Relationship among catheter insertions, vascular access infections, and anemia management in hemodialysis patients

BACKGROUND: Arteriovenous fistulas are the recommended permanent vascular access (VA) for chronic hemodialysis. However, in the United States most patients begin chronic hemodialysis with a catheter. Recent data suggest that VA type contributes to recombinant human erythropoietin (rHuEPO) resistance. We examined catheter insertions, VA infections, and anemia management in Medicare, rHuEPO-treated, chronic hemodialysis patients. METHODS: We compared hemoglobin values and rHuEPO and intravenous iron dosing with concurrent catheter insertions and VA infections in 186,348 period-prevalent patients in 2000. We studied anemia management after catheter insertions and VA infections in 67,410 incident patients from 1997 to 1999. Multiple linear regression models examined follow-up hemoglobin and rHuEPO dose per week (rHuEPO/wk) by numbers of catheter insertions and hospitalizations for VA infection. RESULTS: In the prevalent cohort, increasing temporary and permanent catheter insertions and VA infections were associated with slightly lower hemoglobin, higher rHuEPO doses, and higher intravenous iron doses. In the incident cohort, compared to patients with no VA infections or no catheter insertions (temporary or permanent), respectively, patients with 2+ VA infections or 2+ catheter insertions had 0.12 g/dL and 0.06 g/dL lower mean hemoglobin (P = 0.0028 and P < 0.0001), and 25.7% and 12.2% higher mean rHuEPO/wk (P < 0.0001). CONCLUSION: Higher rHuEPO doses may be required to maintain similar or slightly lower mean hemoglobin values among chronic hemodialysis patients with higher numbers of catheter insertions and VA infections, compared to patients without any.     

Hemoglobin variability in epoetin-treated hemodialysis patients

BACKGROUND: Understanding the clinical variability of hemoglobin measurements in epoetin-treated hemodialysis patients is important, particularly when this therapy is aimed at maintaining patient hemoglobin levels within a narrow range, such as the 11 to 12 g/dL range recommended in National Kidney Foundation Kidney Dialysis Outcomes Quality Initiative (NKF-K/DOQI) guidelines. This study examines hemoglobin variability under conditions of standard clinical practice in epoetin-treated hemodialysis patients. METHODS: We studied 987 hemodialysis patients participating in an observational retrospective study that evaluated anemia management practices from October 1, 1996 to December 31, 1997 at 11 United States dialysis centers that were randomly selected from a pool of nearly all United States dialysis facilities. Each participating facility maintained its own anemia management protocols without specific anemia management recommendations or interventions made as part of this study. Hemoglobin variability was determined by calculating the 1-month and 2- to 6-month rolling average hemoglobin for each patient. The range of mean hemoglobin values that included the middle 50% (25th to 75th percentile), 80% (10th to 90th percentile), and 90% (5th to 95th percentile) of values were determined. The hemoglobin ranges that included 1 standard deviation (SD) (67%) of the study values and 2 SD (95%) of the study values for each time period were calculated. RESULTS: The mean hemoglobin was between 10.9 and 11.2 g/dL throughout the study. The hemoglobin range encompassing 50%, 80%, and 90% of values from a single month was 1.7, 3.3, and 4.4 g/dL, respectively. A progressive narrowing in the range of hemoglobin values encompassed by each percentile grouping (i.e., hemoglobin variability) was observed as longer rolling intervals were averaged. The hemoglobin range within the 25th to 75th percentile was 1.7 g/dL using single-month hemoglobin values and 1.1 g/dL using a 6-month rolling average. The range of hemoglobin values that encompassed 90% of patients was 4.4 g/dL using single-month values, 3.7 g/dL using 3-month rolling averages, and 3.2 g/dL using 6-month rolling averages. Fewer than 50% of patients had hemoglobin values within the 1.0 g/dL NKF-K/DOQI recommended range, even when a 6-month rolling average was applied. When hemoglobin values were measured for 1 month, 1 SD was 1.4 g/dL; for the 3-month rolling average, 1 SD was 1.1 g/dL; and for the 4-, 5-, and 6-month rolling averages, 1 SD was 1.0 g/dL. Greater hemoglobin variability correlated with higher mean corpuscular hemoglobin (P = 0.003) and serum ferritin (P = 0.047), and inversely correlated with age (P = 0.006) and serum albumin (P = 0.0001). CONCLUSION: Substantial variability occurs in hemoglobin values in epoetin-treated hemodialysis patients. The NKF-K/DOQI recommended hemoglobin range appears to be too narrow in clinical practice. Expanding the target range and use of rolling average hemoglobin intervals of 3 to 6 months as a clinical and quality assurance measure avoids clinical variability inherent with the use of isolated hemoglobin values or single-month hemoglobin averages.     

Darbepoetin-alfa treatment of anemia secondary to chronic renal failure in dialysis patients: Results of a French multicenter study

Darbepoetin alfa is a unique genetically engineered glycoprotein with a three-fold longer terminal half-life than recombinant human erythropoietin (rHuEPO). The objective of this study was to determine if darbepoetin alfa administered at a reduced dosing frequency relative to the prior rHuEpo regimen is an effective and safe alternative for treating renal anemia in patients undergoing dialysis. A total of 1,008 French hemodialysis and peritoneal dialysis patients receiving stable rHuEPO therapy by either the intravenous (i.v., N = 217) or subcutaneous (s.c., N = 791) route were switched to darbepoetin alfa given by the same route of administration at a reduced dosing frequency. Patients receiving rHuEPO once weekly (N = 248, 25%) were switched to darbepoetin alfa every two weeks, and those receiving rHuEPO two or three times weekly (N = 760, 75%) were switched to darbepoetin alfa once weekly. The doses of darbepoetin alfa were titrated to maintain hemoglobin concentration in the target range of 10.0 to 13.0 g/dl for up to 24 weeks. The primary endpoint was the change in hemoglobin between baseline and the evaluation period (weeks 21-24). Adjusted (for covariates that might influence hemoglobin response) mean change in hemoglobin from baseline to the evaluation period was not clinically significant: +0.11 g/dl (95% CI: -0.30; 0.52). An i.v./s.c. dose ratio of 0.96 (95% CI: 0.86; 1.06) at evaluation confirms previous findings that darbepoetin alfa dose requirements were not different for the s.c. and i.v. routes. At the end of the evaluation period, more than 98% of patients successfully maintained hemoglobin within the target range and at their darbepoetin alfa assigned dosing frequency. Darbepoetin alfa was well tolerated with a safety profile consistent with that observed in previous darbepoetin alfa studies. Darbepoetin alfa administered at a reduced dosing frequency relative to the prior rHuEpo regimen effectively maintains hemoglobin in the target range in dialysis patients with renal anemia.     

Randomized prospective comparison between erythropoietin and androgens in CAPD patients

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

Hemoglobin predicts long-term survival in dialysis patients: a 15-year single-center longitudinal study and a correlation trend between prealbumin and hemoglobin

BACKGROUND: Dialysis patients have much higher mortality rates than the general population. Anemia is a common complication of uremia and a major contributor to morbidity and mortality in dialysis patients. The benefits of anemia correction using recombinant human erythropoietin (rHuEPO) are well established. Optimum hemoglobin level for dialysis patients remain controversial. We have investigated the association of enrollment hemoglobin with long-term survival in hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: We enrolled 529 HD and 326 PD patients from 1987 and followed them to April 2003. Demographics, enrollment, and clinical and laboratory data were recorded. The Kaplan-Meier method was used to compute observed survival, and the multivariate Cox regression analysis was used to identify the independent predictors of mortality risk. RESULTS: Mean ages of HD and PD patients were 60 +/- 16 (SD) and 54 +/- 16 (SD) years, respectively. Forty-seven percent of HD patients and 41% of PD patients were diabetic. Mean enrollment hemoglobin levels of HD and PD patients were 9.44 +/- 1.9 and 9.61 +/- 1.77 g/dL respectively. Cumulative 15 year observed survivals of HD (P = 0.05) and PD (P = 0.032) patients with hemoglobin levels greater or equal to 12 g/dL were higher than those with hemoglobin levels less than 12 g/dL. Hemoglobin <12 g/dL was a better predictor of mortality in nondiabetics than diabetics, particularly in HD patients. Both in HD and PD diabetic patients, hemoglobin was not a significant predictor of mortality. By Cox regression analysis, after adjusting for age, race, gender, and months on dialysis at enrollment, the relative risk of mortality of patients with hemoglobin <12 g/dL was 2.13-fold (P = 0.008) higher for HD and 1.85-fold (P = 0.06) higher for PD compared to those with hemoglobin >/=12 g/dL (P = 0.035). A logistic regression analysis revealed a strong inverse relationship between the hemoglobin level and the odds risk of death in HD (OR = 0.83, P = 0.008) and in PD (OR = 0.85, P = 0.02) patients. CONCLUSION: Enrollment hemoglobin is a predictor of long-term survival in HD and PD patients. Patients with hemoglobin levels that are higher than current treatment recommendations (>12 g/dL) may benefit from long-term survival. Survival of dialysis patients may be improved by better management of malnutrition and anemia.     

Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients

BACKGROUND: Darbepoetin alfa is a glycoprotein with a three-fold longer terminal half-life than recombinant human erythropoietin (rHuEPO). We aimed to determine whether darbepoetin alfa is as effective and well tolerated as rHuEPO for treating renal anemia in dialysis patients when administered at a reduced dose frequency. METHODS: A total of 522 European and Australian hemodialysis and peritoneal dialysis patients receiving stable rHuEPO therapy by either the intravenous (IV) or subcutaneous (SC) route were randomized, open-label in a 1:2 ratio to continue rHuEPO or to receive an equivalent dose of darbepoetin alfa at a reduced dose frequency. Patients receiving rHuEPO once weekly changed to once every other week darbepoetin alfa, and those receiving rHuEPO two or three times weekly changed to once-weekly darbepoetin alfa. The doses of rHuEPO and darbepoetin alfa were titrated to maintain hemoglobin close to the patient's baseline level for up to 52 weeks. The primary endpoint was the change in hemoglobin between baseline and the evaluation period at weeks 25 to 32 of treatment. RESULTS: The mean change in hemoglobin from baseline to the evaluation period was similar in the darbepoetin alfa (-0.03 g/dL; SE 0.11) and rHuEPO (-0.06 g/dL; SE 0.13) groups, and the difference between the two treatments was 0.03 g/dL (95% CI -0.16, 0.21). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. At the end of the evaluation period, >/=95% of patients had their hemoglobin successfully maintained on their assigned dose frequency for darbepoetin alfa (once weekly and once every other week) and rHuEPO (once, twice and three times weekly). The safety profiles of darbepoetin alfa and rHuEPO were similar, and no antibodies to either treatment were detected. CONCLUSIONS: Darbepoetin alfa maintains hemoglobin as effectively as rHuEPO, but with a reduced dose frequency.     

A trial of subcutaneous administration of darbepoetin alfa once every other week for the treatment of anemia in peritoneal dialysis patients

BACKGROUND: Darbepoetin alfa (Aranesp, Amgen) is an erythropoietic stimulating protein with a three fold longer terminal half life than recombinant human erythropoietin (rHuEPO). The purpose of this single center, single arm study was to determine whether darbepoetin alfa is as effective as rHuEPO for the treatment of renal anemia in patients on peritoneal dialysis when administered at a reduced dosing frequency of once every other week irrespective of the initial rHuEPO dose frequency. METHODS: A total of 17 patients on peritoneal dialysis receiving stable rHuEPO therapy were changed to darbepoetin alfa every other week, using the recommended 200:1 conversion factor . The doses of darbepoetin alfa were titrated to maintain hemoglobin within -1.0 to +1.5 g/dL of the patients' baseline value and also within a range of 10.0 to 13.0 g/dL for up to 24 weeks (20 weeks dose titration period followed by 4 week evaluation period). The primary end point was change in hemoglobin levels between baseline and evaluation period. RESULTS: Mean change in hemoglobin levels from baseline to evaluation period was 0.03 g/dL (95% CI -0.62 to +0.69). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. There were no serious or major adverse effects observed with darbepoetin alfa during the study. CONCLUSION: These results show that darbepoetin alfa maintains hemoglobin concentrations effectively and safely in patients on peritoneal dialysis, but with a reduced dose frequency as compared to rHuEPO.     

Anemia, hospitalization, and mortality in patients receiving peritoneal dialysis in the United States

BACKGROUND: The view that hemoglobin levels in peritoneal dialysis patients should be maintained at 11 to 12 g/dL is based largely on the results of studies in hemodialysis patients. METHODS: We studied 13,974 erythropoietin-treated Medicare patients who initiated peritoneal dialysis between 1991 and 1998. Mean hemoglobin levels for the first 6 months of the study and, subsequently, time to first hospitalization and death during a 2-year follow-up were determined. RESULTS: The percentages of patients with hemoglobin levels of <10, 10 to 10.9, 11 to 11.9, and >/=12 g/dL were 24.6%, 40.6%, 27.6%, and 7.2%, respectively. First-hospitalization and death rates, respectively, were 109.5 and 21.6 per 100 patient-years in nondiabetic patients, and 152.9 and 31.5 in diabetic patients. In nondiabetic patients, adjusted hospitalization hazard ratios for hemoglobin levels of <10, 10 to 10.9, 11 to 11.9 (reference category), and >/=12 g/dL were 1.29 (P < 0.0001), 1.15 (P < 0.0001), 1, and 0.98 (NS), respectively. The corresponding adjusted mortality hazard ratios were 1.43 (P < 0.0001), 1.13 (P < 0.05), 1, and 1.14 (NS). In diabetic patients, hazard ratios of 1.26 (P < 0.0001), 1.07 (NS), 1, and 0.82 (P < 0.01) were observed for hospitalization, and 1.34 (P < 0.0001), 1.18 (P < 0.01), 1, and 0.92 (NS) for mortality. CONCLUSION: In peritoneal dialysis patients, anemia is associated with hospitalization and mortality in a manner supporting current Kidney Dialysis Outcomes Quality Initiative (K/DOQI) hemoglobin targets. In addition, hemoglobin levels of >/=12 g/dL are associated with lower hospitalization rates in diabetic patients.     

Use of recombinant erythropoietin in thalassemic patients on dialysis.

We studied the therapeutic benefit of recombinant human erythropoietin (rHuEPO) in dialysis patients with thalassemia minor. Four of the 40 randomly selected patients (22 on hemodialysis [HD], 18 on continuous ambulatory peritoneal dialysis [CAPD]) were identified to be thalassemic prior to a trial of rHuEPO (alpha-thalassemia trait in three and beta-thalassemia minor in one). All patients were initially treated with rHuEPO at a dose of 100 +/- 25 U/kg/wk subcutaneously depending on the hemoglobin level. EPO injections were continued for 16 weeks with further adjustments of the doses according to the hemoglobin level increases attained. All nonthalassemic patients reached a target hemoglobin of 10 g/dL at week 16, with an average maintenance dose of 120 +/- 7.8 U/kg/wk, but the hemoglobin was increased by only 1 g/dL in the thalassemic patients receiving 175 U/kg/wk. Following cessation of rHuEPO therapy for 6 weeks, all four thalassemic patients and 18 randomly selected nonthalassemic patients received a fixed dose of rHuEPO 4,000 U/wk (equivalent to 80 U/kg/wk) for 16 weeks. The hemoglobin remained unchanged in the thalassemic patients, but a progressive and significant increase of hemoglobin was observed in the nonthalassemic patients. At the last phase of the study, the thalassemic patients received rHuEPO at a dose of 100 or 125 U/kg/wk with 4-weekly increments of 25 U/kg/wk until their hemoglobin reached 10 g/dL. One patient developed uncontrolled hypertension with a dose of 150 U/kg/wk, and one reached the target hemoglobin at a dose of 200 U/kg/wk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Novel erythropoiesis stimulating protein for treatment of anemia in chronic renal insufficiency

BACKGROUND: Novel erythropoiesis stimulating protein (NESP) is a glycoprotein with a threefold longer terminal half-life than recombinant human erythropoietin (rHuEPO) in humans. The aim of this study was to determine whether NESP is effective for the treatment of anemia at a reduced dosing frequency relative to rHuEPO in patients with chronic renal failure not yet on dialysis [chronic renal insufficiency (CRI)]. METHODS: This was a multicenter, randomized, open-label study. A total of 166 rHuEPO-naive patients with CRI were randomized in a 3:1 ratio to receive NESP (0.45 microg/kg once weekly) or rHuEPO (50 U/kg twice weekly) administered subcutaneously for up to 24 weeks. Dose adjustments were made as necessary to achieve a hemoglobin response, defined as an increase > or =1.0 g/dL from baseline and a concentration > or = 11.0 g/dL. RESULTS: During the 24-week treatment period, 93% (95% CI, 87 to 97%) of patients receiving NESP and 92% (95% CI, 78 to 98%) of patients receiving rHuEPO achieved a hemoglobin response. The median time to response was seven weeks (range of 3 to 25 weeks) in both groups. After correction of anemia, mean hemoglobin concentrations were maintained within the target range of 11.0 to 13.0 g/dL for the remainder of the 24-week treatment period. The safety profiles of NESP and rHuEPO were similar, and no antibodies were detected to either drug. CONCLUSIONS: These results demonstrate that NESP safely and effectively corrects and maintains hemoglobin concentrations at a reduced dosing frequency relative to rHuEPO in patients with CRI, providing a potential benefit to patients and health care providers.     

Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin

BACKGROUND: Treatment with recombinant human erythropoietin (rHuEPO) has been a major advance for the management of anemia in patients on hemodialysis. Therapy, however, is often observed to be associated with recurrent cyclic fluctuations in hemoglobin levels. The purpose of this analysis was to describe the phenomenology of hemoglobin cycling during rHuEPO treatment. METHODS: Data were analyzed for 281 hemodialysis patients treated at Winthrop-University Hospital Dialysis Centers between 1998 and 2003. Eligible patients' first full 1-year period with less than 10 hospital days was studied. Hemoglobin cycling (cycles with amplitude >1.5 g/dL and duration >8 weeks) and excursions (half of one full cycle) were analyzed. RESULTS: Greater than 90% of patients experienced hemoglobin cycling. The mean number of hemoglobin excursions was 3.1 +/- 1.1 per patient/year. The mean amplitude per hemoglobin excursion was 2.51 +/- 0.89 g/dL. The mean duration of hemoglobin excursions was 10.3 +/- 5.1 weeks. Factors associated with initiation of up excursions included increases in rHuEPO dose (84%), intravenous iron treatment initiation or increase in dose (27%), posthospital discharge (36%), factors associated with down excursions included rHuEPO dose hold (15%) or dose reduction (62%), infection (6%), discontinuation of intravenous iron therapy (5%), and hospitalization (14%). Patients with frequent hemoglobin cycling (>two full cycles per year) were characterized as being more responsive to rHuEPO [index of EPO responsiveness (ERI) 1036 +/- 659 compared to 1992 +/- 701 for other patients] (P = 0.02). CONCLUSION: Hemoglobin cycling is a common occurrence in rHuEPO-treated hemodialysis patients. It is most closely associated with frequent rHuEPO dose changes, hospitalization, and iron treatment practices.     

Current concepts of anemia management in chronic renal failure: impact of NKF-DOQI

Since the introduction of recombinant human erythropoietin (rHuEPO) into clinical nephrology practice 10 years ago, there has been a slow increase in hemoglobin (Hgb) levels, but most patients with the anemia of chronic renal failure are still moderately anemic and have not achieved the target Hgb (11 to 12 g/dL) recommended by the NKF-DOQI anemia guidelines. Functional iron deficiency, insufficient rHuEPO doses and comorbid factors such as inflammation/infection have been the major reasons for not achieving this target. By optimizing iron stores with regular infusions of intravenous iron in the hemodialysis patient (who has significant blood [iron] losses related to the hemodialysis procedure), and giving adequate amounts of rHuEPO, preferably subcutaneously instead of intravenously, the NKF-DOQI recommended target Hb can be achieved in the majority of patients so treated.     

Anemia in pediatric hemodialysis patients: results from the 2001 ESRD Clinical Performance Measures Project

BACKGROUND: Despite improvements in dialysis care, anemia remains a problem in pediatric hemodialysis patients. METHODS: To assess possible explanations for the anemia, clinical data were obtained from the Centers for Medicare and Medicaid Services on all hemodialysis patients ages 12 to <18 years between October and December 2000. Complete data were available for 435 of the 516 patients (84%). RESULTS: A total of 160 (37%) patients had a mean hemoglobin of <11 g/dL (anemic). The mean (+/- SD) age for these patients was 15.5 +/- 1.8 years compared to 15.9 +/- 1.5 years for the target hemoglobin patients (P < 0.05). Mean time on chronic dialysis was similar for both the anemic and target hemoglobin patients (>/=100 g/dL) ( approximately 3 years) but patients on dialysis <6 months were more likely to be anemic (67%). While nearly all patients were treated with erythropoietin, anemic patients received greater weekly erythropoietin doses (intravenous, anemia 374 +/- 232 units/kg/week vs. target hemoglobin 246 +/- 196 units/kg/week, P < 0.001; and subcutaneous, 304 +/- 238 units/kg/week vs. 167 +/- 99 units/kg/week, P < 0.05). A total of 59% of anemic patients had a mean transferrin saturation (TSAT) >/=20% compared to 71% of patients with a target hemoglobin (P < 0.01). A mean serum ferritin >/=100 ng/mL was present in approximately two thirds of the anemic and target hemoglobin patients. Approximately 60% of all children were treated with intravenous iron. The mean Kt/V values were lower for anemic patients (1.46 +/- 0.4 vs. 1.53 +/- 0.3, P < 0.05). Anemic patients were less likely to have a normal serum albumin (29% anemic vs. 52% target hemoglobin patients, P < 0.001). CONCLUSION: In the final multivariable regression model, dialyzing <6 months, a low albumin, and a mean TSAT <20% remained significant predictors of anemia in children.     

Erythropoietin treatment in children with renal failure

 Erythropoietin (EPO) treatment dramatically changes the life of a child with end-stage renal disease. The administration of recombinant human (rHu)EPO is beneficial and safe in the predialysis period, during hemodialysis or peritoneal dialysis, and after renal transplantation. The goal of hemoglobin correction should be the level at which normal quality of life is possible without adverse events: in children this is usually 10–11 g/dl. rHuEPO is administered once to twice a week subcutaneously to children before dialysis, during peritoneal dialysis, and after transplantation. There is no real benefit of intraperitoneal administration. In children on hemodialysis two to three times a week IV administration is preferred. Among the many reasons for non-response to rHuEPO, iron deficiency (absolute or functional), infections, and hyperparathyroidism are the most common in the pediatric renal patient. Hypertension is the most-frequent side effect of rHuEPO treatment and needs careful monitoring. Iron should be supplemented orally or IV. No significant beneficial effect of rHuEPO on growth has been demonstrated. However, the association with recombinant human growth hormone therapy is not detrimental in children. Received: 4 May 1998 / Revised: 31 July 1998 / Accepted: 31 July 1998     

Pilot study of the optimum hematocrit for patients in the predialysis stage after renal transplantation

Anemia is a common complication in patients with chronic kidney diseases including posttransplant patients. Guidelines for the treatment of anemia in chronic kidney disease published by NHF-K/DOQI recommend the target hemoglobin and hematocrit (Hb and Ht) levels to be in the 11 to 12 g/dL and 33% to 36% ranges, respectively, which are somewhat higher than those recommended in Japan (Ht = 30%). However, these guidelines were established mainly from the data on hemodialysis patients with only limited information available as to the impact of anemia control in posttransplant patients. The aim of the present study was to evaluate cardiac function and quality of life (QOL) when the Ht was raised to about 36% by administration of recombinant-human-erythropoietin (rHuEPO) to patients with mild impairment of renal function (s-Cre < 2.0 mg/dL) after renal transplantation. Twenty-five patients were analyzed for cardiac function, blood data, and QOL in a prospective study encompassing 8 months of rHuEPO treatment. Using a once weekly subcutaneous dose of 6000 IU of Epoetin-beta, the Ht became 33% to 36% and Hb was 11 to 12 g/dL. Among the cardiac function tests, left ventricular end-diastolic diameter and left ventricular mass index decreased significantly. QOL did not show any significant changes after administration of rHuEPO. In conclusion, we demonstrated a potential benefit of using rHuEPO to maintain the Hb between 11 and 12 g/dL and the Ht between 33% and 36% in posttransplant patients with regard to the prevention of cardiovascular complications. Further study is required to establish the benefits of correcting anemia by rHuEPO on the outcome of posttransplant patients.     

Renal anemia: comparing current Eastern and Western European management practice (ORAMA)

The Optimal Renal Anaemia Management Assessment trial prospectively examined the impact of implementing European Best Practice Guidelines on outcomes in the management of renal anemia. Baseline data give an insight to standards of clinical care and provide a basis for a future comparison of guideline target attainment with final results. Fifty-three centers from eight European countries enrolled 739 patients with stage II-V chronic kidney disease who were either anemic (hemoglobin <11 g/dL) or treated with erythropoiesis-stimulating agents and/or iron supplementation. Patients were followed over 6-8 months in centers that were randomly allocated to either group A or B (i.e., with or without a computerized clinical decision support tool after baseline). The latter provided guideline-based recommendations to physicians based on patient anemia-related data. We report patient characteristics and hemoglobin values from baseline and the prestudy period, focusing on regional differences. In all, 81% of patients were dialysis-dependent. Baseline mean hemoglobin values in dialysis patients were significantly higher in Western (11.8 g/dL) vs. Eastern Europe (10.6 g/dL; p < 0.0001). Similar proportions of patients (approximately 50%) had mean hemoglobin 10-12 g/dL suggesting Eastern European patients are treated to lower Hb levels. The guideline ferritin target was achieved by 85% of dialysis and 52% of non-dialysis patients; 81% of dialysis and 78% of non-dialysis patients attained the transferrin saturation target. Most patients (96%) were receiving erythropoiesis-stimulating agents. Anemia management in patients with chronic kidney disease shows considerable regional differences across Europe, and target attainment remains suboptimal in many European nephrology centers after the revised 2004 guidelines.     

Safety and efficacy of erythropoietin in children with chronic renal failure

 A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks (mean±SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease. Received: 12 March 1998 / Revised: 24 June 1998 / Accepted: 6 July 1998     

Disparate outcomes in pediatric peritoneal dialysis patients by gender/race in the End-Stage Renal Disease Clinical Performance Measures project

Associations between achievement of adult Kidney Disease Outcomes Quality Initiative (KDOQI) targets for hemoglobin, adequacy and albumin, and race and gender were determined for pediatric peritoneal dialysis patients from the End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project for the period October 2004-March 2005. Fifty-six percent (427/761) of patients were male. Sixty-six percent (500/761) of patients were White. There were no differences in achievement of targets for adults by gender, and no differences in adequacy parameters by race. Blacks had lower mean hemoglobin levels than did Whites (11.1 +/- 1.6 g/dl vs 11.8 +/- 1.4 g/dl, P < 0.0001). Blacks were more likely to have mean hemoglobin levels < 10 g/dl (24% vs 11%, P < 0.0001) and less likely to achieve mean hemoglobin > 11 g/dl (56% vs 72%, P < 0.0001). Whites were more likely to achieve mean serum albumin levels > 4.0/3.7 g/dl [bromocresol green/bromocresol purple (BCG/BCP)] than Blacks were (35% vs 26%, P = 0.0376). In multivariate logistic regression models, White race was associated with mean hemoglobin levels > 11 g/dl [adjusted odds ratio (adj OR) 2.7, 95% confidence interval (CI) 1.7, 4.3] and mean serum albumin > 4.0/3.7 g/dl (BCG/BCP) (adj OR 1.9, 95% CI 1.3, 2.9]. Further study is needed of factors associated with anemia on peritoneal dialysis and barriers to its correction.     

Possible influence of vitamin D receptor gene polymorphisms on recombinant human erythropoietin requirements in dialysis patients

BACKGROUND: Vitamin D receptor (VDR) gene polymorphisms have been widely studied, especially to analyze their effects on calcium-phosphorus metabolism and secondary hyperparathyroidism in patients on dialysis. In this study, we sought to investigate the possible effects of these polymorphisms on the anemia of renal failure and recombinant human erythropoietin (rHuEPO) responses among patients receiving hemodialysis. METHODS: One hundred twenty-eight patients (52 females/76 males) underwent genotyping for the insertion/deletion Bsml (B-->b, restriction site, exon VIII-->IX) and Tagl (T-->t, 352 exon IX) VDR gene polymorphisms. The mean value of the last 6 months' monthly evaluated laboratory values (C-reactive protein, hemoglobin, iron indices, PTH, and albumin) and clinical findings (rHuEPO requirement, cumulative iron supplementation doses, and body weight) were analyzed retrospectively excluding patients with chronic inflammation, hemolytic anemia, or active blood loss such as gastrointestinal bleeding. RESULTS: Mean age and dialysis durations were 41.5 +/- 11.8 years and 91.8 +/- 45.3 months, respectively. Polymorphism percentages were as follows: Bsml; BB/Bb/bb: 32.2/63.6/4.2 and Tagl; TT/Tt/tt: 40.5/55.4/4.1%, respectively. BB variant of Bsml gene was related to lower rHuEPO needs (P < .05) and also higher hemoglobin levels (P < .005) when compared with the Bb/bb variant. Considering Tagl variants, transferrin saturation levels were lower (P < .03) among patients with the Tt/tt variant, but there was no other significant difference in the mean values of other data between TT and Tt/tt variants. CONCLUSION: The BB variant of Bsml was related to decreased rHuEPO requirements to achieve higher hemoglobin levels among maintenance hemodialysis patients without chronic inflammation.     

Fluctuations in haemoglobin levels in haemodialysis, pre-dialysis and peritoneal dialysis patients receiving epoetin alpha or darbepoetin alpha

Aim: To characterize the haemoglobin variability of haemodialysis, peritoneal dialysis and pre‐dialysis patients treated with either epoetin alpha or darbepoetin alpha in a clinical setting where treatment was administered according to current standard Australian practice. Methods: Data on haemodialysis, pre‐dialysis and peritoneal dialysis patients were extracted from the Renal Anaemia Management database (RAM) from 1 January 2001 to 31 December 2004. The variance in haemoglobin was calculated from patient records with more than five haemoglobin observations over a period of at least 4 weeks following 9 weeks of therapy. A mixed‐model was fitted to the within‐patient variances and weighting was based on the number of observations minus 1 for each record. Results: The mean within‐patient variance in haemoglobin levels for i.v. administered erythropoietin‐stimulating agents (IV) haemodialysis, s.c. administered erythropoietin‐stimulating agents (SC) haemodialysis, predialysis_SC and peritoneal dialysis_SC patients receiving epoetin alpha were 9% (95% CI: 13% to 5%, P < 0.0001), 17% (95% CI: 32% to 0.2%, P = 0.047), 19% (95% CI: 27% to 11%, P < 0.0001) and 26% (95% CI: 33% to 18%, P < 0.0001) lower than that for patients receiving darbepoetin alpha. The mean haemoglobin levels for haemodialysis_IV, haemodialysis_sc predialysis_SC and peritoneal dialysis_SC patients receiving darbepoetin alpha were 11.6 g/dL, 11.2 g/dL, 11.5 g/dL and 11.5 g/dL compared with 11.5 g/dL, 11.6 g/dL, 11.7 g/dL and 11.5 g/dL for patients receiving epoetin alpha. Conclusion: There was 9–26% greater within‐patient fluctuation in haemoglobin levels in patients receiving darbepoetin alpha compared with epoetin alpha. The causes of haemoglobin fluctuations and the implications for patient outcomes and resource use require further study.