Effects of long-term treatment with simvastatin on some hemostatic parameters in continuous ambulatory peritoneal dialysis patients.

BACKGROUND/AIM: Disturbances in serum lipids, hemostasis and platelet functions are frequent features in uremia and may contribute to the progression of atherosclerosis and its thrombotic complications. Recently, attention has been paid to beneficial effects of statins on serum lipids and hemostasis in uremic patients. Peritoneally dialyzed (continuous ambulatory peritoneal dialysis; CAPD) subjects are particularly prone to dyslipidemia and have a high risk of cardiovascular death. The purpose of this work was to assess platelet functions, some hemostatic parameters and serum lipids in 8 hyperlipidemic CAPD patients treated with simvastatin (Zocor, MSD) for 6 months. METHODS: Platelet aggregation in whole blood and in platelet-rich plasma (PRP) induced by collagen (2 microg/ml for whole blood and PRP), arachidonic acid (0.75 mM for whole blood and PRP), ADP (10 microM for whole blood and 5 microM for PRP) and ristocetin (0.75 mg/ml for whole blood and 1.5 mg/ml for PRP) was studied before and after 1, 3 and 6 months of simvastatin (dose: 10 mg at bedtime) treatment. RESULTS: Whole-blood platelet aggregation induced by collagen decreased significantly after 3 and 6 months of the therapy, whereas in PRP, platelet aggregation induced by collagen and ADP decreased significantly after 6 months. Ristocetin-induced platelet aggregation in PRP decreased significantly after 3 and 6 months of simvastatin therapy. P-selectin remained unaltered by 6 months of simvastatin therapy. The fibrinolytic activity index was significantly higher after 3 months of the therapy when compared to the baseline values. Thrombomodulin, a marker of endothelial cell injury, was significantly lower after 3 and 6 months of the therapy. Prothrombin fragments 1 + 2 did not change significantly during 6 months of simvastatin administration. Cholesterol and LDL fell significantly as early as after 1 month and remained lowered during further months of the therapy. CONCLUSION: Simvastatin is an effective hypolipemic agent and favorably affects platelet aggregation, endothelial function and fibrinolysis in CAPD patients.     

Leptin and serum erythropoietin in hemodialyzed and peritoneally dialyzed uremic patients during rHuEPO therapy

Leptin produced by fat cell has an unanticipated role in hematopoietic system development. We examined the relationships between leptinemia and requirements of erythropoietin (Epo), endogenous Epo levels as well as markers of inflammation: C-reactive protein, tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1) in rHuEPO-treated patients maintained on chronic hemodialyses or peritoneal dialyses. The studies were performed on 51 chronically hemodialyzed patients, 20 of them did not receive rHuEPO, 31 subjects received rHuEPO, and 22 patients on CAPD, 13 of them did not receive rHuEPO, 9 subjects were given rHuEPO. In hemodialyzed patients (Epo and Non-Epo group) leptin levels were significantly higher when compared to CAPD patients (Epo and Non-Epo group, respectively). Leptin in peritoneal fluid was significantly higher in the Non-Epo group. In ultrafiltrate, leptin levels were below the detection limit of 0.5 ng/ml. Epo levels in the HD + Epo group were significantly lower than in the HD + Non-Epo group and CAPD + Epo group. TNFalpha and IL-1 concentrations were significantly lower in both groups of CAPD patients when compared to respective HD groups. Treatment with rHuEPO resulted in nonsignificant decline in serum leptin (p = 0.07 in HD and p = 0.08 in CAPD) and significant leptin loss in peritoneal fluid. It may be of clinical relevance in dialyzed patients. In both groups of Epo-treated patients, positive physiological correlation between leptinemia and BMI disappeared. Leptin levels do not correlate with rHuEPO requirements and serum Epo in dialyzed patients.     

Leptin in peritoneal dialysate from continuous ambulatory peritoneal dialysis patients.

The adipocyte-derived hormone leptin is the 16-kd product of the ob gene that regulates food intake and body weight. Plasma leptin level is elevated in patients with chronic renal failure, partly because of impaired clearance through the kidney. In this study, we examined whether leptin is cleared into peritoneal dialysate in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). The subjects were 46 CAPD patients and 67 age- and gender-matched healthy subjects. Leptin concentration in peritoneal dialysate from CAPD patients was measurable by a sensitive enzyme-linked immunosorbent assay (ELISA), and the daily loss of leptin by the peritoneal route was estimated to correspond to the amount contained in approximately 2 L plasma. Dialysate leptin concentration correlated positively with plasma leptin level and with percent body fat measured by dual-energy X-ray absorptiometry. The dialysate-to-plasma (D/P) ratio of leptin concentration was twice higher than expected from its molecular weight. D/P ratios of beta2-microglobulin, albumin, and transferrin showed strong correlations with each other (r = 0.768 to 0.801), whereas the correlation between D/P ratios of leptin and beta2-microglobulin was less impressive (r = 0.378). This was also the case with the relationship between apparent peritoneal clearances of these macromolecules, suggesting that dialysate leptin had some origins other than passive transport of plasma leptin. To test the hypothesis that abdominal visceral fat may contribute to the unexpectedly raised peritoneal dialysate leptin concentration, multiple regression analysis was performed. Leptin concentration in peritoneal dialysate showed significant association with plasma leptin level and D/P ratio of beta2-microglobulin, and it also showed an independent association with abdominal visceral fat but not with subcutaneous fat assessed by ultrasonography. These results showed that peritoneal dialysate from CAPD patients contained a significant amount of leptin, which derived presumably from both plasma and local visceral fat tissue.     

Insulin-like growth factor system components in relation to erythropoietin therapy and bone metabolism in dialyzed patients and kidney transplant recipients

Insulin-like growth factor (IGF) system components appear to be the most important regulators of bone cell function. On the other hand, IGF-1 is shown to be an important regulator for erythropoiesis. The aim of the study was to examine the relationships between IGF system, requirements of erythropoietin, endogenous erythropoietin levels, bone metabolism assessed by biochemical markers, markers of nutrition such as cholesterol and albumin in recombinant human erythropoietin (rHuEPO)-treated patients maintained on chronic hemodialyses or peritoneal dialyses as well as in kidney transplant recipients. The studies were performed on 79 chronically hemodialyzed patients; 28 of them did not receive rHuEPO, 51 subjects received rHuEPO, 34 patients on continuous ambulatory peritoneal dialysis (CAPD), 16 of them did not receive rHuEPO, 18 were given rHuEPO and 46 kidney allograft recipients. Endogenous erythropoietin concentration, bone-specific alkaline phosphatase and serum CrossLaps were assayed by ELISA. Intact PTH, osteocalcin, 1,25-(OH)(2) D(3), 25-OH D(3), IGF-1, procollagen type I carboxy-terminal extension peptide (PICP) and procollagen type I cross-linked carboxy-terminal telopeptide (ICTP) were studied by RIA, whereas IGFBP-1 and IGFBP-3 concentrations were assayed by IRMA. We found a significantly higher IGF-1 and IGFBP-3 in rHuEPO-treated HD patients when compared to CAPD subjects given rHuEPO as well as to hemodialysis (HD) patients not treated with rHuEPO. IGF-1 was significantly higher in kidney transplant recipients when compared to dialyzed patients without rHuEPO therapy. IGFBP-1 was similar in all groups of patients (including kidney transplant recipients) studied. In CAPD patients not given rHuEPO concentrations of ICTP and PICP were significantly lower when compared to rHuEPO-treated CAPD subjects and HD patients not receiving rHuEPO therapy. Serum CrossLaps in CAPD patients treated with rHuEPO were significantly higher when compared to CAPD subjects without rHuEPO treatment and to kidney transplant recipients. In rHuEPO-treated CAPD subjects IGF-1 and IGFBP-1 correlated positively with serum CrossLaps (r = 0.61, p < 0.05 and r = 0.64, p < 0.05, respectively), whereas in hemodialyzed patients without rHuEPO a significant negative correlation between IGFBP-3 and serum CrossLaps was found (r = --0.69, p < 0.001) as well as between IGFBP-3 and aluminium (r = 0.51, p < 0.05), IGF-1 and ICTP (r = --0.43, p < 0.05). In conclusion, our data indicate a probable functional relationship between IGF system components, erythropoietin treatment in dialyzed patients and bone metabolism in renal replacement therapy in a form of hemodialyses, peritoneal dialyses and kidney transplantation. Dialyzed patients exhibit more pronounced renal osteodystrophy than kidney allograft recipients. IGF system components are influenced by erythropoietin therapy, but are not related to serum erythropoietin levels and rHuEPO requirements.     

Serum leptin, resistin, and lipid levels in patients with end stage renal failure with regard to dialysis modality

Little information is available on the relationship between serum resistin levels and other adipokines with serum lipid levels and insulin resistance in uremic patients under different dialysis modalities. METHODS: This study investigated the effects of dialysis modality on serum leptin, adiponectin, resistin, interleukin 6 (IL-6), and tumor necrosis factor (TNF) alpha levels in age, sex, and total adipose tissue mass (TATM); matched 30 hemodialysis (HD) patients, 30 continuous peritoneal dialysis (CAPD) patients, and 30 healthy controls; and evaluated the relationship between these adipokines and dyslipidemia and insulin resistance. RESULTS: Serum resistin, adiponectin, IL-6, TNF-alpha, and high sensitive C reactive protein (hsCRP) levels were significantly increased in dialysis patients compared to controls (p < 0.05). In CAPD patients, serum leptin, resistin, triglycerides, and total cholesterol levels were higher than those in HD patients (p < 0.05). Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and low density lipoprotein (LDLc) levels in both dialysis groups. Resistin levels were found to positively correlate with TATM and triglycerides in CAPD patients. No relationship was found between the homeostasis model assessment-insulin resistance index (HOMA-IR) and adipokines studied. CONCLUSION: Serum leptin, resistin, triglycerides, and total cholesterol levels were higher in CAPD patients. Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and LDLc levels in dialysis patients. Resistin levels were positively correlated with TATM and triglycerides in CAPD patients. Glucose load during CAPD may be an important factor in increased in leptin, resistin, triglycerides, and total cholesterol levels in CAPD patients. These results highlight the importance of leptin and resistin as determinants of dyslipidemia, especially in CAPD patients.     

Plasma and dialysate immunoglobulin G in continuous ambulatory peritoneal dialysis patients: a multicenter study

Peritoneal dialysate immunoglobulin (Ig)G concentrations were measured in 120 continuous ambulatory peritoneal dialysis (CAPD) patients evaluated at four dialysis centers in different countries to assess the normal range for dialysate IgG and to investigate the relationships of this protein levels with peritoneal episodes, For 65 of these patients, plasma IgG levels were determined, and IgG clearances were calculated. The mean dialysate concentration of IgG was 6.9 +/- 4.2 mg/dl, and there was no difference between men and women or between patients who had or had not previously undergone hemodialysis. Dialysate IgG concentrations were significantly related to residual renal creatinine clearance and negatively correlated with dialysate volume, plasma albumin and total protein. There were no significant correlations between IgG levels in the dialysate and age, protein losses in the dialysate, time on CAPD or time from the last peritonitis episode. Plasma and dialysate IgG were unrelated to the incidence of peritonitis, statistical analysis being performed with different methods. These results suggest that IgG levels in the dialysate or plasma are not a major factor in the prevention of CAPD peritonitis.     

Serum Leptin,Resistin, and Lipid Levels in Patients with End Stage Renal Failure with Regard to Dialysis Modality

Little information is available on the relationship between serum resistin levels and other adipokines with serum lipid levels and insulin resistance in uremic patients under different dialysis modalities. Methods. This study investigated the effects of dialysis modality on serum leptin, adiponectin, resistin, interleukin 6 (IL-6), and tumor necrosis factor (TNF) α levels in age, sex, and total adipose tissue mass (TATM); matched 30 hemodialysis (HD) patients, 30 continuous peritoneal dialysis (CAPD) patients, and 30 healthy controls; and evaluated the relationship between these adipokines and dyslipidemia and insulin resistance. Results. Serum resistin, adiponectin, IL-6, TNF-α, and high sensitive C reactive protein (hsCRP) levels were significantly increased in dialysis patients compared to controls (p < 0.05). In CAPD patients, serum leptin, resistin, triglycerides, and total cholesterol levels were higher than those in HD patients (p < 0.05). Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and low density lipoprotein (LDLc) levels in both dialysis groups. Resistin levels were found to positively correlate with TATM and triglycerides in CAPD patients. No relationship was found between the homeostasis model assessment-insulin resistance index (HOMA-IR) and adipokines studied. Conclusion. Serum leptin, resistin, triglycerides, and total cholesterol levels were higher in CAPD patients. Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and LDLc levels in dialysis patients. Resistin levels were positively correlated with TATM and triglycerides in CAPD patients. Glucose load during CAPD may be an important factor in increased in leptin, resistin, triglycerides, and total cholesterol levels in CAPD patients. These results highlight the importance of leptin and resistin as determinants of dyslipidemia, especially in CAPD patients.     

Serum concentration and peritoneal transfer of aluminum during treatment by continuous ambulatory peritoneal dialysis

The evolution of the aluminum (A1) serum levels during a 2-year follow-up and the peritoneal transfer of A1 were studied in 22 patients treated by continuous ambulatory peritoneal dialysis (CAPD), using a dialysate with a very low A1 concentration (r = 0.25 - 0.30 mumoles/liter). Patients were divided in three groups. A transfer of A1 from the patient to the dialysate was observed in all patients. In group 1, patients exclusively treated by CAPD and who have never received aluminum-containing phosphate binders (ACPB), mean level (+/- SD) of serum A1 stabilized within a safe range (0.60 +/- 0.28 mumoles/liter). In group 2 the oral administration of ACPB in patients exclusively treated by CAPD induced a slow and progressive increase of A1 serum concentration despite the increase of the A1 excretion through the peritoneal route. In group 3, patients previously treated by hemodialysis and receiving ACPB, the high serum A1 levels observed before treatment by CAPD decreased rapidly on CAPD. A1 removal through the peritoneum was higher in group 3 than in group 2 despite serum A1 levels not statistically different in both groups. A1 removal through the peritoneum is mainly influenced by serum and dialysate A1 concentration. A1 body stores could play a role in the transfer of A1 through the peritoneum. Three cases of A1 poisoning due to the accidental use of a dialysate with a high A1 content are reported.     

Leptin in CAPD patients: serum concentrations and peritoneal loss.

BACKGROUND: To determine whether serum leptin concentrations in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are influenced by peritoneal loss of leptin and to compare serum leptin levels of normal subjects with those of patients receiving renal replacement therapy such as haemodialysis (HD), CAPD, or kidney transplantation. SUBJECTS AND METHODS: Eighty-four individuals were investigated: six females and 14 males on standard CAPD; 13 females and 13 males on chronic HD; 10 female and eight male kidney transplant recipients, and 10 female and 10 male subjects as controls. Morning serum, 8-h and 24-h samples of peritoneal fluid concentrated to 6-20-fold by Centricon 3 (cutoff 3000 daltons), and 24-h urinary concentrations of leptin were measured with commercial RIA (Linco Research, Inc., USA). Venous blood and peritoneal fluid samples of albumin, beta2-microglobulin, glucose, urea, and creatinine were determined by standard laboratory techniques. Serum insulin levels were measured by radioimmunoassay. RESULTS: Patients (men and women) on CAPD and after kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/BMI ratios than control subjects. These increased values did not reach statistical significance in HD patients. Serum leptin concentrations were correlated very significantly with BMI in all cases (r=0.380, P<0.001). Moreover, in CAPD patients (r=0.630, P<0.007) and in HD patients (r=0.668, P<0.005), but not in kidney transplant recipients or control subjects, significant correlations were observed between serum leptin and insulin concentrations. Residual renal function (RRF) in the range 0-12.8 ml/min and serum beta2-microglobulin levels in the range 7.9-47.1 mg/l did not influence serum leptin levels in CAPD and HD patients. As expected, leptin was detected in the peritoneal fluid of CAPD patients. Twenty-four-hour peritoneal loss (30.95+/-21.05 ng/min) and 24-h peritoneal clearance (0.01+/-0.01 ml/kg/min) of leptin account for only 3.9% of estimated whole-body leptin production rate and 0.7% of leptin clearance from plasma respectively. Twenty-four-hour urinary losses of leptin in CAPD patients were negligible, accounting for 5.6+/-1.8% (range 0.3-15.2%) of total (peritoneal and urinary) loss of this hormone. CONCLUSIONS: These findings suggest that serum leptin levels are not affected by continuous peritoneal loss of leptin during CAPD and that insulin resistance and hyperinsulinaemia contribute to elevated serum leptin concentrations in CAPD and HD patients. The aetiology of increased serum leptin levels in kidney transplant recipients is probably different from that in dialysis patients.     

Increased incidence of renal allograft thrombosis under cyclosporine immunosuppression

Six of 325 patients undergoing renal transplantation under combined cyclosporine (CsA)-prednisone immunosuppression displayed renal artery thrombosis between 4 and 12 days after transplantation. All six patients had satisfactory initial revascularization, as ascertained by radionuclide scan and renal function. In none was the thrombosis considered to be secondary to rejection, either by clinical course or upon renal biopsy. Since there was no clear etiologic factor and since none of the overlapping 297 patients treated with azathioprine-prednisone displayed this complication, these cases appear to support the hypothesis that CsA alters intravascular hemostatic homeostasis. Data in experimental models are consistent with a predisposing factor to thrombosis, namely CsA reduces the synthesis of prostacyclin stimulating factors, leading to decreased prostacyclin production by vascular endothelial cells, and to failure to inhibit platelet aggregation.     

CAPD的内分泌激素与rHuEPO疗效的相关性

目的：探讨在连续性非卧床腹膜透析(CAPD)干预治疗下慢性肾衰竭尿毒症内分泌激素与人类重组促红细胞生成素(rHuEPO)疗效的关系。方法：对经CAPD治疗的慢性肾衰竭尿毒症患内分泌激素等多重因素及血红蛋白进行多元回归分析。结果：非CAPD组贫血改善程度显低于CAPD组，内生肌酐清除率、甲状旁腺素、甲状腺激素、血皮质酵及透析治疗均与Hb显相关。结论：单用rHuEPO对改善肾衰竭尿毒症的贫血状态存在较大的局限，主要和包括PTH等在内的尿毒症红细胞生长抑制因子(inhibitors of erythropoiesis，IE)有关。rHuEPO配合CAPD是清除IE、改善贫血状态、提高生活质量的很好的组合治疗方法。     

Ultrapure dialysate improves iron utilization and erythropoietin response in chronic hemodialysis patients - a prospective cross-over study

BACKGROUND: The impact of ultrapure dialysis on dialysate-related chronic inflammatory status and anemia in uremic patients on maintenance hemodialysis (HD) remains uncertain. We evaluated ultrapure dialysate effects on erythropoietin (EPO) response and inflammatory status in a prospective, randomized, cross-over study. METHODS: Thirty-four HD patients were divided into two groups. One group was treated with conventional dialysate and the other group with ultrapure dialysate for 6 months and crossed over for another 6 months. Bacteria growth and dialysate endotoxin were examined. Parameters including C-reactive protein (CRP), recombinant human erythropoietin (rHuEPO) dose, ferritin, iron saturation and serum albumin were measured at the start, and at 6 and 12 months. RESULTS: The endotoxin levels reduced significantly in the ultrapure dialysate by adding a dialysate ultrafilter. After a 6-month treatment with ultrapure dialysate, there were statistically significant differences in the systemic inflammation markers between both groups. Changing from conventional to ultrapure dialysis fluid significantly reduced CRP (7.01 +/- 5.059 to 4.461 +/- 3.754 mg/L, p<0.05), and resulted in reduced rHuEPO doses (12500 +/- 7060 to 10440 +/- 7050 U/month, p<0.05). Continuous conventional dialysate use was not associated with significant alternations in CRP (from 5.849 +/- 7.744 to 6.187 +/- 7.997 mg/L, p=0.456) and rHuEPO dose (14060 +/- 6210 to 15060 +/- 7250U/month, p>0.05). The ferritin level reduced significantly (422 +/- 183 to 272 +/- 162 mcg/L, p<0.05) in the ultrapure dialysate group. After another 6-month cross-over, the study parameters were reversed among the two groups indicating the beneficial effect of ultrapure dialysis. CONCLUSIONS: Through endotoxin reduction in conventional dialysate, ultrapure dialysis in dialysis patients manifested a reduced inflammatory parameter, reduced rHuEPO dose and improved iron utilization; and therefore, could be beneficial in anemia treatment.     

Heparin-induced platelet activation in sixteen surgical patients: diagnosis and management

Heparin-induced platelet activation (HIPA) is a syndrome associated with thrombocytopenia, intravascular thrombosis, and arterial emboli. We have evaluated 16 patients for presumed HIPA because of the occurrence of thrombocytopenia or a new thrombotic complication during heparin therapy. In this group, 16 thrombotic events occurred in 10 patients with a mortality rate of 18.8%. Diagnosis was confirmed in vitro by the demonstration of at least 20% platelet aggregation and/or 6% 14C-serotonin release after heparin (0.1 to 3 U/ml) was added to a mixture of patient platelet-poor plasma (PPP, two parts) and aspirin-free donor platelet-rich plasma (PRP, three parts). After heparin was discontinued, seven patients continued to have HIPA in their own PRP although it could no longer be observed in donor PRP. Iloprost, a potent prostacyclin analog that reversibly inhibits platelet activation, completely prevented HIPA and release in all of nine patients. Aspirin, an irreversible cyclooxygenase inhibitor, failed to prevent HIPA in four of these nine patients. In conclusion, HIPA is associated with an extremely high morbidity and mortality rate. Evaluation of the patients' PRP in response to heparin may improve the diagnostic sensitivity of this assay. Aspirin does not reliably prevent HIPA, which suggests participation of thromboxane-independent pathways. Thus, if further exposure to heparin is unavoidable, a more effective platelet inhibitor such as iloprost is required to reliably prevent in vivo HIPA.     

Randomized prospective comparison between erythropoietin and androgens in CAPD patients

BACKGROUND: Anemia and malnutrition are significant complications in peritoneal dialysis (PD) patients. Previous studies in hemodialysis have shown that androgens are effective as therapy for anemia; however, this has not been tested in a randomized prospective trial in PD patients. Furthermore, the anabolic properties of androgens may exert additional benefits on the nutritional status in this population. METHODS: Twenty-seven stable male patients over 50 years who were under maintenance continuous ambulatory peritoneal dialysis (CAPD) therapy were randomized to receive recombinant human erythropoietin (rHuEPO; N = 14) or nandrolone decanoate (ND; 200 mg/week IM; N = 13) as therapy for anemia. The evolution of hematologic parameters and the impact on both nutritional anthorpometric and biochemical variables were evaluated after six months of treatment. RESULTS: Hemoglobin and hematocrit experienced similar increases in both groups: from 8.5 +/- 0.9 g/dL and 25.8 +/- 2.7% to 11.7 +/- 0.6 g/dL and 34.7 +/- 1.6% (P < 0.001) in patients receiving rHuEPO, and from 8.9 +/- 0.8 and 27 +/- 2.2% to 11.8 +/- 0.4 g/dL and 35.1 +/- 1.5% (P < 0.001) in subjects treated with ND. At the end of the study, out of the diverse nutritional variables included in this investigation, only weight and body mass index significantly increased in the rHuEPO group. Conversely, both anthropometric [weight, body mass index, triceps skinfold, mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum total proteins, albumin, prealbumin and transferrin) were significantly increased in patients treated with ND. In this group, serum urea nitrogen, urea net excretion and protein equivalent of nitrogen appearance significantly decreased. These facts, together with an increase in serum creatinine and no changes in dietary intake during the study, suggest a rise in muscle mass related to an anabolic effect of nandrolone decanoate. Interestingly, serum levels of insulin-like growth factor type 1 (IGF-1) increased in patients on the androgen group compared to subjects treated with rHuEPO. Moreover, there was a positive and significant correlation between the rise in IGF-1 concentrations and the increase in hemoglobin, hematocrit, MAC and MAMC. CONCLUSIONS: Androgens therapy improved the anemia in elderly male CAPD patients in a similar manner to that observed with rHuEPO. Furthermore, compared with rHuEPO, androgen administration was associated with beneficial effects on nutritional status. The mechanism of action of androgens on hematologic and nutritional parameters might be mediated, at least in part, by IGF-1.     

Evaluation of coagulation and fibrinolysis in haemodialysis patients at different haematocrit levels: Comparison between patients with and without diabetes

SUMMARY: There is an insufficient number of reports concerning the optimal haematocrit level for haemodialysis patients with diabetes. Although many reports have indicated that recombinant human erythropoietin (rHuEPO) therapy does not influence the incidence of intravascular thrombosis, no study has focused its attention on the difference of the coagulation-fibrinolysis system between haemodialysis patients with and without diabetes. We studied eight patients with diabetes and seven patients without diabetes who had been undergoing regular haemodialysis. In all 15 patients, rHuEPO administration was started at a haematocrit level of 20% and toe haematocrit tevels were gradually increased from 20 to 30%. Coagulation and fibrinolysis functions, measured at haematocrit levels of 20,25 and 30%, respectively, were compared between the two groups. In the diabetic group, platelet count, fibrinogen, thrombin-antithrombin III complex, frtmn/fibrinogen degradation products = D dimer, platelet factor 4 and platelet adhesion were statistically higher ( P < 0.05), and plasminogen and α2-plasmin inhibitor was statistically lower ( P < 0.05) than those in the non-diabetic group, even at the 20% level. These abnormalities at the baseline were extremely enhanced in connection with haematocrit increased by rHuEPO. the diabetic group, in particular, showed greater increases of platelet factor 4, platelet adhesion and thrombomodulin and a decrease of α2-plasmin inhibitor from the 20% to the 30% level ( P < 0.05) than the non-diabetic group. These findings suggest that haemodialysis patients with diabetes generally have enhanced thrombotic parameters compared with haemodialysis patients without diabetes, and the increase of haematocrit makes the difference greater. Accordingly, the target level of haematocrit for patients with diabetes should be set separately from that of patients without diabetes.     

Peritoneal clearance of leptin in CAPD patients: impact of local insulin administration.

INTRODUCTION: The ob gene product leptin is secreted by fat cells and the serum leptin levels reflects the body fat content. Markedly elevated serum leptin levels have been reported in patients with chronic renal failure. The aim of the present study was to assess if the dialysate leptin levels in peritoneal dialysate are similar to what can be expected from passive diffusion or if intraperitoneal synthesis of leptin may occur. METHODS: We studied 39 patients (20 males), mean age 54+/-12 years, who had been treated with peritoneal dialysis for 17+/-12 months. Ten of the patients were diabetics of which seven used intraperitoneal insulin. A 24-h collection of dialysate was performed and dialysate and fasting blood samples were analysed for leptin, albumin and beta2-microglobulin, and the peritoneal clearances (PCl) were calculated for these solutes. RESULTS: Serum leptin (mean 47+/-76, range 3-350 ng/ml) was related to body mass index (r=0.35, P<0.05). In multiple regression analysis, serum leptin also correlated to serum TNF-alpha. Although dialysate leptin levels correlated to serum leptin, they were higher than expected from the molecular weight of 16 kD. PCl of leptin was 1.3 ml/min (range 0.2-5.9 ml/min), which was 1.6 times higher than expected from the molecular weight of leptin and PCl for albumin and beta2-microglobulin, not taking the protein binding of leptin into account. A strong correlation was found between PCI for albumin and beta2-microglobulin (r = 0.68, P < 0.0001) but neither PCl albumin, nor PCl beta2-microglobulin correlated to PCI leptin. The PCl of leptin was markedly higher in diabetics using intraperitoneal insulin (n = 7) compared to the other 32 patients (2.6+/-2.0 vs 1.1+/-0.7 ml/min, P<0.05). CONCLUSION: Serum leptin is locally produced in the peritoneal cavity, and intraperitoneal insulin enhances local production of leptin.     

Effect of recombinant human erythropoietin on synthesis of methylguanidine in uraemic patients on haemodialysis or continuous ambulatory peritoneal dialysis

The effect of recombinant human erythropoietin (rHuEPO) on synthesis of methylguanidine was studied in 6 uraemic patients on haemodialysis and 5 uraemic patients on continuous ambulatory peritoneal dialysis (CAPD). The Two groups of patients were started on a 24-week course of thrice weekly 1500 IU of rHuEPO by the intravenous route. Serum methylguanidine level and methylguanidine/creatinine ratio were comparable in these groups. In the two groups no significant differences were observed in these measurements comparing the pretreatment values with those 4, 8, 12 or 24 weeks after starting rHuEPO administration. During rHuEPO therapy, serum methylguanidine levels and methylguanidine/creatinine ratio showed no considerable difference between the two groups. These findings suggest that administration of rHuEPO does not alter methylguanidine synthesis in uraemic patients on haemodialysis and CAPD.     

Hemostatic abnormalities in total artificial heart patients as detected by specific blood markers.

We retrospectively evaluated the hemostatic system of 13 patients during implantation (2 to 35 days) of the Jarvik 7-70 total artificial heart (TAH). Although all patients were clinically manageable while on the TAH, 5 had excessive generalized bleeding. After the heart transplant procedure, 2 patients had neurological events and 1 patient, thrombosis of the leg. While the patients were supported by the TAH, the routine coagulation assays (prothrombin time, activated partial thromboplastin time, fibrinogen, factor assays, and platelet count) showed slight abnormalities but no correlation to hemorrhagic or thrombotic events. In contrast, plasma and cellular activation markers, which are highly sensitive and specific for hypercoagulability, fibrinolysis, or platelet activation, revealed activation in all patients. Most striking was the marked activation of the fibrinolytic system (p less than 0.05 to 0.001). Correlations of individual patient data compared with the average TAH group response could be made between excessive enhancement of fibrinolysis (increased D-dimer and tissue plasminogen activator and decreased plasminogen activator inhibitor) and bleeding. A hypercoagulable state (increased fibrinogen and thrombin-antithrombin complex and decreased antithrombin III and protein C), decreased fibrinolysis (decreased tissue plasminogen activator and D-dimer), activated platelets (increased thromboxane B2), or combinations of these were associated with thrombosis. The hemostatic activation returned to normal 1 day after removal of the TAH. These data suggest that the patient with a TAH requires more sophisticated laboratory monitoring and individualized treatment for excessive fibrinolysis, hypercoagulable state, or platelet activation to avoid thrombotic and hemorrhagic complications.     

Vaccination for prevention of CAPD associated staphylococcal infection: results of a prospective multicentre clinical trial.

124 stable CAPD patients from 8 Australian and 3 New Zealand centers were randomly assigned in a blinded fashion to one of two groups to study the effect of vaccination using commercial preparations consisting of a combined staphylococcus toxoid and whole killed staphylococci (SB) or normal saline solution (SS) on the incidence of peritonitis and exit site infection and S. aureus nasal carriage over a 12-month prospective period. In addition, levels of IgG, IgA, IgM, C3 and C4 were monitored during the trial period in serum and dialysate; serum levels of anti-alpha hemolysin and dialysate levels of fibronectin and specific antistaphylococcal antibodies were also measured. Over the period, treatment with SB or SS did not affect the incidence of peritonitis, catheter-related infection or S. aureus nasal carriage. However, vaccination with SB elicited a significant increase in the level of serum anti-alpha hemolysin throughout the 12 month duration of the study, although the level of increase was unrelated to the subsequent rate of peritonitis. Vaccination with SB but not SS elicited a significant increase in the dialysate level of specific antibodies against S. aureus. Serum levels of IgG, IgA, IgM, complement C3 and C4 were within the normal range in the CAPD patients studied and remained unaffected by vaccination with SB. In addition, dialysate levels of IgG, IgA, IgM, complement C3 and C4 were 50-100 times lower than corresponding serum levels and remained unaffected by vaccination. In summary, immunisation with an anti-staphylococcal agent was not successful in reducing peritonitis or exit site infection in CAPD patients.     

Evaluation of continuous ambulatory peritoneal dialysis

This study was undertaken to ascertain whether 19 patients maintained on continuous ambulatory peritoneal dialysis (CAPD) for at least 1 year experienced any deterioration in peritoneal membrane function. Selected serum chemistries and skinfold measurements were also evaluated to determine whether patients dialyzed by CAPD could maintain a normal nutritional status. This study demonstrates that patients maintained on CAPD had stable dialysate protein losses, glucose absorption from the dialysate, and constant urea, creatinine, and sodium removal. When these patients were subdivided by incidence of peritonitis, the group with a lower incidence of peritonitis (one episode every 349 +/- 155 SEM days) showed stable serum protein concentration and improvement in upper arm area whereas the group with a high incidence of peritonitis (one episode every 95 +/- 7 SEM days) showed a reduction in upper arm muscle area. Thus, our data suggest that over a 1-year period, there is no deterioration in peritoneal membrane characteristics and CAPD is effective in maintaining the nutritional status of the patient. However, both membrane function and nutritional status may be impaired by frequent episodes of infection.