The absorption of iron is disturbed in recombinant human erythropoietin-treated peritoneal dialysis patients

Background. Intravenous iron supplementation is often necessary in recombinant human erythropoietin (r-HuEPO)-treated haemodialysis (HD) patients, but rarely in r-HuEPO-treated peritoneal dialysis (PD) patients. This may be due to differences in iron absorption or blood loss. Method. Iron absorption (whole-body counting after ingestion of a radiolabelled iron test dose) and iron metabolism were compared in eight iron-replete r-HuEPO-treated PD patients (serum ferritin 100-500 &mgr;g/l) and 68 healthy iron-replete controls (sufficient iron in bone marrow specimen). Results. Mucosal uptake (13.4±9.8), mucosal transfer (0.34±0.18) and iron retention (4.9±4.0) in PD patients was significantly lower than in controls (42.9±18.8%, P<0.0001, 0.63±0.18, P<0.0001, and 28.0±16.7%, P<0.0001). Conclusion. Iron absorption is impaired in PD patients, as we have shown previously for HD patients. One reason for higher iron needs in HD patients may be higher blood losses due to the dialysis procedure and blood sampling for laboratory tests.     

The therapeutic equivalence of oral and intravenous iron in renal dialysis patients.

Oral and intravenous iron were compared in patients treated with renal dialysis by a cross-over trial. Intravenous iron was given over 2 weeks as an iron dextran (equivalent to 100 mg elemental iron). Oral iron was given daily as ferrous sulphate (equivalent to 100 mg elemental iron) in a wax matrix tablet. Each treatment period lasted 26 weeks. There was no significant difference in therapeutic or unwanted effects between the treatments.     

不同透析方式对非糖尿病患者胰岛素抵抗的影响

在维持性血液透析(MHD)非糖尿病患者中,稳态模型胰岛素抵抗指数(HOMA-IR)可作为心血管疾病的独立预测因素.血液透析滤过(HDF)和HD在改善胰岛素抵抗方面有何差异尚不清楚.本研究比较二者对非糖尿病患者IR的影响,并探讨其影响因素.     

Gastric emptying in diabetic and non-diabetic patients on continuous ambulatory peritoneal dialysis

Summary: As anorexia is common in continuous ambulatory peritoneal dialysis (CAPD) particularly in diabetic patients, we conducted this study to investigate gastric motility and the effect of 2 L of intraperitoneal dialysate in diabetic (DM) and non-diabetic (NDM) CAPD patients. A standard test meal labeled with technetium-99m was given after an overnight fast to 11 DM and 10 asymptomatic NDM CAPD patients (matched for age and sex) on two occasions, each 1 week apart, with an empty (postdrainage) and 2 L dialysate-lilled (pre-drainage) peritoneal cavity. Serial anterior images of the abdomen were taken in a standard manner for up to 2 h. the percentage of radioactivity retained at the end of 2 h (%2h), half emptying time (ET_1/2), and emptying rate (ER) were determined. These three parameters were also obtained from six normal individuals matched for age and sex. the mean age was 53.9 for NDM and 54 for DM patients; the mean dialysis duration was 37.9 and 22.3 months, respectively. the mean age in the control group was 49.5. Comparing the DM and NDM groups individually and with the control group, there were no statistical differences in the three gastric emptying parameters, but the latter were slightly more often abnormal in DM (8) than in NDM (6) patients. There was also a significant difference in the fractional changes of all three parameters pre- and postdrainage in the DM group, but not in the NDM group. We conclude that gastric emptying is impaired in the presence of peritoneal dialysate in DM but not in NDM patients. These findings may explain the higher prevalence of anorexia among DM CAPD patients.     

Relationship between glucose exposure via peritoneal dialysis solutions and coronary artery calcification in non-diabetic peritoneal dialysis patients

Introduction

Vascular calcification is frequent in dialysis patients and is associated with increased mortality. Impaired glucose metabolism is proposed as a contributing factor for vascular calcification. We investigated whether glucose exposure via dialysate may have a role in vascular calcification in non-diabetic peritoneal dialysis patients.

Method

We measured coronary artery calcification by multi-slice computerized tomography in 50 prevalent non-diabetic peritoneal dialysis patients and assessed its relations with fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose exposure from peritoneal dialysis fluid.

Results

Twenty-four patients (48%) had no coronary calcification. When patients were grouped according to the presence or absence of calcification, patients with calcification were mostly men and had higher burden of cardiovascular disease history, vitamin D dose intake, serum calcium, total glucose exposure from dialysis solution, and lower total weekly Kt/V _urea. In multivariate analysis, dialysate glucose exposure was an independent predictor of coronary artery calcification score, besides serum calcium and Kt/V _urea.

Conclusion

These data suggest that high glucose exposure from dialysis solution, which is potentially correctable, is a risk factor for vascular calcification in non-diabetic PD patients.     

Correlation between glycosylated hemoglobin and carotid intima-media thickness in non-diabetic peritoneal dialysis patients

Objective To investigate the correlation between glycosylated hemoglobin (HbA1c) and carotid intima?media thickness (CIMT) in non?diabetic peritoneal dialysis patients. Methods Forty?two non?diabetic peritoneal dialysis adult patients were enrolled in this study [mean age was (48.2±12.3) years, 50% was male]. CIMT was determined by carotid ultrasound. Patients were divided into two groups according to CIMT: CIMT normal group (CIMT＜0.9 mm) and CIMT thickening group (CIMT≥0.9 mm). HbA1c, 2?hour postprandial blood glucose (2hPBG) and other factors of the patients were analyzed with Spearman rank correlation and multiple linear regression. Results CIMT was correlated with age, 2hPBG, LDL?C, TG, TC, HbA1c in non?diabetic peritoneal dialysis patients (r＝0.355, 0.373, 0.416, 0.345, 0.351, 0.456, all P＜0.05). Multiple linear regression showed that HbA1c was the most powerful influence factor of CIMT（β＝0.459）. Conclusion HbA1c level is positively correlated with CIMT and may be a predictor of carotid atherosclerosis in non?diabetic peritoneal dialysis patients.     

Peritoneal permeability to proteins in diabetic and non-diabetic continuous ambulatory peritoneal dialysis patients

Peritoneal permeability to proteins was measured in diabetic and non-diabetic continuous ambulatory peritoneal dialysis patients during peritonitis and control periods. Clearances of albumin, transferrin, IgG, C3 and alpha 2-macroglobulin appeared to decrease as molecular weight increased. This relationship could be described by a power curve fit. The decrease was more than could be explained by differences in free diffusion only, indicating a size-selective barrier in the peritoneum. For all measured proteins clearances were higher in the diabetic patients. This may reflect a generally increased permeability due to their microangiopathy. The largest increase in protein loss and protein clearances was found during peritonitis. Our results do not suggest increased local production of any of the investigated proteins during the inflammation. Therefore, an increase in either peritoneal permeability or effective surface area or both is the most likely explanation. It is concluded in this study that peritoneal protein clearances are dependent on their molecular weight and that they are proportionally increased in patients with diabetes and during peritonitis.     

The biological and economic value of oral organic iron in maintenance dialysis

With the widespread use of recombinant erythropoietin (EPO) for patients with end-stage renal disease (ESRD), management of iron deficiency is an ongoing issue for the renal team. Effective iron replacement and maintenance play a vital role in efficient use of EPO. For hemodialysis patients, intravenous (i.v.) iron has proven convenient and, as an ancillary drug outside of the composite rate, generates profits for dialysis facilities. Improvements in the vehicle with which i.v. iron is administered have led to a reduction in severe or fatal reactions common with iron dextran products. Oral iron has had a spotty track record as an effective therapy for dialysis patients. Compliance has been hindered by patient discomfort when taking oral iron. Patients on peritoneal dialysis and those with chronic kidney disease remain good candidates for oral iron because of convenience, and oral formulas could prove more effective even in the hemodialysis patient population if they were better tolerated and better absorbed, and if using them would not place an economic burden on the patient and/or an economic hardship on the facility. In a capitated/bundled payment environment, oral iron may become a blessing rather than a curse for facilities that need to find more economic ways of providing services. Heme-iron, now undergoing clinical studies, may be a reliable replacement for i.v. iron in that scenario.     

A prospective crossover trial comparing intermittent intravenous and continuous oral iron supplements in peritoneal dialysis patients.

BACKGROUND: Concomitant iron supplementation is required in the great majority of erythropoietin (Epo)-treated patients with end-stage renal failure. Intravenous (i.v.) iron supplementation has been demonstrated to be superior to oral iron therapy in Epo-treated haemodialysis patients, but comparative data in iron-replete peritoneal dialysis (PD) patients are lacking. METHODS: A 12-month, prospective, crossover trial comparing oral and i.v. iron supplementation was conducted in all Princess Alexandra Hospital PD patients who were on a stable dose of Epo, had no identifiable cause of impaired haemopoiesis other than uraemia, and had normal iron stores (transferrin saturation >20% and serum ferritin 100-500 mg/l). Patients received daily oral iron supplements (210 mg elemental iron per day) for 4 months followed by intermittent, outpatient i.v. iron infusions (200 mg every 2 months) for 4 months, followed by a further 4 months of oral iron. Haemoglobin levels and body iron stores were measured monthly. RESULTS: Twenty-eight individuals were entered into the study and 16 patients completed 12 months of follow-up. Using repeated-measures analysis of variance, haemoglobin concentrations increased significantly during the i.v. phase (108+/-3 to 114+/-3 g/l) compared with each of the oral phases (109+/-3 to 108+/-3 g/l and 114+/-3 to 107+/-4 g/l, P<0.05). Similar patterns were seen for both percentage transferrin saturation (23.8+/-2.3 to 30.8+/-3.0%, 24.8+/-2.1 to 23.8+/-2.3%, and 30.8+/-3.0 to 26.8+/-2.1%, respectively, P<0.05) and ferritin (385+/-47 to 544+/-103 mg/l, 317+/-46 to 385+/-47 mg/l, 544+/-103 to 463+/-50 mg/l, respectively, P=0.10). No significant changes in Epo dosages were observed throughout the study. I.v. iron supplementation was associated with a much lower incidence of gastrointestinal disturbances (11 vs 46%, P<0.05), but exceeded the cost of oral iron treatment by 6.5-fold. CONCLUSIONS: Two-monthly i.v. iron infusions represent a practical alternative to oral iron and can be safely administered to PD patients in an outpatient setting. Compared with daily oral therapy, 2-monthly i.v. iron supplementation in PD patients was better tolerated and resulted in superior haemoglobin levels and body iron stores.     

The impact of diabetes on patients' survival in dialysis patients with non-diabetic renal disease and in patients who develop diabetes during chronic dialysis

BACKGROUND.: It is well known that dialysis patients with diabetic nephropathyhave a poor prognosis, but data concerning the survival of dialysispatients with diabetes plus a non-diabetic primary nephropathyor the survival of patients who develop diabetes after the startof regular dialysis are scarce. AIM AND METHODS.: We reviewed the survival of two cohorts of dialysis patientsin whom diabetes mellitus was associated with non-diabetic primarynephropathy. In the first cohort (18 patients with a primarydiagnosis of APKD) diabetes mellitus preceded hyperazotaemia,whilst the second cohort of 34 patients developed diabetes afterthe start of regular dialysis. We compared the survival of eachgroup of patients to the survival of a group of dialysis patientswith a primary diagnosis of diabetic nephropathy, and to thesurvival of a control group of non-diabetic dialysis patients.Within each case series, groups were similar according to age,sex, age at start of RRT, and place of treatment. All patientswere selected among those alive on treatment at 31 December1987 and were followed up to 31 December 1991. RESULTS.: In both case series the survival of patients with diabetes wassimilar irrespective of the primary diagnosis (Lee—Desustatistics: first cohort P=0.43; second cohort, P=0.08). Moreover,the survival of patients either with diabetic nephropathy orwith diabetes in association with non-diabetic primary nephropathywas significantly worse compared to the survival of the non-diabeticpatients (Lee—Desu statistics: first case series P=0.02and P<0.01; second case series P<0.05 andP<0.01). Logisticregression showed that survival was negatively associated todiabetes and age but not to sex, duration of diabetes and diagnosisof diabetic nephropathy. CONCLUSIONS.: Our limited data show that the survival of diabetic patientson regular dialysis is poor, irrespective of the primary causeof renal failure and of the duration of diabetes. These dataneed confirmation and further study.     

Diagnosis and management of iron deficiency in chronic dialysis patients

Tests have become available that not only give an index of iron stores and availability but also provide an integrated assessment of the efficacy of its utilization. This has allowed the revision of previously accepted criteria of iron deficiency as well as the most appropriate strategies for iron administration. By optimizing the response to erythropoietin, target haemoglobin levels may be reached with smaller doses, resulting in substantial savings.     

Short-term small-dose intravenous iron trial to detect functional iron deficiency in dialysis patients

BACKGROUND/AIM: Management of renal anemia in end-stage renal disease requires careful evaluation of the iron status before and in particular during erythropoietin treatment. However, there is no simple and practical iron index accurately predictive of functional iron deficiency in these patients till now. The purpose of this prospective study, therefore, is to evaluate whether a short course of low-dose intravenous iron challenge can detect functional iron deficiency in hemodialysis patients. METHODS: Twenty-four patients with baseline serum ferritin levels between 100 and 500 ng/ml were treated with intravenous saccharated ferric oxide, 960 mg over 24 hemodialysis treatments, and the hemoglobin level was checked every week. RESULTS: Patients whose hemoglobin value increased at least by 1 g/dl within the 8-week period were classified as having functional iron deficiency or as responders (n = 26; 81.2%). All other subjects were classified as having adequate iron levels or as nonresponders (n = 6; 18.8%). There were no significant differences in age, sex, dialysis years, Kt/V, dialyzers, hemoglobin, and basal and final transferrin saturation and ferritin between responders and nonresponders. In addition, there were no iron indices with acceptable levels of sensitivity and specificity. On the contrary, the cutoff value of increments of hemoglobin of at least 0.2 g/dl after a 2-week intravenous iron trial had a sensitivity of 96.2% and a specificity of 100% in all patients (n = 32) and a sensitivity of 100% and a specificity of 100% after patients with transferrin saturation <20% were excluded (n = 24). These values had the greatest utility of the tests studied in this work. CONCLUSION: A 240-mg intravenous iron challenge during a 2-week period may be a simple, accurate, and straightforward method to detect a functional iron deficiency status in hemodialysis patients undergoing erythropoietin therapy.     

Pharmacokinetics of oral cephradine in continuous ambulatory peritoneal dialysis patients

Parenteral cephalosporins are widely used to treat peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Few data exist on oral antibiotics in treating this disease. This study examined the pharmacokinetics of oral cephradine in noninfected patients on CAPD. Assays for cephradine in dialysate and urine were performed by high-performance liquid chromatography. Following a 500-mg dose, the peak dialysate cephradine concentration was 8.7 +/- 1.4 micrograms/ml. The peak urinary concentration was 201 +/- 119 micrograms/ml. The maximum peritoneal clearance was 4.3 +/- 0.3 ml/min/1.73 m2. Dialysate cephradine concentrations were inadequate against Staphylococcus epidermidis and most gram-negative bacteria found in CAPD-associated peritonitis, but may be adequate for most strains of other gram-positive organisms causing this disease.     

Excess fluid distribution affects tacrolimus absorption in peritoneal dialysis patients

Background

Excess fluid distribution is a common disorder in peritoneal dialysis (PD) patients. Tacrolimus malabsorption may also occur in PD patients, and may lead to acute allograft rejection after transplantation. The purpose of this study was to evaluate the relationship between tacrolimus pharmacokinetics and excess fluid distribution according to pre-transplant dialysis modality.

Methods

We retrospectively analyzed 41 adult living-donor kidney transplantations, including nine PD patients and 32 hemodialysis (HD) patients. We examined tacrolimus pharmacokinetics in the peri-operative period and determined the association between the tacrolimus absorption rate and body weight reduction. The absorption efficacy of tacrolimus was evaluated as the dose-normalized tacrolimus absorption rate. Tacrolimus concentrations in PD effluent were measured by high-performance liquid chromatography.

Results

The tacrolimus absorption rate on the day before kidney transplantation tended to be lower in PD patients than in HD patients; however, the rate improved after kidney transplantation and was similar in both groups of patients. The peak tacrolimus concentration time was later in PD patients than in HD patients. The body weight reduction after kidney transplantation was greater in PD patients than in HD patients, and was significantly associated with the change in tacrolimus absorption rate (p = 0.04, r = 0.32). Only 0.002 % of the oral tacrolimus dose was removed by PD itself.

Conclusion

Excess fluid distribution in PD patients appears to contribute to tacrolimus malabsorption rather than PD itself. We should consider the risk of tacrolimus malabsorption in patients with possible excess fluid distribution, particularly in PD patients.     

Therapy of iron deficiency anemia in patients on maintenance dialysis.

A controlled, prospective study compared the effectiveness of oral ferrous sulfate to intravenous iron dextran, each with and without concurrent intramuscular androgen for therapy of iron deficiency anemia in patients with chronic renal failure treated with maintenance hemodialysis. During the 12-week period of therapy, the patients who received oral ferrous sulfate and androgens showed an increment in their mean hematocrit of 16.3% and those who received oral ferrous sulfate alone had an increase of 8.3%. Patients treated with intravenous iron dextran androgens showed an increment in their mean hematocrit of 9.4% and those given iron dextran alone showed an increase of 3.5%. Serum ferritin levels increased with iron repletion but correlated inversely with the erythropoietic response. The serum ferritin assay provides a simple and reliable method to demonstrate iron repletion, and oral ferrous sulfate is the preferred method of iron repletion in compliant patients.