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      Association of Serum 25 (OH) Vitamin D With Chronic Kidney Disease Progression in Type 2 Diabetes

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          Abstract

          Objectives

          Growing evidence demonstrated that vitamin D levels had been linked to type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in light of various extraskeletal effects. Therefore, the present study aimed to evaluate the association of 25-hydroxyvitamin D [25(OH)D] level with the clinicopathological features and CKD progression in T2DM.

          Methods

          A total of 182 patients with T2DM with CKD stages 1 through 4 (G1–G4) were retrospectively included. Identification of the serum 25(OH)D level associated with CKD progression was executed by Kaplan–Meier survival analysis and Cox proportional hazards models. We further performed sensitivity analyses with a time-weighted average (TWA) of the serum 25(OH)D level in 75 participants to reinforce the findings.

          Results

          The median serum 25(OH)D level was 26 (IQR, 14; 39) nmol/L in the study participants. Median follow-up time was 42 months, during which 70 (38%) patients confronted CKD progression. Cumulative kidney outcomes were significantly higher in the lowest tertile of the serum 25(OH)D level in Kaplan–Meier analyses ( P < 0.001). Consistently, the analyses of Cox proportional hazards regression models indicated a significantly greater risk for CKD progression in the lowest tertile of the serum 25(OH)D level compared with the highest tertile of the serum 25(OH)D level ( P = 0.03). These relationships remained robust with further sensitivity analysis of data with TWA of the serum 25(OH)D level, showing an independent association between lower TWA of the serum 25(OH)D level and an unfavorable renal outcome in patients with T2DM with CKD.

          Conclusions

          Our findings demonstrated that patients with T2DM with a decreased 25(OH)D level had deteriorated renal function. Both lower levels of baseline and TWA of serum 25(OH)D were associated with an increased risk of CKD progression in patients with T2DM, which suggested that the long-term maintenance of optimal vitamin D levels from early in life might be associated with reduced future risk of CKD development in T2DM.

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          Most cited references34

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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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            Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

            The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
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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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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                30 June 2022
                2022
                : 13
                : 929598
                Affiliations
                [1]Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China
                Author notes

                Edited by: Maria Margherita Rando, Agostino Gemelli University Polyclinic (IRCCS), Italy

                Reviewed by: William B. Grant, Sunlight Nutrition and Health Research Center, United States; Conghui Guan, First Hospital of Lanzhou University, China

                *Correspondence: Yanggang Yuan, ygyuan@ 123456njmu.edu.cn ; Bo Zhang, zhangbo@ 123456jsph.org.cn ; Changying Xing, cyxing62@ 123456126.com

                †These authors share first authorship

                ‡These authors have contributed equally to this work and share senior authorship

                This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.929598
                9279917
                9c115bb3-cc23-4dda-9873-2302f881302c
                Copyright © 2022 Duan, Lu, Wu, Zhang, Nie, Sun, Huang, Guo, Zhang, Xing and Yuan

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 April 2022
                : 30 May 2022
                Page count
                Figures: 5, Tables: 6, Equations: 0, References: 35, Pages: 13, Words: 8433
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82170699, 81870469, 82100767
                Funded by: Natural Science Foundation of Jiangsu Province , doi 10.13039/501100004608;
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                25-hydroxyvitamin d,type 2 diabetes mellitus,ckd progression,diabetic kidney disease,non-diabetic kidney disease

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