Anemia Of Chronic Renal Disease Research Articles

Adaptability of clinical pharmacist led interventions in the management of anemia of chronic renal disease: optimizing care

Renal anemia is a common comorbidity in chronic kidney disease (CKD) patients, typically treated with erythropoiesis-stimulating agents (ESAs) like erythropoietin. However, both over- and under-treatment are prevalent. In 2008, the Pharmacy Council of India introduced the Pharm.D course to enhance pharmaceutical care in clinical settings. While extensive studies in other countries highlight the benefits of clinical pharmacists' interventions, Indian research on this topic is limited. This prospective randomized controlled trial included CKD patients not on dialysis, with serum creatinine levels of 2-6 mg/dL and hemoglobin (Hb) levels below 12 g/dL. Participants were divided into three subgroups based on baseline Hb levels: < 10 g/dL (Group I), 10-12 g/dL (Group II), and >12 g/dL (Group III). ESAs and iron supplements were adjusted to maintain Hb levels of 10-12 g/dL. Quality of life was assessed using the Short Form Health Survey-36 questionnaire. Out of 448 participants, those in the pharmacist intervention group showed a significant shift towards Group II by the trial's end, compared to the control group. The study demonstrated a significant improvement in quality of life and physical performance, particularly for those in Group II, indicating that maintaining Hb levels at 10-12 g/dL is optimal for Indian CKD patients. This trial exemplifies the profound impact clinical pharmacists can have on patient care, highlighting their crucial role in improving healthcare outcomes through active participation and targeted interventions in clinical settings.

Comparison of Dosage Requirement of Erythropoietin Stimulating Agent (ESA) in Maintenance of Hemoglobin Concentration in patients undergoing twice weekly versus thrice weekly Hemodialysis in Pakistani Population

Anemia is one of the major complications of patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) and is associated with left ventricular hypertrophy and also increases morbidity and mortality. Anemia in patients with CKD can be due to two major reasons; iron deficiency or erythropoietin insufficiency. Erythropoietin Stimulating Agent (ESAs) administration is the mainstay in treating anemia if the patient is iron sufficient. However, higher doses of ESAs have been associated with increased cerebrovascular and cardiovascular events. We conducted this study to see how much erythropoietin is required in our setting in iron sufficient patients to maintain hemoglobin(Hb) level and the effect of dialysis frequency on ESA doses. 
 Methods and Findings:
 A cross-sectional study was conducted at the Department of Nephrology at Ziauddin University Hospital. Patients’ charts were reviewed for Hb levels and doses of ESA to maintain Hb between 10-12 mg/dl. Patients were excluded if they had iron deficiency, malignancy, were on immunosuppressive agents, had renal transplant, and with Hb >12 mg/dl or <10 mg/dl and their ferritin levels, transferrin saturation, hemoglobin concentration, frequency of hemodialysis and ESA dosage were monitored. We also compared these variables between patients undergoing hemodialysis thrice weekly with those undergoing hemodialysis twice a week.
 A total of 105 patients were analyzed. 24 were excluded as they did not match the inclusion criteria. 81 patients were included in the study. 36 (44.4%) were males and 45 (55.6%) were females. Mean age of the patient was 56.47 ± 11.72 years. The average dose of ESA was 106.91 ± 61.47 for patients undergoing hemodialysis thrice weekly and 183.94 ± 116.71 for patients undergoing hemodialysis twice a week. Significant difference was found to exist between dosage of patients undergoing thrice weekly dialysis versus twice weekly dialysis(p=<0.001).
 Our study has limitations. First our study only looked at Hb levels, iron stores and dosages of ESA, while other factors like Parathyroid Hormone(PTH) levels and Vitamin B12 were not considered that may have a role in anemia of chronic renal disease. In addition, it was a study limited to one center only and a multicenter trial should be taken to validate the results. We have reported one aspect of dialysis vintage i.e. high ESA dosage requirement
 Conclusion:
 We found that patients undergoing hemodialysis three times a week require recommended dosage of ESA; however those undergoing hemodialysis less than three times a week require higher dosage of ESA to maintain Hb level. Here we report significant effect of hemodialysis on ESA dosage to maintain same level of Hb.

A Review on Pharmacological Use of Recombinant Human Erythropoietin in Renal and Nonrenal Anemia and Other Potential Applications in Clinical Practice

Abstract The introduction of recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of patients with anemia of chronic renal disease. Clinical studies have demonstrated that rHuEPO is also useful in various nonuremic conditions, including hematological and oncological disorders, prematurity, HIV infection, and perioperative therapies. Since the cloning and first clinical introduction of recombinant erythropoietin (epoetin) in the late 1980s, indications and usage of epoetin have expanded significantly. It is estimated that as many as one-third of patients with substantial anemia (hemoglobin less than 10.0 g/dl) resulting from chemotherapy for cancer are treated with epoetin. Research suggests there is considerable variation in epoetin usage in practice. This review highlights the applications of rHuEPO in clinical practice and also addresses the usage of recombinant erythropoietin in situations where benefit is substantiated by high-quality studies.

Anemia and mortality in older persons: does the type of anemia affect survival?

Anemia is a common condition among community-dwelling older adults. The present study investigates the effect of type of anemia on subsequent mortality. We analyzed data from participants of the Third National Health and Nutrition Survey who were aged ≥50 and had valid hemoglobin levels determined by laboratory measurement. Anemia was defined by World Health Organization criteria. 7,171 subjects met our inclusion criterion. Of those with anemia (n=862, deaths=491), 24% had nutritional anemia, 11% had anemia of chronic renal disease, 26% had anemia of chronic inflammation, and 39% had unexplained anemia. We found an overall relative risk (RR) for mortality of 1.8 (p<0.001) comparing those with anemia to those without, after adjusting for age, sex, and race. After we controlled for a number of chronic medical conditions, the overall RR was 1.6. Compared to persons without anemia, we found the following RRs for the type of anemia: nutritional (2.34, p<0.0001), chronic renal disease (1.70, p<0.0001), chronic inflammation (1.48, p<0.0001), and unexplained (1.26, p<0.01). Anemia is common although not severe in older non-institutionalized adults. When compared with non-anemic older adults, those with nutritional anemia or anemia due to chronic renal disease have the highest mortality risk.

Targeting the Hepcidin Pathway with RNAi Therapeutics for the Treatment of Anemia

Abstract 688Hepcidin, a liver-expressed peptide hormone, plays a central role in iron homeostasis by regulating the level of ferroportin. Ferroportin, the only known mammalian cellular iron exporter, is found on enterocytes, hepatocytes, and macrophages and allows the flux of iron from these cells into plasma. Upon binding, hepcidin induces the internalization and degradation of ferroportin, thereby modulating the absorption of iron from the diet and release of iron from cellular stores. Inappropriate hepcidin levels can therefore lead to dysregulation of iron homeostasis. In particular, inappropriately elevated hepcidin levels can limit iron needed for heme production, resulting in anemia. Elevated hepcidin is thought to play an important role in anemia of chronic disease and anemia of chronic kidney disease.RNA interference (RNAi) is a fundamental cellular mechanism for silencing genes and other transcribed elements, including those currently “undruggable” by small molecule and antibody therapeutics. RNAi has already transformed biological research by serving as a powerful tool for studying gene function and is now poised to form the basis of a new class of therapeutics. Small interfering RNAs (siRNAs) were developed against HAMP, the hepcidin gene, as well as other targets involved in iron metabolism (including HJV, TFR2, HFE, Neogenin, BMP6, BMPRI, BMPRII, SMAD4, and IL6R), both as a means to identify a therapeutic for the treatment of anemia and as a means to further characterize the hepcidin signaling pathway.Hepcidin was effectively silenced in mice, rats, and nonhuman primates, resulting in concomitant dose-dependent increases in serum iron, with approximately 100% transferrin saturation achievable after a single administration. Treatment with HAMP-targeting siRNA was able to blunt hepcidin induction, hypoferremia, and the onset of anemia in a turpentine-induced mouse model of inflammatory anemia. Silencing other members of the hepcidin pathway resulted in decreases in HAMP expression and increases in transferrin saturation to varying degrees. In particular, TFR2 was found to be an especially attractive target, leading to potent downregulation of HAMP, and rapid and durable increases in transferrin saturation. A single 0.1 mg/kg dose of a TFR2-targeting siRNA, resulted in ∼80% silencing of both TFR2 and HAMP and 100% transferrin saturation within 24 hours post-administration in mice. HAMP silencing and elevated transferrin saturation persisted for over two weeks, with levels returning to baseline after 4 weeks. In addition, TFR2 targeting resulted in the resolution of anemia in rodent models of anemia of inflammation. These data indicate that siRNAs directed at HAMP, TFR2, and other members of the hepcidin pathway represent an attractive novel therapeutic approach for the treatment of anemia of chronic disease and anemia of chronic renal disease. Disclosures:Akinc:Alnylam Pharmaceuticals: Employment. Chan-Daniels:Alnylam Pharmaceuticals: Employment. Sehgal:Alnylam Pharmaceuticals: Employment. Foster:Alnylam Pharmaceuticals: Employment. Bettencourt:Alnylam Pharmaceuticals, Inc.: Employment. Hettinger:Alnylam Pharmaceuticals, Inc.: Employment. Racie:Alnylam Pharmaceuticals, Inc.: Employment. Aubin:Alnylam Pharmaceuticals: Employment. Kuchimanchi:Alnylam Pharmaceuticals: Employment. Epstein-Barash:Alnylam Pharmaceuticals: Employment. Nakayama:Alnylam Pharmaceuticals: Employment.

Prevalence and Risk Factors of Anaemia in Older Hospitalised Patients

Introduction: We aim to investigate the prevalence and risk factors for anaemia among the elderly in a tertiary hospital. Methods: A retrospective study was conducted on 742 consecutive geriatric patients who were admitted to the medical unit of our hospital. The demographic and laboratory values for patients were examined. Anaemia-related data were studied. Patients with no/missing demographical or laboratory data and those who passed away after admission were excluded. Results: There was a high prevalence of anaemia in the study population. Although there were a significant proportion of nutritional causes, non-nutritional causes formed the majority. Significant risk adjusted risk factors associated with anaemia are male gender, Charlson's co-morbidity index and abnormal serum creatinine levels ≤60ml/min. (OR=1.469 [1.177–1.833], p=0.001; OR=1.147 [1.107–1.189], p&lt;0.001; OR=1.335 [1.064–1.675], p=0.013 respectively.) Contributory factors for sub-types of anaemia were further investigated. A non-Chinese ethnicity, NSAID and anti-platelet use were significant risk factors for iron deficiency anaemia. (OR=2.035 [1.207–3.432], p=0.008; OR=8.202 [3.628–18.540], p&lt;0.001; OR=2.080 [1.260–3.435], p=0.004 respectively.) For B12 deficiency, significant risk factors were non-Chinese ethnicity and metformin use. (OR=1.869 [1.036–3.370], p=0.038; OR=3.314 [1.690–6.499], p&lt;0.001 respectively) A high Charleson's co-morbidity score and male gender correlated with anaemia of chronic disease. (OR=1.192 [1.104–1.288], p&lt;0.001; OR=2.030 [1.198–3.440], p=0.009 respectively.) For anaemia of chronic renal disease, no significant predictors were found. Conclusion: Anaemia remains prevalent in the hospitalised geriatric population. Specific risk factors may help in the diagnosis and management of sub-types of anaemia.

Therapeutic implications of recombinant human erythropoietin in anaemic related clinical manifestations

The introduction of recombinant human erythropoietin (RHUEPO) has revolutionised the treatment strategies for patients suffering with anaemia of chronic renal disease and chronic heart failure. Clinical studies and several observational evidences have demonstrated that RHUEPO is also useful in various non-uraemic conditions including haematological and oncological disorders, prematurity, HIV infection and preoperative therapies. The successful treatment of all the anaemic related malfunctions with recombinant human erythropoietin (RHUEPO) has become a standard treatment tool for dialysis patients and as an interesting therapeutic option for several forms of non-renal anaemia. As a conesquence of both, RHUEPO has achieved the highest annual sales worldwide and the potential of it increases its scope in the future prospective also.

Transdermal Androgen Therapy to Augment EPO in the Treatment of Anemia of Chronic Renal Disease

Hypogonadism and anemia are common comorbid conditions in dialysis patients. Testosterone replacement may improve such clinical parameters as anemia, sarcopenia, and low libido. Additionally, by increasing hemoglobin levels, testosterone replacement may allow for a dose reduction in recombinant human erythropoietin (rHuEPO), thereby reducing cost. This phase IV, single-center, placebo-controlled, double-blind study assessed the effect of transdermal testosterone on serum testosterone levels, rHuEPO dose required to maintain hemoglobin level, bone mineral content, lean body mass and fat content, cholesterol level, sexual function, and mood. Forty hypogonadal male hemodialysis patients who were administered rHuEPO were randomly assigned to 100 mg of topical 1% testosterone gel (Testim; Auxilium Pharmaceuticals, Norristown, PA) or placebo, applied daily for 6 months. Forty men with a mean age of 56 years and baseline serum testosterone level less than 300 ng/dL (< 10.4 nmol/L) participated in this trial. In men assigned to administration of transdermal testosterone, there was an increase beyond that in the placebo group in mean serum testosterone (77.1 ng/dL [2.7 nmol/L]), dihydrotestosterone (DHT; 0.8 nmol/L), and estradiol levels (6.3 pg/mL [23.0 pmol/L]) and a decrease in mean serum luteinizing hormone levels (-3.1 IU/L). Compared with subjects administered placebo, participants on testosterone replacement therapy did not show an appreciable change in rHuEPO dose (mean difference adjusted for baseline values, 12.6 U/kg/wk; P = 0.73), bone mineral density, lean body mass or fat content, cholesterol level, sexual function, or mood. Daily administration of 100 mg of topical 1% testosterone gel for 6 months failed to significantly increase serum testosterone or DHT levels in hypogonadal men with end-stage renal disease. Treatment with transdermal testosterone did not impact on rHuEPO requirement or clinical parameters in this small placebo-controlled study. Greater serum testosterone levels may be required to show clinical benefit in men with end-stage renal disease.

Haemoglobin and haematocrit targets for the anaemia of chronic renal disease.

Anaemia affects 60-80% of patients with renal impairment, reduces quality of life and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO) alpha or beta and darbepoetin alfa. Recently higher haemoglobin (Hb) and haematocrit targets have been widely advocated because of positive data from observational studies. However, higher targets may lead to access thrombosis and hypertension and are costly. This review assesses the benefits and harms of low (Hb </= 100 g/L or HCT </= 30%) and high (Hb > 100 g/L or HCT > 30%) targets in pre- and post-dialysis patients receiving any treatment for anaemia. We searched The Cochrane Renal Group specialised register (September 2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and reference lists of retrieved articles. Randomised controlled trials (RCTs) and quasi-RCTs comparing low Hb/HCT targets (Hb</- 100 g/L) with high Hb/HCT targets (Hb > 100 g/dL) in patients with anaemia of chronic renal disease. Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (95% CI). Fifteen trials were identified in which 2096 patients were included. Twelve trials (673 patients) compared placebo with EPO and three trials (1423 patients) compared two doses of EPO. Hb values of 100 g/L (obtained with low EPO doses) were associated with lower mortality compared to Hb values of 140 g/L or more (obtained with high EPO doses) in the population with chronic renal disease and cardiovascular impairment (two trials, 1379 patients: RR 0.82; 95% CI 0.68 to 0.99). Lower targets obtained with a placebo resulted in an increased risk for seizures (four trials, 219 patients: RR 5.25; 95% CI 1.13 to 24.34) as compared to higher targets reached with EPO treatment. Finally, there was a reduced risk for hypertensive episodes with lower Hb targets reached with a placebo as compared to higher targets reached with EPO (six trials, 387 patients: RR 0.50; 95% CI 0.33 to 0.76). Quality of life was not adequately evaluated in the studies. Lower Hb targets of 100 g/L were associated with a lower risk of death in the population with cardiovascular impairment and chronic renal disease as compared to Hb 140 g/L. Lower Hb targets (Hb < 100 g/L) were also significantly associated with an increased risk for seizures and a reduced risk of hypertension compared to Hb > 100 g/L. There is a need of more adequately powered, well-designed and reported trials in this area. In particular, randomised controlled trials comparing the benefits and harms of low (Hb < 100 g/L) versus intermediate (Hb 130 g/L) and high (Hb 140 g/L) targets in the pre-dialysis population with chronic renal disease are necessary. In fact, there is a large deficiency of trials in the pre-dialysis population. The new trials should focus on hard outcomes and also look at outcomes which were previously not studied adequately, such as seizures and quality of life, which is to be assessed with validated measures.

Physical Functioning and Exercise Capacity in Patient on Dialysis

Patients on dialysis have extremely limited exercise capacity, and poor physical functioning has been linked to low quality of life and high mortality in this population. The reason for the debility of patients on dialysis is far from clear despite years of study. The anemia of chronic renal disease is clearly a contributing factor, but uremic myopathy and resulting decreased muscle oxygen utilization have a significant impact on the physical functioning of patients on dialysis as well. Although it is likely that factors related to uremia adversely affect muscle function, some of the abnormalities demonstrated in uremic muscle are consistent with disuse atrophy. The clear contribution of anemia and the possible role of limited physical activity have led to studies of the effects of erythropoietin and aerobic exercise training on exercise capacity in end-stage renal disease patients. Both of these interventions result in increased exercise capacity. Thus vigorous treatment of anemia and uremia and encouragement of physical activity are important interventions to maximize the physical functioning of patients on dialysis. In addition, more studies are needed to clarify the causes of debility in this population and the impact of interventions on physical functioning, quality of life, and mortality.

Increased susceptibility to erythrocyte C5b-9 deposition and complement-mediated lysis in chronic renal failure

Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therapy are frequently exposed to excessive complement activation, we investigated the susceptibility of this patient population to erythrocyte C5b-9 deposition, complement-mediated lysis, and ghost formation. We developed a flow cytometric assay using antibodies to both glycophorin and the C5b-9 complex to detect C5b-9 deposition on intact erythrocytes and erythrocyte ghosts. Serum C5b-9 levels and C5b-9 deposition on erythrocyte ghosts were measured by enzyme-linked immunosorbent assay. A significant increase in C5b-9 deposition on intact erythrocytes was demonstrated in patients with advanced chronic renal failure (2.2 +/- 0.5%) and in patients on chronic maintenance hemodialysis (2.3 +/- 0.4%) compared with normal volunteers (0.9 +/- 0.1%, P = 0.005 vs. chronic renal failure, P < 0.001 vs. chronic hemodialysis patients). There was also a significantly higher percentage of C5b-9-positive erythrocyte ghosts in patients with advanced chronic renal failure (20.6 +/- 5%) and in chronic hemodialysis patients (15.5 +/- 3.1%) compared with normal controls (2.6 +/- 0.9%, P < or = 0.001 vs. advanced chronic renal failure and chronic hemodialysis patients). Treatment of erythrocyte preparations with cobra venom factor, which activates the complement cascade, resulted in dramatic increases in the percentages of C5b-9-positive erythrocyte ghosts in patients with chronic renal failure (49.9 +/- 6.9%) and in chronic hemodialysis patients (45.0 +/- 4.2%) compared with normal volunteers (22.3 +/- 2.7%, P < 0.001 vs. chronic renal failure and chronic hemodialysis patients). Erythrocyte membrane expression of the complement regulatory proteins CD59 and CD55 did not significantly differ between normal controls and hemodialysis patients. Plasma C5b-9 levels after cobra venom factor stimulation were higher in chronic renal failure patients (538 micrograms/ml) compared with normal controls (345 micrograms/ml, P < 0.001). Patients with chronic renal failure and on hemodialysis therapy are susceptible to erythrocyte C5b-9 deposition with subsequent lysis and ghost formation. Susceptibility to complement-mediated erythrocyte injury may contribute to the anemia of chronic renal disease.

The Role of Erythropoietin in the Mother and Fetus

Erythropoietin is one of the main regulators of haematopoiesis in the human and is being used more and more widely in the treatment of such clinical conditions as anaemia of chronic renal disease which would otherwise require transfusion. Recently, this approach has been extended to pregnant patients and the results have been encouraging. Fetal erythropoietin levels appear to be good indicators of anaemia and hypoxia which, if detected, allow for the identification of compromised fetuses. More data are emerging pointing to erythropoietin’s role in fetal central nervous system development and its potential protective role against hypoxia. This carries important implications for the obstetrician/gynaecologist, as erythropoietin is likely to play a major part in the diagnosis and treatment of certain maternal and fetal conditions.

Markers of masked iron deficiency and effectiveness of EPO therapy in chronic renal failure

Recombinant erythropoietin (rHuEPO) is well established in the management of anemia of chronic renal disease. However, a number of clinical issues, including the best laboratory indicators of an imminent marrow response to rHuEPO replacement, the ideal measurements to detect masked iron deficiency, and optimal methods of iron replacement, remain unanswered. To investigate these issues, studies were performed in anemic chronic hemodialysis patients. A number of standard hematologic measurements in addition to automated reticulocyte counts (Sysmex R-1000) and serum transferrin receptors (TfR) were obtained in these patients. A response to initiation of rHuEPO administration could be predicted if the serum TfR concentration was less than 6 mg/L (normal, 3.8 to 8.5 mg/L). In patients on rHuEPO, an imminent hemoglobin response to an increased rHuEPO dose could be predicted after 1 week based on a greater than 20% increase from baseline in the serum TfR or absolute reticulocyte count, with a sensitivity of 92%. In patients on rHuEPO replacement with serum ferritin levels greater than 30 μg/L, none of the panel of tests, including serum TfR, reliably detected masked iron deficiency. In a long-term study over 5 months in patients on a stable maintenance dose of EPO, a gradual decline in total body iron occurred, even in subjects with initial adequate iron stores, and despite taking 50 mg elemental iron daily as oral ferrous sulphate. The serum TfR is useful for predicting a hemoglobin response when initiating rHuEPO therapy, and combined with automated reticulocyte counting it is valuable for predicting a hemoglobin response when increasing the dose of rHuEPO. The serum TfR loses its specificity for detecting tissue iron deficiency in patients on maintenance rHuEPO therapy because of increased erythropoiesis, which itself raises serum TfR levels.

Report from the 1995 Core Indicators for Peritoneal Dialysis Study Group

The 1995 Peritoneal Dialysis Core Indicators Study was conducted by the Health Care Financing Administration to ascertain standard practices and outcomes in chronic peritoneal dialysis patients. Data from 1,202 patients who did not receive hemodialysis but who were on chronic ambulatory peritoneal dialysis (CAPD) for at least part of the 6-month period between November 1, 1994, and April 30, 1995, are reported. The mean serum albumin level for this cohort was 3.5 g/dL by the bromcresol green method and 3.2 g/dL by the bromcresol purple method. Data sufficient to calculate a weekly Kt/V urea or weekly creatinine clearance were available for only 34% of patient submissions. In these patients, the median weekly Kt/V urea was 1.7 using a fixed value for V of 0.58 × body weight and was 2.0 using the Watson equation to calculate V, the median weekly creatinine clearance was 60.7 L/wk/1.73 m 2. The mean hematocrit for this cohort was 32% and the average weekly recombinant human erythropoietin (rHmEPO) dose was 115 μ/ kg. Hematocrit values ≤30% were found in 50% of black patients and 31% of white patients. The average blood pressure among peritoneal dialysis patients was 139/80 mm Hg, with 29% of patients having a systolic blood pressure exceeding 150 mm Hg and 18% a diastolic blood pressure greater than 90 mm Hg. In summary, serum albumin levels were significantly lower in peritoneal dialysis patients than in hemodialysis patients. Approximately one third of peritoneal dialysis patients did not have an adequacy measure obtained during the 6-month observation period. A significant minority of patients had either inadequately treated anemia of chronic renal disease or hypertension. There is an opportunity to substantially improve the medical care provided to chronic peritoneal dialysis patients.

Epoetin alfa in anaemic children or adolescents on regular dialysis

Eighteen patients aged 5-18 years on regular dialysis had a packed cell volume (PCV) less than 0.27. On treatment with epoetin alfa (EA) PCV increased by 0.05 or more in all patients. Iron supplementation was necessary in 13 patients with a ferritinaemia less than 300 micrograms/l before study. During treatment, plasma potassium increased significantly and more vigorous antihypertensive measures were required in 8 patients, 5 of them being already on antihypertensive drugs before EA. Iliofemoral thrombosis occurred in 1 patient 10 days after renal transplant. The data indicate that EA ameliorates the anaemia of chronic renal disease. The main concerns arising during treatment with EA are hyperkalaemia, arterial hypertension and possibly thrombosis.

Treatment of the anemia of progressive renal failure with recombinant human erythropoietin.

To examine the effects of erythropoietin on the anemia of chronic renal disease and on the rate of renal deterioration, we administered recombinant human erythropoietin to 17 patients with anemia and progressive renal failure who did not yet require dialysis (serum creatinine level, 353 to 972 mumol per liter [4.0 to 11.0 mg per deciliter]). The dose of erythropoietin (50 to 150 units per kilogram of body weight) was adjusted according to the hematocrit response. In all 17 patients the anemia responded to erythropoietin. The median hematocrit increased from 0.27 to 0.37. The rate of the response depended on the initial erythropoietin dose and was similar to that observed in patients who were on dialysis. Hypertension was present in 14 patients before therapy, developed during therapy in 2 of the normotensive patients, and worsened in 9 patients, who required additional antihypertensive medications. The rate of the decline in renal function, as measured by serial determination of the reciprocal of the serum creatinine level, did not change significantly as the hematocrit rose (P = 0.78 by the paired t-test) during erythropoietin therapy. All the patients reported improvements in appetite, activity level, and sense of well-being. We conclude that erythropoietin therapy is effective in correcting the anemia of patients with progressive renal failure without affecting renal function, although it may be associated with an increase in blood pressure.

Recombinant human erythropoietin.

Erythropoietin is produced mainly by the kidneys and stimulates erythropoiesis in the bone marrow. Chronic renal failure is characterized by anemia, which is principally caused by erythropoietin deficiency. Recombinant human erythropoietin (r-hEPO) corrects the anemia of chronic renal disease and improves patient well-being, exercise tolerance, and cognitive function. The clinical pharmacology, efficacy, safety, and tolerance of r-hEPO are presented. Four major studies attest to r-hEPO's efficacy in the treatment of anemia of chronic renal disease and document potential toxicities of hypertension, iron deficiency, thrombosis, and bone pain. Careful attention to the extent of correction of the hematocrit, increased heparinization during hemodialysis therapy, and compliance with dietary restrictions may minimize the incidence and severity of adverse reactions. Resistance to r-hEPO may be due to iron deficiency, aluminum toxicity, or inflammation, including infection. Potential future uses of r-hEPO include the treatment of various other anemias, such as those seen in sickle cell anemia, rheumatoid arthritis, and autologous blood donation. Controlled clinical studies in these areas have not been reported.

Myocardial revascularization in patients with chronic renal failure

Symptomatic coronary artery disease in patients with chronic renal failure can complicate their management in a dialysis program. Hypotension associated with hemodialysis and the anemia of chronic renal disease can produce anginal episodes refractory to medical management. Untreated coronary artery disease may be a contraindication to renal transplantation in an otherwise acceptable candidate. We have encountered three cases of coronary artery disease severe enough to necessitate coronary bypass in patients from our long-term hemodialysis program. All three patients had uncomplicated postoperative courses, none had perioperative infarction, and in all three patients postoperative angiography demonstrated patency of all grafts. One patient subsequently underwent successful renal transplantation; the other two patients have continued in hemodialyses since bypass. We believe our experience and the reported experience of others confirm the feasibility of coronary bypass grafting in patients with chronic renal failure.

Anemia of Chronic Renal Disease

The pathogenesis of the anemia of chronic renal disease is related (1) to the etiology of the renal disease, (2) to the failure of renal excretory function, and (3) to the failure of renal endocrine function. Failure of the renal excretory function leads to an increased demand for red blood cells because of shortening of the red blood cell life-span, impaired utilization of iron, decreased responsiveness to erythropoietin and increased blood loss. Failure of renal endocrine function leads to a decreased erythropoietic response to these demands because of impaired production of erythropoietin. A greater degree of anemic hypoxia is required to generate the necessary amount of erythropoietin, and an equilibrium between demand and supply is first established at anemic levels.

Anemia of chronic renal disease

Anemia of chronic renal disease