Association Between Serum Cystatin C and Thyroid Diseases: A Systematic Review and Meta-Analysis

Abstract

BackgroundCystatin C (CysC) is often used to diagnose and monitor renal diseases. Although some studies have investigated the association between serum CysC levels and thyroid diseases, their reported results were inconsistent. Therefore, the relationship between CysC levels and thyroid diseases remains controversial.AimThis meta-analysis aimed to statistically evaluate serum CysC levels in patients with thyroid diseases.MethodsA literature search was conducted using the PubMed, Web of Science, Embase, EBSCO, and Wiley Online Library databases. The following search terms were used for the title or abstract: “Cystatin C” or “CysC” in combination with the terms “thyroid disease”, “thyroid function”, “hypothyroidism”, or “hyperthyroidism”. The results of the systematic analysis were presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs).ResultsEleven articles (1,265 cases and 894 controls) were included in the meta-analysis. The results of the meta-analysis showed that the serum CysC levels of patients with hyperthyroidism were significantly higher than those of the controls (SMD: 1.79, 95% CI [1.34, 2.25]), and the serum CysC levels of patients with hypothyroidism were significantly lower than those of the controls (SMD −0.59, 95% CI [−0.82, −0.36]). Moreover, the treatment of thyroid diseases significantly affected serum CysC levels.ConclusionsTo the best of our knowledge, this meta-analysis is the first to evaluate serum CysC levels in patients with thyroid diseases. Our findings suggest that thyroid function affects serum CysC levels and that serum CysC may be an effective marker for monitoring thyroid diseases.Systematic Review RegistrationPROSPERO [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258022], identifier CRD42021258022].

Comparison of estimated GFR using cystatin C versus creatinine in pediatric kidney transplant recipients

“…There were several limitations in our study, with one attributed to not assessing thyroid function (16,42,43). A meta-analysis evaluating serum CysC levels in 1265 patients with thyroid disease and 894 controls revealed higher CysC levels among hyperthyroid subjects compared to lower CysC values in those with hypothyroidism.…”

“…A meta-analysis evaluating serum CysC levels in 1265 patients with thyroid disease and 894 controls revealed higher CysC levels among hyperthyroid subjects compared to lower CysC values in those with hypothyroidism. Furthermore, with treatment of the thyroid disease, CysC levels were notably affected and therefore, the study concluded that serum CysC could be a marker for monitoring thyroid disease (43). Another limitation of our study was the small sample of 45 patients that only included those who underwent a protocol biopsy in the rst 2 years post-transplant, or a for-cause biopsy, which may have introduced selection bias.…”

Biochemical markers of renal function and maternal hypothyroidism in early pregnancy

“…However, the underlying mechanisms are not clear, and uncertainties prevail regarding the role of thyroid function and thyroid autoimmunity. More recent studies have pointed toward a specific association between autoimmune hypothyroidism and increased levels of CysC ( 8 , 9 ), which contrasts the general hypothesis that lack of thyroid hormones reduces levels of CysC ( 7 , 10 ). With a focus on immunological mechanisms, another thought is on the interaction with the physiological immune suppression seen in a normal pregnancy ( 11 ).…”

“…On the other hand, no thyroid-healthy control group was investigated. Gathering of 11 studies up until 2019 in a meta-analysis led to the conclusion that hyperthyroidism associates with higher levels of CysC whereas hypothyroidism associates with lower levels ( 10 ). However, the studies included showed considerable heterogeneity and small sample sizes, which led the authors to interpret with caution and call for further studies ( 10 ).…”

“…1 ) who had no chronic kidney disease, no adverse outcome of pregnancy, and no known thyroid disease or thyroid autoantibody positivity. These criteria for the reference cohort were based on the existing literature indicating a link between CysC levels and adverse outcomes of pregnancy ( 18 ) as well as thyroid disease ( 10 ). Within the full study cohort and the reference cohort, we established percentile levels for CysC and creatinine with 90% confidence interval (CI) among all individuals and stratified by the pregnancy week of blood sampling (4–8, 9–11, and 12–15).…”