背景:钙调磷酸酶抑制剂(CNIs)广泛用于移植。尽管CNI相关的高钾血症很常见(10%-60.6%),潜在的发病机制尚不清楚,可能导致剂量调整或停药.
目的:本研究的目的是描述成功使用氟氢可的松治疗的小儿移植受者中由于低肾素血症性低醛固酮血症引起的CNI相关高钾血症。
方法:在55个造血干细胞(HSCT)和35个肾移植受者中,我们对被诊断为CNI相关高钾血症的受者进行了回顾.接受静脉输液的接受者,钾,或者被诊断为溶血,急性移植排斥反应,或eGFR<30mL/min/1.73m2被排除。对临床病史和生化研究进行了详细分析,以揭示可能的病理生理学。
结果:三名小儿移植受者(一名HSCT,两次肾移植)发现高钾血症,低钠血症,招募CNI时,血尿素氮轻度升高。尿钾排泄减少,而钠排泄增加。血浆醛固酮水平低,肾素没有增加。原发性肾上腺功能不全被排除,并诊断为低肾素血症性低醛固酮增多症。在患有HSCT(22天)的病例1中较早检测到CNI相关的高钾血症,比第二种和第三种情况,进行了肾脏移植(移植后24和30个月,分别)。假设差异是由于HSCT中使用的血清靶CNI比肾移植更高,因此总体CNI剂量更高。生理剂量氟氢可的松(0.05mg,daily),而在病例1中,在CNI停药后停用了氟氢可的松,这是CNI与低肾素血症性低醛固酮血症的病因学关联的又一证据。
结论:我们的三个案例加强了CNI相关的高钾血症可能是由于低肾素血症性低醛固酮血症的前提,时间和严重程度可能与CNI剂量有关。氟氢可的松是治疗CNI相关性高钾血症安全有效的药物,提供CNI的维护,是小儿移植的重要治疗药物之一。
Calcineurin inhibitors (CNIs) are widely used in transplantation. Although CNI-related hyperkalemia is common (10%-60.6%), the underlying pathogenetic mechanism is not well-elucidated and may lead to dose adjustment or treatment withdrawal.
The aim of this study is to describe CNI-related hyperkalemia due to hyporeninemic hypoaldosteronism in pediatric transplant recipients who were successfully treated with fludrocortisone.
In a total of 55 hematopoietic stem cell (HSCT) and 35 kidney transplant recipients followed according to institutional immunosuppression protocols, recipients diagnosed with CNI-related hyperkalemia were reviewed. Recipients who were receiving intravenous fluid, potassium, or were diagnosed with hemolysis, acute graft rejection, or had an eGFR < 30 mL/min/1.73m2, were excluded. A detailed analysis of clinical history as well as biochemical studies was carried out to reveal possible pathophysiology.
Three pediatric transplant recipients (one HSCT, two kidney transplantation) with findings of hyperkalemia, hyponatremia, and a mild elevation in blood urea nitrogen while on CNIs were recruited. Urinary potassium excretion was diminished while sodium excretion was increased. Plasma
aldosterone levels were low, and renin was not increased in response. Primary adrenal insufficiency was ruled out, and hyporeninemic hypoaldosteronism was diagnosed. CNI-related hyperkalemia was detected earlier in case 1, who had HSCT (22 days), than in the second and third cases, who had kidney transplantation (24 and 30 months post-transplantation, respectively). The discrepancy was hypothesized to be explained by higher overall CNI dose due to higher serum target CNI used in HSCT than kidney transplantation. Electrolyte imbalance was reversed upon administration of physiologic dose fludrocortisone (0.05 mg, daily), while fludrocortisone was ceased after CNI withdrawal in case 1, which is additional evidence for the etiological association of CNIs and hyporeninemic hypoaldosteronism.
Our three cases strengthen the premise that CNI-related hyperkalemia may be due to hyporeninemic hypoaldosteronism, and the timing and severity may be related to CNI dose. Fludrocortisone is a safe and effective treatment in CNI-related hyperkalemia, providing maintenance of CNIs, which are one of the essential therapeutic agents for pediatric transplantation.