Association between hypothyroidism, levothyroxine replacement and kidney function outcomes: a systematic review and meta-analysis

Objective: Regarding the exact association between hypothyroidism, levothyroxine replacement and kidney dysfunction, there is a lack of study to summarize the previous evidence. The aim of this study is to explore these relationships. Methods: The PubMed, Cochrane Library, EMBASE, and Google Scholar were searched for observational studies and RCTs. The included studies were conducted in adult nonpregnant participants and analyzed kidney outcomes of interest in serologically confirmed hypothyroidism patients. Additionally, studies that examined kidney outcomes during levothyroxine treatment were retrieved. Standard Mean Difference (SMD), Odds Ratios (ORs) and Risk Ratios (RRs) were estimated as the effect variables. Results: Totally, 46 studies were included. Both non-distinct hypothyroidism and subclinical hypothyroidism (SHypo) were significantly associated with the prevalence of chronic kidney disease (CKD) (OR 1.94, 95% CI [1.62, 2.32]) (OR 1.87, 95% CI [1.55, 2.27]). Non-distinct hypothyroidism and SHypo were also associated with estimated glomerular filtration rate (eGFR) reduction (SMD -0.68, 95% CI [-0.81, -0.55]) (SMD -0.99, 95% CI [-1.59, -0.38]). No significant association between hypothyroidism and CKD incidence was found, and its association with end-stage renal disease (ESRD) was not significant in patients with underlying kidney dysfunction. No significant improvement in eGFR was observed after levothyroxine treatment, either in non-distinct hypothyroidism or in SHypo patients. Conclusion: This study verifies a cross-sectional association between hypothyroidism and kidney dysfunction. However, no definitive prospective association was found. The bidirectional causal association between hypothyroidism, levothyroxine replacement and kidney outcomes remain controversial based on evidence from extensive observational studies. More large-scale randomized controlled trials are needed to supplement this evidence in practice to avoid overtreatment or undertreatment. Response: The registraton information has been mentioned in the Methods section.