Impact of parathyroidectomy on left ventricular function in end stage renal disease patients

The cohort of this retrospective study consisted of ESRD patients with SHPT received PTX from Oct 1, 2010, to Oct 1, 2016, at the First Affiliated Hospital, Zhejiang University School of Medicine. The inclusion criteria of PTX were according to Kidney Disease Improving Global Outcomes (KDIGO) 2009 guidelines [6]. Accordingly, following patients were excluded: those having severe malnutrition, infection or inflammation; severe liver disease and coagulation disorders; complicated with a hematological disease or malignant tumors; having a history of acute cardiovascular and cerebrovascular events within 6 months; the parathyroid hormone (PTH)>100 ng/L within 1 month post- PTX; those who received the kidney transplantion during the follow-up; with follow-up < 1 year; received the PTX because of recurrence and data missing or insufficiency. Patients enrolled were followed for at least 1 year; baseline characteristics including age, sex, dialysis duration, dialysis modality, the primary diseases of ESRD, the number of parathyroid gland removed, the blood pressure pre- and 1-year post-PTX, the cardiovascular drugs used during the follow-up were collected. This study received approval from the Research and Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine.

The surgery method employed was total PTX with forearm autotransplantation (tPTX+AT). The parathyroid tissues were forwarded for pathological examination intra- and post-operatively. Tiny pieces of parathyroid tissues were transplanted into patients’ forearms. Post-operatively, all patients were given substantial doses of intravenous calcium, oral calcium, and calcitriol supplement.

We collected the biochemical parameters including pre-operative serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, and albumin levels; monitored and observed them at 1 week, 1 month, 3 months and 1 year after the PTX.

We collected the cardiovascular drugs used during the follow-up, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARBs), calcium blockers, cardiotonic β-blockers, isosorbide mononitrate and trimetazidine during the follow-up, and the blood pressure 1-year post-PTX.

We also collected the ultrasonic cardiogram parameter pre- and 1- year post-PTX, including ejection fraction% (EF%), fractional shortening% (FS%), left ventricular end-diastolic diameter (LVDd), interventricular septum thickness (IVST), left ventricular posterior wall end-diastolic thickness (LVPWD), left atrial diameter (LA), aorta (AO), left ventricular end-systolic dimension (LVDs), left ventricular posterior wall end-systolic thickness (LVPWs), ventricular septal end-systolic thickness (IVSs).

We used the Devereux correction formula to calculate the Left ventricular mass index (LVMI).

Left ventricular mass (LVM, g) = 0.8 × 1.04{[LVDd (cm) + IVST (cm) + LVPWd (cm)]³-LVDd³} + 0.6;

Body surface area (BSA) (m², female) = 0.0073 × height (cm) + 0.0127 × weight (kg) -0.2106;

BSA (m², male) = 0.0057 × height (cm) + 0.0121 × weight (kg) + 0.0882;

LVMI (g/m²) = LVM/BSA.

The diagnostic criteria of left ventricular hypertrophy (LVH) are: LVMI≥95 g/m² (female), LVMI≥115 g/m² (male) [7].

The improvement of LV systolic function was defined as the improvement of the EF% measured by echocardiography to an increase of 10% or greater in its absolute value 1-year post-PTX.

The primary evaluation items were: the change of ultrasonic cardiogram parameter pre- and 1-year post-PTX; the influence factor for the overturn of LVH; the influence factor for the improvement of EF%.

The secondary evaluation items included the biochemical parameters change pre- and post-PTX.

There were 293 ESRD patients diagnosed with SHPT between Oct 1, 2010, and Oct 1, 2016 received parathyroidectomy. Out of them, following patients(158) were excluded: 10 patients were excluded because of the PTH>100 ng/L within 1 month post- PTX, 8 because of receiving the kidney transplant during the follow-up, 39 because of the follow-up<1 year, 8 because of receiving the PTX due to recurrence; and 93 because of data missing or insufficiency. In total, 135 ESRD patients (81 male: 54 female) with severe SHPT were included (Fig. 1). The mean age was 45.60 ± 1.0 years, and the media dialysis duration was 6.45(5.0, 9.0) years. There were 121 hemodialysis patients, 12 peritoneal dialysis patients, and 2 ESRD patients who did not start renal replacement therapy when the PTX was performed. The most common primary disease was chronic glomerulonephritis (80%). There were 119 patients (88.1%) had ≥4 parathyroid glands removed, while 16 patients (11.9%) had <4 parathyroid glands removed. Further, all parathyroid glands turned out to be hyperplasia or adenoma by pathological examination. The average systolic pressure pre-PTX was 139.4 ± 22.8 mmHg, while the average diastolic pressure was 88.6 ± 15.4 mmHg; the average systolic pressure 1-year post-PTX was 144.5 ± 23.5 mmHg, and the average diastolic pressure was 80.1 ± 13.3 mmHg. As to the cardiovascular drugs used in the follow-up, 5 (3.7%) patients took ACEI, 30 (22.2%) patients took ARBs, and 50 (37.0%) patients took calcium blockers, only 1 (0.7%) patient took cardiotonics, 48 (35.6%) patients took β-blockers, 11 (8.1%) patients took isosorbide mononitrate, and 8 (5.9%) patients took trimetazidine (Table 1). All the patients were followed up to 1 year.

The serum calcium and phosphate declined immediately after the PTX, and were maintained at a stable level after the PTX all along with the follow-up. The serum PTH declined immediately after the PTX and kept gradually increasing in the follow-up, after 1 year of the PTX, the PTH was 69.15 (27.95, 180.28) ng/L compared with a pre-operative level of 2357.00 (1709.00, 2777.00) ng/L. The serum alkaline phosphatase increased after the PTX, reached peak level after 1 month of the PTX, and gradually declined to normal level after 1 year of the PTX. The serum albumin declined after the PTX, and increased after 3 months of the PTX significantly (Table 2).

In all the patients, the main ultrasonic cardiogram parameter dramatically improved compared with that at pre-PTX. The LVM and LVMI significantly decreased after 1 year of the PTX. The LVM was 172.82 (135.80, 212.91) g after 1 year of PTX, while LVM was 192.76 (157.56, 237.97) g pre- PTX (p<0.001). Furthermore, LVMI pre- PTX was 123.54 (105.49, 146.64) g/m², after 1 year of PTX, the LVMI was 107.01 (86.79,128.42) g/m² (p<0.001). The LVDd, PWd, LVDs, and IVSs also declined significantly after PTX (P<0.05). There was no statistical difference observed in EF%, FS%, LA, AO, IVSd, LVPWs as compared with those during pre-PTX (Table 3).

Even though there was no statistical difference observed in EF%, FS%, the rising tendency could be observed. In the subgroup analysis of 35 patients with EF% ≤ 60% pre-PTX, EF%, and FS% significantly improved after 1 year of the PTX compared with pre-PTX (EF%, 64.90 ± 7.90% vs. 55.71 ± 4.78%, p<0.001; FS%, 35.48 ± 6.34% vs. 29.54 ± 2.88%, p<0.001) (Table 4).

According to the diagnostic criteria of left ventricular hypertrophy (LVH), before the PTX, the incidence of LVH was 59.26% (80), and among them, 43.75% (35) patients recovered from LVH after 1 year of the PTX. To determine the reason for the overturn of LVH, we collected some data maybe related to the overturn of LVH including the cardiovascular drugs (ACEI, ARBs, calcium blockers, cardiotonics, β-blockers, isosorbide mononitrate, trimetazidine) used during the follow-up, and the blood pressure 1-year post-PTX, then we conducted the multiple logistic regression analyses. In the multiple logistic regression analyses, we didn’t observe the significant influence factor for the overturn of LVH (Table 5).

In patients whose EF% ≤ 60% (35), there were 82.86% (29) patients underwent an increase of 10% or greater in its EF% absolute value after 1 year of the PTX, which showed the markedly improvement of the LV systolic function. To determine why the EF% increased, we collected some data maybe related to the improvement of EF% including the cardiovascular drugs (ACEI, ARBs, calcium blockers, cardiotonics, β-blockers, isosorbide mononitrate, trimetazidine) used during the follow-up, and the blood pressure 1-year post-PTX, and then we conducted the multiple logistic regression analyses. In the multiple logistic regression analyses, we didn’t observe the significant relationship between cardiovascular drugs, blood pressure and the improvement of EF% either (Table 6).

Our study has some limitations: this is a single-center retrospective study, and we could not set randomize control group, which makes the study rigorous enough; the sample capacity was not large, especially the subgroup; the confounding bias interference factors were not excluded thoroughly.