Low thyroid function is not associated with an accelerated deterioration in renal function

Meuwese, Christiaan L.; Diepen, Merel van; Cappola, Anne R.; Sarnak, Mark J.; Shlipak, Michael G.; Bauer, Douglas C.; Fried, Linda P.; Iacoviello, Massimo; Vaes, Bert; Degryse, Jean-Marie; Khaw, Kay‐Tee; Luben, Robert; Åsvold, Bjørn Olav; Bjøro, Trine; Vatten, Lars J.; Craen, Anton J. M. de; Trompet, Stella; Iervasi, Giorgio; Molinaro, Sabrina; Ceresini, Graziano; Ferrucci, Luigi; Dullaart, Robin P. F.; Bakker, Stephan J. L.; Jukema, J. Wouter; Kearney, Patricia M.; Stott, David J.; Peeters, Robin P.; Franco, Oscar H.; Völzke, Henry; Walsh, John P.; Bremner, Alexandra; Sgarbi, José Augusto; Maciel, Rui M. B.; Imaizumi, Misa; Ohishi, Waka; Dekker, Friedo W.; Rodondi, Nicolas; Gussekloo, Jacobijn; Elzen, Wendy P. J. den

doi:10.1093/ndt/gfy071

Cited by 33 publications

(30 citation statements)

References 43 publications

(78 reference statements)

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“…Previous studies have shown that the decline in eGFR can be reversed, or at least attenuated, by exogenous thyroid hormone replacement, which indicates that kidney dysfunction could be the end result of functional changes rather than histological damage [7,8]. While a recent large study showed, that there is an association between LFT and renal function deterioration and proteinuria [5], other large sample size studies either failed to demonstrated such association [11] or found opposite result [9]. These discrepancies could be explained by the design of the study (longitudinal vs. cross-sectional) and population enrolled (general vs. CKD).…”

Section: Discussionmentioning

confidence: 99%

“…In a prospective cohort, in patient with normal kidney function, Zhan Y et al found an increased incidence of CKD in patients with hypothyroidism after a median follow-up of 3.5 years [10]. In contrast, Mewese CL et al [11], examining 72,856 individuals with overt hypothyroidism, subclinical hypothyroidism, and euthyroidism, concluded that low thyroid function was not associated with faster decline of renal function.…”

Section: Introductionmentioning

confidence: 98%

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Influence of low free thyroxine on progression of chronic kidney disease

et al. 2020

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Background: Hypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of kidney function. However, there is no consensus whether low free thyroxin (LFT) affects the rate of estimated glomerular filtration rate (eGFR) decline and how the presence of proteinuria influences the progression of renal dysfunction in hypothyroidism. Methods: We assessed thyroid status, proteinuria, and progression of eGFR by Modification of Diet in Renal Disease equation and CKD-EPI equation in a cohort of CKD patients followed in general nephrology clinics. We estimated the association of LFT levels, and the degree of proteinuria on progression of eGFR. We adjusted for other covariables: age, gender, body mass index, diabetes, hypertension, HbA1c, uric acid, cholesterol, and triglycerides levels.. Results: One thousand six hundred ten patients (64 ± 15 years, 46.8% men, 25.3% diabetic) were included. At beggnining of follow up eGFR was between 45 and 60, 30-45 and 15-30 ml/min/1.73m 2 in 479 (29.8%), 551(34.2%), and 580(36.0%) patients, respectively. LFT levels were available at initial evaluation in 288(17.9%) patients and 735(48.5%) had assessment of proteinuria (19.6% with LFT vs. 15.4% without LFT, p = 0.032). Median follow-up time was of 21 months, and 1223(76%) had at least 1 year of follow up. Overall, eGFR decline per month was − 0.05(− 0.26, 0.23) ml/min/1.73m 2 , reaching 1.7(1.3, 2.4) ml/min/1.73m 2 by the end of study period. Similar results were obtained using CKD-EPI. Multivariable mixed linear analysis showed that proteinuria and age were independently associated with eGFR decline, with no effect of LFT, and no interaction between proteinuria and LFT. In patients without proteinuria, there was an improvement of eGFR despite the presence of LFT. Conclusions: We confirmed a faster rate of eGFR declined in patients with proteinuria. However, despite the pathophysiological rational that hypothyroidism can lead to increased rate of CKD progression, we failed to demonstrate an association between LFT and rate of CKD progression. We conclude that the benefit of hypothyroidism treatment in CKD patients needs to be evaluate in prospective studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Influence of low free thyroxine on progression of chronic kidney disease

et al. 2020

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“…Secondly, kidney dysfunction may predispose to thyroid hormone changes, via influence on the metabolism of thyroid hormones or due to chronic illness (as CKD) leading to nonthyroidal illness as potential underlying pathophysiological mechanisms (23,26). A recent individual participant data analysis from 16 independent cohorts of the Thyroid Studies Collaboration found no role for thyroid hormones in kidney dysfunction (15). However, it does not exclude that previously found crosssectional associations between kidney and thyroid (10, 11) may be explained by kidney dysfunction causing thyroid hormone changes.…”

Section: Discussionmentioning

confidence: 99%

“…Longitudinal studies have presented conflicting results, linking kidney function decline to low (13) or high thyroid function (14). Whereas a recent individual participant data analysis found no role for thyroid hormones in renal function decline, it does not exclude reverse causality, indicating that previously found cross-sectional associations between kidney and thyroid may be explained by kidney dysfunction causing thyroid hormone changes (15). Whether or not kidney function causally alters thyroid hormones, several studies have shown an increased prevalence of subclinical thyroid disease and nonthyroidal illness in patients with CKD (16,17), and this may be associated with higher mortality (18).…”

Section: Introductionmentioning

confidence: 89%

The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients

Zijlstra

Velzen

Şimşek

et al. 2020

Endocrine Connections

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Objective Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes. Methods In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke. Results Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism). Conclusions In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.

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“…Current research suggests that the correlation between hypothyroidism and renal function still remains unclear. A meta-analysis of individual patient data showed that, although decreased thyroid function was shown to correlate with lower eGFR values when evaluated cross-sectionally, there was no association between SCH and deterioration of renal function over time [ 35 ]. On the other hand, another recent study evaluating over 15,000 patients found an association between pre-ESRD TSH levels and post-ESRD mortality, with a higher risk of mortality observed among patients with incrementally higher TSH levels [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Levothyroxine on Kidney Function in Chronic Kidney Disease with Subclinical Hypothyroidism in US Veterans: A Retrospective Observational Cohort Study

et al. 2020

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Introduction Chronic kidney disease (CKD) may be associated with overt or subclinical hypothyroidism [SCH; defined as elevated serum thyroid-stimulating hormone (TSH) despite normal free thyroxine levels). Although some studies have demonstrated that thyroid replacement therapy may improve renal function in overt hypothyroidism, there is no consensus on its benefits in SCH. Clinical and limited economic outcomes were evaluated in levothyroxine-treated US veterans with CKD + SCH. Methods Veterans Health Administration claims data from April 2013 to March 2018 for levothyroxine-treated versus nontreated CKD + SCH patients were compared. Eligible patients with CKD + SCH (≥ 2 elevated TSH values recorded; ≥ 2 normal thyroxine values recorded) had ≥ 1 TSH values recorded during 24-month follow-up, and ≥ 1 estimated glomerular filtration rate (eGFR) measurement during baseline and follow-up. Continuous levothyroxine use (treatment cohort) was required during follow-up. The primary endpoint was eGFR at 6, 12, 18, and 24 months; secondary endpoints included eGFR change from baseline, CKD progression, and length of hospital stay (LOS). Propensity score matching (PSM) was performed. Results Of 453 eligible patients, 157 remained in each cohort after PSM. Most were male (96%) and white (88%); mean age was 75 years. No significant differences were observed between cohorts at any time point for eGFR, eGFR change from baseline, or CKD progression. Treated patients had numerically higher mean eGFR at 6 and 12 months, lower proportions of progression to higher CKD stages at 12, 18, and 24 months, and shorter mean all-cause LOS versus nontreated patients (1.92 vs. 3.30 days; P = 0.3483) within the 24-month follow-up period. A significantly shorter mean CKD-related LOS was observed versus nontreated patients (0.11 vs. 1.38 days; P < 0.0001) during the 24-month follow-up. Conclusion Levothyroxine use was associated with economic and clinical benefit in some patients with CKD + SCH, despite an absence of overall benefit on eGFR; confirmatory research is needed.

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Low thyroid function is not associated with an accelerated deterioration in renal function

Abstract: 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.

Cited by 33 publications

References 43 publications

Influence of low free thyroxine on progression of chronic kidney disease

Influence of low free thyroxine on progression of chronic kidney disease

The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients

Effect of Levothyroxine on Kidney Function in Chronic Kidney Disease with Subclinical Hypothyroidism in US Veterans: A Retrospective Observational Cohort Study

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