Stone formation, which is caused by metabolic anomalies and side effects of relevant medical treatments, is frequently observed after renal transplantation. Immunosoppressive agents, such as calcineurin inhibitor glucocorticoid, may cause calculi after transplantation, thus leading to hyperuricemia, hyperoxaluria, and hypocitraturia.[12–15] Therefore, to reduce the risk of calculi formation, alkaline citrate is given to the patients to increase urinary citrate excretion and urinary solubility index.[16–19] Currently, several types of potassium-bearing citrates (PC, sodium PC, potassium magnistium citrate, and PSHC) are available. With its alkalinizing effect, PSHC can reduce urinary saturation of calcium, and then decrease ionic calcium concentration, thus preventing stone formation.[20–23] Therefore, this agent is commonly used for the prevention of stone formation among patients undergoing renal transplantation.
First, in the present study, we found that in both cases, SPCs increased gradually and hyperkalemia only occurred 1 and 6 days after the treatment with PSHC granules for patient 1 and patient 2, respectively (Fig. 2A, B). The degrees of hyperkalemia in the 2 patients were observed to be directly influenced by PSHC. According to previous studies, single oral potassium at a dose of 0.5 mmol/kg produced a minimal increase in serum potassium, while total doses of approximately 1 mmol/kg increased serum potassium by as much as 1 mmol/L in a healthy man.[24,25] The molecular formula of PSHC is K6Na6H3(C6H5O7)5, with the molecular weight of 1321.06. According to the instructions of PSHC granules, each gram of PSHC contains 4.4 mmol potassium. Patient 1 (weight: 58 kg) presented hyperkalemia after orally taking a cumulative dose of 12.5 g PSHC, equal to 0.95 mmol/kg potassium, while patient 2 (weight: 62 kg) developed hyperkalemia after being given a cumulative dose of 62.5 g PSHC, equal to about 1 mmol/kg. For the patients undergoing renal transplantation, the cumulative doses they taking might be a “heavy” load, increasing the risk of hyperkalemia. In addition to PSHC, some other factors might also contribute to the occurrence of hyperkalemia in the 2 patients, such as the application of calcineurin inhibitors, glucocorticoids, and diuretics.[26–28] In this report, both of the cases received tacrolimus (calcineurin inhibitor) and prednisolone (a type of glucocorticoid) in immunosuppressive treatment that might increase the risk of hyperkalemia. Furthermore, blood transfusion might also stand for a potential risk factor for hyperkalemia. It was reported that supernatant potassium concentration of stored blood was frequently higher than potassium levels in normal human plasma, and that rapid intravenous infusion might allow a mass of potassium into receiver's body in a short time, thus swiftly increasing blood potassium concentration.[29,30] However, the specific mechanisms of blood transfusion inducing hyperkalemia remain unclear. Besides, surgical procedure represented another potential risk factor for hyperkalemia. Hirata et al reported that anesthesia contributed to a sharp potassium increase after kidney transplantation. In a word, the application of PSHC together with the uses of calcineurin inhibitors and glucocorticoids, as well as blood transfusion and invasive surgical procedures might contribute to hyperkalemia in the 2 cases.
Second, there was a clear correlation between the application of PSHC and the occurrence of hyperkalemia, the situation also applying to other potassium-bearing citrates. The correlation between PC and hyperkalemia-related complications has been investigated in previous studies.[17–19] Hyperkalemic ventricular fibrillation was even observed in patients with fine renal function after ingesting small amounts of PC (40–60 mmol/L).[23,24] It might be not harmless for patients with normal renal function even at an acceptable dosage, although there is 28 mmol potassium in 10-mL PC mixture. The recommended daily dose is up to 40 mL, more than twice the daily intake of PSHC, which means more dangers of hyperkalemia. Therefore, we suggest that more attentions should be given when potassium-bearing citrate is prescribed, especially for the elderly and those with impaired renal functions.
Third, these cases highlighted potentially serious consequences of PSHC application in patients receiving renal transplantation. We would like to emphasize side effects of potassium alkaline citrate, despite its significant advantage in preventing urinary lithiasis. Physicians should evaluate the role of potassium-bearing citrates besides PSHC in patients after renal transplantation, particularly in those with renal insufficiency or combination medication. It has been suggested that when coprescribing medicine, it would be better to avoid using potassium-bearing citrate that may interfere with potassium homeostasis among patients with renal dysfunction.[26,32] If not, oral dose should be reduced according to the severity of renal dysfunction. In a previous study, sodium bicarbonate did not allow additional potassium into blood, and showed an effect equivalent to potassium-bearing citrate in the treatment of urinary stone, suggesting that sodium bicarbonate might be a better choice for patients who could not tolerate PC. At the moment, people can purchase all types of potassium-bearing citrates from counters in any retail pharmacies in communities, while many patients and even physicians pay little attention on this issue.
Considering the analysis results about the 2 unusual patients in our study, it was not safe to use PSHC or other potassium-bearing citrates (PC, sodium PC, and potassium magnistium citrate) for patients undergoing renal transplantation. Both frequencies and timing of potassium evaluation should be regimented to control the level of serum potassium during the therapy. Besides, the therapy should be better performed in centers with advanced equipment and more experts who make appropriate treatment plans.
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