Reduction in cardiovascular related hospitalization with nocturnal home hemodialysis.

BACKGROUND: Cardiovascular disease remains the leading cause of death among patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) (5 - 6 sessions per week; 6 - 8 hours per session) is a novel form of home-based renal replacement therapy, which has been shown to improve several cardiovascular risk factors. The impact of NHD on hospitalization rate has remained unclear. We hypothesized that augmentation of small and middle molecular clearance by NHD would result in a reduction of dialysis related or cardiovascular specific hospitalizations. METHODS AND RESULTS: In this controlled cohort study, we studied 32 NHD patients (age: 43 +/- 2 [mean +/- SEM]) 1 year before and 2 years after conversion to NHD and 42 CHD patients (mean age: 44 +/- 2) (matched for age, dialysis vintage and controlled for comorbidities) during the same time period. The primary outcome was the change in a composite of dialysis or cardiovascular related admissions rate before and after conversion to NHD. Secondary outcomes included changes in all cause hospitalization rate, visits to emergency, reasons and duration of hospitalization and dialysis-related biochemical parameters. During the study period, dialysis or cardiovascular-related admission rate was stable for the CHD control cohort (from 0.48 +/- 0.14 [baseline] to 0.40 +/- 0.12 [end of study] admission per patient year, p = NS). In contrast, conversion to NHD is associated with a decrease in our composite endpoint (from 0.50 +/- 0.15 to 0.17 +/- 0.06 admission per patient year, p = 0.04). Cardiovascular disease (37%) was the principal cause for hospitalization in the control population. In comparison, vascular access related admission was the primary cause of admission for the NHD cohort (56%), p = 0.001. Of the biochemical parameters, NHD is associated with a decrease in plasma phosphate (from 1.7 +/- 0.1 to 1.3 +/- 0.1 mM, p = 0.01) and an improved control of anemia (from 114 +/- 2 to 122 +/- 3 g/l, p = 0.02). CONCLUSION: Conversion to NHD is associated with a decrease in dialysis and cardiovascular-related hospital admission. The clinical and mechanistic relevance in uremic patients of improved phosphate and anemia management requires further examination.     

Regression of left ventricular hypertrophy after conversion to nocturnal hemodialysis

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for mortality in the dialysis population. LVH has been attributed to several factors, including hypertension, excess extracellular fluid (ECF) volume, anemia and uremia. Nocturnal hemodialysis is a novel renal replacement therapy that appears to improve blood pressure control. METHODS: This observational cohort study assessed the impact on LVH of conversion from conventional hemodialysis (CHD) to nocturnal hemodialysis (NHD). In 28 patients (mean age 44 +/- 7 years) receiving NHD for at least two years (mean duration 3.4 +/- 1.2 years), blood pressure (BP), hemoglobin (Hb), ECF volume (single-frequency bioelectrical impedance) and left ventricular mass index (LVMI) were determined before and after conversion. For comparison, 13 control patients (mean age 52 +/- 15 years) who remained on self-care home CHD for one year or more (mean duration 2.8 +/- 1.8 years) were studied also. Serial measurements of BP, Hb and LVMI were also obtained in this control group. RESULTS: There were no significant differences between the two cohorts with respect to age, use of antihypertensive medications, Hb, BP or LVMI at baseline. After transfer from CHD to NHD, there were significant reductions in systolic, diastolic and pulse pressure (from 145 +/- 20 to 122 +/- 13 mm Hg, P < 0.001; from 84 +/- 15 to 74 +/- 12 mm Hg, P = 0.02; from 61 +/- 12 to 49 +/- 12 mm Hg, P = 0.002, respectively) and LVMI (from 147 +/- 42 to 114 +/- 40 g/m2, P = 0.004). There was also a significant reduction in the number of prescribed antihypertensive medications (from 1.8 to 0.3, P < 0.001) and an increase in Hb in the NHD cohort. Post-dialysis ECF volume did not change. LVMI correlated with systolic blood pressure (r = 0.6, P = 0.001) during nocturnal hemodialysis. There was no relationship between changes in LVMI and changes in BP or Hb. In contrast, there were no changes in BP, Hb or LVMI in the CHD cohort over the same time period. CONCLUSIONS: Reductions in BP with NHD are accompanied by regression of LVH.     

Improvement in exercise duration and capacity after conversion to nocturnal home haemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a reduced exercise capacity as assessed by peak oxygen uptake (VO2peak). Nocturnal haemodialysis (NHD) augments uraemic clearance and vascular responsiveness to nitric oxide and lowers blood pressure (BP) and peripheral resistance. METHODS: To assess the impact of NHD on exercise duration and capacity, 13 consecutive ESRD patients [age: 41 +/- 3; (mean +/- SEM)] and healthy normal subjects (n = 14) matched for age and body mass index exercised to peak effort (VO2peak) as determined by open-circuit spirometry during a graded cycle ergometer test with a ramp increase in work rate (by 17 watts/min). RESULTS: Exercise was performed before, 2 and 3-6 months after conversion from conventional haemodialysis (CHD) (3 sessions per week; 4 h per session) to NHD (5-6 sessions per week; 6-8 h per session). Exercise duration increased progressively [from 617 +/- 50 (CHD) to 634 +/- 47 (NHD 2 months) to 682 +/- 55 [NHD 3-6 months], P = 0.03) as did exercise capacity, expressed as percent of predicted (based on age, sex and body size) VO2peak, [from 66 +/- 8 (CHD) to 72 +/- 6 (NHD 2 months) to 75 +/- 6% (NHD 3-6 months), P < 0.05). CONCLUSION: Enhanced uraemia control by NHD improved both exercise duration and capacity. When coupled with augmented uraemia management, an increase in physical activity, perhaps due to more effective oxygen delivery or improved muscle metabolism, has the potential to improve the quality of life of patients with ESRD.     

Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation.

BACKGROUND: Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associated with improved blood pressure control when compared to conventional haemodialysis (CHD). Current studies suggest that NHD lowers blood pressure through a decrease in peripheral resistance. The graft and blood pressure outcomes of NHD patients who undergo renal transplantation are unknown. METHODS: We reviewed the renal allograft and blood pressure outcomes of 15 NHD patients who underwent renal transplantation. An age and vintage matched cohort of 29 CHD patients was used as controls. RESULTS: The rate of delayed graft function (DGF) tended to be higher in the NHD group compared to the CHD group (64 vs 41%, P = 0.15), however the 1-year graft function (53+/-6 vs 59+/-5 ml/min, P = 0.426) and graft survival (92 vs 95%, P = 0.751) were similar. Intra-operatively, NHD patients had lower minimum systolic (92+/-5 vs 109+/-4, P = 0.03) and diastolic (48+/-3 vs 64+/-2, P = 0.02) blood pressures in comparison to the CHD cohort. Pathologically, acute tubular necrosis accounted for 100% of DGF in the NHD group in contrast to 75% in the CHD population (P = 0.01). Pre-transplant mean systolic BP (sBP) was significantly lower in the NHD group compared to the CHD group (113+/-6 vs 145+/-10 mmHg, P<0.001). At 12 months post-transplant, mean sBP increased from baseline in the NHD group ( triangle up sBP 22+/-7 mmHg, P = 0.009) while in the CHD group mean sBP fell (Delta sBP -14+/-5 mmHg, P = 0.014). Mean arterial and diastolic BP exhibited similar changes. These trends persisted after 24 months of post-transplant follow-up. CONCLUSIONS: One-year graft outcomes and blood pressures are similar for NHD and CHD patients who undergo renal transplantation. Unlike CHD patients, NHD patients experienced a significant fall in their intra-operative blood pressures, which likely contributed towards the delayed graft function in this cohort of patients. Further prospective studies are needed to examine the underlying differences in haemodynamics and long-term graft survival between the two renal replacement modalities.     

Endogenous erythropoietin levels and anemia in long-term renal transplant recipients

BACKGROUND/AIM: Although anemia is a common complication after renal transplantation (RT), data concerning endogenous erythropoietin (EPO) levels in long-term RT recipients are rare. The goal of this study was to evaluate the prevalence of anemia within 6 months to 5 years after RT and to assess the relationship between the serum concentrations of endogenous EPO, graft function and grade of improvement of anemia. METHODS: 140 patients who had undergone RT were included in the group: 89 males (63.6%) and 51 females (36.4%), with an average age 46.8 +/- 12.8 years. The serum concentrations of EPO and creatinine (Cr) were tested in all the individuals and the values of the red blood component of blood count, serum ferritin (SF), plasma iron concentration, plasma total iron-binding capacity (TIBC), transferrin saturation (TS), folic acid and vitamin B(12) levels in the serum were determined. A statistical analysis of the results was performed using the correlation analysis, Mann-Whitney U test and Duncan's multiple range test. RESULTS: Normal blood count values were found in 91 patients (65%), and a mild grade of anemia with a mean hemoglobin (Hb) 114.4 +/- 11.9 g/l was observed in 45 patients (32.1%), and 4 patients (2.9%) fulfilled the diagnostic criteria for post-transplantation erythrocytosis. Individuals with normal Hb values had a mean EPO serum concentration of 39.3 +/- 12.3 mU/ml (median 37.2) and the mean Cr was 133.8 +/- 36.9 micromol/l (median 122). Patients with anemia (Hb <120 g/l in females, Hb <130 g/l in males) had a mean EPO value of 47.0 +/- 26.6 mU/ml (median 36.0) and a mean Cr of 203.8 +/- 108.9 micromol/l (median 181). The difference in the Cr values was statistically significant (p < 0.0001), while the difference between the EPO concentrations was not significant. No relation of EPO serum concentration with regard to graft function was found in the analysis. A lack of storage iron (SF <10 microg/l in females, SF <22 microg/l in males) was found in 16 patients (11.4%), and a lack of functional iron (TS <20%) was found in 27 patients (19.3%). CONCLUSIONS: Theprevalence of anemia in patients after transplantation was 32.1%. The most common cause of anemia is insufficient graft function development. The achieved values of the red component of blood count have no relation to the endogenous EPO serum concentrations.     

Low dose intravenous ascorbic acid for erythropoietin-hyporesponsive anemia in diabetic hemodialysis patients with iron overload

BACKGROUND: Recent report demonstrates that inadequate iron mobilization and defective iron utilization may cause recombinant erythropoieitin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. The effect of intravenous ascorbic acid (IVAA) in HD patients selected on the basis of iron overload and EPO resistance also has been proven. However, it is uncertain whether IVAA still works in diabetic ESRD patients with hyperferritinemia. Therefore, the aim of this study focusing on diabetic ESRD patients was to analyze the potential effect of low dose IVAA on improvement of anemia and erythropoiesis-related parameters when compared with control period. PATIENTS AND METHOD: This study consisted of 22 chronic hemodialysis patients with type II diabetes in a single dialysis unit. In studies of this type, all eligible patients are followed up, but the primary comparison is still between different sequentially treatment including control period and post-IVAA period in same patients. IVAA patients received ascorbic acid, 100 mg each administered intravenously three times per week for eight weeks of treatment and four months of post-treatment follow-up. RESULTS: The demographic characteristics of 22 diabetic uremic patients show that mean age is 63.6 +/- 10.2 years old. The ratio of sex (M/F) = 10/12. Mean duration of HD is 46.7 +/- 33.2 months. As for the urea kinetic study between these two periods including KT/V, nPCR, and URR, there is no significantly different. As for anemia-related parameters, Hb and Hct increased significantly in post-IVAA period after 3 months compared with control period, while MCV did not increase significantly. Serum ferritin significantly decreased at study completion. The same situation is for iron. As for TS, it significantly increased at one month and further markedly increased at subsequent three months. CONCLUSION: This study has demonstrated that short-term low dose IVAA therapy can facilitate iron release from reticuloendothelial system but also increase iron utilization in diabetic hemodialysis patients with iron overload. Therefore, IVAA is a potential adjuvant therapy to treat erythropoeitin-hyporesponsive anemia in iron-overloaded patients.     

Iron deficiency is a common cause of anemia in chronic kidney disease and can often be corrected with intravenous iron

BACKGROUND: There is some epidemiological and clinical evidence that the anemia seen in chronic kidney disease (CKD) in patients not on dialysis could be due to a significant extent to iron deficiency, and that adequate iron replacement could cause a marked improvement in the anemia even without the use of erythropoietin (EPO). The purpose of this work was to study the effects of intravenous (i.v.) iron administration (ferric gluconate - Ferrlecit) on hemoglobin (Hb) of patients with CKD. METHODS: Forty-seven consecutive patients with CKD with Hb <12 g/dL in whom no underlying cause for the anemia could be found underwent sternal bone marrow biopsy and had their red cell and blood iron parameters measured. They then received 250 mg of ferric gluconate (Ferrlecit) intravenously twice monthly for 3 months, and had their blood parameters measured 1 month later. No patient received erythropoietin (EPO). RESULTS: Forty-six patients had no evidence of any iron deposits in the bone marrow - consistent with the presence of severe iron deficiency. The mean serum ferritin and %transferrin saturation prior to treatment were 235.9 +/- 54.3 ug/L and 13.5 +/- 4.1%, respectively, and both increased significantly with the iron treatment. Mean Hb increased from 10.16 +/- 1.32 to 11.96 +/- 1.52 g/dL, an increase of 1.80 +/- 1.72 g/dL (p<0.01). Twenty-six patients (55.3%) reached the target Hb of 12 g/dL. Ten patients (21.3%) had an increase of 0.1-0.9 g/dL, nine patients (19.1%) had an increase of 1-1.9 g/dL and 23 patients (48.9%) had an increase of >or= 2 g/dL. CONCLUSIONS: Iron deficiency is frequently seen in anemic CKD patients not on dialysis and its correction with i.v. iron will often cause a marked increase in the Hb level, and the achievement of the target Hb of 12 g/dL even without EPO.     

Soluble transferrin receptor is correlated with erythropoietin sensitivity in dialysis patients.

BACKGROUND: Iron deficiency is the most common cause of erythropoietin (EPO) resistance in dialyzed patients with renal anemia. Subclinical or functional iron deficiency is difficult to diagnose in these patients. The soluble transferrin receptor (sTf-R) is considered as a sensitive and specific indicator of bone marrow iron availability. PATIENTS AND METHODS: To evaluate the clinical usefulness of this novel marker, we investigated relationships between EPO requirements and various hematological and biochemical parameters of erythropoiesis in 27 pediatric end-stage renal failure patients treated by hemodialysis (HD, n = 11) or chronic peritoneal dialysis (PD, n = 16). Iron was substituted intravenously once or twice per week in HD, and by daily oral administration to PD patients. Serum sTf-R concentrations were measured by an enzyme-linked immunosorbent assay. Serum ferritin and transferrin concentrations were determined using nephelometric assays. Hemoglobin and iron levels were estimated by automated procedures. RESULTS: While neither transferrin saturation nor serum ferritin concentrations were indicative of EPO requirements, a highly significant correlation between the EPO efficacy index (EPO dose divided by hemoglobin concentration) and sTf-R was observed (r = 0.65, p = 0.001). The intravenous iron substitution in HD patients was associated with higher ferritin concentrations compared to the orally substituted PD patients (280+/-100 ng/ml vs. 124+/-83 ng/ml, p<0.002). In contrast, sTf-R concentrations were similar in both treatment groups (25.7+/-7.7 nM vs. 27+/-10.8 nM, n.s.), as were hemoglobin concentrations and EPO requirements. CONCLUSION: Our results suggest that sTf-R is a more sensitive indicator of functional iron deficiency and impaired EPO responsiveness than serum ferritin or transferrin saturation in dialyzed patients. Intensified iron substitution to patients with elevated sTf-R concentrations may considerably improve the cost efficacy of EPO treatment.     

Impact of nocturnal hemodialysis on the variability of heart rate and duration of hypoxemia during sleep

BACKGROUND: Nocturnal hemodialysis (NHD) alleviates uremia-related sleep apnea, a condition characterized by increased sympathetic activity and diminished heart rate (HR) variability. We tested the hypothesis that NHD reduces both hypoxemia and sympathetic neural contributions to HR variability during sleep. METHODS: Episodes of apnea and hypopnea and the duration of nocturnal hypoxemia during sleep were determined in 9 end-stage renal disease (ESRD) patients (age: 44 +/- 2) (mean +/- SEM) before and after conversion from conventional hemodialysis (CHD) to NHD, and in 10 control subjects (age: 45 +/- 3) with normal renal function and without sleep apnea. Low frequency (LF) (0.05-0.15 Hz) and high frequency (HF) (0.15-0.5 Hz) HR spectral power during stage 2 sleep was calculated (Fast Fourier transformation). Patients were studied 4 times (1 day before and on the night after their CHD session) and 6-15 months after conversion to NHD, while receiving NHD and on a non-dialysis night. RESULTS: NHD decreased the frequency of apnea and hypopnea (from 29.7 +/- 9.3 to 8.2 +/- 2.0 episodes per hour, P= 0.02), and duration of nocturnal hypoxemia (from 13.9 +/- 5.2 to 2.6 +/- 1.9% of total sleep time, P= 0.02). As CHD recipients, ESRD patients had faster nocturnal heart rates (79 +/- 2 vs. 58 +/- 1 min-1, P= 0.03) and lower HF (vagal) (78 +/- 27 vs. 6726 +/- 4556 ms2, P= 0.001) spectral power than control subjects. After conversion to NHD, HR fell (from 79 +/- 2 to 66 +/- 1 min-1, P= 0.03) and HF power increased (from 78 +/- 27 to 637 +/- 139 ms2, P= 0.001). The HF/HF+LF ratio, an index of vagal HR modulation, was lower during CHD (0.16 +/- 0.03 vs. 0.42 +/- 0.05 in control subjects, P < 0.05) and increased (to 0.45 +/- 0.05, P < 0.001) after conversion to NHD. The LF/HF ratio, a representation of sympathetic HR modulation, which was significantly higher during CHD than in control subjects (2.77 +/- 0.82 vs. 0.71 +/- 0.11, P < 0.05), was also normalized by NHD (0.74 +/- 0.12, P < 0.05, compared with CHD). CONCLUSION: Higher heart rates and impaired vagal and augmented sympathetic HR modulation during sleep in ESRD patients are normalized by NHD. Potential mechanisms for these observations include attenuation of surges in sympathetic outflow elicited by apnea and hypoxia during sleep, normalization of nocturnal breathing patterns that influence HRV, and removal, by increased dialysis, of a sympatho-excitatory stimulus of renal origin.     

Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial

BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency (FID) often develop resistance to recombinant human erythropoietin (rHuEpo). In these patients, iron therapy may be a hazard, leading to iron overload and consequently to hemosiderosis. Recent studies suggest that intravenous ascorbic acid (IVAA) may circumvent rHuEpo resistance. The aim of our study was to show the effects of IVAA on FID and whether this results in a better correction of anemia in HD patients with stable hemoglobin (Hb) concentration and FID. METHODS: Twenty-seven HD patients with serum ferritin >300 microg/l, transferrin saturation (TS) <20% and hemoglobin (Hb) <10 g/dL were selected andrandomly divided into two groups to enter a cross-over trial with IVAA. In group I IV vitamin C 500 mg was administered three times a week for three months and discontinued in the next three months of the study. Vitamin C was not given the first three months in group II (control group, first three months of the study), who then received 500 mg IV three times a week for the next three months. RESULTS: Hb and TS% significantly increased (baselines vs 3 months, Hb 9.2 +/- 0.2 vs 10.0 +/- 0.3 g/dL, TS% 17.5 +/- 0.6 vs 25.7 +/- 1.7, respectively p < 0.01 and p <0.001) in group I after three months; ferritin fell significantly from 572 +/- 40 to 398 +/- 55 microg/L (p<0.004). Ten patients completed the study: mean Hb and TS% fell significantly (3 months vs final, Hb 9.9 +/- 0.3 vs 8.9 +/- 0.2 g/dL, TS% 25.1 +/- 1.2 vs 19.1 +/- 1.1, respectively p < 0.01 and p <0.001), while mean ferritin did not change. Mean Hb, ferritin and TS% remained unchanged in group II after three months. Hb and TS% mean values rose significantly (3 months vs final, Hb 9.0 +/- 0.2 vs 9.9 +/- 0.2 g/dl, TS% 18.4 +/- 1.0 vs 27.0 +/- 1.0, respectively p < 0.005 and p <0.001), and ferritin markedly decreased from 450 +/- 50 to 206 +/- 24 microg/L (p < 0.001) at the end of the study. The rHuEpo dose was kept unchanged throughout the study. Differences were analyzed after three months. Mean Hb rose (0.8 +/- 0.2 g/dL) in group I but dropped (-0.1 +/- 0.1 g/dL) (p< 0.009) in group II. Ferritin dropped in both groups (group I vs group II, -173 + /-48 vs - 33 +/- 21 microg/L) (p < 0.01) while TS% increased (group I vs group II, 8.2 +/- 1.5 vs 0.4 +/- 0.7) (p < 0.001). CONCLUSION: IVAA may partially correct FID and consequently help rHuEpo hyporesponsive anemia.     

Nocturnal haemodialysis increases pharyngeal size in patients with sleep apnoea and end-stage renal disease.

BACKGROUND: Sleep apnoea is common in patients with end-stage renal disease (ESRD) and is improved by nocturnal haemodialysis (NHD). Recent findings from our laboratory indicate the development of ESRD is associated with pharyngeal narrowing. We hypothesized that NHD increases pharyngeal cross-sectional area and that this is associated with an improvement in sleep apnoea. METHODS: Twenty-four patients (aged 32-68 years), receiving conventional haemodialysis (CHD) (4 h/day, 3 days/week), were recruited for overnight polysomnography and estimation of pharyngeal cross-sectional area at functional residual capacity (FRC) and residual volume (RV). Patients were divided into apnoeic and non-apnoeic groups based on an apnoea-hypopnoea index (AHI) > or = 15/h. Following conversion from CHD to NHD (8 h/night, 3-6 nights/week) all measurements were repeated and apnoeic patients were classified as 'responders' if AHI fell to < 15 events/h. RESULTS: Conversion from CHD to NHD was associated with an increase in pharyngeal cross-sectional area (FRC: 3.29 +/- 0.67 vs 3.39 +/- 0.75 cm(2); RV: 1.91 +/- 0.51 vs 2.13 +/- 0.48 cm(2), P < 0.05), which was not significantly different between groups. Sleep apnoea improved in three patients. CONCLUSIONS: Conversion from CHD to NHD is associated with an increase in pharyngeal cross-sectional area. This may play a role in some patients whose sleep apnoea improves on NHD.     

Lower erythropoietin and iron supplementation are required in hemodialysis patients with hepatitis C virus infection

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common infectious agent in chronic hemodialysis (HD) patients. In this prospective case-control study, we aimed to investigate the influence of chronic HCV infection on erythropoietin (EPO) and iron requirement in HD patients. PATIENTS AND METHODS: 49 HD patients (24 male, 25 female, mean age 47 +/- 15 years) were included. The mean time spent on dialysis was 39 +/- 38 months, and follow-up time was 1 year for this study. Biochemical analyses and complete blood counts together with iron status of the patients (transferrin saturation and serum ferritin levels) were measured monthly. Highly sensitive C-reactive protein (hs-CRP) levels were measured within 3-month intervals. Endogenous EPO levels were measured by enzyme-linked immunoassay 2 weeks after cessation of EPO treatment. RESULTS: Eleven of the HD patients (22%) were anti-HCV(+). There was no difference in age, sex, time on dialysis, distribution of primary renal diseases, predialytic BUN, Kt/V, albumin and i-PTH levels between HCV(+) and (-) patients. Anti-HCV-positive patients required significantly lower weekly doses of EPO (87 +/- 25 IU/kg vs 129 +/- 11 IU/kg, p = 0.042) and iron (16.8 +/- 12.2 mg vs 32.6 +/- 16.1 mg, p = 0.02) replacement than anti-HCV(-) group; hs-CRP levels were similar between study groups. Serum endogenous EPO levels were significantly higher in HCV(+) patients than HCV(-) HD patients (9.43 +/- 6.47 mU/ml vs 3.59 +/- 2.08 mU/ml, p = 0.008). CONCLUSION: Anti-HCV(+) HD patients had higher serum EPO levels and required less EPO and iron replacement as compared to anti-HCV(-) patients. Because of the changes in iron metabolism, iron treatment should be carefully administered in HD patients with HCV.     

Soluble transferrin receptors and reticulocyte hemoglobin concentration in the assessment of iron deficiency in hemodialysis patients

BACKGROUND: Diagnosing iron deficiency in hemodialysis (HD) patients is crucial for correct anemia management. Hypochromic erythrocytes appear to be the best available marker, but they are often unavailable. Transferrin saturation (TSAT) and ferritin are also indicated as reference markers by guidelines. We evaluated the usefulness of soluble transferrin receptor (s-TfR) and reticulocyte hemoglobin concentration (CHr), which have been recently proposed as more sensitive functional iron deficiency indicators. METHODS: A single-center unselected cohort of 39 chronic HD patients underwent a cross-sectional determination of hemoglobin (Hb), hematocrit (Hct), CHr, transferrin, iron, TSAT, ferritin, folate, vitamin B12 and s-TfR. Twenty-nine patients (74.4%) were treated with subcutaneous erythropoietin (EPO) at a dose of 122 +/- 98 U/kg/week and 24 patients (61.5%) were treated with intravenous (i.v.) iron gluconate, 62.5 mg/week. RESULTS: Hb was 11.1 +/- 1.2 g/dL, Hct 34.4 +/- 3.7%, CHr 32.7 +/- 3.8 pg, transferrin 170 +/- 31 mg/dL, iron 60.2 +/- 25.9 mg/dL, TSAT 30 +/- 18%; ferritin 204 +/- 219 ng/mL, folate 4.2 +/- 1.0 mcg/L, vitamin B12 0.58 +/- 0.15 mcg/L, and s-TfR 1.94 +/- 0.83 mg/L. Both TSAT and s-TfR significantly correlated with CHr, but no relationship could be found between s-TfR and TSAT or between s-TfR and ferritin. Dividing the population into two groups based on iron repletion (ferritin >100 ng/mL and TSAT >20%) we found no differences for CHr levels and significantly lower levels of s-TfR in the replete group (s-TfR 1.71 +/- 0.70 vs. 2.29 +/- 0.90 mg/L; p=0.033). Analysis of 2x2 tables demonstrated that 44% of patients with TSAT >20% had elevated (>1.5 mg/L) s-TfR, indicating a possible functional iron deficiency, but covariance analysis showed that TSAT had a better correlation to CHr. CONCLUSIONS: No clear-cut advantages in the use of CHr content and s-TfR levels as single diagnostic tests could be demonstrated by this cross-sectional study. However, our results suggest that the combined use of TSAT <20% and s-TfR >1.5 mg/L (therefore, including all patients with low TSAT, but also patients with high s-TfR despite normal TSAT) could improve functional iron deficiency detection in dialysis patients suspected of having inflammatory conditions.     

Short-term effects of nocturnal haemodialysis on carnitine metabolism.

BACKGROUND: Functional carnitine deficiency [as indicated by an abnormal acyl-carnitine/free-carnitine (AC:FC) ratio] is commonly seen in patients with end-stage renal disease (ESRD), resulting in significant clinical detriments including anaemia, cardiomyopathy and muscle weakness. Nocturnal haemodialysis (NHD) (5-6 sessions per week, 8 h per treatment) has been reported to reverse several surrogate markers of uraemia. Conversely, as a consequence of increased dialysis dose, NHD may have the potential to aggravate plasma nutrient deficiencies. Our objective was to determine the effects of NHD on plasma free-carnitine levels and carnitine metabolism. METHODS: We conducted an observational cohort study with a before and after design. Nine ESRD patients (age: 47 +/- 3; mean +/- SEM) were studied. Routine biochemical, haemodynamic and carnitine metabolic products were analysed at baseline while on conventional haemodialysis and 2 months post-conversion to NHD. Free-carnitine and total-carnitine levels were generated by colorimetric assays. The difference between total- and free-carnitine concentrations was estimated to be the acyl-carnitine level. Paired t-test was used to ascertain statistical significance. RESULTS: After conversion to NHD, there was a significant increase in urea clearance in all patients. Plasma free-carnitine levels fell from 26.54 +/- 2.99 to 15.6 +/- 2.34 micromol/l (P < 000.1). A similar reduction in plasma acyl-carnitine levels was observed (from 13.22 +/- 1.34 to 6.24 +/- 1.20 micromol/l (P < 0.001)). The AC:FC ratio improved from 0.51 +/- 0.03 to 0.39 +/- 0.03 (P < 0.005) (Normal < 0.25). CONCLUSION: NHD is associated with an improvement in AC:FC ratio. Further research is needed to examine the longitudinal clinical impact of this metabolic correction and to examine whether this effect is sustained.     

The influence of l-carnitine supplementation on hematocrit and hemoglobin levels in patients with end stage renal failure on CAPD

The influence of L-carnitine supplementation on hematocrit (Hct) and hemoglobin (Hb) levels, in patients suffering from end stage renal disease (ESRD) on maintenance hemodialysis, are well known from several studies. The data concerning the serum levels of carnitine, in patients with ESRD on continuous ambulatory peritoneal dialysis (CAPD) are contradictory, but most of them support that they are rather normal. In this study the effect of L-carnitine supplementation on Hct, and Hb levels were investigated in patients suffering from ESRD on CAPD. In the study 12 patients were included (5F, 7M), aged from 39 to 92 years old (median 65.5 years), who were on CAPD for more than 6 months (from 6 to 15 months, mean +/- SD = 8.6 +/- 3.6), with normal serum ferrum and ferritin levels at the beginning of the study. Two grams of L-carnitine/ day per os (Superamin, Vianex Hellas), were administered in all the patients and the serum ferrum levels were tried to be kept stable, by exogenous ferrum administration, during the study period. If the Hct levels were more than 36% per month the erythropoietin (rHuEpo) dose of the patient was decreased monthly at the half dose/week. The changes of Hct, Hb, ferrum and ferritin levels, as well as the Indice de Rigidite (IR) of the erythrocytes were recorded, before and after the first, second and third month of the study period. Finally, the rHuEpo dose/ patient was registered monthly before and during the study. During the observations, Hct (35.4 +/- 3.3 vs. 38.1 +/- 3.4, ANOVA, p < 0.03) and Hb levels (11.0 +/- 1.1 vs. 11.9 +/- 1, ANOVA, p < 0.01), were significantly increased. On the other hand, rHuEpo dose necessity/patient/week was decreased significantly (3,833 +/- 3326 vs. 1,292 +/- 1,712, ANOVA, p < 0.01), in order to succeed the target Hct level. Furthermore, red blood cells IR also appeared to have a significant decrease (16.6 +/- 7.4 vs. 13.0 +/- 3.9, paired t-test, p < 0.03). Finally, the ferrum and ferritin levels were stable during the study period. It was concluded, that in patients on, CAPD the per os L-carnitine supplementation decreased, the red blood cells IR which contributes to the: (a) Increase of Hct and Hb levels and (b) decrease of the patients rHuEpo dose/week.     

Intravenous iron treatment of renal anemia in children on hemodialysis

Treatment of anemia in children with end-stage renal disease (ESRD) has been greatly facilitated by the introduction of recombinant human erythropoietin (rHuEPO). A major limiting factor in the treatment of renal anemia is sufficient iron supplementation. Eight children (aged 10–17 years) receiving hemodialysis were treated with intravenous iron (1 mg/kg per week) for 3 months. Hemoglobin (Hb), hematocrit (Hct), and serum ferritin levels were measured regularly. The mean Hct increased from 25% to 30%, the mean Hb increased from 7.8 g/dl to 9.2 g/dl, and the mean ferritin level from 200 to 395 mg/dl. The mean EPO dosage could be tapered from 6,500 IU to 6,150 IU. No adverse side-effects were noted. Hence, in this uncontrolled study intravenous iron was an effective treatment for iron deficiency during rHuEPO therapy in children with ESRD on hemodialysis. Received: 30 October 1997 / Revised: 17 November 1998 / Accepted: 18 November 1998     

Erythropoiesis and renal transplant pregnancy

OBJECTIVE: To examine erythropoiesis in renal transplant pregnancies. METHODS: Retrospective cohort study of 30 renal transplant cases and 30 age, smoking and parity-matched healthy controls with normal index pregnancy. Retrospective chart review and assay of frozen antenatal serum (for serum erythropoietin concentration [serum EPO]), transferrin receptor protein [TfR], ferritin, folate and B12) were performed. The linear regression equation for normal pregnancy controls was used to calculate predicted [serum EPO] and the observed/predicted (O/P) log [serum EPO] was plotted. The relationship between [serum EPO] and haemoglobin (Hb) among transplant cases was considered to be different from that among controls if the slope of the O/P log [serum EPO] versus Hb regression was significantly different from zero. RESULTS: The transplant (14 cadaveric) to conception interval was (median [range]) 33.5 [4, 189] months. Immunosuppressants were azathioprine (n = 25), cyclosporine (n = 22) and/or prednisone (n = 25). Cases were more often primiparous (20 vs. 7 [controls]; p = 0.01), had pre-existent hypertension (20 vs. 0 [controls]; p < 0.001), developed new/increased hypertension or pre-eclampsia (28 vs. 0 [controls]; p < 0.001) and an antenatal rise in creatinine (14 vs. 2 [controls]; p < 0.001). In early pregnancy, cases had similar EPO (15.2 [2.6, 84.6] vs. 15.7 [6.4, 41.0] [controls] U/L) but lower Hb (101 [65, 129] vs. 116 [106, 150] g/L; p < 0.001). Twenty-two (73%) cases had Hb < 100 g/L (vs. 4 [controls]; p < 0.0001); Hb was comparable at 6 wk postpartum. With advancing gestational age (GA), Hb remained stable and serum EPO increased in both groups. The slope of the O/P log [serum EPO] versus Hb for transplant cases was significantly different from zero within both the 17-28 wk (slope +/- SEM: 0.010 +/- 0.002; p < 0.0001) and the 29-42 wk GA categories (0.006 +/- 0.003; p = 0.02). Cases showed smaller rises in serum TfR (change 481 [- 1471, 2780]) vs. 1119 [- 698, 4195] [controls] ng/mL; p = 0.005). CONCLUSIONS: Anaemia frequently complicates renal transplant pregnancies, in which serum EPO is inappropriately low and the rate of erythropoiesis blunted.     

The natural history of coronary calcification progression in a cohort of nocturnal haemodialysis patients.

BACKGROUND: End-stage renal disease (ESRD) is associated with a markedly increased cardiac calcification burden, as reflected by computed tomography scans of the heart. Nocturnal haemodialysis (NHD) is a novel form of renal replacement therapy which has multiple physiologic effects that may affect vascular calcification, including improvements in phosphate and uraemia control. The objective of the present study is the determination of the natural history of coronary calcification progression in patients converted to NHD, and the examination of the relationships between calcification risk factors and calcification progression in these patients. METHODS: Thirty-eight ESRD patients were converted to NHD, and included in our observational cohort study. Coronary artery calcification scores (CACS) were documented at baseline and post-conversion (mean interscan duration 16+/-1 months). Other variables of interest included age, dialysis vintage, Framingham risk profile, phosphate binder and vitamin D usage, and plasma levels of calcium, phosphate and parathyroid hormone. RESULTS: Our cohort was stratified according to baseline calcification burden (minimal calcification: CACS < or = 10 vs significant calcification: CACS > 10). Twenty-four patients had baseline CACS < or = 10. These patients demonstrated no change in coronary calcification after 1 year of NHD (from 0.7+/-0.5 to 6+/-3, P = 0.1). Fourteen patients had higher initial CACS at baseline (1874+/-696), and demonstrated a non-significant 9% increase over 1 year to 2038+/-740 (P = 0.1). Plasma phosphate and calcium x phosphate product were significantly reduced, as were calcium-based phosphate binder and antihypertensive usage. CONCLUSIONS: Our study is the first to document CACS progression in a cohort of NHD patients. Further analysis of the effect of NHD on the physiology of cardiovascular calcification is required.     

Elderly Patients on Chronic Hemodialysis with Hyperparathyroidism: Increase of Hemoglobin Level after Intravenous Calcitriol

In patients on chronic hemodialysis (CHD), hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). In the last few years, calcitriol intravenously (IV) has been used with success in the treatment of the HPTH, secondary to chronic renal failure. However, the effects of calcitriol on the hematological parameters of these patients have never been well evaluated. This study included 11 elderly CHD patients (f = 6, m = 5; mean age = 73.6 years, mean time on CHD = 42.8 months) with HPTH under EPO therapy (IV). They were treated for 12 months with calcitriol IV (mean dose=2.33 mcg/pt/week). Patients with iron deficiency anemia (ferritin < 200 ng/ml) were excluded. The patients were compared before and after 12 months of calcitriol treatment, with respect to several laboratory parameters and with respect to EPO dose. A paired t-test was used. After treatment, we found a decrease of PTH (634 vs. 418 pg/ml, P = 0.029); the serum calcium increased (8.8 vs. 9.9 mg/dl, P = 0.002); no differences were noted in the plasma levels of alkaline phosphatase, phosphorous, BUN, creatinine, Na and K. Mean levels of Hb (10.2 vs. 11.4 g/dl, P = 0.004) and the Hct (30 vs. 34.3, P = 0.004) increased after 12 months of calcitriol; the levels of serum iron (70 vs. 78 μg/dl, P = ns) and ferritin (531 vs. 785 ng/ml, P = ns) and the EPO dose (105 vs. 100 U/kg/week, P = ns) were similar before and after treatment. Our data show that the treatment of HPTH in CHD elderly patients with calcitriol can increase Hb level without increasing EPO dose.