Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes. Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson’s correlation coefficient. Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4–20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography. Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.

中文翻译：

---

失盐性肾小管病中钾稳态的标志物——与醛固酮增多症和低镁血症的关联。

失盐性肾小管病 (SLT) 中钾 (K+) 和镁 (Mg2+) 的肾脏丢失会导致生活质量 (QoL) 显着降低和心律失常的风险增加。K+ 正常化是目前最广泛接受的治疗目标，然而，即使在设计出色的随机对照试验中，K+ 的增加也只是轻微的并且很少正常化。这些发现对 K+ 作为 SLT 中钾稳态的理想标志物的作用提出了质疑。这项假设生成研究的目的是确定 SLT 未来治疗试验的替代终点，以确定其对确定生活质量和重要临床结果的有用性。在这项包括 11 名 SLT 患者的前瞻性横断面研究中，我们评估了生化、临床和心脏病参数及其与生活质量的关系 (RAND SF-36)。主要假设是，生活质量更依赖于较高的醛固酮浓度，通过肾小管钾梯度 (TTKG) 进行评估。使用皮尔逊相关系数评估相关性。纳入的患者主要为女性（82%，平均年龄 34 ± 12 岁）。血清 K+ 和 Mg2+ 分别为 3.3 ± 0.6 mmol/l 和 0.7 ± 0.1 mmol/l（平均值 ± 标准差）。TTKG 为 9.5/3.4–20.2（中值/范围）。虽然心理健康的维度主要与血清 Mg2+（r = 0.68，p = 0.04）和 K+（r = 0.55，p = 0.08）相关，但更好的身体健康与较低的醛固酮水平相关（r = -0.61，p = 0.06） 。TTKG 与醛固酮水平和生活质量参数均不相关。24小时心电图和超声心动图均未观察到相关异常。醛固酮增多症、K+ 和 Mg2+ 是最重要的 QoL 参数。TTKG 不是醛固酮增多症或生活质量的合适标记。SLT 的未来验证性研究应评估生活质量以及醛固酮、K+ 和 Mg2+。