[Two-chamber hemodiafiltration: comparison between exogenous reinfusion (PFD) and endogenous reinfusion (HFR)]. / Emodiafiltrazione a doppia camera: confronto fra reinfusione esogena (PFD) e reinfusione endogena (HFR).

PURPOSE: This research aimed to compare two highly efficient dialysis techniques, paired filtration dialysis (PFD) and on-line hemodiafiltration with endogenous reinfusion (HFR) to evaluate the possible differences from a clinical, rehabilitative and managerial point of view. METHODS: The study was carried out on 14 patients (aged 40-65 yrs) six patients underwent PFD and eight patients underwent HFR. Patients on PFD came from low-flux hemodialysis (HD), while patients on HFR came either from PFD (n=5) or from low-flux HD (n=3). The research was based on the evaluation of patients inverted exclamation mark parameters (depurative and biochemical, level of clinical, medical and social rehabilitation) and of management parameters (technological aspects, cost analysis and medical-legal issues). RESULTS: HFR treatment improved plasmatic albumin values (> or =4.0 g/dL) and had a lower resistance to recombinant human erythropoietin (rHuEPO) therapy (by reducing the rHuEPO doses to reach the maintenance target values of hemoglobin (Hb) although both therapies resulted in equal depurative efficiency, and improved patient rehabilitation. CONCLUSIONS: This preliminary research, which requires further confirmation, demonstrates that HFR seems to provide PFD with other positive benefits and offers the uremic patient a better life style.

Recombinant human erythropoietin resistance in hemodialysis. Effects of paired filtration dialysis.

A percentage of hemodialysis (HD) patients are resistant to recombinant human erythropoietin (rHuEPO), a phenomenon that occurs less frequently in patients dialyzed with biocompatible membranes (M) and in peritoneal dialysis. The authors evaluated the effects of paired filtration dialysis (PFD)--a dialysis technique based on the use of an emophan M in conjunction with a polysulphone M--on erythropoiesis in HD patients resistant to rHuEPO. Twelve HD patients with anemia resistant to long-term therapy with rHuEPO (200.24 U/kg body weight three times per week intravenously for 10.2 months) were studied. Patients had been treated for an average of 46.9 months with bicarbonate HD, using cuprophan M (Phase A) and, successively, for 12 months by PFD (Phase B). The following parameters were evaluated monthly: 1) hemoglobin and hematocrit values; 2) serum levels of erythropoietin (EPO); and 3) serum levels of interleukin (IL)-3, IL-6, IL-10, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). At the end of Phase A and Phase B, patients underwent bone marrow biopsies to evaluate 1) bone marrow burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) proliferative capacity, and 2) bone marrow mononuclear cell EPO-receptor (EPO-R) number. During Phase B, there was a progressive rise in hematocrit and hemoglobin values, so that within the sixth month, the rHuEPO dose was reduced to 80 +/- 15 U/kg body weight three times per week. At the same time, an increase in serum IL-3, IL-6, and IL-10 levels was seen, whereas serum IL-1 beta, TNF-alpha, and IFN-gamma levels decreased. This was accompanied by a rise in BFU-E and CFU-E growth and in bone marrow mononuclear cell EPO-R number. During Phase B, after the dialysis session, serum EPO levels increased by about 30% in comparison with pre dialysis values, whereas during Phase A they decreased by about 14%. In HD patients, EPO resistance may caused either by absorption of rHuEPO to the cuprophan M, or an increased release of cytokines that inhibit erythropoiesis, such as IL-1 beta, TNF-alpha, and IFN-gamma, and to a decrease in stimulatory cytokines such as IL-3, IL-6, and IL-10. These negative phenomena are reversed by the use of biocompatible dialysis techniques such as PFD.

Peritoneal dialysis effluent, cytokine levels, and peritoneal mesothelial cell viability in CAPD: a possible relationship.

Recent studies have emphasized the role of peritoneal mesothelial cell (PMC) in peritoneal immune defense mechanisms in continuous ambulatory peritoneal dialysis (CAPD). The aim of this study was to evaluate a possible relationship between peritoneal dialysis effluent (PDE), cytokine (Cy) levels, and PMC viability and their impact on peritonitis morbidity. Fifteen patients initiating CAPD for end-stage renal failure participated in the study. The following parameters were evaluated: (1) the levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-8 (IL-8) in PDE samples taken 7 days after initiating CAPD, at the end of the first, third, and sixth month of CAPD (determined by a solid phase enzyme amplified sensitivity immunoassay EASIA); (2) peritoneal mesothelial cell viability [determined by the release of lactate dehydrogenase (LDH) and by trypan blue extrusion test] by isolating and culturing peritoneal mesothelial cells at the moment of the placement of the peritoneal catheter and at the sixth month of CAPD; (3) peritonitis incidence during the 24 months after starting CAPD. At the first month of CAPD in all patients there was a slight increase in PDE IL-1 beta and TNF-alpha levels, while other Cy were almost undetectable. Time course studies showed that in 10 patients (Group I) there was a significant increase in PDE levels of IL-6, IL-8, and INF-gamma (p < 0.0005) in comparison to other Cy and a good PMC viability. In the other 5 patients (Group II) there were higher PDE levels of IL-1 beta and TNF-alpha (p < 0.0005). This was associated with a marked reduction in PMC viability determined by the release of LDH and by the trypan blue extrusion test. During the 24 months after starting CAPD, incidence of peritonitis was one episode per 24 patient-months in Group I and one episode per 9.2 patient-months in Group II. Our results show that from the beginning of CAPD there are distinct patterns of Cy in the PDE that correlate with a different PMC viability and peritonitis morbidity. Thus the analysis of the above-mentioned parameters may be useful in the early identification of the risk of peritonitis, thus allowing preventive measures.

Two years of experience with a new device system: a multicenter study.

Peritonitis is a crucial complication of peritoneal dialysis. Over the last few years, new device systems have been developed to reduce episodes of peritonitis caused by exogenous contamination. Remarkable improvement has been obtained by modifying the original connection between the catheter and the bag with the introduction of the Y-set. The aims of this study were to test the reliability and simple use of a double-bag system without disinfectant in-line (Gemini, Gambro) and to evaluate the incidence of peritonitis in a 2-year period of follow-up. In a group of 167 patients, enrolled in 14 dialysis units in Italy, with a follow-up of 2433 patient-months, we observed 82 episodes of peritonitis in 52 patients, with a cumulative incidence of 1 episode every 29.7 patient-months. At 12 months the percentage of patients peritonitis-free was 69.7%, and at 24 months it was 62.8%. The training to complete the bag exchange, assessed by patient and nursing staff, was defined as "easy" in 61% of the cases and "difficult" in only 12% of the cases. The percentage of patients requiring a partner was 23%. For patients this device system presents easy handling in terms of the bag exchange, and it may prevent peritonitis.

Low Ca2+ dialysate. Effects on bone metabolism in the course of paired filtration dialysis.

To evaluate the 1-year effects of PFD performed with low Ca2+ dialysate (1 mmol/l) on calcium metabolism and on bone disease, the authors studied in eight patients who were previously treated with PFD performed with standard Ca2+ dialysate (1.75 mmol/l). On samples from these subjects, the following were evaluated: 1) serum Ca2+ and PO4 levels, 2) serum PTH levels, 3) serum Al levels, and 4) bone morphology. All the patients were hypercalcemic, four with high serum PTH levels (high turnover bone disease, group 1) and four with low serum PTH levels (low turnover bone disease, group 2). In both groups, a decrease in serum Ca2+ and an increase in serum PTH was observed within the third month. In group 2, PTH levels reached the normal range. Because serum Ca2+ levels decreased to normal in both groups, it was possible to administer oral CaCO3 (10.5 +/- 2 g/day) to control serum PO4 and to stop Al gels. This did not induce any increase in serum Ca2+, whereas serum Al fell significantly. In group 1, to prevent a further rise in PTH, patients were treated with intravenous calcitriol (5 +/- 2 micrograms/week). This induced a reduction in the serum PTH without increasing serum Ca2+ or PO4. Within 12 months, an improvement in bone morphology was seen in both groups. It is concluded that the use of low Ca2+ dialysate corrects hypercalcemia in patients with PFD treated with high oral doses of CaCO3, and improves low turnover bone disease. The combination of low Ca2+ dialysate and intravenous calcitriol also improves high turnover bone disease.

Peritoneal dialysis solution pH and Ca2+ concentration regulate peritoneal macrophage and mesothelial cell activation.

We evaluated the in vitro effects of pH and Ca2+ concentration of peritoneal dialysis solution (PDS) on (1) the release of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) from peritoneal macrophages (PM0) and peritoneal mesothelial cells (PMC); (2) the release of IL-6 and IL-8 by PMC; and (3) the PM0 and PMC intracellular Ca2+ concentration. Aliquots of 5 x 10(6) PM0 and PMC were incubated (2 hr, 37 degrees C) in 1 ml of physiologic growth medium (RPMI 1640) and in 1 ml of four different PDS (1.36 g/dl glucose): (1) type A PDS (pH 5.5, Ca2+ 1.75 mM), (2) type B PDS (pH 5.5, Ca2+ 1.25 mM), (3) type C PDS (bicarbonate buffered pH 7.4, Ca2+ 1.75 mmol/L, and (4) type D PDS (bicarbonate buffered pH 7.4, Ca2+ 1.25 mM); each was stimulated with S. epidermidis. Results showed that type A PDS samples induced an average 60% increase in PM0 and PMC cytoplasmic levels and in cytokine release, whereas with type B PDS samples there was a 90% decrease. Type C PDS samples did not modify the PM0 and PMC IL-6 and IL-8 production, whereas a 3-fold rise in the production of IL-1 and TNF-alpha by PM0 was seen; this was associated with an increase in PM0 and PMC Ca2+ cytoplasmic levels. When type D PDS samples were incubated, however, there was an average 40% decrease in PM0 and PMC cytoplasmic Ca2+ levels and in cytokine release.(ABSTRACT TRUNCATED AT 250 WORDS)

A biocompatibility study on peritoneal dialysis solution bags for CAPD.

Numerous factors related to the composition of peritoneal dialysis solutions (PDS) contribute to the pathogenesis of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD). They include high osmolarity, low pH, and the presence of lactate, which may be responsible for stimulating the proliferation of peritoneal fibroblasts (PF) and for the toxicity on the peritoneal mesothelial cells (PMC). Similar effects could be hypothesized for the plasticizers released from the PDS bags, usually made of polyvinyl chloride (PVC), such as the acid esters of phthalic acid, particularly bis-(2-ethylhexyl) phthalate (BEHP). Recently, however, new BEHP-free bags (Clear-Flex, Bieffe, Italy) made of three layers (polyethylene, nylon, and polypropylene) have been introduced. The aim of this work is to evaluate in vitro the effects of samples of PDS contained in PVC bags (Bieffe) and in Clear-Flex bags on the proliferative capacity of peritoneal fibroblasts and peritoneal mesothelial cells, and the release of interferon gamma (IFN gamma), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) from peritoneal T lymphocytes (PTLs) and macrophages (PM phi s). Results have shown that in the presence of PDS samples contained in PVC bags, the proliferative capacity of peritoneal fibroblasts was higher than in Clear-Flexbags. There was also an increased release of IFN-gamma and IL-1 from PTLs and PM phi s (cytokines that stimulate the collagen synthesis) and a decreased release of PGE2 (cytokines which inhibit the collagen synthesis). An inhibiting action on peritoneal mesothelial cells was also seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Ca2+ concentration in the peritoneal dialysis solution regulates peritoneal fibroblast proliferation and peritoneal macrophage and lymphocyte cytokine release.

Peritoneal fibrosis remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis (CAPD), because it reduces ultrafiltration capacity. Since studies in vitro have demonstrated that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, we evaluated in 8 uremic patients at the start of CAPD and in 4 control patients the effects in vitro of different peritoneal dialysis solution Ca concentrations (1, 1.25, 1.75, and 2 mmol/L) on peritoneal fibroblast (PF) proliferation, peritoneal macrophages (PM phi), and peritoneal lymphocyte (PLy) release of interleukin-1 (II-1) and interferon-gamma (IFN-gamma) (cytokines which are known to induce PF proliferation), and cytoplasmic Ca2+ concentration in PF, PM phi, and PLy. Results showed that in both the uremic and control patients, increasing the dose of Ca2+ in the medium induced a dose-dependent increase in PF proliferation and the release of IL-1 and IFN-gamma from PM phi and PLy. Meanwhile, the cytoplasmic parameters PF, PM phi, and PLy Ca2+ in the uremic patients were below normal; they exceeded the norm with a Ca2+ concentration of 1.75 and 2 mmol/L and were normal with a Ca2+ concentration of 1.25 mmol/L. These data suggest that in CAPD patients the use of a physiological Ca peritoneal dialysis solution (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma thus preventing peritoneal sclerosis.

Low- and high-turnover bone disease in continuous ambulatory peritoneal dialysis: effects of low-Ca2+ peritoneal dialysis solution.

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (Al) intake. By maintaining high serum Ca2+, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. In order to evaluate the effects of a low-Ca peritoneal dialysis solution (PDS) (1.25 mmol/L) on Ca metabolism, we studied the following in 12 continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (6 with low PTH levels, low-turnover bone disease, group 1, and 6 with high PTH levels, high-turnover bone disease, group 2, documented by bone biopsies): serum Ca2+; serum PTH; bone morphology. The follow-up was 12 months. Results show that in both groups within the third month there was a decrease in serum Ca2+. In group 1 serum PTH increased, reaching the norm, and in group 2 it further increased exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to increase oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels and to stop Al gels. In group 2, in order to avoid the further rise of serum PTH, the low-Ca PDS was supplemented with 2 micrograms/day of 1,25(OH)2D3 (vitamin D3); this was followed by a reduction in serum PTH with no increase in Ca2+ and PO4. The use of low-Ca PDS may be useful in preventing hypercalcemia in CAPD patients treated with high oral doses of CaCO3 and in improving low-turnover bone disease, while low-Ca PDS supplemented with vitamin D3 improves high-turnover bone disease.

Peritoneal dialysis solution calcium concentration regulates peritoneal fibroblast proliferation in CAPD.

Peritoneal fibrosis remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis (CAPD), by reducing ultrafiltration capacity. Since studies in vitro have shown that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, eight uremics and four controls at the start of CAPD were evaluated for the in vitro effects of different peritoneal dialysis solution (PDS) Ca2+ concentrations (1, 1.25, 1.75, and 2 mmol/L) on: 1) peritoneal fibroblast (PF) proliferation; 2) peritoneal macrophage (PM) and peritoneal lymphocyte (PL) release of interleukin-1 (IL-1) and interferon-gamma (IFN-gamma)--cytokines that are known to induce PF proliferation; and 3) cytoplasmic Ca2+ concentrations in PF, PM, and PL. Results showed that in both the uremics and controls, increasing the dose of Ca2+ in the medium induced a dose-dependent rise in PF proliferation, and in the release of IL-1 and IFN-gamma from PM and PL. Meanwhile, the cytoplasmic Ca2+ concentration of PF, PM, and PL also increased. With a PDS containing 1 mmol/L of Ca2+ in the uremics, these parameters were below normal; they exceeded the norm with a Ca2+ concentration of 1.75 and 2 mmol/L, and were normal with a Ca2+ concentration of 1.25 mmol/L. These data suggest that in CAPD patients, the use of a low Ca2+ PDS (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma from PM and PL, thereby preventing peritoneal sclerosis.

Low calcium peritoneal dialysis solution. Effects on calcium metabolism and bone disease in CAPD patients.

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (AI) intake. By maintaining high serum Ca2+ levels, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. To evaluate the effects of a low Ca2+ peritoneal dialysis solution (PDS; 1.25 mmol/L) on calcium metabolism, the following were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (six with high PTH levels, and high turnover bone disease [Group 1], and six with low PTH levels, and low turnover bone disease [Group 2] documented by bone biopsies): 1) serum Ca2+ and PO4 levels; 2) serum PTH levels; 3) serum AI levels; and 4) bone morphology. The follow-up was 12 months. In both groups, within the third month, there was a decrease in serum Ca2+. In Group 2, serum PTH increased, reaching the norm, and in Group 1 it further increased, exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to give oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels while stopping AI gels. This did not induce any increase in serum Ca2+, whereas serum AI fell significantly. In Group 1, to avoid a further rise of serum PTH, the low Ca2+ PDS was supplemented with calcitriol (mean 3.5 +/- 0.5 microgram/day); this was followed by a reduction in serum PTH with no increase in serum Ca2+ or PO4.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetate free biofiltration. Effects on peripheral blood monocyte activation and cytokine release.

Acetate free biofiltration (AFB), a new hemodiafiltration (HDF) technique characterized by a buffer free dialysate and postdilution infusion of a sterile HCO3 solution, was recently proposed as an alternative to HDF performed with acetate or bicarbonate dialysate. To evaluate the effects of dialysate buffer on immune cell activation, release of interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) from peripheral blood monocytes was studied in 12 uremic patients before and after HDF with polyacrylonitrile membranes (Filtral 12, Hospal Laboratories, Bologna, Italy) and consecutive dialysis with acetate, bicarbonate, and AFB. Data were correlated with the monocyte cytoplasmic concentration of Ca++, an index of early cell activation. Levels of bacterial endotoxins in the acetate, bicarbonate, buffer free dialysate, and infusate for AFB were also determined. Results showed that release of IL-1, PGE2, and LTB4, was greater after HDF with acetate than with bicarbonate; after bicarbonate dialysis, however, TNF production was significantly higher. On the other hand, after AFB, minimal production of these cytokines was seen and TNF, in particular, was undetectable. There was a direct correlation between release of cytokines in the monocytes and cytoplasmic Ca++ content. In the bicarbonate dialysate, detectable levels of bacterial endotoxins were found, whereas the acetate, buffer free dialysate, and infusate were endotoxin free. It was concluded that acetate dialysis directly activates peripheral blood monocytes to produce IL-1, PGE2, and LTB4, whereas bicarbonate induced TNF activation occurs through endotoxins. In AFB, which uses a buffer free dialysate and sterile bicarbonate infusion, monocyte activation is negligible.

Bone marrow erythroid precursor Ca++ regulates the response to human recombinant erythropoietin (rHuEPO) in hemodialysis patients.

The modulation of erythropoiesis by erythropoietin is conditioned by the concentration of Ca++ in the cytoplasm of the bone marrow erythroid precursors. We evaluated in vitro erythroid colony development from bone marrow erythroid precursors incubated with increasing concentrations of Ca++ or Ca++ plus 1,25 (OH)2 D3, and bone marrow erythroid precursor cytoplasmic Ca++ concentrations in 10 anemic hemodialysis (HD) patients before and during rHuEPO therapy. Results showed that: a) in vitro: in uremics patients before rHuEPO therapy, bone marrow erythroid precursor cytoplasmic Ca++ was lower than in normal subjects; the addition of Ca++ to the bone marrow erythroid precursors induced a dose-dependent Ca++ and erythroid colony development increase; 1,25 (OH)2 D3 potentiated this effect; b) in vivo: rHuEPO normalized bone marrow erythroid precursor Ca++ and erythroid colony development. An inverse correlation was seen between bone marrow erythroid colony development, precursor CA++ before therapy, the in vitro erythroid and the rHuEPO dose needed in vivo to normalize hematological parameters. These data emphasize the role of Ca++ in erythropoiesis and may aid understanding of the mode of action of rHuEPO in HD.

Modulation of peritoneal macrophage antimicrobial activity by peritoneal dialysis fluid, Ca++, and 1,25(OH)2D3 in CAPD patients.

Previous in vitro studies showed that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients. Twenty-four CAPD patients were evaluated in vivo (12 who had never had peritonitis, and 12 with an overall peritonitis incidence of more than one episode per 8 patient/months), for the effects of different peritoneal dialysis fluids (PDF) and Ca++ concentrations (1.25, 1.75, and 2.25 mmol/L) on PM0: cytoplasmic Ca++ concentration; superoxide generation; leukotriene B4 (LTB4) release; and bacterial killing for Staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PM0 Ca++ levels, superoxide and LTB4 generation, and bacterial killing such that, with 2.25 mmol/L of Ca++, these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca(++)-induced effects. On the other hand, with PDF Ca++ levels of 1,25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PM0 antibacterial function in CAPD patients, and may be useful in determining the prophylaxis and therapy of peritonitis.

Bacterial peritonitis and beta-2 microglobulin (B2M) production by peritoneal macrophages (PM0) in CAPD patients.

To evaluate the role of bacterial peritonitis in peritoneal macrophage (PMO) Beta-2 Microglobulin (B2M) production and its relationship with PMO Interleukin-1 (IL-1) and Leukotriene B4 (LTB4) release we analyzed in 20 CAPD patients (10 with peritonitis): 1. in vivo plasma and peritoneal dialysis effluent (PDE) B2M, IL-1 and LTB4 levels; 2. in vitro B2M, IL-1 and LTB4 release by PMO. Values were compared with those seen in the plasma or with peripheral blood monocytes of 30 hemodialysis (HD) patients (10 treated with Cuprophan-CU-, 10 with Polyacrylonitrile - PAN, and 10 with Cellulose Acetate - CA). Results showed that in CAPD patients with bacterial peritonitis B2M, IL-1 and LTB4 concentrations in the PDE were significantly higher than those seen in CAPD patients without peritonitis or in the plasma of HD patients treated with PAN or CA, but were similar to those seen in HD patients treated with CU. At the same time, in vitro, PMO from CAPD patients with bacterial peritonitis produced more B2M, IL-1 and LTB4 than did PMO from CAPD patients without peritonitis or peripheral blood monocytes from HD patients treated with PAN or CA. We conclude that in CAPD patients bacterial peritonitis is able to induce PMO B2M production, probably via a cytokine-mediated process, which may be analogous to what occurs with peripheral blood monocytes of HD patients treated with CU.

Peritoneal dialysis fluid (PDF) C++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients.

Our previous in vitro studies have shown that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PMO) antimicrobial activity in CAPD patients. We thus evaluated in vivo in 24 CAPD patients (12 who had never had peritonitis and 12 with an overall peritonitis incidence of more than one episode per 8 patient/month), the effects of different peritoneal dialysis fluid (PDF) Ca++ concentrations (1.25, 1.75 and 2.25 mmol/L) on PMO: 1. cytoplasmic Ca++ concentration; 2. superoxide generation; 3. Leukotriene B4 (LTB4) release; 4. bacterial killing for staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PMO Ca++ levels, superoxide and LTB4 generation, and bacterial killing, such that with 2.25 mmol/L of Ca++ these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca++ - induced effects. On the contrary, with PDF Ca++ levels of 1.25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients and may be useful in the prophylaxis and therapy of peritonitis.

Treatment of anaemia in CAPD patients with recombinant human erythropoietin.

EPO is an effective therapy of anaemia in CAPD patients. Monitoring serum iron level during EPO therapy is essential. Hypertension is frequently seen in patients with EPO therapy.

Ca++ and 1,25(OH)2D3 regulate in vitro and in vivo the response to human recombinant erythropoietin in CAPD patients.

In vitro studies indicate that the culture medium Ca++ concentration conditions the response to erythropoietin of bone marrow erythropoietic cells which also have specific receptors for 1,25(OH)2D3. We therefore evaluated in 12 anemic CAPD patients: 1) in vitro with increasing concentrations of Ca++ alone or Ca++ plus 1,25(OH)2D3 a) Ca++ in the bone marrow erythroid cell cytoplasm; b) colony (BFU-E and CFU-E) growth from bone marrow erythroid cells. 2) in vivo before and after 24 weeks of i.v. recombinant human erythropoietin (rHuEPO) therapy a) bone marrow erythroid cell cytoplasmic Ca++; b) BFU-E and CFU-E growth. Results showed that in CAPD patients, in vitro cytoplasmic Ca++ in bone marrow erythroid cells, and BFU-E and CFU-E growth were lower than in normals and the addition of Ca++ caused a dose-dependent increase; 1,25(OH)2D3) potentiated these effects; 2, in vivo rHuEPO therapy normalized the aforementioned parameters. An inverse relationship was seen between the bone marrow erythorid cell cytoplasmic Ca++ levels before therapy and the duration of therapy necessary to correct anemia. These data underline the role of Ca++ and 1,25(OH)2D3 in erythropoiesis in uremic patients and may aid the understanding of the mode of action and the degree of response to rHuEPO in CAPD patients.