SHPT is a common and serious problem in patients with chronic kidney disease (CKD). With the increasing number of patients receiving long-term maintenance dialysis, SHPT appears more in patients receiving dialysis and eventually develops to refractory secondary hyperparathyroidism (rSHPT). Elevated serum concentrations of PTH may contribute to active vitamin D treatment resistance, bone and joint pain, pruritus, fractures, skeletal malformations, and cardiovascular calcification and are independently associated with all-cause and cardiovascular-related mortality [
Patients under study were from five hospitals, including China-Japan Friendship Hospital and the Aerospace Center Hospital in Beijing, Dalian University Affiliated Xinhua Hospital in Liaoning, the Fourth Hospital of Jilin University in Jilin, and Cangzhou People’s Hospital in Hebei. Patients were followed up for 1–11 years.
The following data were retrieved from the patients’ charts and computer-based records. Demographic details would include age, sex, primary cause of end-stage renal disease (ESRD) (diabetes, hypertension, chronic glomerulonephritis, and polycystic kidney), preoperative and postoperative PTX laboratory biochemical indexes correction of serum calcium (
All the samples were collected in the morning or before performing the hemodialysis, from the PTX database in the above said five hospitals. Laboratory indicators were referred to the criteria serum Ca 2.1–2.54 mmol/L (8.4–10.1 mg/dl). Serum Ca was adjusted for serum albumin according to an equation commonly used in the general population: adjusted Ca
PTX surgical operation was standardized in the five hospitals through a training program and a unified postoperative treatment process was implemented and managed by the China-Japan Friendship Hospital. The procedures would include total parathyroidectomy (tPTX), subtotal parathyroidectomy (sPTX), and tPTX with total autotransplantation (tPTX + AT). The Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines were referred to as the post-PTX management processes, which also include daily monitoring of serum Ca once or twice a week after surgery. Patients were provided with foods, rich in protein, calcium, and phosphorus. Post-PTX, orally administered drugs would include calcium carbonate and calcitriol. We also adjusted the dose according to each serum calcium level until calcitriol reached 4 ug per day [
All the postoperative PTX-related data were entered into the follow-up database. All patients were divided into four groups according to the levels of serum iPTH, one week after surgery, regardless of the PTX. The groupings were A: iPTH ≤ 20 pg/mL (
Stata 12.0 program was performed for statistical analysis. Normal distribution values were expressed as mean ± standard deviation (SD), and
Between January 2004 and December 2014, 525 patients underwent the PTX. Under the exclusion criteria, 404 patients (215 males and 189 females) were qualified for analysis (median age as
Patients characteristics by baseline iPTH category
Characteristics | iPTH ≤ 20 pg/mL | iPTH 20–150 pg/mL | iPTH 151–600 pg/mL | iPTH > 600 pg/mL | Total |
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Gender (male) | 112 (54.6%) | 58 (51.2%) | 24 (43.6%) | 21 (67.7%) | 215 (53.2%) |
Age (year) |
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Dialysis vintage (month) |
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Primary cause of ESRD | |||||
Chronic glomerulonephritis | 95 (46.3%) | 61 (54%) | 27 (49.1%) | 20 (64.5%) | 203 (50.2%) |
Diabetic nephropathy | 1 (0.5%) | 1 (0.9%) | 0 (0%) | 1 (3.2%) | 3 (0.7%) |
Hypertensive nephropathy | 21 (10.2%) | 2 (1.8%) | 1 (1.8%) | 1 (3.2%) | 25 (6.2%) |
Polycystic kidney | 13 (6.3%) | 4 (3.5%) | 1 (1.8%) | 2 (6.5%) | 20 (5%) |
Other | 25 (12.2%) | 14 (12.4%) | 6 (10.9%) | 3 (9.7%) | 48 (11.9%) |
Unknown | 50 (24.5%) | 31 (27.4%) | 20 (36.4%) | 4 (12.9%) | 105 (26%) |
Serum |
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Serum P (mmol/L) |
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Serum ALP (IU/L) |
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Serum iPTH (pg/mL) |
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Death ( |
17 (8.29%) | 4 (3.54%) | 6 (10.91%) | 9 (29.3%) | 36 (8.91%) |
Mean ± standard deviation is described if the variable is normally distributed.
During the 1–11-year follow-up period, the median duration was
Unadjusted Kaplan–Meier survival curve. Note: pthg: 1 = iPTH ≤ 20 pg/mL; 2 = iPTH 21–150 pg/mL; 3 = iPTH 151–600 pg/mL; 4 = iPTH > 600 pg/mL.
We used the following criteria as the basis of grouping iPTH was administered for one week after PTX to compare the mortality rates of patients in different groups. The all-cause mortality rates appeared as 8.29% (17/205) in group A (iPTH ≤ 20 pg/mL), as 3.54% (4/113) in group B (iPTH 21–150 pg/mL), as 10.91% (6/55) in group C (iPTH 151–600 pg/mL), and as 29.03% (9/31) in group D (iPTH > 600 pg/mL) (
We used logistic regression model to set group A as the reference to compare the risk ratios on all-cause mortality, between different groups. Table
Results of baseline multivariate logistic regression model for all-cause mortality.
Parameter | OR | Standard error |
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95% confidence interval |
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iPTH | ||||
Group B 21–150 pg/mL | 0.42 | 0.24 | 0.13 | 0.13~1.29 |
Group C 151–600 pg/mL | 1.35 | 0.69 | 0.56 | 0.49~3.69 |
Group D >600 pg/mL | 5.17 | 2.6 | 0.001 | 1.93~13.88 |
Age | 1.07 | 0.02 | 0.000 | 1.04~1.11 |
Adjusted for age, gender, dialysis vintage, primary cause of end-stage renal disease, serum
Results of baseline multivariate Cox regression and competing risk regression analysis for all-cause mortality.
Parameter | HR |
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95% confidence interval |
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iPTH | |||
Group B 21–150 pg/mL | 0.57 | 0.32 | 0.19~1.72 |
Group C 151–600 pg/mL | 1.43 | 0.46 | 0.55~3.68 |
Group D >600 pg/mL | 3.45 | 0.004 | 1.49~7.99 |
Age | 1.06 | 0 | 1.03~1.09 |
Dialysis vintage2 | 1.0006 | 0.04 | 1.00~1.001 |
Adjusted for age, gender, dialysis vintage, primary cause of end-stage renal disease, serum
For all-cause mortality, data from univariate analysis confirmed that factors as age (HR = 1.06, 95% CI 1.03–1.09,
We used the predictive margins to analyze the relative hazard of mortality. Figure
Multivariate adjusted hazard ratio comparison between different groups. Note: pthg: 1 = iPTH ≤ 20 pg/mL; 2 = iPTH 21–150 pg/mL; 3 = iPTH 151–600 pg/mL; 4 = iPTH > 600 pg/mL. Adjusted for age, gender, dialysis vintage, primary cause of end-stage renal disease, serum
Patients were followed for different time spans after the PTX with different period as 1 week, 3 months, 1 year, 3 years, 5 years, 10 years, or more. Four groups of patients showed significant decreases on serum iPTH, after the PTX. Under the early follow-up program, four groups of patients showed different degrees of hypocalcemia postoperatively, during hospitalization. Hypocalcemia could be recovered or partially remitted by intravenous or oral calcium supplements. After the PTX, all patients showed different degrees of improvement or complete remission on bone pain, pruritus, and ectopic calcification during the follow-up period. When using the Cox proportional regression model to analyze the multivariable adjusted results, the increase of HR on death was noticed in patients of group B (iPTH 21–150 pg/mL). Patients in group D (iPTH > 600 pg/mL) showed the worst outcomes and in group C (iPTH 151–600 pg/mL) showed the poor outcomes. Prognosis of patients in group A (iPTH < 21 pg/mL) stood the second place among all the groups (Figure
Cox proportional hazards regression model survival curves. Note: pthg = 1: A: iPTH ≤ 20 pg/mL; pthg = 2: B: iPTH 21–150 pg/mL; pthg = 3: C: iPTH 151–600 pg/mL; pthg = 4: D: iPTH > 600 pg/mL. Adjusted for age, gender, dialysis vintage, primary cause of end-stage renal disease, serum
In this study, more patients with chronic glomerulonephritis (50.2%) were seen than the ones with DN (0.7%). Chronic glomerulonephritis seemed one of the primary causes for ESRD while DN was less commonly seen in China [
It is recognized that SHPT is a common complication of chronic renal failure. In the early stage of CKD, in order to adapt for the disorders of bone-mineral metabolism, parathyroid would excessively secrete the PTH, causing the disorders of bone-mineral metabolism to make the burden on cardiovascular systems aggravated and increased. SHPT is controlled under the treatments of phosphate binders, vitamin D analogs, or calcimimetics. With long-term uremia, patients would develop resistance to treatments and finally require PTX to participate. This can prevent the development of skeletal malformations and metastatic calcification, such as cardiovascular calcification. Known to each stage of CKD, the best serum PTH levels were considered different. Findings from our studies suggested that both extra high or low PTH could increase the mortality in CKD patients [
Because of the high variability in the number and location of parathyroid glands, they are difficult to be completely removed. Eventually, SHPT appears to be of high incidence in ESRD patients. Even after the PTX, the incidence remains relatively high [
In 2008, the Dialysis Outcomes and Practice Pattern Study (DOPPS) identified the optimal PTH level as 101–300 pg/mL, with mortality risk being the lowest under this range [
Fernandez-Martin et al. examined 6797 adult patients with hemodialysis. They found that either high or low PTH was associated with high risk of mortality. Serum iPTH 398 pg/mL was associated with the minimum relative risk of mortality. Based on the published risk values on mortality, the lowest value being adopted was 168–674 pg/mL, for serum iPTH [
Only few studies specifically targeted on the value of PTH levels had been carried out. Considerable studies from home or abroad confirmed that SHPT patients could improve the survival outcomes after the PTX. Results from studies also showed that when patients underwent PTX, the levels of serum phosphorus, serum calcium, Ca × P, and iPTH were significantly reduced, ending in an effective improvement of quality of life on patients [
Komaba et al. [
Since the sample size was not large enough in our long-term follow-up study, no significant statistical differences were noticed. Rhee et al. [
Results from our study showed that, during the long-term follow-up period, all-cause mortality was associated with different iPTH levels in dialysis patients with SHPT, followed by the PTX. After the PTX, iPTH > 600 pg/mL seemed to be associated with the risk of all-cause mortality. When iPTH levels were positively and effectively decreasing, the risk of all-cause mortality also reduced. The most appropriate level of iPTH was found as 21–150 pg/mL after the PTX. We noticed that both the iPTH levels and the risk of mortality were under U-shapes. Unfortunately, because of the small sample size and inadequate number of patients that completed the whole course of the study, our findings were not able to reach the statistical significance as expected. Sampling error seemed another shortcoming of this study. However, we are planning to continue the study through increasing the sample size to confirm the postoperative best iPTH levels under the PTX and associations with the quality of life.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Ling Zhang and Cheng Gang Jin were responsible for conceptualization. Qiu Ping Xi, Xi Sheng Xie, and Rui Zhang were responsible for data curation. Cheng Gang Jin and Yan Bo Li were responsible for formal analysis. Ling Zhang was responsible for funding acquisition, project administration, and supervision. Ling Zhang, Qiu Ping Xi, Rui Zhang, Yue Fei Xiao, Lin Wang, Xiao Xuan Zhang, and Shu Tong Du were responsible for investigation. Ling Zhang, Yue Fei Xiao, Lin Wang, Xiao Xuan Zhang, and Shu Tong Du were responsible for resources. Qiu Ping Xi and Rui Zhang were responsible for software. Ling Zhang and Cheng Gang Jin were responsible for validation and visualization. Qiu Ping Xi, Ling Zhang, and Xi Sheng Xie were responsible for methodology and writing of original draft. Qiu Ping Xi and Xi Sheng Xie contributed equally to this work. Qiu Ping Xi, Xi Sheng Xie, and Ling Zhang were responsible for writing, review, and editing of the manuscript.
The study was supported by the capital characteristic clinical medicine application development projects—Evaluation of Cardiovascular Calcification in Maintenance Hemodialysis Patients with Parathyroidectomy by a Prospective Cohort Study—grant from the Beijing Municipal Science and Technology Commission Program (no. Z151100004015112).