinary protein were detected even in the subjects with FE beta 2-m level below 1 percent compared with the reference group. Fractional phosphate reabsorption (percent TRP) was significantly decreased in the subjects with FE beta 2-m level above 10 percent. Creatinine clearance (CCr) decreased with increase in FE beta 2-m, and the subjects with FE beta 2-m above 30 percent showed significantly decreased CCr values compared to those with FE beta 2-m below 30 percent. In summary, FEUA, FECa, FENa, and FECl, as well as low-molecular-weight proteins such as beta 2-m, are increased in the early stage of Cd-induced renal tubular dysfunction. Although percent TRP was maintained by the decreased CCr, there was a marked decrease in percent TRP in subjects with progressive stage showing FE beta 2-m level above 10 percent. No sex difference in renal tubular dysfunction was found in this cross-sectional study.

Structure of dialysis membranes and long-term clinical outcome.

The present comparative evaluation aims at establishing whether the basic structure of dialysis membrane is able to predict long-term clinical outcome. From a population of 1,256 patients on renal dialysis treatment, treated by the Institute of Nephrology and Dialysis of the St. Orsola University Hospital of Bologna from 1963 to 1993, 122 patients were retrospectively selected for the present study. Patients were divided into two different groups according to the kind of dialysis membrane used--cellulose-based (64 patients) and synthetic-based (58 patients) membranes. The parameters considered were: intradialytic biology, long-term biocompatibility, survival and morbidity, and cost/benefit. The results obtained demonstrate that cellulosic membranes can be said to cause a greater acute intradialytic biological response than synthetics, though not to a significant degree. There are, however, no significant differences in the biological changes from group to group. Nonsignificant differences were noted in long-term survival general morbidity. In terms of sheer cost, synthetic membrane treatment is anything up to 200% dearer than cellulosic.

Monte Carlo study of the effect of beta 2-microglobulin on the binding cleft of the HLA-A2 complex.

Peptide recognition by class I products of the major histocompatibility complex requires association of the class I heavy chain with beta 2-microglobulin. We present results of Monte Carlo simulations of the beta-pleated sheet floor of the human class I MHC molecule, HLA-A2, with and without beta 2-microglobulin. We find a significant effect of beta 2-microglobulin on the side chains of residues near a region that would accommodate the C-terminus of a bound peptide. By modeling simultaneously each loop and its neighboring strand at either end of the class I cleft, we find that beta 2-microglobulin restricts the conformational space of residues that are central to binding peptides. The effect is most pronounced for R97 and H114 and somewhat less important for Y99 and Y116, the latter forming strong hydrogen bonds with neighboring residues in the heavy chain itself.