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      Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

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          Abstract

          Objective

          We investigated the correlation between zinc levels and Nrf2 expression and potential effects on the clinicopathology of patients with diabetic nephropathy (DN).

          Methods

          We selected 30 patients with DN, diagnosed via renal biopsy at our hospital from March 2018 to November 2019, and enrolled 30 healthy individuals from a medical examination center as the control group. Patients with DN were divided into normal-zinc and low-zinc groups. We detected the levels of zinc, copper, and Nrf2 mRNA in their serum, and collected the clinical and pathological data of DN patients.

          Results

          Serum zinc level and Nrf2 mRNA expression were significantly decreased in patients with DN compared to those of healthy people ( P < 0.05). Of the 30 patients, 16 had low zinc (53.3%) and 14 had normal zinc levels (46.7%). There was no significant difference in the blood Nrf2 mRNA expression between the two groups ( P > 0.05). However, the expression of Nrf2 in the kidney tissue of the low-zinc group was significantly lower compared to the normal-zinc group ( P < 0.05). Diastolic blood pressure and copper levels were significantly higher in the low-zinc group ( P < 0.05). In contrast, body mass index, red blood cell count, Hb level, and the ratio of zinc to copper were significantly lower in the low-zinc group ( P < 0.05). The pathological classifications of the low-zinc group were more severe ( P < 0.05).

          Conclusion

          Patients with DN were more likely to have zinc deficiency and lower expression of Nrf2. Additionally, DN patients with zinc deficiency were prone to have more severe clinical and pathological manifestations.

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          Most cited references36

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          2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018.

          (2017)
          The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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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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              Advanced glycation end-products: a review.

              Advanced glycation end-products are a complex and heterogeneous group of compounds that have been implicated in diabetes related complications. At present it is not known if they are the cause or the consequence of the complications observed. We discuss the chemistry of advanced glycated end-product formation and their patho-biochemistry particularly in relation to the diabetic microvascular complications of retinopathy, neuropathy and nephropathy as well as their role in the accelerated vasculopathy observed in diabetes. The concept of carbonyl stress as a cause for advanced glycated end-product toxicity is mentioned. We discuss alterations in the concentrations of advanced glycated end-products in the body, particularly in relation to changes occurring with age, diabetes and its complications such as nephropathy. Problems relating to current methods of advanced glycated end-product detection and measurement are highlighted including the lack of a universally established method of detection or unit of measurement. Agents used for the treatment of advanced glycated end-product accumulation are reviewed, with an emphasis on the results of the recent phase III trials using aminoguanidine and diabetes related complications.
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                Author and article information

                Contributors
                luopingjen@163.com
                weiguangzhang1@163.com
                li_bing2020@jlu.edu.cn
                Journal
                Nutr Diabetes
                Nutr Diabetes
                Nutrition & Diabetes
                Nature Publishing Group UK (London )
                2044-4052
                6 August 2022
                6 August 2022
                2022
                : 12
                : 37
                Affiliations
                [1 ]GRID grid.452829.0, ISNI 0000000417660726, Department of Nephropathy, , The Second Hospital of Jilin University, ; Changchun, Jilin Province China
                [2 ]GRID grid.488137.1, ISNI 0000 0001 2267 2324, Department of Nephrology, Chinese PLA General Hospital, , Chinese PLA Institute of Nephrology, ; Beijing, China
                Author information
                http://orcid.org/0000-0003-2029-4432
                http://orcid.org/0000-0003-0029-0872
                http://orcid.org/0000-0001-6997-5066
                http://orcid.org/0000-0001-7640-9468
                Article
                212
                10.1038/s41387-022-00212-4
                9357008
                35933424
                c7691bee-b0fe-49a9-8b52-039de806cabe
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 December 2020
                : 14 March 2022
                : 13 June 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100011789, Department of Science and Technology of Jilin Province (Jilin Province Science and Technology Department);
                Award ID: 20190304042YY
                Award ID: 20200201488JC
                Award Recipient :
                Funded by: The Open Research Fund of National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital (No. kfkt202020)
                Funded by: FundRef https://doi.org/10.13039/501100010211, Education Department of Jilin Province (Jilin Provincial Department Education);
                Award ID: JJKH20190056KJ
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100005227, Jilin Department of Health (Department of Health, Jilin Province);
                Award ID: 2018J048
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Endocrinology & Diabetes
                kidney diseases,nutrition disorders
                Endocrinology & Diabetes
                kidney diseases, nutrition disorders

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