Risk factors of hyperkalemia after total parathyroidectomy in patients with secondary hyperparathyroidism

Abstract

Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease (ESRD) and parathyroidectomy (PTX) is an effective treatment for SHPT. To examine the differential risk of post-surgical hyperkalemia after PTX for primary versus secondary hyperparathyroidism, we conducted a single-center retrospective observational study in 103 PTX patients admitted to the Third Affiliated Hospital of Soochow University between January, 2013 and August, 2019. Patients were divided into two groups according to pathogeny. PHPT group included symptomatic PHPT and asymptomatic PHPT with hypercalcemia. SHPT group included patients with maintenance hemodialysis for more than 3 months and having undergoing successful PTX. All SHPT patients received endoscopic total parathyroidectomy and forearm autotransplantation (tPTX + AT), while PHPT patients underwent open or endoscopic parathyroid adenomaectomy. Table 1 shows the clinical characteristics of patients. No patients in PHPT group were diagnosed as hyperkalemia after surgery, while postoperative serum potassium (K+ post) was more than 5.3 mmol in 28 (52.8%) patients with SHPT. Then, SHPT patients were further divided into hyperkalemia group and nonhyperkalemia group according to K+ post. Compared with nonhyperkalemia group, K+ base and K+ pre were significantly higher in hyperkalemia group (Table 2, p < 0.001). Preoperative iPTH and the decline range of iPTH in hyperkalemia group were higher than those in nonhyperkalemia group, but there was no statistical significance (p = 0.095, p = 0.066). There was no significant difference in age, gender, BMI, dialysis age, HCO3-, Hb, BUN, SCr, ALP, Chol, TG, UA, serum-corrected calcium, phosphorus, magnesium, ACEI/ARB, Cinacalcet between two groups (Table 2). We chose the variables with p < 0.1 for multivariate Logistic regression analysis. K+ pre was an independent influencing factor of postoperative hyperkalemia (OR = 18.888, 95%CI = 1.798–198.450, p = 0.014). ROC curve analysis showed that area under the curve (AUC) of K+ pre in predicting postoperative hyperkalemia was 0.844 (p < 0.001). The optimal cutoff value of K+ pre to predict hyperkalemia in SHPT patients after tPTX + AT was 4.30 mmol/L, with a sensitivity of 96.4% and a specificity of 56% (Figure 1). Figure 1. Receiver operating characteristic (ROC) curve of preoperative serum potassium associated with postoperative hyperkalemia. Table 1. Comparison of perioperative clinical data of patients with SHPT and PHPT. Characteristics SHPT (n = 53) PHPT (n = 50) p value Gender (n, male/female) 31/22　 　20/30 0.061 Age (year) 48.98 ± 12.39 53.70 ± 13.48 0.067 BMI (kg/m2) 21.41 ± 2.89 22.53 ± 3.43 0.075 Whether or not taking ACEI/ARB(n, yes/no) 7/46　 　5/45 0.612 preoperative iPTH (pg/ml) 2104.90 (1394.85,2739.00) 238.85 (130.93,485.78) <0.001* preoperative ALP (u/L) 453.00 (235.50, 930.00) 145.00 (113.50,214.00) <0.001* preoperative K+ (mmol/L) 4.60 (4.23, 4.98) 4.27 (3.79,4.50) <0.001* preoperative HCO3- (mmol/L) 22.79 ± 2.80 23.02 ± 2.74 0.676 preoperative BUN (mmol/L) 15.56 (12.80,19.83) 4.41 (3.55,5.47) <0.001* preoperative Scr (umol/L) 700.00 (579.25,850.00) 73.50 (54.75,98.00) <0.001* preoperative UA (umol/L) 313.93 ± 89.89 328.55 ± 114.27 0.471 preoperative Alb (g/L) 37.36 ± 4.72 40.85 ± 5.04 <0.001* preoperative P (mmol/L) 2.13 (2.34,1.94) 0.82 (0.64,0.96) <0.001* preoperative Mg (mmol/L) 1.07 (0.97,1.22) 0.93 (0.81, 1.06) <0.001* Chol (mmol/L) 3.82 (3.16, 4.73) 4.72 (3.96, 5.21) 0.001 TG (mmol/L) 1.37 (1.09, 2.09) 1.47 (1.17,1.99) 0.165 preoperative Ca2+ (mmol/L) 2.69 (2.54,2.86) 2.89 (2.77,3.27) <0.001* postoperative P (mmol/L) 2.04 (1.72,2.32) 0.75 (0.61,0.94) <0.001* postoperative Ca2+ (mmol/L) 2.33 (2.05,2.46) 2.35 (2.16,2.69) 0.175 postoperative iPTH (pg/ml) 38.900 (19.60,61.00) 15.05 (8.15,28.94) <0.001* postoperative K+ (mmol/L) 5.51 (4.74, 6.12) 4.09 (3.80,4.40) <0.001* Decrease of iPTH (pg/ml) 2048.80 (1277.25, 2589.05) 228.75 (115.65, 482.50) <0.001* ACEI: angiotensin-converting enzyme inhibitor; Alb: serum albumin; ALP: alkaline phosphatase; ARB: angiotensin receptor blockers; BMI: body mass index; BUN: blood urea nitrogen; Ca2+: serum-corrected calcium; Chol: cholesterol; HCO3-: bicarbonate; iPTH: intact parathyroid hormone; K+: serum potassium; Mg: serum magnesium; P: serum phosphorus; PHPT: primary hyperparathyroidism; Scr: serum creatine; SHPT: Secondary hyperparathyroidism; TG: triglyceride;UA: uric acid; *: p < 0.05. Table 2. Demographic features of hyperkalemic and nonhyperkalemic groups of postoperative patients with SHPT. Characteristics non-hyperkalemic group (n = 25) hyperkalemic group (n = 28) p value Age(year) 50.00 ± 11.15 48.07 ± 13.53 0.576 Gender (n, male/female) 15/10 16/10 0.833 Current smoking (n, no/yes) 22/3 25/3 0.883 Dialysis duration year 7.44 ± 2.89 8.18 ± 3.04 0.371 BMI (kg/m2) 21.13 ± 2.34 21.66 ± 3.333 0.507 Interval time from dialysis to operation(h) 18.00 (14.50, 26.00) 18.00 (14.68, 20.75) 0.674 operating time (min) 134.80 ± 40.43 136.79 ± 43.62 0.865 preoperative Hb (g/L) 111.44 ± 16.38 109.89 ± 20.05 0.761 preoperative iPTH (pg/ml) 1824.92 ± 845.54 2212.57 ± 813.83 0.095 preoperative ALP (u/L) 401.00 (189.50, 872.00) 508.50 (344.50, 1062.75) 0.31 K+ base (mmol/L) 4.58 ± 0.59 5.28 ± 0.64 <0.001* preoperative K+ (mmol/L) 4.24 (3.86, 4.65) 4.94 (4.58, 5.00) <0.001* preoperative HCO3− (mmol/L) 23.12 ± 3.21 22.49 ± 2.40 0.418 preoperative BUN (mmol/L) 15.44 ± 4.24 17.94 ± 6.21 0.096 preoperative Scr (umol/L) 740.48 ± 201.00 701.51 ± 164.40 0.441 preoperative UA (umol/L) 311.69 ± 83.99 315.92 ± 96.36 0.866 preoperative Alb (g/L) 37.62 ± 4.72 37.13 ± 4.70 0.706 preoperative P (mmol/L) 2.15 ± 0.38 2.19 ± 0.36 0.728 preoperative Mg (mmol/L) 1.04 (0.95, 1.18) 1.07 (0.99, 1.24) 0.199 Chol (mmol/L) 3.65 (3.04, 4.86) 3.85 (3.41, 4.76) 0.669 TG (mmol/L) 1.26 (1.01, 2.21) 1.42 (1.14, 2.09) 0.643 preoperative Ca2+ (mmol/L) 2.59 ± 1.16 2.52 ± 0.68 0.781 postoperative P (mmol/L) 2.05 ± 0.52 2.02 ± 0.39 0.797 postoperative Ca2+ (mmol/L) 2.42 (2.12, 2.46) 2.27 (2.03, 2.48) 0.373 postoperative iPTH (pg/ml) 46.0 (18.02, 61.00) 32.15 (20.60, 61.13) 0.796 Decrease of iPTH (pg/ml) 1711.10 ± 798.38 2310.99 ± 826.81 0.066 Alb: serum albumin; ALP: alkaline phosphatase; BMI: body mass index; BUN: blood urea nitrogen; Ca2+: serum-corrected calcium; Chol: cholesterol; Hb: hemoglobin; HCO3-: bicarbonate; iPTH: intact parathyroid hormone; K+: serum potassium; K+base: baseline level of serum potassium; Mg: serum magnesium; P: serum phosphorus; Scr: serum creatine; SHPT: Secondary hyperparathyroidism; TG: triglyceride; UA: uric acid; *: p < 0.05. Hyperkalemia after PTX in hemodialysis patients is common. Previous study has found that serum potassium could rise rapidly from 4.4 mmol/L to 6.2 mmol/L within operation time [1]. Rapidly rised severe hyperkalemia could lead to serious arrhythmia, even life-threatening [2]. Risk of hyperkalemia is more ominous in face of coexisting hypocalcemia (which is expected take place after PTX), so this issue is getting more and more attention in recent years. In our study, the incidence rate of hyperkalemia in hemodialysis patients after PTX is 52.8%, which is consistent with 25-80% occurrence reported in previous studies [3–7]. We speculate that the rapid decline of iPTH in a short time is an important reason for hyperkalemia after PTX. The possible interpretations are shown in Figure 2. Due to a rapid decline of iPTH after patients undergoing PTX, a large number of calcium ions influx into the bone make the level of calcium in extracellular fluid (ECF) in skeletal muscle cells (SMC) decrease [8]. An increased influx of sodium ions into SMC via membrane barrier action of sodium–calcium exchanger may influence the activation of Na/K ATPase pump which can promote efflux of sodium ion and influx of potassium. These result in increased level of potassium in ECF, reducing resting potential and increasing excitability of SMC [9–10]. A small sample study showed that ESRD patients with prior treatment with cinacalcet had a higher risk of hyperkalemia and hypocalcemia during and immediately after PTX [11]. However, we did not detect the significant association. Recent study has found preoperative serum potassium level <3.9 mmol/L would reduce the risk of developed potassium level >5.3 mmol/L in hemodialysis patients [12]. According to our study, reducing the K+ pre below 4.30 mmol/L is helpful to decrease the incidence of postoperative hyperkalemia. Figure 2. The possible interpretations of postoperative hyperkalemia undergoing parathyroidectomy in patients with secondary hyperparathyroidism. Yun Zou Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, China Liwei Zhang Department of Infection Management, The Third Affiliated Hospital of Soochow University, Changzhou, China Hua Zhou, Yan Yang, Min Yang and Jia Di Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, China [e-mail]