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      Prevalence and Severity of Anaemia in Patients with Type 2 Diabetic Nephropathy and Different Degrees of Chronic Renal Insufficiency

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          Abstract

          Background/Aim: Type 2 diabetes mellitus is the single most common cause of chronic kidney disease (CKD); however its real impact on renal anaemia has not been established. The aim of this study was to evaluate whether onset, severity, and prevalence of anaemia during the course of CKD is different between type 2 diabetic and non-diabetic patients. Methods: We enrolled 281 patients with: (1) type 2 diabetes and no CKD (n = 75); (2) type 2 diabetes plus CKD (n = 106), and (3) CKD without type 2 diabetes (n = 100). According to K/DOQI guidelines, the patients with renal insufficiency (i.e., those with a glomerular filtration rate <60 ml/min) were subgrouped into three tertiles of CKD: (1) stage 3 (creatinine clearance 60–30 ml/min); (2) stage 4 (creatinine clearance 29–15 ml/min), and (3) stage 5 (creatinine clearance <15 ml/min). Results: Anaemia was observed in 16% of the diabetic patients without CKD; it was more frequent in the diabetic patients with CKD than in the non-diabetic patients with CKD (61.7 vs. 52%, p < 0.05). The comparison among the tertiles showed that the prevalence of anaemia was significantly higher only in diabetic CKD patients of stages 4 and 5. The prevalence was higher in females independently of type 2 diabetes mellitus. In diabetics with a normal renal function, the haemoglobin levels were higher than in diabeticsand non-diabetics with CKD, but the diabetics showed lower levels of haemoglobin than non-diabetics at stage 3 and stage 4 of CKD. Conclusions: Diabetic patients with CKD of stages 4 and 5 have a higher prevalence of anaemia than non-diabetic patients with comparable glomerular filtration rate. A higher awareness of this risk will allow earlier diagnosis and treatment.

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          Most cited references 16

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          Oxidative stress in uremia: nature, mechanisms, and potential consequences.

          Oxidative stress has emerged as a constant feature of chronic renal failure (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance of lipid, carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients and animals. We recently have shown that oxidative stress in CRF animals is associated with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase (SOD). The functional significance of these findings was confirmed by favorable response to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays an important role in the pathogenesis of the associated hypertension (oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension, and autoimmune diseases, which independently increase production of reactive oxygen intermediates, and frequently are associated with CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane and dialysate impurities), acute and chronic infections (blood access infection, hepatitis, and so forth), and excessive parenteral iron administration intensify CRF-associated oxidative stress and its adverse consequences in patients with end-stage renal disease. The problem is compounded by limited intake of fresh fruits and vegetables (K(+) restriction), which contain numerous natural phytochemicals and antioxidant vitamins.
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            Unrecognized anemia in patients with diabetes: a cross-sectional survey.

            Anemia is common in diabetes, potentially contributing to the pathogenesis of diabetes complications. This study aims to establish the prevalence and independent predictors of anemia in a cross-sectional survey of 820 patients with diabetes in long-term follow-up in a single clinic. A full blood count was obtained in addition to routine blood and urine test results for all patients over a 2-year period to encompass all patterns of review. Predictors of the most recent Hb concentration and anemia were identified using multiple and logistic regression analysis. A total of 190 patients (23%) had unrecognized anemia (Hb 2 times (odds ratio [OR] 2.3) and macroalbuminuric patients >10 times (OR 10.1) as likely to have anemia than normoalbuminuric patients with preserved renal function (GFR >80 ml/min). Anemia is a common accompaniment to diabetes, particularly in those with albuminuria or reduced renal function. Additional factors present in diabetes may contribute to the development of increased risk for anemia in patients with diabetes.
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              Anemia with erythropoietin deficiency occurs early in diabetic nephropathy.

              The normochromic normocytic anemia of erythropoietin (EPO) deficiency is recognized in advanced renal failure but not in early renal disease. The aim of this study was to determine whether anemia with EPO deficiency is found in type 1 diabetic patients with diabetic nephropathy in the absence of advanced renal failure and to compare them with patients with nondiabetic renal disease of similar severity. A total of 27 type 1 diabetic patients with diabetic nephropathy (DN), defined as having persistent proteinuria (mean 1,086 mg/day [CI 120-5,1901), a serum creatinine < or = 180 micromol/l, and retinopathy, were compared with 26 nondiabetic patients with glomerulonephritis (GN) and persistent proteinuria (1,874 mg/day [349-5,005]). The Hb concentration, red cell indexes, and serum EPO levels were measured, and other causes for the anemia were excluded. The EPO values were compared with a normal reference range obtained from nondiabetic patients with a microcytic anemia. The DN patients were tested for signs of diabetic peripheral and autonomic neuropathy. We found that 13 of the 27 DN patients were anemic (Hb 10.6 +/- 0.9 g/dl) in marked contrast to none of the GN patients (Hb 13.7 +/- 1.4 g/dl, P < 0.005). In the DN group, serum EPO concentrations failed to increase in response to anemia compared with the response seen in patients with microcytic anemia. Thus, the anemia of the DN group was associated with EPO deficiency. The anemic DN patients showed evidence of more severe proteinuria and diabetic neuropathy than the nonanemic DN patients. Anemia associated with EPO deficiency can occur early in DN before the onset of advanced renal failure, but does not normally occur in nondiabetic renal disease of similar severity. The pathogenesis requires elucidation.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2007
                January 2007
                29 November 2006
                : 105
                : 2
                : c62-c67
                Affiliations
                Chairs of Nephrology, aUniversity of Palermo, Palermo, bUniversity of Catanzaro, Catanzaro, and cUniversity of Rome Tor Vergata, Rome, Italy
                Article
                97600 Nephron Clin Pract 2007;105:c62–c67
                10.1159/000097600
                17135770
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Tables: 2, References: 25, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/97600
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