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      Impact of Diabetic Lesions on Pathology, Treatment, and Outcomes of Glomerular Diseases

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          Abstract

          Abstract

          Key Points

          • People with glomerular disease (GD) and comorbid diabetes have similar baseline characteristics irrespective of superimposed diabetic lesions.

          • Immunosuppression for GD with comorbid diabetes is the same regardless of superimposed diabetic glomerular lesions.

          • ESKD or death is more rapid in GD and comorbid diabetes only in the presence of moderate-severe diabetic glomerular lesions.

          Background

          We aimed to evaluate whether concomitant diabetic glomerulosclerosis (DGS) and its severity affect the treatment and outcomes of primary glomerular diseases (GDs) with comorbid diabetes.

          Methods

          We conducted a retrospective review of people with diabetes and GD. We searched the GD Collaborative Network for biopsies from 2008 to 2015 among persons with diabetes and any of the following diagnoses: FSGS, IgA nephropathy, minimal change disease, membranous nephropathy, or antineutrophil cytoplasmic autoantibody GN. Data were abstracted from health records and histologic diabetic glomerular class scored. The primary composite end point was ESKD or death. Multivariable Cox regression models tested whether any or the severity of diabetes histopathology affected the primary end point.

          Results

          Data from 134 cases were available for analysis (78 DGS+GD and 56 GD alone). Diabetes duration and glycemic control were similar between the two groups ( P = 0.2; P = 0.09, respectively). Use of immunosuppression did not differ between the two groups ( P = 0.3). The composite end point was significantly higher in DGS+GD (22.5 cases per 100 person-years [95% confidence interval (CI), 16.6 to 30.5]) versus GD alone (10.2 cases per 100 person-years [95% CI, 6.4 to 16.2]). Regression analyses demonstrated that compared with the GD-alone group, the risk for the composite end point was similar in the group with mild DGS+GD (DGS class 1, 2a) (hazard ratio, 1.15 [95% CI, 0.54 to 2.43]) while the group with severe DGS+GD (DGS class 2b, 3, 4) had a greater risk (hazard ratio, 3.60 [1.79 to 7.22]).

          Conclusions

          Among people with diabetes and GD, mild diabetic glomerular lesions on biopsy do not affect outcomes, but moderate-severe lesions increase the risk for ESKD and death. Whether use of immunosuppression, particularly glucocorticoids, is less successful in inducing GD remission in people with moderate-severe diabetic lesions will be a focus of future study in a larger population.

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          Most cited references28

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            Pathologic classification of diabetic nephropathy.

            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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              Prevalence of Diabetes by Race and Ethnicity in the United States, 2011-2016

              During 2011-2016, how prevalent was diabetes among major race/ethnicity groups and subgroups of Hispanic and non-Hispanic Asian adults in the United States? In this cross-sectional study that included 7575 adults, the age- and sex-adjusted diabetes prevalence was 12.1% for non-Hispanic white, 20.4% for non-Hispanic black, 22.1% for Hispanic, and 19.1% for non-Hispanic Asian groups. The diabetes prevalence also differed significantly among Hispanic or non-Hispanic Asian subgroups. In the United States in 2011-2016, the prevalence of diabetes varied across racial/ethnic groups. The prevalence of diabetes among Hispanic and Asian American subpopulations in the United States is unknown. To estimate racial/ethnic differences in the prevalence of diabetes among US adults 20 years or older by major race/ethnicity groups and selected Hispanic and non-Hispanic Asian subpopulations. National Health and Nutrition Examination Surveys, 2011-2016, cross-sectional samples representing the noninstitutionalized, civilian, US population. The sample included adults 20 years or older who had self-reported diagnosed diabetes during the interview or measurements of hemoglobin A 1c (HbA 1c ), fasting plasma glucose (FPG), and 2-hour plasma glucose (2hPG). Race/ethnicity groups: non-Hispanic white, non-Hispanic black, Hispanic and Hispanic subgroups (Mexican, Puerto Rican, Cuban/Dominican, Central American, and South American), non-Hispanic Asian and non-Hispanic Asian subgroups (East, South, and Southeast Asian), and non-Hispanic other. Diagnosed diabetes was based on self-reported prior diagnosis. Undiagnosed diabetes was defined as HbA 1c 6.5% or greater, FPG 126 mg/dL or greater, or 2hPG 200 mg/dL or greater in participants without diagnosed diabetes. Total diabetes was defined as diagnosed or undiagnosed diabetes. The study sample included 7575 US adults (mean age, 47.5 years; 52% women; 2866 [65%] non-Hispanic white, 1636 [11%] non-Hispanic black, 1952 [15%] Hispanic, 909 [6%] non-Hispanic Asian, and 212 [3%] non-Hispanic other). A total of 2266 individuals had diagnosed diabetes; 377 had undiagnosed diabetes. Weighted age- and sex-adjusted prevalence of total diabetes was 12.1% (95% CI, 11.0%-13.4%) for non-Hispanic white, 20.4% (95% CI, 18.8%-22.1%) for non-Hispanic black, 22.1% (95% CI, 19.6%-24.7%) for Hispanic, and 19.1% (95% CI, 16.0%-22.1%) for non-Hispanic Asian adults (overall P  < .001). Among Hispanic adults, the prevalence of total diabetes was 24.6% (95% CI, 21.6%-27.6%) for Mexican, 21.7% (95% CI, 14.6%-28.8%) for Puerto Rican, 20.5% (95% CI, 13.7%-27.3%) for Cuban/Dominican, 19.3% (95% CI, 12.4%-26.1%) for Central American, and 12.3% (95% CI, 8.5%-16.2%) for South American subgroups (overall P  < .001). Among non-Hispanic Asian adults, the prevalence of total diabetes was 14.0% (95% CI, 9.5%-18.4%) for East Asian, 23.3% (95% CI, 15.6%-30.9%) for South Asian, and 22.4% (95% CI, 15.9%-28.9%) for Southeast Asian subgroups (overall P  = .02). The prevalence of undiagnosed diabetes was 3.9% (95% CI, 3.0%-4.8%) for non-Hispanic white, 5.2% (95% CI, 3.9%-6.4%) for non-Hispanic black, 7.5% (95% CI, 5.9%-9.1%) for Hispanic, and 7.5% (95% CI, 4.9%-10.0%) for non-Hispanic Asian adults (overall P  < .001). In this nationally representative survey of US adults from 2011 to 2016, the prevalence of diabetes and undiagnosed diabetes varied by race/ethnicity and among subgroups identified within the Hispanic and non-Hispanic Asian populations. This national survey study uses National Health and Nutrition Examination Survey (NHANES) 2011-2016 data to estimate differences in the prevalence of diagnosed and undiagnosed diabetes among US adults 20 years or older by major race/ethnicity groups and selected Hispanic and non-Hispanic Asian subpopulations.
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                Author and article information

                Contributors
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                Journal
                Kidney360
                Kidney360
                KIDNEY
                Kidney360
                Kidney360
                American Society of Nephrology
                2641-7650
                October 2023
                29 August 2023
                : 4
                : 10
                : 1445-1453
                Affiliations
                [1 ]University of North Carolina Kidney Center, UNC School of Medicine, Chapel Hill, North Carolina
                [2 ]University of Minnesota Division of Nephrology and Hypertension, UM School of Medicine, Minneapolis, Minnesota
                [3 ]Division of Nephropathology, Cedars-Sinai Medical Center, Los Angeles, California
                Author notes
                Correspondence: Dr. Amy K. Mottl, University of North Carolina Kidney Center, UNC School of Medicine, 5020C Burnett Womack, Chapel Hill, NC 27599. Email: amy_mottl@ 123456med.unc.edu
                Author information
                https://orcid.org/0009-0007-6533-6794
                https://orcid.org/0000-0002-5890-2862
                https://orcid.org/0000-0001-8243-9073
                https://orcid.org/0000-0002-4258-1726
                Article
                K360-2023-000428 00016
                10.34067/KID.0000000000000247
                10615380
                37642555
                57561e4c-37e3-477e-9960-ae67ff51e3f5
                Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 May 2023
                : 16 August 2023
                Page count
                Figures: 2, Tables: 3, References: 28, Pages: 9
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases
                Award ID: 1R01DK126959-01
                Award Recipient : Not Applicable
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases
                Award ID: 1R01DK126959-01
                Categories
                Original Investigation
                Glomerular and Tubulointerstitial Diseases
                Custom metadata
                TRUE
                T
                YES

                diabetes,glomerular disease,biopsy,pathology,eskd,death,hospitalization

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