Keywords
kidney transplantation - hyperparathyroidism - calcium homeostasis - osteoporosis - parathyroidectomy - body mass index
Introduction
Chronic kidney disease-mineral and bone disorders (CKD-MBD) is a complex disease that
is caused by a disturbance in metabolic and hormone levels, including altered levels
of calcium, phosphorus, parathyroid hormone (PTH), and vitamin D that impairs bone
quality and bone remodelling.
Elevated PTH level is a crucial factor contributing to the development of
osteodystrophy, vascular calcification, and anemia resistant to
erythropoiesis-stimulating agents [1].
Also, studies demonstrated that a higher level of PTH correlated with
osteopenia/osteoporosis and bone fracture risk in patients with chronic kidney
disease treated by dialysis (CKD-G5D) [2]
[3]. Optimization of the PTH
levels should be the primary goal to reduce all these risks.
Current guidelines suggest maintaining intact PTH levels in the range of 2 to 9 times
the normal upper limits in CKD-G5D patients and only recommend parathyroidectomy
(PTX) in patients refractory to medical therapy [4]. In these patients, PTX was associated with improved survival in large
observational dialysis cohorts, with a reported 20–37% and 33–41% reduction in
all-cause and cardiovascular mortality, respectively [5]
[6]
[7]. Besides, it was found
that CKD-G5D patients undergoing PTX have increased bone mineral density (BMD) and
decreased fracture risk. [8]
[9]. On the other hand, there was a
significant decrease in the frequency of PTX after calcimimetics therapy was
introduced in severe secondary hyperparathyroidism (sHPT) [10]. However, the effects of calcimimetics
on major cardiovascular events, fractures or mortality are still controversial [11]
[12]. In addition, side effects, patient adherence, calcium derangements,
and drug cost significantly limit the use of these agents [13].
Although kidney transplantation (KT) is the best option for CKD-G5D patients and is
associated with increased survival and health-related quality of life, the reduction
in BMD within the first year is still observed, which could lead to adverse events
[14]
[15]. So, fracture rates in the first two
years after transplantation have been reported to be 34% higher than in the previous
year on dialysis, and the risk remains significantly higher even ten years after
transplantation [16]
[17]. Fracture outcomes are prominently
worse, with higher hospitalization and mortality rates in KT recipients [18]. Additionally, sHPT can persist after
KT in up to 66% of patients, despite an initial decrease in PTH levels, leading to
hypophosphatemia, hypercalcemia, loss of bone mineral density (BMD), and increased
risk of fractures [19]
[20]. Although PTX after KT resolves
electrolyte disturbances in patients with persistent hyperparathyroidism (perHPT),
the BMD increase is lower than in CKD-G5D patients [21].
However, the long-term effect of PTX performed in KT recipients before
transplantation remains unclear. The aim of this study was to compare the effects of
PTX and calcimimetic agents used in severe sHPT before transplantation on the perHPT
and long-term change in BMD after KT.
Materials and Methods
Study population
We conducted a retrospective analysis of PTX and calcimimetic therapy for severe
sHPT on long-term outcomes after KT. All patients who underwent kidney
transplantation at our center between 2000 and 2017 were included. The inclusion
criteria were as follows; age+≥+18 years at transplantation, patients treated
with maintenance HD at least three times a week for+>+6 months before KT, and
had plasma iPTH levels+>+800 pg/ml (at least three months) in the
pre-transplantation period. Patients who received preemptive transplantation, an
estimated glomerular filtration rate (eGFR)<30 ml/min/1.73 m2 on
day 15 after KT, and patients with insufficient data and PTX after KT were
excluded from the present study. Thus, the total eligible cohort for analysis
was made of 68 patients ([Fig.
1]).
Fig. 1 Flow chart of the patients included in the study.
All of the patients received induction therapy with basiliximab, daclizumab or
anti-thymocyte globulin. An intravenous bolus of 500 mg on day 1 (D1), then
250 mg (D2) on day 2, then 20 mg/ day orally, the prednisolone dose was tapered
by 5 mg every week until the dose was 5–10 mg. All patients were kept on a
minimum of 5 mg of prednisolone. Maintenance therapy was with prednisolone as
above and the calcineurin inhibitors cyclosporine or tacrolimus and the
antimetabolite mycophenolate mofetil or azathioprine. In case of development of
intolerable side effects, mammalian target of rapamaycin (mTOR) inbitors were
used. Vitamin D supplementation was performed all patients who had vitamin D
levels below 30 ng/ml according to “Kidney disease: improving global outcomes”
(KDIGO) clinical practice guideline for the care of kidney transplant recipients
[22]. Acute allograft rejection
episodes are confirmed by renal biopsy and were treated in accordance with the
KDIGO guideline [22].
Data collection
Medical records were reviewed for patient data. Patient demographics were
determined as age, sex, diabetes mellitus, cardiovascular disease (coronary
artery or peripheral arterial disease), cause of ESRD (diabetes mellitus,
hypertension, glomerulonephritis, urological abnormalities, unknown or “other”
(including, amyloidosis, Alport syndrome, and polycystic kidney disease),
dialysis vintage, dialysis types (hemodialysis, peritoneal dialysis or both
modalities), baseline serum calcium, phosphate, and PTH. Kidney transplant data
included donor type, delayed graft function (requiring dialysis within the first
week after transplantation), rejection episodes (antibody-mediated or cellular
rejection), allograft loss, and overall survival. Serum PTH, calcium, and
phosphate levels at first, second and third year and last follow up
post-transplantation were also collected.
We used bone mineral densitometry (BMD) at the hip (neck of the femur and total),
and lumbar spine using dual-energy X-ray absorptiometry (DEXA Horizon; Hologic
Inc., Marlborough, Massachusetts, USA) at first year after KT and at the last
follow-up were noted. All the patients are followed up with BMD annually
according to the KDIGO 2009 guideline in our clinic. BMD values were expressed
in absolute values, g/cm2, as well as T-scores. Osteoporosis was
defined as a T-score+≤+–2.5 at least one site, and osteopenia as a T-score
between –1 and –2.5. Cases of symptomatic AVN were diagnosed by standard
anterior-posterior X-ray views of the pelvis or magnetic resonance imaging (MRI)
of the pelvis, hip, knee or shoulder. The presence of fractures was determined
through a combination of electronic data base and medical records of the
patients. Fractures associated with trauma were excluded.
The primary outcome was long-term changes in BMD measurements of patients with
severe sHPT prior to KT. The secondary outcomes were serum PTH, calcium, and
phosphate levels after kidney transplantation. Persistent HPT was defined as
PTH+>+88 pg/ml after the first year of KT. Calcium (8.5–10.5 mg/dl) and
phosphate (2.5–4.5 mg/dl) disturbances were defined as detecting values outside
the reference ranges in the same direction on at least two consecutive
visits.
Statistical analysis
According to distribution, continuous data are presented as mean±standard
deviation or median (interquartile range). Categorical data are presented as
number (n) and percentage. Baseline characteristics were compared between groups
using the Student t-test or non-parametric tests for continuous variables
(according to distribution) and the chi-square test for categorical variables.
Additionally, to identify independent risk factors for last femoral neck BMD,
univariate and multivariate analysis was performed. Only variables with a
p-value of<0.1 were considered for multivariate analysis. A p-value
of<0.05 was considered significant. SPSS 16.0 (IBM Corp., Chicago, IL, USA)
software was used for the statistical analyses.
Results
A total of 68 patients were included in the analysis (20 received PTX and 48 received
calcimimetic prior transplantation) with a mean 92.3±46.9 months follow-up time. The
mean age of participants was 35.4±11.8 years, 47% were male and mean BMI of the
cohort was 25.06±4.4 kg/m2. The PTX group had significantly more patients
with female gender (p=0.004), whereas the baseline BMI value was higher in the
calcimimetic group (p=0.02). Other demographic characteristics of the study
population were similar and were demonstrated in [Table 1].
Table 1 Baseline characteristic of study
population.
|
Total patients n=68
|
Parathyroidectomy n=20 (29%)
|
Calcimimetic n=48 (71%)
|
p-Value
|
|
Age at transplantation (years)
|
35.4±11.8
|
35.45±12.25
|
35.44±11.8
|
0.9
|
|
BMI
|
25.06±4.4
|
23.2±3.7
|
25.8±4.5
|
0.02
|
|
Gender (female/male)
|
36 (53%)/32 (47%)
|
16 (80%)/4 (20%)
|
20 (42%)/28 (58%)
|
0.004
|
|
Hypertension (n)
|
49 (72%)
|
12 (60%)
|
37 (77%)
|
0.1
|
|
CAD pre-transplantation (n)
|
7 (10%)
|
3 (15%)
|
4 (8%)
|
0.3
|
|
Pretranspl. glucocorticoid (n)
|
19 (28%)
|
5 (25%)
|
14 (29%)
|
0.4
|
|
NODAT (n)
|
11 (16%)
|
3 (15%)
|
8 (17%)
|
0.9
|
|
Cause of ESRD (n)
|
|
HT
|
8 (12%)
|
3 (15%)
|
5 (10%)
|
0.7
|
|
DM
|
2 (3%)
|
1 (5%)
|
1 (2%)
|
0.8
|
|
Glomerulonephritis
|
17 (25%)
|
3 (15%)
|
14 (29%)
|
0.5
|
|
Urological abnormalities
|
6 (9%)
|
3 (15%)
|
3 (6%)
|
0.3
|
|
Others
|
20 (30%)
|
6 (30%)
|
14 (29%)
|
0.9
|
|
Unknown
|
15 (22%)
|
4 (20%)
|
11 (23%)
|
0.9
|
|
Dialysis modality
|
|
PD
|
11 (16%)
|
3 (15%)
|
8 (17%)
|
0.9
|
|
HD
|
36 (53%)
|
10 (50%)
|
26 (54%)
|
0.9
|
|
PD and HD
|
21 (31%)
|
7 (35%)
|
14 (29%)
|
0.8
|
|
Dialysis vintage (years)
|
9.2±4.4
|
10.4±5.3
|
8.7±4.0
|
0.1
|
|
Donor type (n)
|
|
|
|
0.1
|
|
Deceased donor
|
35 (52%)
|
13 (65%)
|
22 (46%)
|
0.1
|
|
Living donor
|
33 (48%)
|
7 (35%)
|
26 (54%)
|
|
|
Relative
|
20 (61%)
|
6 (86%)
|
14 (54%)
|
|
|
Induction with thymoglobulin (n)
|
44 (65%)
|
14 (70%)
|
30 (63%)
|
0.4
|
|
Delayed graft function (n)
|
13 (19%)
|
6 (30%)
|
7 (15%)
|
0.1
|
|
Immunosuppressive treatment
|
|
CNI (n)
|
61 (90%)
|
20 (100%)
|
41 (85%)
|
0.07
|
|
Antimetabolite (n)
|
54 (79%)
|
14 (70%)
|
40 (83%)
|
0.2
|
|
mTORi
|
16 (24%)
|
6 (30%)
|
11 (23%)
|
0.5
|
|
Steroid usage at last follow-up
|
65 (96%)
|
18 (90%)
|
47 (98%)
|
0.2
|
|
Follow-up time (months)
|
92.3±46.9
|
84.9±44.4
|
95.4±48.1
|
0.4
|
BMI: Body mass index; CAD: Coronary artery disease; NODAT: New onset diabetes
after transplantation; HT: Hypertension; DM: Diabetes mellitus; PD:
Peritoneal dialysis; HD: Hemodialysis; CNI: Calcineurin inhibitors; mTORi:
Mammalian target of rapamycin inhibitors.
PTH was significantly lower in the PTX group on the day of KT and most of the
follow-up visits after KT ([Fig. 2a]).
Mean serum calcium was lower in the PTX group only in the third month after KT
(p=0.04) and the mean phosphate levels were similar over both groups during the
follow-up ([Fig. 2b, c]). The incidence
of hypercalcemia episodes was significantly higher in the group of patients who were
treated with calcimimetic (50% vs. 22%, p=0.04). In contrast, hypocalcemia episodes
were higher in the PTX group (17% vs 0%, p=0.02) ([Fig. 3a, b]). There were no differences in
the incidence of hypophosphatemia or hyperphosphatemia episodes between groups
([Fig. 3c, d]).
Fig. 2 Trends for calcium (a), phosphate (b), and
parathyroid hormone (c) levels during follow-up period.
Fig. 3 Serum calcium and phosphate disturbances after kidney
transplantation.
Overall rates of allograft loss and death with functional allograft were comparable
between the two groups. However, perHPT incidence was significantly higher in the
calcimimetic group (75% vs. 40%, p=0.007). The DXA assessments were performed at a
mean interval of 11.7±2.4 months for the first year and 7.2±2.9 years for the last
follow-up after KT. At the first assessment, the overall rate of osteoporosis among
the participants was 31%, whilst the proportion of people who had osteopenia was
37%. The median femoral neck, total hip and lumbar spine T-scores were –1.0 (–3.6 to
1.4), – 0.8 (–3.3 to 1.6), –1.6 (–3.7 to 2.1) respectively. In patients with PTX
compared to the calcimimetic group, BMDs were significantly higher (T-scores) at all
three measurement sites, that is, the femoral neck, total hip and lumbar spine, the
median values of which were – 0.4 (–2.3 to 1.0) versus –1.2 (–3.6 to 1.36) (p=0.01);
– 0.4 (–2.3 to 0.8) versus –1.0 (–3.3 to 1.6) (p=0.05); and 0.2 (–2.8 to 1.1)
versuss –1.7 (–3.7 to 2.1) (p=0.02), respectively. The mean femoral neck, total hip
and lumbar spine BMD measurements (g/cm2) of the patients were
0.766±0.131, 0.875±0.138, 0.929±0.163, respectively. In patients with PTX compared
to calcimimetic group, BMD measurements (g/cm2) were higher at femoral
neck and lumbar spine, the mean values of which were 0.818±0.114 versus 0.744±0.134
(p=0.04) and 1.005±0.170 versus 0.897±0.151 (p=0.01), respectively. At last
follow-up, DXA showed osteoporosis in 9 patients (15%) and osteopenia in 33 patients
(53%). The BMD comparison (T-score) between patients treated with PTX and
calcimimetic prior KT found a significant difference only in the femoral neck [– 0.6
(–1.6 to 1.3) vs –1.2 (–3.1 to 1.4) (p=0.006), respectively]. Similar with that, BMD
measurement (g/cm2) of femoral neck was significantly different between
two groups (0.835±0.118 vs. 0.758±0.129; p=0.03). During an average of 94.1±49.2
follow-up time, 12% (8 patients) of the total study population sustained a fracture.
Localization of the fracture sites were ankle (3/8; 38%), fibula (2/8; 25%),
metacarpal bones (1/8; 13%), hip (1/8; 13%), and lumbar spine (1/8; 13%). Bone
related parameters and clinical outcomes of the patients are summarized in [Table 2].
Table 2 Bone parameters and clinical outcomes of the
patients.
|
Total patients n=68
|
Parathyroidectomy n=20 (29%)
|
Calcimimetic n=48 (71%)
|
p-Value
|
|
First DXA assessment after KT (months)
|
11.7±2.4
|
11.1±2.2
|
12.0±2.4
|
0.9
|
|
First DXA T score
|
|
Femur neck
|
– 1.0 (– 3.6 to 1.4)
|
– 0.4 (– 2.3 to 1.0)
|
– 1.2 (– 3.6 to 1.3)
|
0.01
|
|
Total hip
|
– 0.8 (– 3.3 to 1.6)
|
– 0.4 (– 2.3 to 0.8)
|
– 1.0 (– 3.3 to 1.6)
|
0.05
|
|
Lumbar spine
|
– 1.6 (– 3.7 to 2.1)
|
0.2 (– 2.8 to 1.1)
|
– 1.7 (– 3.7 to 2.1)
|
0.02
|
|
First BMD measurement (g/cm2)
|
|
Femur neck
|
0.766±0.131
|
0.818±0.114
|
0.744±0.134
|
0.04
|
|
Total hip
|
0.875±0.138
|
0.925±0.137
|
0.854±0.135
|
0.06
|
|
Lumbar spine
|
0.929±0.163
|
1.005±0.170
|
0.897±0.151
|
0.01
|
|
Last DXA assessment after KT (years)
|
7.2±2.9
|
7.1±2.9
|
7.3±3.0
|
0.8
|
|
Last DXA T score
*
|
|
Femur neck
|
– 1.1 (– 3.1 to 1.4)
|
– 0.6 (– 1.6 to 1.3)
|
– 1.2 (– 3.1 to 1.4)
|
0.006
|
|
Total hip
|
– 0.5 (– 2.9 to 2.2)
|
– 0.3 (– 2.8 to 0.8)
|
– 0.8 (– 2.9 to 2.2)
|
0.1
|
|
Lumbar spine
|
– 1.2 (– 3.3 to 3.0)
|
– 0.4 (– 2.5 to 3.0)
|
– 1.4 (– 3.3 to 2.1)
|
0.1
|
|
Last BMD measurement (g/cm2)*
|
|
Femur neck
|
0.781±0.129
|
0.835±0.118
|
0.758±0.129
|
0.03
|
|
Total hip
|
0.908±0.142
|
0.932±0.119
|
0.898±0.153
|
0.4
|
|
Lumbar spine
|
0.965±0.158
|
1.015±0.178
|
0.943±0.147
|
0.09
|
|
First BMD category (n)
|
|
Normal
|
22 (32%)
|
9 (45%)
|
13 (27%)
|
|
|
Osteopenia
|
25 (37%)
|
7 (35%)
|
18 (38%)
|
1
|
|
Osteoporosis
|
21 (31%)
|
4 (20%)
|
17 (35%)
|
0.3
|
|
|
|
|
|
|
Last BMD category (n)*
|
|
Normal
|
20 (32%)
|
9 (50%)
|
11 (25%)
|
|
|
Osteopenia
|
33 (53%)
|
8 (44%)
|
25 (57%)
|
0.4
|
|
Osteoporosis
|
9 (15%)
|
1 (6%)
|
8 (18%)
|
0.3
|
|
MOF
|
8 (12%)
|
1 (5%)
|
7 (15%)
|
0.4
|
|
AVN (n)
|
7 (10%)
|
2 (10%)
|
5 (10%)
|
0.9
|
|
Bisphosphonates (n)
|
6 (9%)
|
2 (10%)
|
4 (8%)
|
0.6
|
|
perHPT (n)
|
44 (65%)
|
8 (40%)
|
36 (75%)
|
0.007
|
|
Cardiovascular events (n)
|
7 (10%)
|
2 (10%)
|
5 (10%)
|
0.9
|
|
eGFR at last follow-up (ml/min/1.73 m2)
|
66.8±35.6
|
65.1±35.5
|
67.5±36.0
|
0.8
|
|
Rejection episode (n)
|
8 (12%)
|
2 (10%)
|
6 (13%)
|
0.8
|
|
ACR
|
4 (50%)
|
1 (50%)
|
3 (50%)
|
|
|
ABMR
|
4 (50%)
|
1 (50%)
|
3 (50%)
|
|
|
Allograft lost (n)
|
13 (19%)
|
3 (15%)
|
10 (21%)
|
0.4
|
|
Death with functional allograft (n)
|
5 (7%)
|
2 (10%)
|
3 (6%)
|
0.6
|
ACR: Acute cellular rejection; ABMR: Antibody mediated rejection; AVN:
Avascular necrosis; BMD: Bone mineral density; DXA: Dual–energy X–ray
absorptiometry; eGFR: Estimated glomerular filtration rate; MOF: Major
osteoporotic fractures; perHPT: Persistent hyperparathyroidism.
*Patients who used bisphosphonate were excluded from
analysis.
Univariate and multivariate regression analysis was performed to determine the
affecting factors for the last femoral neck BMD measurement (g/cm2).
Linear regression revealed a positive association between the last BMD of femoral
neck with BMI [Correlation coefficient (CC): 0.251, 95% confidence interval (CI),
0.001– 0.016] and PTX performed prior KT (CC: 0.276, 95% CI, 0.007– 0.146).
Additionally, BMI and PTX prior KT maintained their statistical significance in
multivariate analysis (CC: 0.297, 95% CI, 0.002– 0.017 and CC: 0.319, 95% CI,
0.021– 0.156, respectively) ([Table
3]).
Table 3 Factors affecting the last BMD measurement of femoral
neck.
|
Correlation coefficient
|
95% Confidence interval
|
p-Value
|
|
Univariate analysis
|
|
Age
|
– 0.158
|
– 0.004 and 0.001
|
0.2
|
|
BMI
|
0.251
|
0.000 and 0.016
|
0.05
|
|
Male gender
|
0.065
|
– 0.050 and 0.083
|
0.6
|
|
Dialysis vintage
|
– 0.004
|
– 0.008 and 0.007
|
0.9
|
|
Delayed graft function
|
0.098
|
– 0.054 and 0.119
|
0.5
|
|
NODAT
|
– 0.162
|
– 0.152 and 0.034
|
0.2
|
|
Smoking
|
– 0.091
|
– 0.091 and 0.044
|
0.5
|
|
CNI
|
– 0.099
|
– 0.108and 0.049
|
0.4
|
|
Anti metabolite
|
– 0.132
|
– 0.130 and 0.042
|
0.3
|
|
mTORi
|
0.102
|
– 0.047 and 0.108
|
0.4
|
|
perPHP
|
– 0.086
|
– 0.093 and 0.047
|
0.5
|
|
eGFR (last follow-up)
|
0.147
|
– 0.003 and 0.012
|
0.3
|
|
PTX
|
0.276
|
0.007 and 0.146
|
0.03
|
|
Multivariate analysis
|
|
BMI
|
0.297
|
0.002 and 0.017
|
0.02
|
|
PTX
|
0.319
|
0.021 and 0.156
|
0.01
|
BMI: Body mass index; NODAT: New onset diabetes after transplantation; CNI:
Calcineurin inhibitors; eGFR: Estimated glomerular filtration rate; mTORi:
Mammalian target of rapamycin inhibitors; perHPT: Persistent
hyperparathyroidism; PTX: Parathyroidectomy.
Discussion
The aim of our study was to evaluate changes in BMD in patients with severe sHPT who
were treated with PTX or calcimimetic before KT. Our result showed that DXA
assessment the first year after KT was significantly better in patients with PTX
than those with calcimimetics. Besides, DXA assessment at the last follow-up
revealed femoral neck BMD better in the PTX group and significantly associated with
PTX.
Secondary hyperparathyroidism is a common problem in CKD-G5D patients, and the main
factors for the development of sHPT were hypocalcemia, hyperphosphatemia, low
1,25D3, and high FGF23 levels [23]. sHPT
is characterized by increased PTH synthesis and secretion accompanied by parathyroid
cell hyperplasia. After introducing calcimimetics, the management of sHPT has
changed, and utilization of PTX has decreased over time. Calcimimetics improved
phosphate, PTH levels, and BMD in patients with sHPT, but many patients have
treatment adherence issues [24]. If severe
sHPT cannot be controlled in the pre-transplant period, it could lead to perHPT,
increased risk of graft failure and bone loss after KT [25]
[26]
[27].
Our study showed that 65% of the patients had perHPT after KT, similar to other
studies [19]. The percentage of the perHPT
is significantly lower in the PTX group (40%) than in the calcimimetic treated group
(75%) prior to KT. Previous studies reported high pre-transplant PTH levels along
with calcium, phosphate and, dialysis vintage are risk factors for perHPT [28]. Besides, during the entire follow-up
period after KT, patients with PTX had lower PTH levels than the calcimimetic
treated group. A single-center study conducted by Callender et al. suggested that
PTX prior to KT was associated with a lesser risk of graft failure. However,
allograft loss in our study was similar in patients with or without PTX [25]. In addition, we found no difference in
rejection episodes, cardiovascular events, or death with functional graft between
the two groups. As expected, more hypercalcemia episodes were seen in the
calcimimetic-treated group, compatible with the previous study [29].
Osteoporosis is one of the significant problems in kidney transplant recepients
(KTRs). However, the clinical focus is on allograft function after KT and bone
disease management is usually neglected. In this study, the percentage of patients
with osteoporosis and osteopenia in the first DXA assessment was 31% and 37%,
respectively. In a French cohort study, Segaud et al. reported 41% and 43%
incidences of osteoporosis and osteopenia at the first assessment, respectively
[30]. However, our study population
was younger than this study, and we may attribute this difference to the lower mean
age of our cohort.
KTRs have legacy bone mineral disease from chronic kidney disease that worsens with
the drugs used after transplantation. Julian et al. reported a loss of 6.8±5.6% in
the lumbar spine in BMD 6 to 12 months after KT, suggesting that it was due to the
toxic effect of glucocorticoids [31].
Other associated risk factors with bone loss after KT were duration of dialysis
before transplantation, age at transplantation, vitamin D deficiency,
BMI<23 kg/m2, and higher initial parathyroid hormone level [27]
[31]
[32]. Modifiable risk
factors such as perHPT, BMI, and early transplantation should be managed and treated
promptly, as glucocorticoid therapy is mandatory in a patient with KT. In this
context, we found that patients with a history of PTX had significantly better
femoral neck, total hip or lumbar spine T scores in the first DXA assessments than
those treated with calcimimetics. Chandran et al. found that patients with PTX prior
to KT have better BMD and trabecular bone scores at the time of transplantation than
patients with tertiary hyperparathyroidism [33]. That may explain the better BMD of these patients after the first
year of KT, and it could be thought that controlling PTH levels before
transplantation may contribute to preventing bone loss in the early period after
KT.
In this study, we also examined the long-term effect of PTX performed before
transplantation on BMD, and we found that the femoral neck T score and BMD at the
last follow-up were better in the PTX group than those with calcimimetic. Also, we
showed in the multivariate analysis that PTX and BMI are the independent factors
correlated with better femoral neck BMD. There is no study in the literature that
examines the impacts of PTX prior to KT on BMD. However, the only randomized,
controlled trial investigating the role of PTX for perHPT revealed that PTX was
superior to cinacalcet for increasing femoral neck BMD, but, the long-term
effectiveness remains unclear [34]. Our
results can be interpreted that surgical interventions before transplantation in
severe sHPT will have an additional contribution in the long term in this particular
patient group. In the general population, higher BMI has been shown to be protective
against osteoporosis. Similarly to previous studies, we observed that BMI correlates
with the better femoral neck BMD of the patients. [32]
[35]. On the other hand, Akaberi et al. demonstrated high persistent PTH
values correlated with significant bone loss at the hip after KT [36]. The last femoral neck BMD was not
correlated with perHPT in our cohort; however, the presence of patients treated for
perHPT in both groups after KT may have impacted this outcome.
The primary and major limitation is that this is a single-center study with a
retrospective design. Within the limits of a single center, the study population was
localized and included a small number of patients, which limited the analytic
possibilities. Second, PTX time before KT was not standardized in this study. Also,
bone turnover biomarkers were not available. Last, another limitation is that BMD
values provide limited information on bone microarchitecture.
Our study has several strengths. First, to the best of our knowledge, this is the
first study to demonstrate the long-term efficacy of PTX in femoral neck BMD
measurements. Second, it is a study with an average mean follow-up time of 8 years
after KT. Although this study includes a small number of patients, it was designed
to evaluate a specific subgroup of patients with sHPT before KT.
Conclusion
In conclusion, pre-transplant PTX was associated with a significantly lower incidence
of perHPT in patients with severe sHPT and better femoral neck BMD measurements
(g/cm2) and T scores in the final DXA assessments. Therefore, further
studies with a prospective manner are needed to define the impact of PTX performed
before KT on the BMD of patients after transplantation.
