Characteristics of Anemia and Iron Deficiency After Kidney Transplant

BackgroundNumerous studies have shown that iron deficiency is common in patients with end-stage renal disease. However, change of iron deficiency after kidney transplant (KT) is not fully understood. This study was undertaken to examine sequential changes of iron level after KT.MethodsA total of 1080 KT recipients enrolled in a multicenter observational cohort study between July 2012 and August 2018. A total of 786 patients with transferrin saturation and ferritin level at pretransplant and 1 year after KT were reviewed. Iron deficiency was defined as ferritin <200 ng/mL and total saturation of transferrin (TSAT) < 20%. Anemia was defined as hemoglobin (Hb) < 13 g/dL (male) or <12 g/dL (female).ResultsHemoglobin at 1 year after KT was higher than Hb at KT (13.64 [SD, 1.87] g/dL vs 10.53 [SD, 1.63] g/dL; P < .001). The TSAT decreased from baseline at 1 year after KT (33.89% [SD, 18.73%] vs 29.09% [SD, 14.54%]; P < .001), and ferritin level decreased from baseline at 1 year (190.63 [SD, 217.43] ng/mL vs 141.39 [194.25] ng/mL; P < .001). In patients with anemia at pretransplant, the group with anemia at 1 year after KT (persistent group) and the group without anemia at 1 year after KT (improved group) were compared. The persistent group showed higher pretransplant TSAT, lower 1-year TSAT, and lower estimated glomerular filtration rate at 1 year after KT than the improved group. In multivariate analysis, low ferritin at KT, low TSAT at 1 year, and high ferritin at 1 year were the risk factors for low Hb level at 1 year after adjusting multiple variables.ConclusionAnemia improved within 1 year after KT, although patients with iron deficiency increased. While ferritin reflected the inflammatory status, low TSAT at 1 year after KT was a risk factor for anemia at 1 year after KT.     

A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD

BACKGROUND: Although iron deficiency frequently complicates anemia in patients with nondialysis-dependent CKD (ND-CKD), the comparative treatment value of IV iron infusion and oral iron supplementation has not been established. METHODS: In a randomized, controlled multicenter trial, we compared the efficacy of iron sucrose, given as 1 g in divided IV doses over 14 days, with that of ferrous sulfate, given 325 mg orally thrice daily for 56 days in patients with ND-CKD stages 3 to 5, Hb < or =11 g/dL, TSAT < or =25%, and ferritin < or =300 ng/mL. Epoetin/darbepoetin therapy, if any, was not changed for eight weeks prior to or during the study. RESULTS: The proportion of patients achieving the primary outcome (Hb increase > or =1 g/dL) was greater in the IV iron treatment group than in the oral iron treatment group (44.3% vs. 28.0%, P= 0.0344), as was the mean increase in Hb by day 42 (0.7 vs. 0.4 g/dL, P= 0.0298). Compared to those in the IV iron group, patients in the oral iron treatment group showed a greater decline in GFR during the study (-4.40 vs. -1.45 mL/min/1.73m2, P= 0.0100). No serious adverse drug events (ADE) were seen in patients administered IV iron sucrose as 200 mg IV over two to five minutes, but drug-related hypotension, including one event considered serious, occurred in two females weighing less than 65 kg after 500 mg doses were given over four hours. CONCLUSION: IV iron administration using 1000 mg iron sucrose in divided doses is superior to oral iron therapy in the management of ND-CKD patients with anemia and low iron indices.     

Secondary hyperparathyroidism and anemia. Effects of a calcimimetic on the control of anemia in chronic hemodialysed patients. Pilot Study

The main cause of resistance to erythropoiesis-stimulating agents (ESA) used for treatment of anemia in chronic hemodialysed patients (CHP) is the iron deficiency, absolute or functional. Secondary hyperparathyroidism (SHPT) is a secondary factor of resistance. Indeed, it has been reported in the literature an improvement of anemia parameters after surgical parathyroidectomy (PTX). The objective of this study is to assess in CHP, the impact of the correction of SHPT by a calcimimetic, cinacalcet (CI), (which is considered as a pharmacological PTX) on the response to ESA, measured by the erythropoietin resistance index (ERI). Twenty-two CHP with severe SHPT documented by an intact parathyroid hormone (iPTH) above 800pg/mL were included in this prospective pilot study. Mineral bone metabolism, anemia and nutritional parameters were measured baseline and after 6 months of treatment by CI. The effect on anemia was assessed at the end of study by the ERI, the change in Hb concentration, and the proportion of patients with Hb levels above 11g/dL. RESULTS: At the end of study there was a significant decrease (M6 vs M0) in iPTH (1302 vs 674pg/mL or -48%, p=0.006), serum calcium (2.39 vs 2.15mmol/L or -10%), serum phosphate (2 vs 1.7mmol/L or -15%), serum calcium-phosphorus product (CaxP) (4.8 vs 3.8mmol(2)/L(2) or - 20% (p<0.05), and the number of patients with CaxP>4.4mmol(2)/L(2) (64 vs 32%, p<0.05). The level of bone alkaline phosphatase remained stable during the study (28 vs 27?IU/L). The Hb levels increased from 11 to 11.4g/dL, as did the proportion of patients whose Hb concentration reached 11g/dL or higher (50 vs 70%, p<0.05) without important change of the median weekly ESA dosis in the majority of patients, 18?cases (81%) vs four (19%). Two subgroups were identified from the median decreases in iPTH (delta iPTH) between M0 and M6, Group?1 (delta iPTH≥400pg/mL, n=10) and group?2 (delta iPTH<400pg/mL, n=12): in group?1, we found a correlation between the decrease in iPTH by CI and the stability or decrease in ERI (group?1), at comparable dose of dialysis, nutritional and iron intakes and inflammatory profiles; in group?2 without a significant effect of CI on PTH reduction the levels of ERI and ESA dosis were more elevated. CONCLUSION: A treatment by calcimimetic improves the control of anemia by ESA in CHP and interferes positively on a cause of secondary resistance to ESA represented by SHPT. The mechanism of these effects could be linked to the decreased of bone marrow fibrosis and inflammation and to the triptych formed by the reduction in iPTH, CaxP and phosphate.     

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.     

Cholecalciferol supplements improve vitamin D deficiency in renal transplant recipients

Most renal transplant recipients display vitamin D deficiency or insufficiency. The KDIGO guidelines suggest that this deficit should be treated as in the general population. Since there are few studies about the effects of cholecalciferol in de novo renal transplant recipients, we sought to assess these effects in long-term kidney graft recipients. Among 37 renal transplant recipients (19 males, 18 females) at a mean of 105 ± 82 months posttransplantation, vitamin D insufficiency or deficiency was treated with cholecalciferol (400-800 IU/d) plus calcium supplements (600-1200 mg/d of elemental calcium). These subjects were compared with 37 untreated recipients for a period between 6 and 12 months. At baseline, there were no differences between the groups in age at transplantation, sex, length of follow-up after grafting, function measured by estimated glomerular filtration rate (44.4 ± 16.8 treated vs 42.0 ± 15.0 mL/min/1.73 m² untreated; P = .527); iPTH (157 ± 103 treated vs 176 ± 118 pg/mL untreated; P = .461); 25OHD (14.7 ± 4.7 treated vs 15.7 ± 9.7 ng/mL untreated; P = .584); or 1.25OHD (34.1 ± 26.0 treated vs 34.0 ± 13.0 pg/mL untreated; P = .950). When compared with baseline values, iPTH (157 ± 103 vs 144 ± 89 pg/mL; P = .11) and 1.25OHD levels at 6 months (34.1 ± 26.0 vs 35.9 ± 26.3 pg/mL; P = .282) showed no change but 25OHD levels (14.7 ± 4.7 vs 22.6 ± 7.4 ng/mL; P = .000) and phosphate tubular reabsorption (64% ± 17% baseline vs 69% ± 14% at 6 months; P = .030) were increased in the treated patients. There were no differences in the parameters studied in untreated patients. Among the 27 recipients followed at 12 months, iPTH was decreased compared with baseline values (157 ± 103 vs 124 ± 62 pg/mL; P = .024) and 25OHD remained stable with respect to the values at 6 months (21.1 ± 5.3 ng/mL). No adverse effects of cholecalciferol were observed such as those to increase urinary calcium excretion. Low doses of cholecalciferol improved vitamin D status and decreased iPTH levels at 12 months. Higher doses than those used in our study are needed to increase serum 25OHD concentrations above 30 ng/mL.     

Therapeutic Effect of Roxadustat on Patients With Posttransplant Anemia

BackgroundRoxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has been reported to be effective in treating conservative renal failure and renal anemia in patients undergoing dialysis. Nonetheless, its effect on posttransplant anemia (PTA) has not yet been analyzed.MethodsThis study was conducted in accordance with the 1975 Declaration of Helsinki, as revised in 2013. Roxadustat was administered in 31 patients with a hemoglobin level ≤11 g/dL after renal transplant. The mean hemoglobin, serum iron, ferritin, and low-density lipoprotein (LDL) cholesterol levels and the estimated glomerular filtration rate at 4, 8, 12, 16, and 20 weeks after administration were compared with those before administration.ResultsThe average (standard deviation) hemoglobin level in 25 patients (6 patients dropped out) increased from 9.8 (0.78) g/dL before administration to 12.1 (1.44) g/dL (P < .001) after 12 weeks of roxadustat administration. The mean ferritin level in patients decreased from 107.6 (84.95) ng/mL before administration to 51.7 (44.04) ng/mL (P = .022) after 8 weeks of roxadustat administration. The mean LDL cholesterol level decreased from 114.1 (31.67) mg/dL before administration to 78.7 (18.26) mg/dL (P = .0012) after 8 weeks of roxadustat administration. Complications observed in patients after roxadustat administration included reduced hemoglobin levels in 3 patients, gastrointestinal symptoms in 2 patients, and myocardial infarction in 1 patient.ConclusionsHemoglobin levels significantly increased, whereas ferritin and LDL cholesterol levels significantly decreased in patients with PTA after roxadustat administration. Roxadustat seems to be an effective treatment for patients with PTA; however, the blood clotting tendency due to iron deficiency should be monitored in patients.     

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.     

Management of iron deficiency and anemia after Roux-en-Y gastric bypass surgery: An observational study

BackgroundIron deficiency (ID) is common after Roux-en-Y gastric bypass surgery (RYGB). Optimal iron management in this population is unclear. The objective of this study was to assess our management of RYGB patients with ID and anemia.MethodsClinic visit records of RYGB patients with ID or anemia from January 1, 2008, to February 1, 2010 were evaluated. Demographic characteristics, postsurgery iron and anemia indices, and prescribed treatments were recorded. Three separate definitions for ID and anemia were used (standard textbook, ASBMS, and recent literature). An intravenous iron protocol was later implemented, and follow-up laboratory values were obtained.ResultsA total of 125 with ID or anemia (89% female, 86% Caucasian), mean (SD) age 44.7 (8.6) years, and BMI 47.3 (10.8) kg/m² at time of RYGB, were included. Proportion of values meeting criteria for ID or anemia at first follow-up: standard textbook, hemoglobin (Hb, 35%), transferrin saturation (T_sat, 48%), ferritin (28%); ASBMS, ferritin (43%); recent literature, ferritin (58%), serum iron (21%). At mean follow-up of 45.7 (43) months, oral iron (n = 49) or intravenous iron (n = 4) had been prescribed for 53 (42.4%) patients, and 32 (25.6%) patients received multiple blood transfusions. Nine patients received intravenous iron using the new protocol (400–1400 mg), resulting in increases in Hb (1.8 g/dL; P<.05) and ferritin (31.8 ng/mL; P< .002).ConclusionIron management was inadequate. Hematologic values often were deficient for sustained periods. Initially, few patients received intravenous iron after oral iron failure, many received no iron supplementation, and there was high use of blood transfusions. Subsequently, administration of intravenous iron was beneficial.     

TOTAL DOSE IRON INFUSION: SAFETY AND EFFICACY IN PREDIALYSIS PATIENTS

Iron deficiency anemia isnot uncommon in predialysis patients. Oral iron often cannot maintain adequate iron stores. Hence we evaluated the safety and efficacy of total infusion (TDI) of iron in these patients. Anemic predialysis patients were screened and those with Hb < 7.0g/dL and serum ferritin < 200ng/mL were selected. Patients with active bleeding and acute livere disease were excluded. All patients were on oral iron 100mg/day. None of the patients were on erytropoeitin. 11 patients (6 males and 5 females). aged 45.9 + 15yrs. were suitable. Hb was 5.9 ± 1.0g/dL and serum ferritin was 89.5 + 50 ng/mL. The preparation used was iron dextran. A test dose of 25mg in 100mL normal saline was administeted over 1 hr to all patients. One patient had fever and chills during the test dose and was not given TDI. 10 patients received TDI. None of these patients had any problem during the infusion. The dose of iron administered was 900 + 316.2 mg. One patient who received 1600mg had arthralgia-myalgia and another patient had thrombophlebitis following TDI. One month after TDI, Hb was 8.0 + 1.0g/dL and serum ferritin was 362ng/mL. We feel that TDI is a safe and effective method of correcting iron deficiency in predialysis patients.     

Intravenous iron replacement for persistent iron deficiency anemia after Roux-en-Y gastric bypass

BackgroundIron deficiency is a major postoperative complication of Roux-en-Y gastric bypass surgery. Oral replacement can fail to correct the deficiency. Thus, recourse to parenteral iron administration might be necessary. Our objective was to evaluate the effectiveness and safety of a standardized 2 g intravenous iron dextran infusion in the treatment of iron deficiency after Roux-en-Y gastric bypass surgery. The setting was a university-affiliated community hospital in the United States.MethodsWe reviewed the medical records of 23 patients at our institution who had received 2 g of iron dextran intravenously for recalcitrant iron deficiency after Roux-en-Y gastric bypass surgery. We obtained the demographic data and the complete blood count and serum iron studies obtained before treatment and at outpatient visits after infusion.ResultsBefore treatment, all 23 patients were iron deficient (average ferritin 6 ng/mL) and anemic (average hemoglobin 9.4 g/dL). By 3 months, the average ferritin and hemoglobin had increased to 269 ng/mL and 12.3 g/dL, respectively. The hemoglobin levels remained stable throughout the follow-up period. The iron stores were adequately replaced in most patients. Four patients required a repeat infusion by 1 year, because the ferritin levels had decreased to <15 ng/mL. The probability of remaining in an iron replete state was 84.6% (95% confidence interval 78–91.2%). One patient required warm compresses for superficial phlebitis. No other significant adverse events were reported.ConclusionIntravenous administration of 2 g of iron dextran corrects the anemia and repletes the iron stores for ≥1 year in most patients. This therapy is safe, tolerable, efficient, and effective.     

Total dose iron infusion: safety and efficacy in predialysis patients

Iron deficiency anemia is not uncommon in predialysis patients. Oral iron often cannot maintain adequate iron stores. Hence we evaluated the safety and efficacy of total dose infusion (TDI) of iron in these patients. Anemic predialysis patients were screened and those with Hb < 7.0 g/dL and serum ferritin < 200 ng/mL were selected. Patients with active bleeding and acute liver disease were excluded. All patients were on oral iron 100 mg/day. None of the patients were on erythropoeitin. 11 patients (6 males and 5 females), aged 45.9 +/- 15 yrs, were suitable. Hb was 5.9 +/- 1.0 g/dL and serum ferritin was 89.5 + 50 ng/mL. The preparation used was iron dextran. A test dose of 25 mg in 100 mL normal saline was administered over 1 hr to all patients. One patient had fever and chills during the test dose and was not given TDI. 10 patients received TDI. None of these patients had any problem during the infusion. The dose of iron administered was 900 + 316.2 mg. One patient who received 1600 mg had arthralgia-myalgia and another patient had thrombophlebitis following TDI. One month after TDI, Hb was 8.0 + 1.0 g/dL and serum ferritin was 362 ng/mL. We feel that TDI is a safe and effective method of correcting iron deficiency in predialysis patients.     

Oral Iron Replacement Normalizes Fibroblast Growth Factor 23 in Iron-Deficient Patients With Autosomal Dominant Hypophosphatemic Rickets

Autosomal dominant hypophosphatemic rickets (ADHR) is caused by mutations impairing cleavage of fibroblast growth factor 23 (FGF23). FGF23 gene expression increases during iron deficiency. In humans and mice with the ADHR mutation, iron deficiency results in increased intact FGF23 concentrations and hypophosphatemia. We conducted a prospective open label pilot clinical trial of oral iron replacement over 12 months in ADHR patients to test the hypothesis that oral iron administration would normalize FGF23 concentrations. Eligibility criteria included: FGF23 mutation; and either serum iron <50 μg/dL; or serum iron 50 to 100 μg/dL combined with hypophosphatemia and intact FGF23 >30 pg/mL at screening. Key exclusion criteria were kidney disease and pregnancy. Oral iron supplementation started at 65 mg daily and was titrated based on fasting serum iron concentration. The primary outcome was decrease in fasting intact FGF23 by ≥20% from baseline. Six adults (three male, three female) having the FGF23-R176Q mutation were enrolled; five completed the 12-month protocol. At baseline three of five subjects had severely symptomatic hypophosphatemia (phosphorus <2.5 mg/dL) and received calcitriol with or without phosphate concurrent with oral iron during the trial. The primary outcome was met by 4 of 5 (80%) subjects all by month 4, and 5 of 5 had normal intact FGF23 at month 12. Median (minimum, maximum) intact FGF23 concentration decreased from 172 (20, 192) pg/mL at baseline to 47 (17, 78) pg/mL at month 4 and 42 (19, 63) pg/mL at month 12. Median ferritin increased from 18.6 (7.7, 82.5) ng/mL at baseline to 78.0 (49.6, 261.0) ng/mL at month 12. During iron treatment, all three subjects with baseline hypophosphatemia normalized serum phosphorus, had markedly improved symptoms, and were able to discontinue calcitriol and phosphate. Oral iron repletion normalized FGF23 and phosphorus in symptomatic, iron-deficient ADHR subjects. Thus, the standard approach to ADHR should include recognition, treatment, and prevention of iron deficiency. © 2019 American Society for Bone and Mineral Research.     

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.     

Anemia after kidney transplantation in adult recipients: prevalence and risk factors

Objective

To evaluate the prevalence of anemia and appraise its risk factors at 6 months after renal transplantation.

Materials and Methods

This retrospective study was performed between 2008 and 2010 in 2713 adult kidney transplant recipients to determine the prevalence of posttransplantation anemia. Anemia was defined as hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men.

Results

The prevalence of posttransplantation anemia was 52.7%, with severe anemia (hemoglobin ≤11 g/dL) detected in 24.4% of patients. Impaired renal function was the only risk factor associated with anemia (odds ratio, 3.6; P = .047). However, severe anemia after kidney transplantation was correlated with female sex (P = .001), renal allograft dysfunction (P = .00), and cytomegalovirus infection (P = .002).

Conclusion

The present study demonstrated a quite high prevalence of posttransplantation anemia, in particular associated with impaired renal allograft function. Severe anemia was correlated with female sex, degree of kidney graft dysfunction, and cytomegalovirus infection.     

Anemia management and treatment response in patients on hemodialysis: the MAR study

BACKGROUND: Anemia management guidelines describe the importance of anemia as a risk factor in hemodialysis and the need for clinical prospective studies focused on this role of anemia. Response to treatment with iron and epoetin is multifactorial, and results are still far from the targets set by the guidelines. The Morbidity and Mortality Anemia Renal study (MAR) is a multicenter prospective cohort study of hemodialysis (HD), designed to assess the burden of anemia on morbidity and mortality. We report here a cross-sectional analysis of the management of anemia, and response-to-treatment factors. METHODS: A total of 1,710 patients were included (60% male, mean age 64.4 +/- 13.6 years, mean 16.2 +/- 11.1 months on HD) with a high comorbidity (hypertension 75.8%, diabetes 25.9%, heart failure 13.9% and coronary disease 16.7%) and a mean Charlson Index of 6.5 +/- 2.3. RESULTS: There were 28.7% of patients who had started epoetin before end-stage renal disease (pre-ESRD), 81.4% of patients displayed Hb <11 g/dL when initiating HD with a mean Hb of 9.7 g/dL. Only 67.9% of prevalent HD patients attained a hemoglobin (Hb) level above 11 g/dL, 89.5% achieved a ferritin level above 100 ng/mL, 76.7% a transferrin saturation index (TSI) above 20%, and 61.1% met all 3 objectives. The multivariate analysis identified the following risk factors for Hb <11g/dL: low albumin (odds ratio, OR = 1.75), HD efficacy below objectives (OR = 1.44) and female sex (OR = 1.36), corrected for comorbidity, epoetin treatment, transfusion, surgery or hospital admission. CONCLUSIONS: As compared with previous surveys, we found an improved but still inadequate anemia management in Spanish HD patients. Our results are comparable with those of Euro-DOPPS. Several modifiable factors related to a lower Hb concentration were assessed. On behalf of the MAR Study Group.     

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.     

Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously

Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m²), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) < 20% and/or serum ferritin of less than 100 μg/L. Patients received treatment by ESA in 16 cases out of 29. One month after treatment, hemoglobin (Hb) increased significantly (11.4 ± 1.6 vs 10.4 ± 1.4 g/dL, P = 0.0003) along with a significant increase in TSAT (21.3 ± 7.3 vs 13.3 ± 3.8%, P = 0.000003) and serum ferritin (286 ± 253 vs 91 ± 60 μg/L, P = 0.00005). Six patients had a serum ferritin greater than 500 μg/L after treatment, which may put them at risk of iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self-limiting myalgia and arthralgia. No venous inflammatory reaction was noted. The administration of high doses of LMWID is effective in treating anemia of CKD in the predialysis stage with a satisfactory tolerance, without affecting kidney function and helps preserve the venous capital. It should be reserved for patients whose serum ferritin is less than or equal to 150 μg/L.     

Causes of anemia in renal transplant recipients

Iron-deficiency anemia is one of the major problems encountered in renal transplant recipients. The aim of this retrospective study was to reevaluate the causes of anemia among 100 anemic kidney recipients. Patients with serum creatinine levels greater than 2 mg/dL were excluded from the study. Female patients were considered to be anemic if the hemoglobin was <12 g/dL for males, <13 g/dL. Complete blood count, serum creatinine, serum iron, iron-binding capacity, ferritin, transferrin saturation, erythrocyte folate, and serum vitamin B(12) levels were measured in all patients. Mean hemoglobin value was 10.2 +/- 1.4 g/dL for female and 9.9 +/- 1.3 for male patients, mean corpuscular volume (MCV) 91.3 +/- 4.9 fL. We observed normocytic anemia in 60, macrocytic anemia in 30, and microcytic anemia in 10 patients. A low level of serum folate was observed in 9 (15%) and of vitamin B(12) in 5 (8.8%) of 60 patients with normocytic anemia. Folate deficiency was found in 18 (60%) and vitamin B(12) deficiency in 12 (40%) of 30 patients with macrocytic anemia. All patients with microcytic anemia had iron deficiency. Splenomegaly was seen significantly more often in patients with macrocytic than normocytic anemia (P =.008). Folate and vitamin B(12) deficiency were the major causes of nutritional anemia; oral or parenteral supplementation with these vitamins is likely to cure the anemia in the majority of cases.     

Iron deficiency in patients with chronic kidney disease: potential role for intravenous iron therapy independent of erythropoietin

The prevalence of iron deficiency and its contribution to the anemia of end stage renal disease has been extensively studied, but much less is known about the role of iron deficiency in the pathogenesis of the anemia of chronic kidney disease in predialysis patients. All new hemodialysis patients entering a single hemodialysis unit between July 1999 and April 2002 were included in the study. The admission laboratory tests and the Health Care Financing Administration (HCFA) 2728 form were examined to determine the prevalence of erythropoietin use, anemia (Hb < 11 g/dl), and iron deficiency (ferritin < 100 ng/ml and transferrin saturation % < 20%). In a second part of the study, the effect of intravenous iron gluconate replacement in patients with stage III & IV chronic kidney disease was examined. Anemia was present in 68% of all patients starting hemodialysis. Iron deficiency was a common feature occurring in 29% of patients taking erythropoietin (49% of all patients) and 26% of patients without erythropoietin (51% of all patients). Following the administration of intravenous iron gluconate to four patients, there was a significant rise in hemoglobin levels from 10.6 ± 0.19 to 11.7 ± g/dl (p = 0.02). Conclusion: Iron deficiency is common in predialysis patients. Replenishing iron stores in anemic patients with chronic kidney disease significantly increases hemoglobin levels and should be considered as an integral part of the therapy for treating anemia in the predialysis population.     

Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin <10 g/dL

BACKGROUND: Left ventricular hypertrophy (LVH) frequently complicates chronic renal insufficiency. Anemia is also common in these patients and may contribute to LVH. METHODS: We conducted an open-label interventional trial to evaluate the effect of recombinant erythropoietin (rhEPO) on left ventricular mass index (LVMI) in anemic patients with renal insufficiency. Adults with creatinine clearance 10 to 30 mL/min (nondiabetics) or 20 to 40 mL/min (diabetics) were recruited, and rhEPO was given to those with anemia (hemoglobin level <10 g/dL). Baseline and 6-month LVMI and LVH (LVMI >130 g/m(2) in men and >100 g/m(2) in women), hemoglobin levels, creatinine clearance, blood pressure, medications, and medical history were obtained. Forty anemic and 61 nonanemic control subjects were enrolled. RESULTS: Overall, the prevalence of LVH was 68.3% (95% CI 58.3-77.2), and entry hemoglobin level was the only significant predictor of baseline LVH (adjusted OR 0.69 per g/dL increase in hemoglobin, 95% CI 0.50-0.94). After 6 months, LVMI decreased in anemic patients receiving rhEPO (142 +/- 56 vs. 157 +/- 56 g/m(2)) (P= 0.007), with an increase in hemoglobin (11.3 +/- 1.9 vs. 9.1 +/- 0.7 g/dL) (P= 0.001). There were no changes in LVMI or hemoglobin level among controls. After adjusting for confounders and change in hemoglobin, receipt of rhEPO was associated with a significant reduction in LVMI (P= 0.01). CONCLUSION: Treatment with rhEPO was not independently associated with significant changes in blood pressure or renal function. LVH is a common finding in chronic renal insufficiency and is associated with lower hemoglobin levels. Treatment with rhEPO may decrease LVH in patients with severe renal insufficiency and anemia.