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      Relationships of Chronic Kidney Disease and Thyroid Dysfunction in Non-Dialysis Patients: A Pilot Study

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          Abstract

          Context: Patients with chronic kidney disease (CKD) usually manifest with disorder of thyroid hormone; however, the correlation is unknown. Objective: The study was designed to explore the relationships between CKD and thyroid dysfunction. Design, Setting, and Participants: A total number of 905 non-dialysis participants were collected at Nanjing First Hospital from August 2009 to October 2012 according to the case records system. Patients were grouped via the estimated glomerular filtration rate (eGFR) according to the KDIGO guideline. Levels of thyroid hormone and biomarkers in different CKD groups were compared by ANOVA. Prevalence of different thyroid diseases was calculated by χ<sup>2</sup> test. Results: We found that FT3 or T3 became more prevalent with increasing eGFR with the lowest level in CKD5 ( p < 0.01). No significant differences were found between groups in FT4, T4, or TSH ( p > 0.05). Frequency of euthyroid sick syndrome (ESS) in CKD groups was high, especially in CKD stage 5 (69.1%, p < 0.01). eGFR had positive correlation with T3 and FT3 ( r = 0.239, p = 0.0001; r = 0.292, p = 0.0001). ESS had correlations with prealbumin, β2-microglobin, eGFR, and C-reactive protein ( r = 0.095, p = 0.004; r = –0.12, p = 0.001; r = 0.091, p = 0.007; r = –0.096, p = 0.008; r = 0.154, p = 0.001). After adjustment for prealbumin, uric acid, HbA1c, age, gender, eGFR, and β2-microglobin, binary regression revealed that hemoglobin, C-reactive protein, and albumin were independent influence factors of ESS ( p = 0.016, r = 1.014; p = 0.023, r = 1.007; p = 0.029, r = 0.996). Conclusion: CKD patients have a high morbidity of ESS, mainly low T3 syndrome. Anemia, inflammation, and malnutrition may contribute to ESS in CKD.

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          Most cited references29

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          Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities.

          An equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provides more accurate estimates of the glomerular filtration rate (eGFR) than that from the modification of diet in renal disease (MDRD) Study, although both include a two-level variable for race (Black and White and other). Since creatinine generation differs among ethnic groups, it is possible that a multilevel ethnic variable would allow more accurate estimates across all groups. To evaluate this, we developed an equation to calculate eGFR that includes a four-level race variable (Black, Asian, Native American and Hispanic, and White and other) using a database of 8254 patients pooled from 10 studies. This equation was then validated in 4014 patients using 17 additional studies from the United States and Europe (validation database), and in 1022 patients from China (675), Japan (248), and South Africa (99). Coefficients for the Black, Asian, and Native American and Hispanic groups resulted in 15, 5, and 1% higher levels of eGFR, respectively, compared with the White and other group. In the validation database, the two-level race equation had minimal bias in Black, Native American and Hispanic, and White and other cohorts. The four-level ethnicity equation significantly improved bias in Asians of the validation data set and in Chinese. Both equations had a large bias in Japanese and South African patients. Thus, heterogeneity in performance among the ethnic and geographic groups precludes use of the four-level race equation. The CKD-EPI two-level race equation can be used in the United States and Europe across a wide range of ethnicity.
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            C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.

            High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP > or =3.0 mg/L (N= 414) versus low CRP<3.0 mg/L (N= 283)], and serum albumin, with all-cause and cardiovascular mortality. Median follow-up time was 125 months, all-cause mortality was 20% (N= 138) and cardiovascular mortality was 10% (N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality. Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.
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              Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease.

              Chronic inflammation associated with chronic kidney disease predicts all-cause and cardiovascular mortality in hemodialysis patients. Here we sought to evaluate the association between plasma levels of the inflammatory mediator interleukin-6 (IL-6) and mortality and aortic calcification/stiffness in 125 patients at different stages (2-5D) of chronic kidney disease. Using multivariate linear regression, we found that plasma IL-6 was independently associated with C-reactive protein, albumin and the stage of chronic kidney disease, but not the aortic calcification score or pulse wave velocity. During follow-up studies (median of 829 days), 38 patients died, 22 from cardiovascular events. Plasma IL-6 significantly predicted overall and cardiovascular mortality; this association persisted after multiple adjustments or restricting the analysis to pre-dialysis patients. Moreover, IL-6 was a significantly better predictor of mortality than C-reactive protein, albumin or tumor necrosis factor-alpha. Hence, plasma IL-6 independently predicted overall and cardiovascular mortality in patients at different stages of chronic kidney disease; however, whether lowering plasma IL-6 will affect the outcome of chronic kidney disease will require more direct evaluation.
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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
                2019
                May 2019
                23 April 2019
                : 44
                : 2
                : 170-178
                Affiliations
                [_a] aDepartment of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
                [_b] bDepartment of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
                Author notes
                *Changchun Cao, Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Longmian Road 109#, Nanjing 211166 (PR China), E-Mail caochangchun@njmu.edu.cn
                Article
                499201 Kidney Blood Press Res 2019;44:170–178
                10.1159/000499201
                31013508
                c85d64ab-9d16-40ef-b06d-591ee393686d
                © 2019 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. 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
                : 25 February 2019
                : 27 February 2019
                Page count
                Figures: 4, Tables: 2, Pages: 9
                Categories
                Research Article

                Cardiovascular Medicine,Nephrology
                Chronic kidney disease,Anemia,Albumin,Euthyroid sick syndrome,C-reactive protein

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