Christiaan L Meuwese1, Merel van Diepen1, Anne R Cappola2, Mark J Sarnak3, Michael G Shlipak4, Douglas C Bauer5,6, Linda P Fried7, Massimo Iacoviello8, Bert Vaes9,10, Jean Degryse9,10, Kay-Tee Khaw11, Robert N Luben11, Bjørn O Åsvold12,13, Trine Bjøro14, Lars J Vatten12, Anton J M de Craen15, Stella Trompet15,16, Giorgio Iervasi17, Sabrina Molinaro18, Graziano Ceresini19, Luigi Ferrucci20, Robin P F Dullaart21, Stephan J L Bakker21, J Wouter Jukema16, Patricia M Kearney22, David J Stott23, Robin P Peeters24,25, Oscar H Franco24, Henry Völzke26, John P Walsh27,28, Alexandra Bremner29, José A Sgarbi30, Rui M B Maciel31, Misa Imaizumi32, Waka Ohishi32, Friedo W Dekker1, Nicolas Rodondi33,34, Jacobijn Gussekloo35, Wendy P J den Elzen36. 1. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. 2. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. 3. Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, MA, USA. 4. Department of Medicine, UCSF School of Medicine, San Francisco, CA, USA. 5. Department of Medicine, University of California, San Francisco, CA, USA. 6. Department of Epidemiology and Biostatistics, University of San Francisco, CA, USA. 7. Mailman School of Public Health and Columbia University Medical Center, New York, NY, USA. 8. University Cardiology Unit, Cardiothoracic Department, University Policlinic Hospital, Bari, Italy. 9. Institute of Health and Society, Université catholique de Louvain (UCL), Brussels, Belgium. 10. Department of Public Health and Primary Care, Katholieke Universiteit Leuven (KUL), Leuven, Belgium. 11. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 12. Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. 13. Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 14. Department of Medical Biochemistry, Oslo University Hospital, and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 15. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. 16. Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands. 17. National Council Research Institute of Clinical Physiology, Tuscany Region G. Monasterio Foundation, Pisa, Italy. 18. National Council Research Institute of Clinical Physiology, Pisa, Italy. 19. Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Parma, Italy. 20. National Institute on Aging, Baltimore, MD, USA. 21. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 22. School of Public Health, University College Cork, Cork, Ireland. 23. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. 24. Department of Internal Medicine, Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands. 25. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 26. Institute for Community Medicine, SHIP/Clinical-Epidemiological Research & German Centre of Cardiovascular Research, University of Greifswald, Greifswald, Germany. 27. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia. 28. Medical School, The University of Western Australia, Crawley, Western Australia. 29. School of Population Health, The University of Western Australia, Crawley, Western Australia. 30. Division of Endocrinology, Faculdade de Medicina de Marília, Marília, Brazil. 31. Division of Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil. 32. Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima and Nagasaki, Japan. 33. Department of General Internal Medicine, Inselspital, University of Bern, Bern, Switzerland. 34. Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland. 35. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands. 36. Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
BACKGROUND: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. METHODS: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. RESULTS: A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. CONCLUSIONS: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.
BACKGROUND:Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. METHODS: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, freethyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. RESULTS: A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. CONCLUSIONS: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.
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