Effect of recombinant human erythropoietin on renal function in predialysis patients

To assess the effect of recombinant human erythropoietin (EPO) on renal function, the slopes of the regression lines of the reciprocal of serum Cr versus month (l/Cr) were studied in 8 pre-dialysis outpatients (2.9 ml/min. less than Ccr less than 17.0, 21.4% less than Ht less than 27.9) who had been followed for a period of 19 to 94 months. EPO was initially given 3000-6000 U (133 +/- 31 U/Kg/week) once weekly by the intravenous route and was later switched to the dose to achieve a Ht level of 30-35%. Mean Ht increased from 23.6 +/- 0.9 to 33.2 +/- 1.1%, and quality of life and exercise capacity were significantly improved in all patients. The mean slopes of l/Cr after EPO (-0.0050 +/- 0.0020) were not significantly different from the values before EPO (-0.0064 +/- 0.0010). The slopes of l/Cr were significantly decreased by EPO therapy in three patients observed for more than 17 months, however in one patient, it increased significantly during EPO treatment. There were no significant differences in the other 4 patients. The renal function at the initiation of EPO in a patient with increase slope of l/Cr had been the worst, and Ht was mildly increased from 21.4% to 24.1% and the blood pressure did not change significantly. The good effect on renal function observed in 3 patients may, in part, be due to better control of blood pressure and physical condition (including cardiac and immunological function) by the more close follow-up of the patients and the improvement of anemia during the period of EPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autologous blood transfusion aided with erythropoietin in transurethral resection of the prostate]

Erythropoietin (EPO) with an established clinical efficacy in renal anemia has in recent years become applied as an aid to autologous blood transfusion in surgical patients. This report describes our experience with autotransfusion along with the use of EPO in transurethral resection of the prostate (TUR-P), indicating its usefulness. Ten patients with benign prostatic hypertrophy aged 60 to 74 years received 3000 units of EPO, with an iron preparation, nine times beginning 3 weeks prior to operation. Autologous blood of 300 ml was collected from the patient each at 2 and 1 week before operation and was used at TUR-P. Five other patients who underwent TUR-P with the same volume of autotransfusion accompanied by preparative medication with the iron alone served as controls. In the EPO treated group (mean age, 68.3 years) the mean value for hemoglobin concentration (Hb) was 14.0 +/- 1.6 g/dl on the day of operation, which showed a recovery rate of 94.9 +/- 5.4% (Hb recovery rate) as against the pre-EPO treatment value (mean: 14.8 +/- 1.3 g/dl). This Hb recovery rate was significantly greater (p less than 0.001) when compared to 82.2 +/- 2.5% in the control group (mean age, 68.2 years). Of the EPO treated patients, those in their sixties (n = 6; mean age, 66.3 years) exhibited a significantly higher Hb recovery rate (98.3 +/- 3.5%) than the rate (89.9 +/- 3.0%) for patients in their seventies (N = 4; mean age, 71.3 years) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

An underappreciated problem in renal transplant recipients: anemia

PURPOSE: Posttransplant anemia (PTA) is associated with a higher risk of cardiac mortality, which is the most frequent cause of death among renal transplant recipients. In this study, we sought to determine the prevalence and causes of PTA among Turkish patients. PATIENTS AND METHODS: The study included 75 (52 male, 23 female) adults. Anemia was defined as an hemoglobin (Hb) level < or = 13 g/dL for men and < or = 12 g/dL for women. RESULTS: The prevalence of PTA was 49.3% at a mean duration of 60.45 months after renal transplantation. The most frequent causes of PTA were erythropoietin (EPO) and iron deficiency. The mean Hb level of 12.76 +/- 2.31 g/dL was significantly higher in male compared to female patients (13.26 +/- 2.31 g/dL vs 11.64 +/- 1.93 g/dL, P = .005). The Hb value was positively correlated with creatinine clearance and serum albumin level, and negatively correlated with serum creatinine level, the amount of proteinuria, and cyclosporine level. Creatinine clearance and serum albumin level were found to be an independent risk factors for PTA upon multivariate analysis. Only 12 of 37 anemic patients received treatment for anemia: 5 (13.5%) with EPO and 7 (18.9%) with iron preparations. CONCLUSION: PTA a common complication was unfortunately neglected in this setting. Impaired renal allograft function and decreased serum albumin were major risk factors for PTA. Increased cyclosporine levels were also correlated with decreased Hb concentrations.     

Serum erythropoietin levels and their correlation with the erythropoietic system in hemodialysis patients and renal allograft recipients

BACKGROUND: Following renal transplantation, serum erythropoietin (EPO) levels gradually increase during the first 2 to 3 months. However, some transplant recipients continue to remain anemic. The aim of the present study was to correlate serum EPO concentrations with hematocrit (Hct) and hemoglobin (Hb) levels in hemodialysis (HD) patients and renal allograft recipients. METHODS: In a comparative cross-sectional study, serum EPO concentrations and Hb and Hct levels were measured in 35 chronic HD patients and 40 transplant recipients who had stable kidney function for at least 6 months after transplantation (group 1). The HD patients were further divided based on their recombinant human (rHu) EPO supplementation into those who received rHu EPO during dialysis (group 2A, n=15) and those who were not on rHu EPO (group 2B, n=20). Data are presented as mean values +/- SD. The statistical analysis was performed by SPSS version 11.0 using chi-square, ANOVA, and Pearson correlation tests. A general linear model (GLM) was used to compensate for the effects of age. The P value for significance was set at .05. RESULTS: Group 2B patients tended to be older than groups 1 and 2A (P=.014). The sex ratios were comparable among groups. Mean EPO level was 17.09 +/- 10.99 mIU/mL in recipients, which was comparable with that of HD patients (18.54 +/- 26.18 mIU/mL; P>.05). No significant correlation was observed between the serum EPO concentrations and Hb and Hct levels in recipients (P>.05). When comparing the 3 groups, EPO was not correlated with Hct and Hb in any group. Hb and Hct were significantly higher among HD patients not on rHu EPO therapy (P=.02). GLM, with age as a covariate, did not yield a significant difference between EPO levels of the studied groups (P=.36). CONCLUSIONS: This study showed that serum EPO level was in the normal range in recipients and HD patients. We were not able to find any correlation between Hb and Hct levels and EPO concentrations in any group of patients irrespective of rHu EPO supplementation. Hence, impaired EPO stimulatory effects may be considered a potential contributor to anemia in these patients.     

The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome

BACKGROUND: The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. METHODS: A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. RESULTS: Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. CONCLUSIONS: EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.     

Efficacy of erythropoietin administration in the treatment of anemia immediately after renal transplantation

Anemia negatively impacts cardiovascular comorbidity and hospitalization. In animals, recombinant erythropoietin (RhuEPO) leads to faster recovery after acute tubular necrosis. This study evaluates the effect of RhuEPO (Recormon, Hoffman-La Roche, Basel, Switzerland) on the correction of anemia and kidney function after renal transplantation. Patients receiving a renal transplant were randomized to receive or not receive RhuEPO 100 U/kg three times per week if the hemoglobin (Hb) level was less than 12.5 g/dL. The time to reach an Hb level greater than 12.5 g/dL was 66.5+/-14.5 days versus 52.6+/-23.7 days in the non-EPO and EPO groups, respectively (P=0.05). After 3 months, Hb levels were not different between the non-EPO and EPO groups (12.6+/-1.5 g/dL vs. 12.0+/-1.5 g/dL, respectively), although there was a higher increase in the EPO group (4.1+/-1.1 g/dL vs. 3.2+/-1.1 g/dL, P=0.02). In a Cox regression analysis, EPO use (relative risk 7.2, P=0.004) and dose (relative risk=0.63, P=0.04) were retained as independent variables predicting the time to reach an Hb level greater than 12.5 g/dL. In the EPO group, 14 of 22 patients reached the target Hb level of more than 12.5 g/dL versus 12 of 18 patients in the non-EPO group (P=not significant). Serum creatinine levels were not different between groups. RhuEPO in the immediate posttransplantation period seems to have no relevant clinical impact on the correction of anemia. There was no difference in the evolution of serum creatinine levels. In view of the cost, the use of RhuEpo in the posttransplantation period should be limited to high-risk patients.     

Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease

AIM: Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. METHODS: In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. RESULTS: There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up. CONCLUSIONS: Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.     

Effect of cyclosporine and delayed graft function on posttransplantation erythropoiesis

The effect of delayed graft function and immunosuppressive drugs on posttransplant erythropoiesis was studied prospectively in 18 living-related (LR) and 84 cadaver-donor (CD) recipients. Eight of 18 LR and 20 of 84 CD recipients received antilymphoblast globulin (ALG) in addition to azathioprine and prednisone. Sixty-four CD recipients received cyclosporine (CsA) with prednisone. In the absence of rejection reticulocytosis began 6.7 +/- 0.2 days following graft implantation in azathioprine-only-treated LR recipients. This was lengthened by ALG to 9.4 +/- 0.3 and 9.9 +/- 0.7 days in LR and CD recipients, respectively, whose grafts functioned immediately. Delayed graft function prolonged onset of reticulocytosis to 15.9 +/- 0.9 days in ALG-treated but not in CsA-treated recipients (5.8 +/- 0.4 days). The shortest latency was noted in CsA-treated recipients (4.9 +/- 0.5 days) with immediately functioning grafts. The earlier onset of reticulocytosis of CsA-treated recipients was followed by statistically significant blunting of peak reticulocytosis, which correlated with a slower rate of correction of anemia (delta Hct = 0.19/day) compared with non-CsA-treated recipients (delta Hct = 0.34/day). Early rejection was associated with abrogation of reticulocytosis and correction of anemia without regard to immunosuppressive regimen) until rejection was reversed. Erythropoietin (EPO) was measured sequentially in 5 patients with immediate function. In 4 of 5 cases changes in EPO preceded those in reticulocytosis. EPO rose from a mean of 13 mU/ml pretransplant to a peak of 50 within 3 weeks and decreased to 18 mU/ml within 6 weeks of graft implantation. At six months posttransplant, normalized reticulocyte counts were only 55% higher (1.75 vs. 1.13%) but hematocrit had increased from 26 +/- 1% to 42 +/- 1%. Hematocrit varied inversely with serum creatinine, which was highest in CsA-treated patients with initial delayed graft function. We conclude that correction of anemia posttransplantation is driven by EPO but other factors may also be important, that neither ATN nor ALG-therapy have clinically important effects on erythropoiesis, and that CsA reduced "effective" erythropoiesis and influences correction of anemia--particularly if delayed graft function complicates the initial course posttransplantation.     

The effect of i.v. iron alone or in combination with low-dose erythropoietin in the rapid correction of anemia of chronic renal failure in the predialysis period

BACKGROUND: It is now more and more evident that anemia of predialysis chronic renal failure (CRF) should be actively treated, since long-standing anemia may cause irremediable damage to the heart. The most common form of treatment of this anemia is subcutaneous erythropoietin (EPO). iron (Fe) deficiency can also contribute to anemia in predialysis CRF, and intravenous iron (i.v. Fe) can frequently improve it. It is possible, therefore, that the combination of EPO and i.v. Fe may have an additive effect, and cause a rapid improvement in anemia with relatively small doses of EPO. PURPOSE: The purpose of this study was an initial study: to assess the ability of a combination of low-dose EPO and i.v. Fe, given weekly for 5 doses, to correct the anemia of predialysis CRF patients compared to the use of i.v. Fe alone in a randomized study. In the follow-up study: to assess the ability of the maintenance of adequate iron stores for one year to achieve and maintain the target Hct of 35% with the minimum dose of EPO. Initial study: METHOD: Ninety predialysis CRF patients (creatinine clearance 10-40 ml/min/1.73 m2 received either: Group A (45 patients): 200 mg i.v. Fe as Fe sucrose (Venofer, Vifor Int.) once per week for 5 doses in combination with 2,000 international units (IU) EPO (Eprex, Cilag-Janssen), subcutaneously given simultaneously also for 5 doses. Group B (45 patients): the same dose of i.v. Fe as in Group A but without EPO. RESULTS: The mean increase in hematocrit (Hct) and hemoglobin (Hb) by one week after the last dose was greater in group A, 4.54 +/- 2.64% (p < 0.01) and 1.37 +/- 0.84 g% (p < 0.01), respectively, than in Group B, 2.74 +/- 2.72% (p < 0.05) and 0.91 +/- 0.78 g% (p < 0.05), respectively. 80% of those in Group A had an increase in Hct of 3 vol% or more compared to 48.9% in Group B (p < 0.01). 40% of those in Group A reached the target Hct of 35% compared to 28.9% in Group B (p > 0.05). Follow-up study: During a 12-month follow-up period, enough i.v. iron was given to maintain the Hct at 35%, while keeping the serum ferritin at < 400 ug/l and % Fe Sat at < 40%. If the i.v. Fe alone was not capable of maintaining the target Hct, EPO was given in increasing doses. Eighteen patients required dialysis. Of the 72 patients who did not require dialysis, 24 (33.3%) maintained the target Hct with i.v. Fe alone, without EPO. All the remaining 48 patients (66.7%) continued to receive EPO in addition to the i.v. Fe, and 47 achieved and maintained the target Hct with a mean EPO dose of 2,979 +/- 1,326 IU/week. CONCLUSION: The combination of low-dose EPO and i.v. Fe had a rapid and additive effect on the correction of anemia in CRF predialysis patients. Maintaining adequate iron stores with i.v. Fe during a subsequent maintenance phase allowed the target Hct of 35% to be reached and maintained with low-dose EPO in two-thirds of the predialysis patients and with no EPO at all in one-third.     

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.     

Current management of renal anemia in patients with chronic kidney disease at the predialysis stage

OBJECTIVE: Patients with chronic kidney disease (CKD) are frequently complicated by renal anemia as renal function declines. However, clinical guidelines on erythrocyte stimulating agents (erythropoietin : EPO) for such patients have not been established. Current clinical practice for EPO administration is based on the recommendations of the Japanese health insurance regulations, which have not always been supported by clinical evidence. MATERIALS & METHODS: The study subjects were 49 patients with CKD staged above 3 who had developed renal anemia requiring EPO. These patients were treated with EPO S. C. at the dose of 6,000 IU/week together with iron supplementation as deemed necessary for more than 24 weeks. RESULTS: The hemoglobin (Hb) value was 9.2 +/- 1.0 g/dL at the start, 10.9 +/- 1.6 g/dL at the peak (n = 49, p < 0.001 the start vs. the peak), and 9.0 +/- 1.6 g/dL at the commencement of dialysis (n = 49, p < 0.001 the peak vs. the commencement of dialysis). Seventy-one percent (35/49) of the patients achieved Hb levels over 10 g/dL, and 51% (25/49) achieved Hb levels over 11 g/dL. Conversely, 28% (14/49) of the patients failed to reach an Hb level over 10 g/dL. Factors explaining the good response to EPO (good responders were defined as those achieving Hb levels over 11 g/dL) had shown high Hb levels at the start (Logistic multiple regression analysis, p = 0.03) along with low creatinine concentration at the start (Cox's proportional hazard models, p = 0.015). Transferrin saturation (TSAT) at the start was 33.6 +/- 13.6%, 34.0 +/- 19.9% at the peak, and 24.7 +/- 11.6% at the commencement of dialysis, showing a significant reduction in TSAT at the commencement of dialysis compared to that at the start (n = 49, p = 0.0383, the start vs. the commencement of dialysis). Serum ferritin concentration was 140.7 +/- 139.5 pg/mL at the start, 107.9 +/- 110.8 pg/mL at the peak, and 131.9 +/- 112.4 pg/mL at the commencement of dialysis, indicating an absence of significant differences among the three time points. CONCLUSION: The current health insurance regulations in Japan seem to be inappropriate in that the permitted EPO dosage of 6,000 IU/week might not be sufficient to achieve the target Hb level of more than 11 g/dL in most patients with CKD. To more efficiently achieve renoprotection, both early and timely initiation of EPO and reconsideration of the recommended EPO dosage appear to be warranted.     

Low-dose subcutaneous erythropoietin corrects the anaemia of renal transplant failure.

Although erythropoietin (Epo) is known to correct anaemia in dialysis and pre-dialysis patients, there is limited experience with its use in immunosuppressed patients suffering from chronic renal graft dysfunction. We report the results of a pilot study of Epo in seven patients with failing grafts and normocytic normochromic anaemia attributable to renal failure. All entering patients had controlled blood pressure and serum ferritin greater than 100 micrograms/l. Three patients were taking triple immunotherapy (prednisone/azathioprine/cyclosporin), two patients prednisone/azathioprine, and two patients CsA monotherapy. Study duration mean was 15 +/- 2 (SEM) weeks, and Epo was started at 4000 units subcutaneously (s.c.) once weekly, adjusted to achieve a target haemoglobin (Hb) of 100 g/l. Mean Hb at initiation was 68 +/- 5 g/l and significantly increased to 96 +/- 6 at end of follow-up, P less than 10(-4). All patients responded. Maintenance Epo dosage was 120 +/- 32 U/kg bodyweight/week, roughly 4000 units/week. There was no significant change in serum creatinine: pre-study 392 +/- 45 mumol/l; post-study 430 +/- 62 mumol/l. There were no complications but blood pressure did rise significantly: pre- 124 +/- 11/74 +/- 4 mmHg to post- 142 +/- 10/86 +/- 3, P less than 0.05 for systolic and diastolic. Low-dose s.c. Epo effectively corrects anaemia in graft failure despite azathioprine and/or CsA therapy, without obvious acceleration of graft failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence and management of anemia in renal transplantation: an observational-French study

The management of anemia after kidney transplantation remains poorly explored. The Management of Anemia in French Kidney Transplant Patients (MATRIX) study is an observational study conducted in 10 academic hospitals among kidney-transplant patients designed to evaluate the prevalence, associated factors and management of post-transplant anemia. Over two consecutive weeks, 418 recipients (males: 248; age: 50.8+/-12.7 years) were included, all were transplanted for more than six months. Mean serum creatinine (Scr) was 152+/-67 micromol/l and mean hemoglobin (Hb) was 12.4+/-1.8 g/dl (males: 12.8+/-1.9 g/dl; females 11.9+/-1.6 g/dl). Irrespective of the delay following transplantation, 23% of patients (n=95) were severely anemic (Hb < or = 11 g/dl). Eighteen percent of the patients received an antianemic treatment (10% oral iron, 7% erythropoiesis stimulating agents (ESA), 4% folic acid) and only 35% of the severely anemic patients were actually treated (n=33). A significantly-negative correlation was observed between eGFR and Hb levels (R= -0.347, p<0.02). Ninety-six percent of the 193 patients transplanted for more than six months and a Scr greater than 150 micromol/l (n=185) suffered at least one comorbidity (89% hypertension, 32% hypercholesterolemia, 13% diabetes); this group represent the second cohort. Seventy-four percent of them were treated with mycophenolate mofetil, 16% with azathioprine, and 62% with an ACEI or angiotensin II receptor antagonists. Since the transplantation, 127 patients (66%) have been anemic (Hb < or = 11 g/dl) and 58% (n=112) were treated (iron and/or ESA, respectively 81 and 55%). Among the patients not treated for anemia, 74% had an Hb level below 12g/dl. ESA-treated patients received a mean dose of 8500 UI+/-2800 per week. Anemia is under-diagnosed and under-treated in renal-transplant recipients, despite its high prevalence. As expected, a correlation between renal function and Hb levels was observed, as in CKD patients. Prospective studies are underway to assess the consequences of postkidney transplant anemia on quality of life, cardiovascular morbidity and chronic allograft nephropathy and to define the benefit of the treatment.     

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.     

Perioperative erythropoietin efficacy in renal transplantation

BACKGROUND: There is no consensus on the usage of erythropoietin in the immediate postoperative period to prevent anemia and delayed graft function. METHODS: A retrospective case note audit of renal transplants included hemoglobin (Hb) and serum creatinine (Scr) values preoperatively as well as at days 7, 14, 30, 60, and 90. Patients were categorized as those receiving erythropoietin during the first 6 months posttransplant (Epo+ve) and those not receiving any erythropoietin (Epo-ve). RESULTS: Hb decreased from 12.4 +/- 1.6 g/L preoperatively to 9.5 +/- 1.5 g/L at day 14 and then rose to 10.5 +/- 1.6 g/L at 1 month and 12.4 +/- 1.7 g/L at 3 months. There was no difference in absolute Hb values in three transplant groups. Scr decreased from 597.0 +/- 200.1 mmol/L preoperatively to 254.1 +/- 196.9 mmol/L at day 14 and continued to fall to 163.8 +/- 98.9 mmol/L at 1 month and 147.8 +/- 66.9 mmol/L at 3 months. There was no difference in absolute Hb values and delayed graft function in the three transplant groups. CONCLUSION: With respect to anemia and delayed graft function, the use of erythropoietin in the first 3 months had little impact. We suggest that such an expensive medication may be safely omitted in the immediate postoperative period.     

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.     

Anemia in pediatric renal transplant recipients

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B₁₂, and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron (P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day (P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of –1.8 compared with –0.9 for those with normal Hb (P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.     

生血宁治疗慢性肾脏病患者贫血的疗效观察

目的观察生血宁治疗慢性肾脏病(CKD)3～4期患者肾性贫血的疗效。 方法收集2012年1月至2014年12月在无锡市锡山人民医院肾内科住院治疗的CKD患者的临床资料,根据其使用治疗贫血药物不同将其分为A、B两组,A组予生血宁片口服,B组予右旋糖酐铁片口服,两组同时接受重组人促红细胞生成素(rhEPO)的治疗,疗程12周(随访至12周)。观察治疗前后患者血红蛋白(Hb)、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)的变化及重组人促红素(rhEPO)的用量,并观察基础指标血清白蛋白(ALB)、尿素氮(BUN)、肌酐(SCr)、C反应蛋白(CRP)的变化。采用SPSS 17.0软件包进行统计学分析。 结果治疗后两组患者的贫血均有改善。A组Hb、SF、TSAT上升的幅度高于B组,差异有统计学意义(P<0.05)。A组rhEPO用量少于B组,差异有统计学意义(Z＝3.058, P<0.05)。治疗后两组肾功能和CRP均无明显变化(P>0.05),A组ALB水平较治疗前明显升高,差异有统计学意义(t＝2.811, P<0.05),A组未见明显不良反应。 结论生血宁可改善铁代谢,治疗CKD患者肾性贫血安全有效,并可以减少rhEPO的用量。     

Treatment of Anemia in Renal Transplantation: Impact of a Stricter Application of Hemoglobin Targets

Objective

The CREATE and CHOIR studies showed a higher risk for cardiovascular events associated with hemoglobin (Hb) values >13 g/dL in patients with stage 3-4 chronic kidney disease. In 2007, a stricter policy on the use of erythropoietin (EPO) was adopted at our center, with an Hb target of 11 to 12 g/dL and withdrawal or reduction of EPO when Hb was >12.5 to 13 g/dL. This study was designed to evaluate this new approach.

Materials and Methods

The study included patients under follow-up at the transplant outpatient clinic on December 31, 2006 (n = 725), and December 31, 2007 (n = 768). Data were compared between the study populations concerning renal function, Hb, use of EPO, and associated costs.

Results

No significant differences in creatinine or Hb values were observed between the 2 groups (1.47 ± 0.6 vs 1.42 ± 0.9 mg/dL and 13.7 ± 1.5 vs 13.7 ± 1.6 g/dL, respectively). After implementation of the new protocol, the frequency of severe anemia (Hb <11 g/dL) increased (2% vs 4%; P = .10), the use of EPO decreased (22.1% vs 17.2%; P = .017), and the mean Hb of EPO-treated patients decreased (12.5 ± 1.4 vs 11.9 ± 1.0; P < .001). The Hb target (11-12 g/dL) was met in fewer than one third of patients, with no significant differences between the 2 study times.

Conclusions

A strict policy on EPO application reduces its use and the rate of patients with “excessive” Hb values (which are associated with increased cardiovascular risks), with an acceptable slight increase in severe anemia cases.     

Efficacy,safety and tolerance of continuous erythropoietin receptor activator intravenous administration on anemia correction in dialysis patientswith chronic renal anemia

Objective To evaluate the efficacy, safety and tolerance of continuous erythropoietin receptor activator (CERA) once every 2 weeks intravenous injection on anemia correction in dialysis patients compared to Epoetin?β (EPO?β) administration. Methods An open?label, randomized, parallel, active?control and multi?center clinical trial was performed. All the hemodialysis or peritoneal dialysis patients with chronic renal anemia who had not been treated with erythropoiesis?stimulating agents (ESAs) for at least 8 weeks before entering the treatment phase were randomized (1∶1) to receive either CERA once every 2 weeks intravenous administration (CERA group, n=132) or intravenous EPO?β three times weekly (EPO group, n=133) for 24 weeks including 16?week correction period and 8?week efficacy evaluation period. At week 25, the patients who reached the target Hb (defined as Hb≥110 g/L and increase in Hb≥10 g/L from baseline without red blood cell transfusion during the 24 weeks after the first dose) were kept on CERA or EPO?β treatment regimen for the subsequent 28 weeks to evaluate the long?term safety and tolerability. The starting dose of CERA was 0.4 μg/kg. Two primary endpoints were (1) the Hb response rate during the first 24 weeks; and (2)the mean change in Hb between the baseline and the evaluation periods (week 17 to week 24). Results Totally 232 patients (87.5%) completed the first 24?week treatment and 198 patients (74.7%) completed the whole study treatment (52 weeks). The response rate in CERA group during the first 24 weeks was 87.12%[95% CI（80.2% to 92.3%）]. Since the lower limit of the 95%CI was greater than 60% (P＜0.01), CERA once every 2 weeks intravenous administration was considered as effective in correction of renal anemia. The difference between CERA group and EPO group in mean change of Hb from evaluation periods to baseline in the per?protocol (PP) population was -4.7 g/L [95%CI (-7.38 g/L to -1.92 g/L)]. Since the lower limit of 95%CI was greater than the pre?defined non?inferiority margin -7.5 g/L (P=0.0205), CERA was considered as non?inferior to EPO in the maintenance of Hb after anemia correction. The Hb level remained stable during the subsequent 28?week extension period in both CERA and EPO groups. During the whole study period, the overall safety findings were similar in CERA and EPO groups, 50.0% and 54.6% of patients experienced at least one adverse event (AE) respectively. The findings from AEs were in accordance with the characteristics of the studied population. Conclusions Intravenous CERA once every 2 weeks is safe and effective for correcting anemia in dialysis patients. Treatment with CERA once every 2 weeks is also non?inferior to 3 times weekly EPO in maintaining the Hb level after the correction. In general, long?term intravenous administration of CERA is well tolerated by dialysis patients with chronic renal anemia.