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      Non-Proteinuric Diabetic Nephropathy

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          Abstract

          Diabetic nephropathy patients traditionally show significant macroalbuminuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. Epidemiological surveys confirm that chronic kidney disease (CKD) diagnosed by a low glomerular filtration rate (GFR) is more common in diabetic patients than in the non-diabetic population but a low number of patients had levels of proteinuria above that which traditionally defines overt diabetic nephropathy (>500 mg/g). The large number of patients with low levels of proteinuria suggests that the traditional clinical paradigm of overt diabetic nephropathy is changing since it does not seem to be the underlying renal lesion in most of diabetic subjects with CKD.

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          Pathologic classification of diabetic nephropathy.

          Thijs W Cohen Tervaert, Antien Mooyaart, Kerstin Amann … (2010)
          Although pathologic classifications exist for several renal diseases, including IgA nephropathy, focal segmental glomerulosclerosis, and lupus nephritis, a uniform classification for diabetic nephropathy is lacking. Our aim, commissioned by the Research Committee of the Renal Pathology Society, was to develop a consensus classification combining type1 and type 2 diabetic nephropathies. Such a classification should discriminate lesions by various degrees of severity that would be easy to use internationally in clinical practice. We divide diabetic nephropathy into four hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement. Biopsies diagnosed as diabetic nephropathy are classified as follows: Class I, glomerular basement membrane thickening: isolated glomerular basement membrane thickening and only mild, nonspecific changes by light microscopy that do not meet the criteria of classes II through IV. Class II, mesangial expansion, mild (IIa) or severe (IIb): glomeruli classified as mild or severe mesangial expansion but without nodular sclerosis (Kimmelstiel-Wilson lesions) or global glomerulosclerosis in more than 50% of glomeruli. Class III, nodular sclerosis (Kimmelstiel-Wilson lesions): at least one glomerulus with nodular increase in mesangial matrix (Kimmelstiel-Wilson) without changes described in class IV. Class IV, advanced diabetic glomerulosclerosis: more than 50% global glomerulosclerosis with other clinical or pathologic evidence that sclerosis is attributable to diabetic nephropathy. A good interobserver reproducibility for the four classes of DN was shown (intraclass correlation coefficient = 0.84) in a test of this classification.
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            Acute kidney injury increases risk of ESRD among elderly.

            Areef Ishani, Jay L Xue, Jonathan Himmelfarb … (2009)
            Risk for ESRD among elderly patients with acute kidney injury (AKI) has not been studied in a large, representative sample. This study aimed to determine incidence rates and hazard ratios for developing ESRD in elderly individuals, with and without chronic kidney disease (CKD), who had AKI. In the 2000 5% random sample of Medicare beneficiaries, clinical conditions were identified using Medicare claims; ESRD treatment information was obtained from ESRD registration during 2 yr of follow-up. Our cohort of 233,803 patients were hospitalized in 2000, were aged > or = 67 yr on discharge, did not have previous ESRD or AKI, and were Medicare-entitled for > or = 2 yr before discharge. In this cohort, 3.1% survived to discharge with a diagnosis of AKI, and 5.3 per 1000 developed ESRD. Among patients who received treatment for ESRD, 25.2% had a previous history of AKI. After adjustment for age, gender, race, diabetes, and hypertension, the hazard ratio for developing ESRD was 41.2 (95% confidence interval [CI] 34.6 to 49.1) for patients with AKI and CKD relative to those without kidney disease, 13.0 (95% CI 10.6 to 16.0) for patients with AKI and without previous CKD, and 8.4 (95% CI 7.4 to 9.6) for patients with CKD and without AKI. In summary, elderly individuals with AKI, particularly those with previously diagnosed CKD, are at significantly increased risk for ESRD, suggesting that episodes of AKI may accelerate progression of renal disease.
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              Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus.

              Holly Kramer, Quan Nguyen, Gary Curhan … (2003)
              Kidney disease in type 2 diabetes mellitus (DM) is more heterogeneous than in type 1 DM. Reduced glomerular filtration rate (GFR) among individuals with type 2 DM may not always be due to classic diabetic glomerulosclerosis, which is associated with albuminuria and retinopathy. To determine the prevalence of chronic renal insufficiency (CRI), defined as a GFR less than 60 mL/min per 1.73 m2 body surface area (BSA) in the absence of microalbuminuria or macroalbuminuria and diabetic retinopathy among adults with type 2 DM. Cross-sectional analysis of adults aged 40 years or older with type 2 DM in the Third National Health and Nutrition Examination Survey, a probability sample of the total civilian US noninstitutionalized population conducted from 1988-1994. The GFR per 1.73 m2 BSA, calculated with serum creatinine, urea nitrogen, and serum albumin levels using the Modification of Diet in Renal Disease Study prediction equation; albuminuria, assessed using spot urine albumin/creatinine ratio; and presence of retinopathy, determined with fundus photography. Overall, 13% (sampled n = 171) of adults with type 2 DM (n = 1197) had CRI with a population estimate of 1.1 million. Among these adults with CRI, diabetic retinopathy was noted in 28% (n = 58), while the frequencies of microalbuminuria and macroalbuminuria were 45% (n = 64) and 19% (n = 47), respectively. Retinopathy and albuminuria (microalbuminuria or macroalbuminuria) were both absent in 30% (n = 51) of adults with type 2 DM and CRI. The population estimate of adults with type 2 DM and CRI in the absence of diabetic retinopathy or albuminuria was approximately 0.3 million. A substantial burden of CRI among persons with type 2 DM in the United States is likely due to renal parenchymal disease other than classic diabetic glomerulosclerosis. Approaches to screening renal disease in the type 2 DM population should incorporate assessment of GFR in addition to monitoring urine albumin excretion and funduscopic changes to ensure that individuals with type 2 DM and CRI not due to diabetic glomerulosclerosis will receive appropriate intervention.
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                Author and article information

                Contributors
                Juan F. Navarro-González: Role: Academic Editor
                Desirée Luis: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): J Clin Med
                Journal ID (iso-abbrev): J Clin Med
                Journal ID (publisher-id): jcm
                Title: Journal of Clinical Medicine
                Publisher: MDPI
                ISSN (Electronic): 2077-0383
                Publication date (Electronic): 07 September 2015
                Publication date Collection: September 2015
                Volume: 4
                Issue: 9
                Pages: 1761-1773
                Affiliations
                [1 ]Cátedra de Riesgo Vascular, Facultad de Medicina, Universidad de Salamanca, Salamanca 37007, Spain
                [2 ]Servicio de Nefrologia, Hospital Infanta Cristina, Badajoz 06070, Spain; E-Mails: jvilla_19@ 123456hotmail.com (J.V.); romanhg78@ 123456hotmail.com (R.H.G.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: nrrobles@ 123456yahoo.es ; Tel.: +34-924218117; Fax: +34-924239821.
                Article
                Publisher ID: jcm-04-01761
                DOI: 10.3390/jcm4091761
                PMC ID: 4600158
                PubMed ID: 26371050
                SO-VID: 83efc931-00d2-4e7b-8545-f75a5e17e086
                Copyright © © 2015 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 13 May 2015
                Date accepted : 26 August 2015
                Categories
                Subject: Review

                Keywords: chronic kidney disease,proteinuria,microalbuminuria,diabetes mellitus
                Data availability:
                Keywords: chronic kidney disease, proteinuria, microalbuminuria, diabetes mellitus

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