Bocchetta Alberto, Ardau Raffaella, Fanni Tiziana, Sardu Claudia, Piras Doloretta, Pani Antonello, Del Zompo Maria
Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Via Ospedale 54, Cagliari 09124, Italy.
BMC Med. 2015 Jan 21;13:12. doi: 10.1186/s12916-014-0249-4.
The effects of lithium treatment on renal function have been previously shown, albeit with discrepancies regarding their relevance. In this study, we examined glomerular filtration rate in patients treated with lithium for up to 33 years.
All lithium patients registered from 1980 to 2012 at a Lithium Clinic were screened. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine concentration using the Modification of Diet in Renal Disease Study Group equation. A cross-sectional evaluation of the last available eGFR of 953 patients was carried out using multivariate regression analysis for gender, current age, and duration of lithium treatment. Survival analysis was subsequently applied to calculate the time on lithium needed to enter the eGFR ranges 45 to 59 mL/min/1.73 m² (G3a) or 30 to 44 mL/min/1.73 m² (G3b). Finally, 4-year follow-up of eGFR was examined in subgroups of patients who, after reduction to an eGFR lower than 45 mL/min/1.73 m² either i) continued lithium at the same therapeutic range or ii) discontinued lithium or continued at concentrations below the therapeutic range (0.5 mmol/L).
In the cross-sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73 m²), in older patients (0.73 mL/min/1.73 m² per year of age), and in patients with longer lithium treatment (0.73 mL/min/1.73 m² per year). Half of the patients treated for longer than 20 years had an eGFR lower than 60 mL/min/1.73 m². The median time on lithium taken to enter G3a or G3b was 25 years (95% CI, 23.2-26.9) and 31 years (95% CI, 26.6-35.4), respectively. Progression of renal failure throughout the 4-year follow-up after a reduction to an eGFR lower than 45 mL/min/1.73 m² did not differ between the subgroup who continued lithium as before and the subgroup who either discontinued lithium or continued at concentrations below the therapeutic range.
Duration of lithium treatment is to be added to advancing age as a risk factor for reduced glomerular filtration rate. However, renal dysfunction tends to appear after decades of treatment and to progress slowly and irrespective of lithium continuation.
锂治疗对肾功能的影响此前已有报道，尽管在其相关性方面存在差异。在本研究中，我们对接受锂治疗长达33年的患者的肾小球滤过率进行了检测。
对1980年至2012年在一家锂治疗诊所登记的所有锂治疗患者进行筛查。使用肾脏疾病饮食改良研究组方程根据血清肌酐浓度计算估计肾小球滤过率（eGFR）。采用多因素回归分析对953例患者的末次可用eGFR进行横断面评估，分析性别、当前年龄和锂治疗持续时间的影响。随后应用生存分析计算进入eGFR范围45至59 mL/min/1.73 m²（G3a）或30至44 mL/min/1.73 m²（G3b）所需的锂治疗时间。最后，对eGFR降低至低于45 mL/min/1.73 m²后的患者亚组进行了4年的eGFR随访，这些患者分为：i）继续在相同治疗范围内服用锂；ii）停用锂或继续服用低于治疗范围（0.5 mmol/L）的锂。
在横断面评估中，发现女性的eGFR较低（低3.47 mL/min/1.73 m²），老年患者较低（每年低0.73 mL/min/1.73 m²），锂治疗时间较长的患者较低（每年低0.73 mL/min/1.73 m²）。接受锂治疗超过20年的患者中有一半的eGFR低于60 mL/min/1.73 m²。进入G3a或G3b所需的锂治疗中位时间分别为25年（95%CI，23.2 - 26.9）和31年（95%CI，26.6 - 35.4）。在eGFR降低至低于45 mL/min/1.73 m²后的4年随访期间，继续按原方案服用锂的亚组与停用锂或继续服用低于治疗范围锂的亚组之间，肾衰竭进展情况无差异。
锂治疗持续时间应作为肾小球滤过率降低的危险因素，与年龄增长一并考虑。然而，肾功能障碍往往在数十年治疗后出现，进展缓慢，且与是否继续服用锂无关。
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