Schultheiss Ulla T, Steinbrenner Inga, Nauck Matthias, Schneider Markus P, Kotsis Fruzsina, Baid-Agrawal Seema, Schaeffner Elke, Eckardt Kai-Uwe, Köttgen Anna, Sekula Peggy
Institute of Genetic Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.
Department of Medicine IV - Nephrology and Primary Care, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.
Clin Kidney J. 2020 Jun 4;14(3):959-968. doi: 10.1093/ckj/sfaa052. eCollection 2021 Mar.
Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function.
Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status.
Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality ( = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65-0.82; = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint.
Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.
甲状腺功能减退和低游离三碘甲状腺原氨酸（FT3）综合征[甲状腺刺激激素（TSH）正常但FT3水平降低]与估算肾小球滤过率（eGFR）严重降低的慢性肾脏病（CKD）患者或终末期肾病（ESKD）患者的肾功能横断面降低有关。关于甲状腺功能受损对eGFR严重降低患者或基于人群队列的肾脏事件和死亡率的前瞻性影响的结果相互矛盾。在此，我们在一个大型前瞻性队列中评估了甲状腺与肾功能之间的关联，该队列中的CKD患者肾功能轻度至中度降低，包括横断面的eGFR以及前瞻性的肾脏事件和死亡率。
在德国慢性肾脏病研究中的CKD患者中测量甲状腺标志物。从医院记录和死亡证明中提取首次发生的肾脏终点事件（合并ESKD、急性肾损伤和肾性死亡）和全因死亡率。对4600名患者从基线到4年随访（中位随访时间4.04年）的完整数据进行首次事件时间分析。对单个和联合的连续甲状腺标志物[TSH、游离甲状腺素（FT4）、FT3]和甲状腺状态进行多变量线性回归和Cox比例风险模型拟合。
横断面分析中，低FT3综合征的存在与eGFR呈显著负相关；单独的连续FT3水平与eGFR呈显著正相关；与FT4和TSH联合时，FT3水平也与eGFR呈正相关，FT4水平与eGFR呈负相关。前瞻性分析中，较高的FT4和较低的FT3水平与全因死亡率较高显著相关（ =297）。FT3水平每升高每皮摩尔每升，达到复合肾脏终点的风险降低0.73倍（95%置信区间0.65 - 0.82； =615）。与甲状腺功能正常者相比，低FT3综合征患者发生复合肾脏终点的风险高2.2倍；甲状腺功能减退患者发生复合肾脏终点的风险高1.6倍。
随着时间推移，患有甲状腺功能异常的轻度至中度CKD患者发生不良肾脏事件和全因死亡率增加风险。
