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Faced with the shortcomings of conventional dialysis on a long-term basis, as illustrated by the dialysis-related pathology, a need for a new strategy exists to improve the overall quality of treatment in end-stage renal failure (ESRF) patients. On-line haemodiafiltration (HDF) seems to be the best therapeutic option to achieve this goal at the present time. By enhancing convective clearances through highly permeable membranes, HDF offers the greatest solute fluxes both for low and higher molecular weight uraemic toxins. As for example, in our routinely performed HDF programme based on 3 weekly sessions lasting 3-4 h each, double-pool urea Kt/V achieved was 1.55+/-0.20 and beta2-microglobulin Kt/V was 0.91. By producing substitution fluid from fresh dialysate, the technique of HDF is simplified and becomes economically affordable. By improving the haemodynamic tolerance, HDF allows more elderly and high risk cardiovascular patients to be treated more safely. By using bicarbonate-buffered infusate, HDF facilitates the correction of acidosis. Both by using ultrapure bicarbonate dialysate and down-regulating the membrane reactivity via a 'protein cake', HDF introduces the first step for a full haemocompatibility concept. Finally, by giving access to virtually unlimited amounts of sterile and non-pyrogenic fluid, HDF should introduce new therapeutic options such as a totally automated and feed-back-controlled machine. Today's on-line HDF is already a step forward to enhance the overall efficacy of renal replacement therapy and to improve the global care of ESRF patients.

Background: Recent approaches to prevent and treat secondary hyperparathyroidism in dialysis patients include decreasing dialysate Ca content from 1.75 to 1.5 mM or lower. We have recently observed that by decreasing dialysate Ca to 1.25 mM a rise in intact parathormone serum levels occurs despite adequately controlled predialysis Ca and phosphate serum levels. In that study complementary treatment with high-dose 1 alpha(OH) vitamin D3 was required to suppress the parathormone. In the present study we aimed to assess the total Ca balance as well as the modifications in parathormone induced by the dialysis session in order to understand the reasons for which the rise in parathormone was induced., Methods: Fourteen HD patients treated with haemodiafiltration three times/week gave their informed consent for the study. They were distributed in two groups with identical treatment but for the dialysate Ca content which was 1.5 and 1.25 mM respectively and for the amount of oral CaCO3 received. Total and ionized Ca, phosphate, pH, and albumin as well as parathormone were measured in serum before and after dialysis and in the spent dialysate during two dialysis sessions., Results: Serum ionized Ca (normalized to pH 7.4) did not change during 1.25 mM dialysate Ca and significantly increased with 1.5 mM (P < 0.001). The end-dialysis values being 1.25 +/- 0.02 and 1.38 +/- 0.02 mM respectively. Total Ca significantly decreased with 1.25 mM dialysate Ca (P < 0.04) and increased with 1.5 mM (P < 0.003), the end-dialysis values being 2.51 +/- 0.03 and 2.75 +/- 0.04 mM respectively. In the dialysate the difference in ionized Ca concentrations, fresh minus spent dialysate was -1.78 +/- 1.12 mmol/l (NS) and 4.26 +/- 1.47 mmol/l (P < 0.02) respectively for 1.25 and 1.5 mM dialysate Ca. The difference in total Ca concentrations, fresh minus spent dialysate was -0.1 +/- 0.01 mmol/l (P < 0.05) and -0.002 +/- 0.01 mmol/l (NS) respectively. Phosphate removal was higher in 1.25 mM dialysate-Ca-treated patients (40.4 +/- 1.75 mmol/session versus 34 +/- 1.3 mmol/session respectively, P < 0.015). The use of 1.25 mM dialysate Ca did not result in a change in serum parathormone, while the use of 1.5 mM resulted in a decrease of 43 +/- 15% (P < 0.02) in patients with marked hyperparathyroidism., Conclusions: Our data remind us of the difficulty in assessing Ca balances and identifies the phosphate content as one of the factors influencing the amount of ionized Ca in the dialysate. Although the long-term parathormone increase we observed using 1.25 mM dialysate Ca may well not be explained only by the acute intradialytic modifications, the negative Ca balance identified here (which was missed with the analysis of ionized Ca alone), and the lack of parathormone inhibition may participate in the relapse of hyperparathyroidism.

While the mathematical modelling of urea kinetics is in wide use for evaluating treatment adequacy and protein nutrition in dialysis patients, the kinetics of creatinine generation in dialysis patients has been relatively unexplored. In this study creatinine kinetic modelling as a clinical tool was investigated in a group of 90 patients treated by haemodialysis (n = 20), haemodiafiltration (60), haemofiltration (7), or biofiltration (3) over a 6-36-month period. A single pool model of creatinine kinetics was employed to obtain monthly values of creatinine distribution space and creatinine appearance rate. Extrarenal creatinine degradation rate, estimated using a clearance of 0.038 l/kg/24 h as suggested by Mitch and co-workers, was added to creatinine appearance rate in urine and dialysate to calculate a corrected creatinine index (CI). Extrarenal degradation accounted for 12 +/- 2% of CI. CI was higher in males (22.4 +/- 4.5 mg/kg/24 h) than females (19.8 +/- 4.8) and decreased with age, falling off more sharply for the female group (CI = 29.9-0.185.age, R = 0.72) than the males (CI = 24.1-0.030.age, R = 0.31). CI was found to correlate strongly with protein catabolic rate determined by urea kinetic modelling (CI = 8.84 +/- 10.91.PCR). Low or reduced CI was associated in this study group with severe malnutrition status and high mortality rate. CI is suggested as a strong predictor of patient morbidity and mortality.

Leukocyte activation during haemodialysis (HD) was evaluated by reactive oxygen species (ROS) production and cell surface markers expression (CD11b: C3bi receptor and CD25: IL2 receptor). Eight end-stage renal disease patients were exposed to three dialysis phases according to a A/B/A protocol study. During phase A polysulphone (PS) membranes were used and during phase B cuprophane (CU) membranes were used. Each phase lasted 3 weeks. Timed samples were collected during the last session of each phase at 0, 15, and 30 min of HD. Flow cytometry analysis was performed both on monocytes (MO), polymorphonuclears (PMN), and lymphocytes (Ly). Hydroethydine was used as a marker of cell-ROS production. Specific monoclonal antibodies were used to analyse the cell surface markers. CU increased ROS production in PMN and MO by 10- and 2.4-fold respectively and had no significant effect on Ly. CU enhanced 16-fold CD11b expression on PMN, and increased also CD11b and CD25 expression on MO by 7- and 40-fold respectively. On the contrary, PS did not affect either ROS production or cell surface markers expression in MO, PMN, Ly. We conclude that oxydative metabolism and cell surface markers expression of PMN and MO were significantly increased with cuprophane membranes and not with polysulphone membranes, suggesting that complex cell-cell interactions were involved in membrane-related bioincompatibility phenomena.

The estimation of Kt/V by utilization of the pre- and postdialysis urea concentrations (per cent reduction in urea and In(Upre/Upost)) provides a simple, quick technique that can be applied at the bedside. However, the accuracy of such techniques has been questioned. One possible reason for this inaccuracy may be the frequently observed postdialysis rebound in serum urea. We assessed the urea rebound at 30 min postdialysis in 34 haemodiafiltered patients and compared the calculation of Kt/V using this urea concentration with that using the immediate postdialysis concentration. These results were then compared to the Kt/V calculated by urea kinetic modelling (UKM), also utilizing the delayed serum urea concentration. The degree of urea rebound observed was large, 21.4%, being a reflection of the short-duration, rapid-flux dialysis. The formulae for calculation of Kt/V all significantly correlated with Kt/V by UKM but all gave results significantly different from Kt/V by UKM (P < 0.001 by paired t test). For assessment of Kt/V by these formulae or by UKM, the urea rebound is too large to ignore in the setting of short-duration, rapid-flux dialysis.

The pathogenesis of dialysis related amyloidosis remains unresolved despite the identification of beta 2-microglobulin (beta 2M) as the major protein constituent, as well as other proteins being present in the deposits. Among the latter we have assessed the serum concentrations of alpha 2-macroglobulin (alpha 2M) both in the baseline stage and during the haemodialysis (HD) procedure. We have also assessed the influence of the membrane on alpha 2M kinetics. Fifteen HD patients with histologically proven dialysis-related amyloidosis (DRA group) and 15 HD patients clinically and radiologically considered dialysis-related amyloidosis free (control group) were included in the baseline study. Blood was sampled the day before the second dialysis of the week and alpha 2M, beta 2M and alpha 1 antitrypsin were determined along with the routine biological analysis of these patients. Serum alpha 2M was greater in dialysis-related amyloidosis than in control patients (t = 2.35; P < 0.026). Serum beta 2M was similar in both groups. The serum alpha 2M and beta 2M correlated in patients with dialysis-related amyloidosis (r = 0.64; P < 0.01), while no correlation was found in controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis-related amyloidosis as the dependent variable retained the serum alpha 2M concentration as the first variable in the model (F = 4.4; partial r = 0.38; P < 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Since the identification of beta 2 microglobulin (beta 2-M) in haemodialysis-associated amyloidosis, the biochemical characterization of the different forms of beta 2-M has been sought by several groups. New beta 2-M isoforms (pI 5.1 and lower) have been identified in amyloid deposits, and it has been suggested that they are of pathogenetic importance. The finding of N-terminal proteolysed beta 2-M in amyloid deposits prompted the hypothesis that proteolysis would render beta 2-M more amyloidogenic. Finally, a 'novel beta 2-M' (pI 5.2) with a single amino acid replacement (Asn by Asp at position 17) has been reported as possibly specific for patients with dialysis associated amyloidosis, and consequently proposed as 'the amyloidogenic' form. We purified beta 2-M from serum of a newly haemodialysed patient and from urine of a transplanted patient in the early recovery period. Both patients were clinically amyloid free. Three pure isoforms were obtained from serum (pI 5.7, 5.3, and 5.1) and only two from urine (5.7 and 5.3). Further purification of each isoform was obtained by HPLC in a C4 column. Sequence analysis showed that all isoforms had an intact N-terminus. Tryptic digestion of the serum isoforms was performed after alkylation with iodoacetic acid and the peptides were isolated by HPLC in a C18 column. The 5.3 and 5.1 isoforms had identical peptide patterns with the appearance of an early peak missing in the 5.7 form. The sequence of this peptide showed a replacement of the D 42 (Asp 42) by N (Asn) after K41 (Lys 41).(ABSTRACT TRUNCATED AT 250 WORDS)

In an attempt to return to normal serum beta 2-microglobulin levels in a group of seven ESRD patients, a programme of daily HF with highly permeable AN69 membranes was undertaken. Pre-HF beta 2-M serum levels stabilized after 4 days at 20 mg/l, only 40% lower than the initial concentration. A total of 985 +/- 20 mg beta 2-M was removed over the week. The beta 2-M release rate averaged 97 micrograms/min with a broad range of values (63-128 micrograms/min). beta 2-M release peaked at 602 micrograms/min 1 h after the end of the HF session before returning to baseline by 12 h post-HF. We conclude that a return to normal blood beta 2-M concentrations in ESRD patients seems quite unrealistic despite a highly intensive extracorporeal therapy. Therefore other therapeutic alternatives have to be designed to prevent or cure beta 2-M amyloidosis.

In this study we evaluate the effectiveness of a newly available peroxyacetic acid solution (Dialox) as a disinfecting agent in the re-use of highly permeable dialysers. The germicidal properties of Dialox were tested in an in vitro trial on previously used haemodiafilters (HF80, Fresenius) highly contaminated with Pseudomonas aeruginosa, Mycobacterium smegmatis or sporulated Bacillus cereus. Complete freedom from bacterial contamination was observed 5 min after the reprocessing treatment on a Renatron reprocessing machine, using the currently marketed Dialox concentrate.

Deterioration of renal function is a major concern during treatment by converting enzyme inhibitors of hypertensive kidney recipients with transplant renal artery stenosis. However, there has been no assessment of the frequency of this complication and its specificity for converting enzyme inhibitors as compared to other antihypertensive drugs. The effect of acute administration of captopril on mean arterial pressure, glomerular filtration rate (GFR) (creatinine clearance) and effective renal plasma flow (clearance of 131I-hippuran) was assessed in eight hypertensive patients with transplant renal artery stenosis. Captopril induced a decrease in mean arterial pressure (128 +/- 6-121 +/- 7 mmHg) and a reduction in GFR (59 +/- 8-44 +/- 8 ml/min per 1.73 m2, P less than 0.05). The decrease in GFR was observed in seven out of eight patients and varied between 0% and 100% of the pre-captopril value. Effective renal plasma flow was maintained (157 +/- 47-141 +/- 24 ml/min per 1.73 m2) and filtration fraction decreased by 15 +/- 7%. The effect of captopril was compared to that of nifedipine (N = 20 mg) in four patients. Despite a larger decrease in mean arterial pressure (130 +/- 7-109 +/- 10 mmHg), no reduction in GFR was observed (68 +/- 13-71.4 +/- 8). Effective renal plasma flow was unchanged and filtration function slightly increased. Surgical or percutaneous transluminal angioplasty in five patients suppressed the captopril-induced decrease in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)