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      Proteinuria in Diabetic Patients – Is It Always Diabetic Nephropathy?

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          Abstract

          Background: Diabetic nephropathy (dNP) is a consequence of type 1 and type 2 diabetes, typically occurring between 5 and 15 years after diabetes has been diagnosed. The coincidence of dNP and diabetic retinopathy (dRP) is well known. In this study we correlated the histological findings of the kidney biopsy with the clinically expected diagnosis of dNP. Patients and Methods: Over a 4-year period with a total of 326 kidney biopsies, 85 biopsies were performed on patients with diabetes. In all of these patients we had information about duration of diabetes and ophthalmological status. Additionally, data about proteinuria, urine sediment and autoantibodies were available. The nephrologist had to give the suspected diagnosis before the biopsy was performed, using the clinical data available. Results: In 57 patients (67%) dNP was predicted clinically before biopsy. In 28 patients we expected a different kind of kidney disease. Only 43 patients had dNP histologically. In 16 out of 19 patients with dRP we also found dNP. 26 patients with dNP did not have dRP. So dRP was very specific but not sensitive to predict dNP. On the other hand, all patients without dRP but acanthocytes in urine sediment had non-diabetic kidney disease (NDKD). In the case of patients with neither dRP nor acanthocytes, it was very difficult to distinguish between dNP and NDKD. Acanthocytes and antineutrophil cytoplasmatic antibodies with positive antibodies for proteinase 3 or myeloperoxidase were found only in NDKD, but ANAs were detected in a wide titer range in dNP and NDKD. The known duration of the diabetes ranged from 1 to 40 years. There were no additional parameters to differentiate this group. Conclusions: Diabetic patients with dRP and proteinuria frequently have dNP. In patients without typical retinal findings dNP is less likely, thus a kidney biopsy is necessary to confirm the diagnosis. Additional knowledge about urine sediment and autoantibodies is helpful, but is not sufficient to differentiate NDKD from dNP in the majority of patients.

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          Patterns of renal injury in NIDDM patients with microalbuminuria.

          Microalbuminuria predicts overt nephropathy in non-insulin-dependent diabetic (NIDDM) patients; however, the structural basis for this functional abnormality is unknown. In this study we evaluated renal structure and function in a cohort of 34 unselected microalbuminuric NIDDM patients (26 male/8 female, age: 58 +/- 7 years, known diabetes duration: 11 +/- 6 years, HbA1c: 8.5 +/- 1.6%). Systemic hypertension was present in all but 3. Glomerular filtration rate (GFR) was 101 +/- 27 ml.min-1.1.73 m-2 and albumin excretion rate (AER) 44 (20-199) micrograms/ min. Light microscopic slides were categorized as: C I) normal or near normal renal structure; C II) changes "typical" of diabetic nephropathology in insulin-dependent diabetes (IDDM) (glomerular, tubulo-interstitial and arteriolar changes occurring in parallel); C III) "atypical" patterns of injury, with absent or only mild diabetic glomerular changes associated with disproportionately severe renal structural changes including: important tubulo-interstitial with or without arteriolar hyalinosis with or without global glomerular sclerosis. Ten patients (29.4%) were classified as C I, 10 as C II (29.4%) and 14 as C III (41.2%); none of these patients had any definable non-diabetic renal disease. GFR, AER and blood pressure were similar in the three groups, while HbA1c was higher in C II and C III than in C I patients. Diabetic retinopathy was present in all C II patients (background in 50% and proliferative in 50%). None of the patients in C I and C III had proliferative retinopathy, while background retinopathy was observed in 50% of C I and 57% of C III patients. In summary, microalbuminuric NIDDM patients are structurally heterogeneous with less than one third having "typical" diabetic nephropathology. The presence of both "typical" and "atypical" patterns of renal pathology was associated with worse metabolic control, suggesting that hyperglycaemia may cause different patterns of renal injury in older NIDDM compared to younger IDDM patients.
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            Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients.

            A prospective study of the prevalence and causes of persistent albuminuria (greater than 300 mg/24 hr) was conducted in non-insulin-dependent diabetic (NIDDM) patients, age less than 66 years, attending a diabetic clinic during 1987. All eligible patients (N = 370) were asked to collect at least one 24-hour urine sample for albumin analysis. Urine collection was obtained in 224 males and 139 females (98%). Fifty patients (7 women) suffered from persistent albuminuria (13.8%). The prevalence of albuminuria was significantly higher in males (19%) than in females (5%). A kidney biopsy was performed in 35 patients (70%). The kidney biopsies revealed diffuse and/or nodular diabetic glomerulosclerosis in 27 patients (77%), while the remaining eight patients (23%) had a variety of non-diabetic glomerulopathies, such as minimal lesion and mesangioproliferative glomerulonephritis. Diabetic retinopathy was present in 15 of 27 patients (56%) with diabetic glomerulosclerosis, while none of the eight patients with a non-diabetic glomerulopathy had retinopathy. Our cross sectional study has revealed a high prevalence of albuminuria and of non-diabetic glomerulopathy as a cause of this complication in NIDDM patients. Presence of diabetic retinopathy strongly suggests that a diabetic glomerulopathy is the cause of albuminuria. Albuminuric non-insulin-dependent diabetic patients without retinopathy require further evaluation, that is, kidney biopsy.
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              Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies.

              The frequency of various types of renal changes in patients with type 2 diabetes is not clearly defined in the literature. Reported discrepancies likely are caused by ethnic and geographic factors. However, policies used in nephrological centers for the selection of patients to undergo renal biopsy also may have an influence. The present study reports 393 renal biopsies in patients with type 2 diabetes performed in a group of centers in northwestern Italy using different (restricted [CRPs] or unrestricted [CUP]) biopsy policies. On the basis of light microscopic, immunofluorescence, and ultrastructural findings, cases were subdivided into three classes characterized by the presence of diabetic glomerulosclerosis (class 1), prevailing vascular (arterioarteriolosclerotic) and ischemic glomerular changes (class 2), other glomerulonephritides superimposed on diabetic glomerulosclerosis (class 3a), or glomerulonephritides without the presence of diabetic glomerulosclerosis (class 3b). Although no significant differences were found for class 2 (detected in 15% and 16% of patients from CRPs and the CUP, respectively), the frequency of the other two classes was strongly biased by the biopsy policy. Class 1 was found in 29% and 51% of cases, and class 3 in 57% and 33% of cases from CRPs and the CUP, respectively. Moreover, class 3a was more common (67%) in the CUP, and class 3b (78%) in CRPs. Our findings may explain conflicting data from the literature and the influence that type of adopted biopsy policy may have on an epidemiological evaluation. This study helps clarify the frequency of renal changes in patients with type 2 diabetes and suggests more extensive use of renal biopsy to obtain reliable prognostic indications and plan a rational therapeutic approach. Copyright 2002 by the National Kidney Foundation, Inc.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2006
                June 2006
                06 June 2006
                : 29
                : 1
                : 48-53
                Affiliations
                aMedical Clinic A, Klinikum der Stadt Ludwigshafen, and bInstitute for the Prevention of Hypertension and Kidney Diseases, Ludwigshafen, Germany
                Article
                92850 Kidney Blood Press Res 2006;29:48–53
                10.1159/000092850
                16636578
                8e3b8eb5-b7fd-4219-ad61-033dc26d0ae1
                © 2006 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.

                History
                : 26 July 2005
                : 16 February 2006
                Page count
                Figures: 4, Tables: 2, References: 31, Pages: 6
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Diabetic nephropathy,Acanthocytes,Kidney biopsy,Diabetic retinopathy,Non-diabetic kidney disease,Proteinuria

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