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Effects of Erythropoietin Therapy on the Lipid Profile in End-Stage Renal Failure

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Effects of Erythropoietin Therapy on the Lipid Profile in End-Stage Renal Failure View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 45 (1994), pp. 897—902 Effects of erythropoietin therapy on the lipid profile in end- stage renal failure CAROL A. POLLOCK, ROGER WYNDHAM, PAUL V. COLLETT, GRAHAME ELDER, MICHAEL J. FIELD, STEVEN KAL0wsKI, JAMES R. LAWRENCE, DAVID A. WAUGH, and CHARLES R.P. GEORGE Department of Renal Medicine, Concord Hospital, New South Wales, Australia Effects of erythropoietin therapy on the lipid profile in end.stage renal on cardiovascular disease in uremia. The resultant increase in failure. To evaluate the effects of erythropoietin (EPO) therapy on the hemoglobin causes improved tissue oxygenation, not only to lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatorythe heart, but also to the vascular endothelium. Increased peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, exercise tolerance is well documented [I] to improve the 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cardiovascular risk profile in nonuremic patients. An improve- cholesterol and the LDL and HDL subfractions, triglycerides, lipopro- ment in the known carbohydrate intolerance of uremia has also tein (a), apoproteins A and B], full blood count, iron studies, Bl2,been demonstrated [2]. folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients Conversely, there are also potentially adverse effects of EPO were reassessed 5.20.3 (mean SEM) months later and 53 patients treatment on cardiovascular risk factors. An increase in hemo- underwent a further assessment 13.1 0.6 months after the commence- globin leads to an increase in blood viscosity, hypertension may ment of EPO, giving an overall follow-up of 10.0 0.6 months in 95 be exacerbated and increased appetite may lead to weight gain patients. As expected, EPO treatment was associated with an increase [1]. Thus an alteration in metabolic conditions may occur as a in hemoglobin (7.7 0.1 vs. 9.90.2 g/dl; P < 0.001) and a decrease in ferritin (687 99 vs. 399 69 pg/liter; P < 0.01). A significant fall in result of EPO treatment which may theoretically be beneficial, total cholesterol occurred (5.80.1 vs. 5.40.2 mmollliter; P < 0.05) or conversely, adversely affect the lipid profile. The net effect of in association with a fall in apoprotein B (1.15 0.04 vs. 1.04 0.06; these changes is not well documented. The current study P <0.05) and serum triglycerides (2.26 0.14 vs. 1.990.21; P <0.05) prospectively assessed the changes in the blood profile which during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement. These changesoccurred in association with EPO treatment in patients on correlated with the increase in Hb (P < 0.001 in each case), and the long-term dialysis. reduction in ferritin for total cholesterol (P < 0.02), LDL cholesterol (P <0.03), and to a lesser extent apoprotein B (P < 0.07). No difference was observed in patients using maintenance HD or CAPD, and similar Methods trends were observed in male and female patients. Improvements in the lipid profile occurred independently of the time on dialysis prior to the commencement of EPO. We conclude that EPO treatment is associated The study included patients from three dialysis units in with alterations in the lipid profile which may suggest a long-termSydney, Australia. All patients on hemodialysis, which in- improvement in the vascular morbidity of chronic renal failure. The cluded both single pass and sorbent dialysis, and patients on causes of the improved lipids are not addressed by this study and mayCAPD who were commencing erythropoietin treatment were be equally due to a direct or secondary benefit of EPO therapy. enrolled into the prospective study. Patients prescribed phar- macological lipid lowering agents were excluded from the study from the time these agents were commenced. Dialytic prescrip- Erythropoietin (EPO) deficiency is an undoubted factor in thetion, EPO doses and other drug therapy was at the discretion of pathogenesis of uremic anemia, and its widespread use hasthe primary care physician. Attempts were made to keep arguably been the most important development impacting ondialytic regimens uniform throughout the study unless clinical dialysis patients in recent years. However, the long-term effectsconsiderations dictated otherwise. Hemodialysis patients were of erythropoietin on cardiovascular disease have not yet beendialyzed using cupraphan or cellulose acetate membranes assessed. In particular, the effect of EPO on the blood lipidwhich were not altered during the course of the study. Kinetic profile has not been well documented. modeling was not routinely used to monitor dialysis delivery. There are theoretical benefits resulting from the use of EPOPatients on CAPD used standard peritoneal dialysate (Dianeal, Baxter Healthcare, Round Lake, Illinois, USA). No patient on CAPD required a significant variation in the dialysate glucose Received for publication July 6, 1993 content, nor in dialysate volume instilled during the study and in revised form October 20, 1993 period. All patients were similarly advised by a dietician Accepted for publication October 21, 1993 regarding a diet appropriate to their dialysis and low in satu- © 1994 by the International Society of Nephrology rated fats. 897 898 Pollock et a!: EPO and lipids in renal failure Assessments were made prior to the commencement of EPO,used either form of hemodialysis, and no center effect was at three to six months (follow-up 1) and 12 to 18 monthsevident. Thus the hemodialysis group was regarded as uniform. (follow-up 2) after EPO treatment was started. MeasurementsThirty-one patients were on continuous ambulatory peritoneal included hemoglobin and hematocrit; pre-dialysis blood urea;dialysis (CAPD). iron status as determined by serum iron and ferritin; serum B12 The primary causes of end-stage renal failure were: primary and folate; as well as factors known to be associated with EPOglomerulonephritis 36.6%; analgesic nephropathy 21.4%; diabe- resistance, that is, serum parathyroid hormone and aluminumtes mellitus 8%; unclassified 7.5%; chronic interstitial nephritis levels. The lipoprotein profile was assessed by measuring the4.5%; renovascular 3.6%, hypertension 3.6%; reflux nephropa- following parameters: total cholesterol, LDL cholesterol, HDLthy 3.6%; polycystic kidneys 2.7%; multiple myeloma 2.7%, cholesterol, triglycerides, apoproteins Al and B, and lipopro-amyloid 2.7%, other 3.1%. This reflects the study population at tein (a). All lipid measurements were performed in a singlethe study centers, but differs from the Australian experience in laboratory. Other measurements were standard laboratory pro-general, where analgesic nephropathy accounts for 11% and cedures and performed in individual laboratories. diabetic nephropathy for 14% of the end-stage renal failure Total cholesterol was measured by a spectrophotometricpopulation [3]. colorimetric end-point determination using the Boehringer Those on hemodialysis and CAPD were aged similarly, being Mannheim Enzymic Method run on the Hitachi 705 analyzer.59.5 1.75versus 61.2 2.4years, respectively, and had been HDL cholesterol was measured using the Seba Diagnostics kiton dialysis for a similar length of time 30.54.6versus 28.7 which employs polyethylene glycol as the precipitant. LDL was6.7months. directly measured by subtracting the HDL cholesterol from the Patients were followed from 3 to 18 months from commence- cholesterol content of the lowermost fraction following ultra-ment of the study. During this period 22 patients died, 5 centrifugation at 100,000 g for 24 hours. Triglycerides wereunderwent renal transplantation and 4 commenced pharmaco- determined by Boehringer Mannheim GPO-PAP method on thelogical lipid lowering agents. The causes of death were: cere- Hitachi 705 analyzer. Apoproteins were measured by nephe-brovascular accident 4, myocardial infarction 5, withdrawal lometry using the Beckman nephelometer, with the apoproteinfrom dialysis 4, malignancy 3, infection 3, pancreatitis 1, B assay specific for apoprotein B 100. Lipoprotein (a) wasaccidental 1, and cardiac tamponade 1. The excess death rate is measured by radioimmunoassay using a Pharmacia kit. accounted for by the high representation of patients with Due to ethical considerations, a control group of patients withanalgesic nephropathy and the elderly in the study population. a similar degree of anemia not treated with EPO was not Ninety-five patients completed at least one follow-up at 5.2 available for comparison on a prospective basis. Thus, in order0.3months, and 53 patients completed a second follow-up 13.1 to determine whether increased time on dialysis per Se was 0.6months after the initial assessment. Overall, the follow-up associated with alterations in the lipid profile, patients in whomin 95 patients was 10.0 0.6months. EPO was commenced within one year of the commencement of The hematological, biochemical and lipid results for the initial dialysis were compared with those who had been on mainte-and follow-up assessments are presented in Table 1. As ex- nance dialysis for greater than one year. pected the hemoglobin increased significantly in association with decreased serum ferritin. Parathyroid hormone fell at the Statistical analysis second assessment, but showed no difference from baseline at Statistical analyses were made using Statview Il® software.the time of the final measurement. No significant difference in Longitudinal changes in measured parameters were compareddialysis efficiency as measured by pre-dialysis urea was evident using paired t-tests. Comparisons between two groups wereduring the course of the study. Serum albumin levels increased made using unpaired t-tests or chi-squared statistics. Analysisby a small but significant amount following the introduction of of variance was used to detect differences between threeEPO, with the major effect evident at the time of first follow-up.
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