Changes in High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) in teenagers undergoing a first renal transplantation between baseline and 6 months

doi:10.21203/rs.3.rs-3763742/v1

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Research Article

Changes in High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) in teenagers undergoing a first renal transplantation between baseline and 6 months

https://doi.org/10.21203/rs.3.rs-3763742/v1

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Background
Mineral bone disorders associated to chronic kidney disease (CKD-MBD) frequently persist after renal transplantation (R-Tx), being due to pre-existing CKD-MBD, immunosuppressive therapies and post-Tx hypophosphatemia. We aimed to evaluate bone biomarkers and microarchitecture at the time of and 6 months after R-Tx.

Methods
Here we present the single-center sub-group of patients included between 10 and 18 years of age from the prospective TRANSOS study (NCT02729142). Patients undergoing a first R-Tx were matched on a 1:2 basis on gender, puberty and age with healthy controls (HC) from the VITADOS cohort. Results are presented as median (Q1-Q3). Non-parametric tests were performed.

Results
At a median age of 15 (13-16) years, 19 patients (6 girls, 7 pre-emptive R-Tx, 7 steroid-sparing immunosuppressive strategies) underwent a first R-Tx, with PTH levels of 1.9 (1.4-2.9) the upper limit of normal (ULN).

When comparing HC and patients at the time of R-Tx, bone parameters assessed with High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) were significantly better in patients. Six months after R-Tx, patients displayed significantly impaired trabecular parameters at radius compared to baseline; results were not different at the weight-bearing tibia, neither cortical parameters at both sides.

Six months after R-Tx, 6 (31%) patients displayed acidosis, 10 (53%) persistent hyperparathyroidism (always < 2 ULN) and 5 (26%) increased FGF23 levels; 11 (58%) received phosphate supplementation.

Conclusion

Data on bone health in teenagers receiving a first R-Tx seem reassuring, but radial trabecular bone microarchitecture impairment observed 6 months post-Tx may reflect subtle albeit present post-Tx CKD-MBD.

CKD-MBD

Transplantation

HR-pQCT

During childhood, common symptoms of mineral and bone disorders associated to chronic kidney disease (CKD-MBD) can include growth retardation, bone pain, fractures, skeletal deformities, osteopenia, osteonecrosis and vascular calcifications. Frequently persisting after renal transplantation (R-Tx), CKD-MBD is associated with significant morbidity [1–5]. Up to 40 percent of pediatric R-Tx recipients describe bone-related symptoms [1–2]. The rate of vertebral and peripheral fractures is high, with an incidence of all fractures 6-fold higher and vertebral fractures 160-fold higher in the pediatric R-Tx recipients compared with control populations [3]. Last, around one half of pediatric R-Tx patients display persistent short stature [4].

Risk factors include pre-existing renal CKD-MBD and osteodystrophy, immunosuppressive therapies including not only corticosteroids but also calcineurin inhibitors and mTor inhibitors, reduced graft function, acidosis, malnutrition, hypogonadism, reduced physical activity and disruption of the PTH-25OH vitamin D-FGF23 axis with persisting increased FGF23 and PTH levels for months after transplantation, further inducing hypophosphatemia and subsequent mineralization defects [6–8].

Even if it is rarely performed in routine, bone biopsy is the gold standard technic to assess lesions of bone turnover and mineralization: Sanchez et al describe in 47 pediatric R-Tx patients, 30% of persistent renal osteodystrophy, with adynamic bone disease in 10% and high turnover lesions in 23% [9]. Unfortunately, biochemical parameters are poor predictors of the underlying renal osteodystrophy [10]. The most widely used two-dimensional imaging technic to assess skeletal mineral content and structure, namely dual X-ray absorptiometry (DXA), does not correlate with fracture risk nor with the underlying bone disease, and is usually normal in pediatric transplant recipients after correction for growth retardation [11–12]; DXA is not recommended in daily practice for the follow-up of pediatric CKD-MBD [10]. Attempting to overcome these drawbacks, high-resolution peripheral quantitative computed tomography (HR-pQCT) is a tridimensional imaging technique that is more informative by providing both compartmental volumetric and microarchitectural bone evaluations [13]..This research tool has proved its interest in pediatric CKD-MBD [14–17], but has rarely been performed in pediatric R-Tx[18–21].

The aims of this prospective study are 1/ to determine the evolution of HR-pQCT parameters and biomarkers in teenagers receiving a first R-Tx, between baseline and 6 months after R-Tx, and 2/ to compare their bone parameters to matched healthy controls (HC).

Study design and population

Here we present only the sub-group of pediatric patients included between 10 and 18 years of age, undergoing a first R-Tx, from the single-center prospective TRANSOS study (NCT02729142). The overall aim of the TRANSOS study was to evaluate the evolution of bone biomarkers, DXA and HR-pQCT in teenagers and adults receiving a first renal transplantation or a combined pancreas/renal transplantation in the pediatric nephrology and the adult transplantation units of the Hospices Civils de Lyon, and the adult transplantation unit of the University Hospital of Saint Etienne.

These teenagers were included in our unit of Pediatric Nephrology from June 2016 to December 2019. Bone status was evaluated at the time of R-Tx and six months later by performing DXA and HR-pQCT; since transplantations mainly came from deceased donors, the baseline bone imaging evaluation could be performed until the end of the fourth week after R-Tx. Clinical and biochemical data were collected at the exact time of R-Tx (just before the surgical procedure), one-month after R-Tx and 6 months after R-Tx. Each patient was matched on age (+/- 1 year old),, gender and pubertal status (Tanner stage) to two healthy controls (HC) from the local VITADOS pediatric cohort (NCT 01832623) [22]. A local independent ethics committee (CPP Lyon Sud-Est II) and the French National Agency for Medicines and Health Products Safety (ANSM) approved the study, respectively in February and March 2016. A written informed consent from both parents/legal guardians were required.

Patients’ characteristics

The following clinical data were collected: height and body weight in standard deviation units according to French pediatric growth charts, blood pressure in percentile using Pediatric Blood Pressure Reference Charts directly calculated from the Baylor College of Medicine and Tanner status. We collected causes of kidney failure, dialysis and transplantation characteristics, presence or absence of any bone-related symptoms (history of fracture, bone deformations, and/or bone pains), immunosuppressive therapy, bicarbonate and phosphate supplementation and antihypertensive therapy. The LVM index was calculated as recommended by the American Society of Echocardiography using the modified Devereux formula [24]. An auto-questionnaire was used, to evaluate physical activity over a 7-day period including exercise and sports performed at school, at home or in a club but also activities from daily life such as house duties, transports, artistic activities [25]. For the most common activities, metabolic equivalents were determined using the reference standard, namely double-labeled water [25]. All different sports and activities have been associated to a given metabolic equivalent depending on the intensity of activity [26]. One metabolic equivalent (ME) corresponds to 1 kcal/kg per hour or 4.184 kJ/kg per hour. The total energetic expense (TEE) was therefore calculated as follow: TEE (MJ/day) = ME (h/j) x body weight (kg) x 4.184 / 1000[27]. The auto-questionnaire is available in supplementary material.

Biomarkers

Serum calcium, phosphate, magnesium, bicarbonate, IDMS-standardized creatinine, intact parathyroid hormone (3rd generation, chemiluminescence, Liaison XL DiaSorin, DiaSorin reagent, normal values 5.5– 38.4 pg/ml), 25-OH vitamin D (immunological-electrochemical luminescence technique, Elecsys Roche assay, Cobas, Switzerland, target range 75–120 nmol/L), 1–25 OH₂ vitamin D (1–25-D, chemiluminescence, Liaison XL DiaSorin, DiaSorin reagent, normal values 69–200 pmol/L) and total alkaline phosphatase (ALP) levels were measured on fasting blood sample in the morning by routine methods in the same laboratory. FGF23 (ELISA, C-terminal 2nd generation Immutopics), total osteocalcin (serum, CLIA, Liaison XL Dia Sorin, Dia Sorin reagent) and β-Crosslaps (serum, electro-chimi-luminescence ECLIA, Cobas 411 Roche diagnostics, Roche Diagnostic reagents) were assessed; local reference values have been previously published in teenagers depending on pubertal stage and gender [22].

Bone-imaging techniques

Two bone imaging techniques were used for bone evaluation, namely DXA and HR-PQCT. DXA Z-scores of the spine and total body were calculated in comparison to age, puberty and gender reference charts. Lean mass (kg) and fat mass (kg) were calculated from the whole body DXA scan excluding the skull. As previously described [16], bone geometry, density and trabecular bone structure were assessed at the non-dominant radius and tibia by performing HR-pQCT (XtremeCT, Scanco Medical AG, Brüttisellen, Switzerland) with the following settings: effective tension of 60 kVp, X-ray tube current of 900 µA and matrix size of 1536 × 1536. A stack of 110 parallel CT slices is acquired leading to a 3D representation of 9 mm in the axial direction (voxel size 82 µm³). The total scan time is 2.8 min with a low radiation exposure of approximately 3 µSv. This technic has excellent precision for both structural parameters (1.5–4.4%) and volumetric bone mineral density (0.7–1.5%) [13]. A trained operator generates semi-automatic contours around the periosteal surface and the entire volume of interest is automatically separated into a cortical and trabecular region. The outcome variables include volumetric bone mineral density (vBMD, mg HA/cm³) for total (Tt.BMD), trabecular (Tb.BMD), and cortical (Ct.BMD) compartments: cortical thickness (Ct.Th, mm), trabecular number (Tb.N, mm^− 1), thickness (Tb.Th, mm), separation (Tb.Sp, mm), cortical and total area (Ct.Ar (mm²)-Tt.Ar (mm²).

Statistical analyses

Results are presented as median (range). Non-parametric tests were performed (Mann-Whitney test, Wilcoxon test for paired groups and Kruskal-Wallis in case of multiple groups). To assess the correlations between biological, bone, and cardiovascular (CV) parameters, Spearman bivariate analyses were performed. Statistical significance was set at the two-sided 0.05 level for all analyses. Statistical analyses were performed using the SPSS software version 17.0 (SPSS, Inc., Chicago, Il, USA). Results are presented as median (Q1-Q3) for quantitative data and percentage (number) for qualitative data.

Patients

At a median age of 15(13-16) years, 19 pediatric R-Tx recipients (6 girls) were included, as well as 38-matched HC. Seven patients underwent preemptive transplantation and seven received steroid-sparing immunosuppression. No patient developed fractures or presented bone pain or skeletal deformities during follow-up but three had a past of high kinetic energy trauma fracture. Clinical data for patients are summarized in Table 1.

Height and weight SDS were not significantly different from baseline to 6 months after R-Tx. Systolic and diastolic BP significantly improved between baseline and 6 months after R-Tx, and the proportion of patients with normal (<90th percentile) systolic and diastolic blood pressure raised significantly from 37% at baseline to 74% 6 months after R-Tx (p=0.01). Sixteen patients (84 %) received antihypertensive therapy 6 months after R-Tx. On the 17 (89%) cardiac US available for analysis and performed 9 (4-13) months before R-Tx, only two patient (11%) displayed left ventricular hypertrophy. Left ventricular mass index was not correlated with systolic or diastolic blood pressure percentile (r: 0.3, p=NS; r: 0.3, p=NS). Anthropometric and cardiovascular data for patients and controls are summarized in Table 2.

TTE was significantly lower at baseline compared to matched HC (15857 MJ [12404-21533] vs 20325 MJ [16046-28165] p=0.02). However not statistically significant, TTE appeared to increase between baseline and 6 months post transplantation (15857 MJ [12404-21533] vs 21477 MJ [11287-25328], respectively, p=NS). TTE at baseline and 6 months post transplantation was correlated with PAS percentile (r=0.46, p=0.046 and r=0.52; p=0.026) but not with PAD percentile nor with LVM index.

Biomarkers

Median PTH levels at R-Tx was 74 (53-113) pg/ml, corresponding to 1.9 (1.4-2.9) the upper limit of normal (ULN). Serum phosphate levels, PTH, FGF 23, osteocalcin and β-Crosslaps levels significantly decreased between R-Tx and 6 months after R-Tx, and were significantly higher compared to HC. Bicarbonate values were significantly higher 6 months after R-Tx and in HC compared to patients at the time of R-Tx. In contrast, no significant differences were observed for calcium and ALP levels. Six months after R-Tx, six (31%) patients displayed acidosis, 10 (53%) persistent hyperparathyroidism (but always < 2 ULN) and five (26%) increased FGF23 levels. In terms of management, 11 patients (58%) received phosphate supplementation and 10 (53%) received alkali supplementation (i.e., sodium bicarbonate). Despite native vitamin D supplementation, only one patient had vitamin D levels within the target range at 6 months post R-Tx. Table 3 and Figure 1 summarize all the biological parameters for patients and HC.

Bone-imaging techniques

DXA

HC had significantly higher whole-body bone mineral content Z scores compared to patients at the time of R-Tx (0.1 [-0.5; 0.9] vs -0.4 [-1.5; 0.2] p=0.04). Patients at the time of R-Tx had significantly higher whole-body bone mineral content Z scores compared to 6 months after R-Tx (-0.4 [-1.5;0.2] vs -0.6 [-1.8; 0.1] p=0.002). Spine DXA Z-scores were not different at the time of R-Tx compared to 6 months after R-Tx and to HC (-0.8 [-1.2;+0.2] vs -0.8 [-1.3;0] vs -0.35 [-0.7;0.4], p= 0.05 and p= 0.12). Lean body mass (kg) was significantly lower at the time R-Tx compared to 6 months after R-Tx and to HC (37 [34-40] vs 40 [36-43] vs 44 [36-50], respectively, p<0.001 and p=0.09). TTE 6 months post transplantation was correlated with lean body mass (r=0.65, p=0.0036).

HR-PQCT

Total and trabecular densities at radius were significantly higher at the time of R-Tx compared both to HC and to 6 months after R-Tx. Similarly, trabecular micro-architecture was significantly better at the time of R-Tx compared to HC and to 6 months after R-Tx. No differences were observed on cortical parameters at radius (Table 4). In contrast, at the weight-bearing tibia, no significant differences were observed between HC and patients or between the time of R-Tx and 6 months after R-Tx (Table 5).

LVMI was not associated with any of the Hr-PQCT parameters.

No correlation was found between TTE at R-Tx and HR-pQCT parameters.

TTE 6 months after R-Tx was correlated with cortical parameters at radius (Ct.BMD (r: 0.5, p=0.041) and Ct.Th (r: 0.5, p=0.042)). No correlation was found between TTE 6 months after R-Tx and other Hr-PQCT parameters.

Exploratory sub-group analyses were performed: no differences were observed on Hr-PQCT parameters between patients with or without steroid-sparing immunosuppression, between patients with or without alkali supplementation at 6 months post transplantation, and between patients with persistent hyperparathyroidism or not. (Supplementary material -Table 1).

Using HR-PQCT, an accurate and non-invasive technique for bone evaluation, we find satisfactory results on bone quantity and quality in 19 adolescent R-Tx recipients at the time of R-Tx and 6 months after R-Tx compared to matched HC. We also describe the evolution of mineral and bone biomarkers after R-Tx.

Major changes in serum mineral metabolism occur immediately after R-Tx [20]. PTH levels usually decrease but persistent secondary hyperparathyroidism is described in 10 to 60% of patients 12 months after R-Tx [29–30], hyperparathyroidism being an independent risk factor for allograft dysfunction in pediatric R-Tx [31]. In our series, 6 months after R-Tx, 53% patients still display elevated PTH levels (but always < 2 ULN). Hyperparathyroidism and persistent elevated circulating FGF-23 levels can promote renal phosphate wasting and low calcitriol levels [32]. Indeed, up to 10% of patients may present with hypophosphatemia 12 months after R-Tx, correlated with FGF23 levels [30]. Nearly 60% of our patients require phosphate supplementation 6 months after R-Tx, and a quarter of patients present with elevated FGF23 levels. The interest of phosphate supplementation in this setting remains debated, but one should not forget that hypophosphatemia is a main driver of mineralization defects; alternatively, giving too much phosphate on a renal transplant with normal or near-normal renal function may also induce secondary hyperparathyroidism, thus justifying a close and regular control of CKD-MBD parameters after pediatric R-Tx. Of note, even though the interest of cinacalcet after pediatric R-Tx has been discussed [33], none of the patients here received cinacalcet during the study period.

Shroff and al describe 25-OH vitamin D deficiency in half of pediatric R-Tx recipients [34]. Only one of our patients has vitamin D within the target range 6 months after R-Tx, despite native vitamin D supplementation. Given the fact that vitamin D is also a natural inhibitor of the mTor pathway [35], and that native vitamin D supplementation is able to prevent the onset of hyperparathyroidism in pediatric CKD [36], these data highlight the need of a close follow-up of 25D levels and an adequate correction of vitamin D deficiency if necessary [37]. They also highlight that CKD-MBD is closely controlled in dialysis, but maybe less after Tx, because of concomitant other comorbidities and specific post-Tx follow-up. Metabolic acidosis is found in 30% of patients whereas it is associated with altered growth hormone axis, protein degradation and glucocorticoid production [38]. Although these various parameters are poorly correlated with bone histomorphometry, they should be regularly monitored after transplantation in accordance with KDIGO guidelines, with particular interest in the evolution of trends [39–40]. Although, not recommended in daily practice for the follow-up of pediatric CKD-MBD [10], our DXA follow up revealed a significant increase in lean body mass, likely reflecting renutrition.

Few pediatric studies describe HR-pQCT post R-Tx [18–21]. In a cross-sectional study including 55 adolescent R-Tx recipients in 2000, Rüth et al identify a decrease in cortical thickness, at an average of 4.9 years after transplantation [21]. More recently, a study including 14 adolescent R-Tx recipients reveals significantly lower trabecular BMD Z-score 12 months after R-Tx in association with greater glucocorticoid exposure [19]. This study also describes cortical bone loss at transplantation associated with hyperparathyroidism severity and a significant increase of cortical BMD Z-score 12 months after R-Tx, correlated with low glucocorticoid exposure and lower PTH levels. However, this study is characterized by high median PTH level (3.6 ULN) at baseline and a high fracture rate in the first 6 months post R-Tx (10% within 6 months post R-Tx). This study is, therefore, not comparable with our series since our patients are better controlled in terms of median PTH levels at the time of Tx, i.e., 1.9 ULN; moreover, we did not observe any fracture during the 6-month follow up.

Counter-intuitively, we describe higher total and trabecular densities and better trabecular bone at the time of R-Tx compared with HC. These findings are probably due to a rigorous control of mineral biomarkers pre-transplantation, notably for PTH and phosphate levels. Using the same HR-pQCT technique in the 32 teenagers from Lyon included in the 4C study (median GFR of 33 mL/min per 1.73m²), we already provided reassuring data concerning bone health in these children with moderate CKD with tightly controlled mineral biomarkers [14]. However, this study also suggested an inverse bone-vascular cross talk in pre-dialysis: “the better the bone, the worse the vessel”. Higher serum calcium levels as well as higher trabecular bone thickness were indeed associated with higher diastolic and mean blood pressure[14]. This raises the question of whether trying to optimize calcium balance on the growing skeleton can lead to vascular calcifications. A recent longitudinal follow-up study in a cohort of children and young adults with stage 4–5 CKD on dialysis also shows a bone-vessel interaction [41]. Patients with increased trabecular vBMD have worse carotid intimal thickness Z-score. However, due to the buffering capacity of the growing skeleton, which requires calcium accumulation to reach peak bone mass, patients from this cohort showing persistent linear grow display an attenuated pejoration of these vascular measures. Our cohort provides reassuring data concerning cardiovascular outcomes with only two patients displaying left ventricular hypertrophy on the baseline echocardiography. No correlation was found between left ventricular mass index and HR-pQCT parameters and the proportion of patients with normal systolic and diastolic blood pressure 6 months after R-Tx significantly improved from 37–74%. However, neither ambulatory blood pressure monitoring nor any other cardiovascular imaging test were performed. Future studies should focus on the crucial issue of assessing and optimizing skeletal mineralization while avoiding vascular calcification development.

Puberty is a crucial period for the acquisition of optimal bone mass, which has an impact on the risk of osteoporosis later in life [42–43]. In the general adolescent population, physical activity and its associated osteogenic effects have been shown to modify bone strength and quality during this particular period in various studies using DXA and HR-pQCT [44–46]. However, compared with the general population, physical activity levels are lower in pediatric kidney recipients and do not always improve after transplantation [47–48]. We show here that TEE tended to improve 6 months post-transplant and that TEE 6 months post R-Tx correlated with lean body mass and cortical bone parameters. This provides a rationale to promote early physical activity after transplantation, likely having beneficial effects on bone to prevent fractures on the long-term.

We observe a slight degradation of trabecular microarchitecture 6 months after R-Tx at the radius. Such impairment may be partly explained by a less rigorous control of mineral metabolism but also by the combination of bone risk factors that is maximal in the early post-Tx period, such as the use of corticosteroids and calcineurin inhibitors, and the presence (even if supplemented) of hypophophosphatemia and acidosis. Limitations of our study are our small sample size and the assessment of physical activity using a self-administered questionnaire, easier than double-labeled water technic or podometers.

Our cohort provides reassuring data regarding bone health in teenagers receiving a first R-Tx, but radial trabecular bone microarchitecture impairment observed 6 months post transplantation may reflect subtle albeit present post-Tx CKD-MBD.

Funding

The TRANSOS study received a grant from the French Health Ministry (PHRC-I 2013), from the Agence de la Biomédecine and from Novartis.

Conflicts of interest

None to disclose in association with this manuscript.

Availability of data and material

The datasets generated during and/or analyzed during the current study are not publicly available due to confidential data, but are available from the corresponding author on reasonable request.

Ackowldgements

The authors would like to thank Dr Duy-Anh Nguyen, MD, for his help in the standardized analysis of cardiac ultrasounds. The authors would like to thank Nadège Trehet Mandel, Catherine Planckaert and the PMO research Center for their help to conduct HRpQCT assessment.

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Table 1: Patients’ characteristics

N	19
Age (years)	15 (13-16)
Girls (%)	6 (32)
Underlying renal diagnosis
Hereditary nephropathies (%)	8 (42)
CAKUT (%)	6 (32)
Glomerulopathy (%)	2 (10)
Undetermined nephropathy (%)	2 (10)
Polycystic disease (%)	1 (5)

Pre-emptive transplantation (%)	7 (37)
Living Donor (%)	4 (21)

Dialysis
Hemodialysis (%)	1 (5)
Peritoneal dialysis (%)	11 (58)
Duration of dialysis, months	6.1 (3.1, 12)

CKD-MBD manifestations
Fracture history (%)	3 (16)
Post R-Tx follow up
Bone pain	0
Skeletal deformities	0
Fracture	0

Immunosuppressive drug scheme at transplantation
Basiliximab (%)	19 (100)
Tacrolimus (%)	18 (95)
Mycophenolate Mofetil (%)	19 (1)
Eculizumab (%)	1 (5)
Immunosuppressive drug scheme at 6 months
Tacrolimus (%)	19 (1)
Mycophenolate mofetil (%)	16 (84)
Azathioprine (%)	2 (10)
Everolimus (%)	1 (5)
Eculizumab (%)	1 (5)
No corticosteroids (%)	7 (37)

CAKUT: Congenital anomalies kidney and urinary tract, R-Tx: Renal Transplantation

Table 2: Biometry and blood pressure characteristics

	At R-Tx		6 months after R-Tx		*Healthy controls*
Height SDS	-0.6*	(-1.2;-0.14)	-0.7	(-1.3;0)	0.25	(-0.5;1.2)
Weight SDS	-1*	(-2;0.1)	-0,5	(-1.7;0.6)	0.65	(-0.4;1.4)
BMI	18	(17; 20)	19.3	(18.1; 21.5)	19	(17;20)
Systolic BP percentile	85*#	(61-98)	65	(50-74)	45	(24-66)
Diastolic BP percentile	97*#	(50-98)	70	(41-82)	45	(22-66)

SDS: standard deviation score; BMI: Body Mass Index (kg/m²); BP: Blood pressure

* p<0.05 when comparing HC and patients at baseline

# p<0.05 when comparing patients at baseline and 6 months post RTx

Table 3: Biological parameters

	At R-Tx		1 month post R-Tx		6 months post R-Tx		*Healthy controls*
Creatinine (µmol/l)			96	(79-108)	83	(69-99)	61	(53-72)
Bicarbonate (mmol/l)	22 *	(19-23)	21	(20-23)	22	(20-23)	27	(25-28.2)
Calcium (mmol/l)	2.41	(2.29-2.53)	2.45	(2.4-2.55)	2.45	(2.41-2.53)	2.41	(2.36-2.53)
Phosphate (mmol/l)	1.56 *#	(1.34-1.83)	1.09	(0.97-1.35)	1.25	(1.11-1.42)	1.31	(1.11-1.45)
Phosphate SDS	0.5 *#	(-0.35 ;1.86)	-1.8	(-2.43 ; -0.62)	-1.3	(-1.65 ;0.15)	-0.95	(-1.47 ;-0.31)
ALP (UI/l)	156	(101-268)	136	(110-185)	168	(107-202)	150	(90-210)
PTH (pg/ml)	74 *#	(53-113)	29	(21-40)	39	(27-41)	17	(14-23)
PTH-ULN	1.9	(1.4-2.9)	0.7	(0.5-1)	1	(0.7-1.1)	0.4	(0.4-0.6)
25-OH vitamin D (nmol/L)	68 ¤*	(58-78)	65	(55-77)	47	(38-57)	63	(50-86)
1,25 OH vitamin D (pmol/l)	64 *#	(23-91)	65	(22-132)	134	(98-164)	126	(92-152)
FGF23 (RU/ml)	1002 *#	(347-1642)	108	(85-174)	118	(76-165)	50	(40-62)
β-Crosslaps (pg/ml)	3366 *#	(2715-4339)	2223	(1636-2960)	2769	(1790-3276)	1421	(971-1734)
Osteocalcin (μg/L)	355 *#	(290-390)	66	(43-124)	93	(65-137)	59	(38-81)

Results expressed as median (Q1-Q3) ALP: Alkaline phosphatase; FGF23: Fibroblast growth factor 23; PTH Parathyroid hormone; R-Tx: renal transplantation

* p<0.05 when comparing HC and patients at baseline. # p<0.05 when comparing patients at baseline, 1 month post RTx and 6 months post RTx

¤ p<0.05 when comparing patients at baseline and 6 months post RTx

Table 4. Radial HR-pQCT

	At R-Tx		6 months post R-Tx		*Healthy controls*
Density
Tb.vBMD (mg/cm³)	*238^#**	(210-265)	217	(190-246)	*182*	(164-213)
Tt.vBMD (mg/cm³)	*322^#**	(300-354)	306	(284-331)	*285*	(250-315)
Ct.vBMD (mg/cm³)	721	(639-790)	717	(641-768)	712	(618-780)
Trabecular structure
Tb.N (mm⁻¹)	2.1^*	(1.93-2.21)	2.04	(1.94-2.14)	*2.0*	(1.80-2.12)
Tb.Th (mm)	*0.09^#**	(0.09-0.10)	0.09	(0.08-0.09)	*0.08*	(0.07-0.09)
Tb.Sp (mm)	*0.38^#**	(0.35-0.43)	0.40	(0.37-0.44)	*0.44*	(0.39-0.47)
Geometry
Ct.Ar (mm²)	33	(18-46)	30	(22-44)	31	(19-51)
Tt.Ar (mm²)	183	(160-219)	184	(163-219)	216	(172-248)
Ct.Th (mm)	0.55	(0.33-0.69)	0.53	(0.37-0.68)	0.54	(0.32-0.78)

Results expressed as median (Q1-Q3)

* p<0.05 when comparing HC and patients at baseline

# p<0.05 when comparing patients at baseline and 6 months post RTx

vBMD: volumetric bone mineral density for total (Tt.vBMD), trabecular (Tb.vBMD), and cortical (Ct.vBMD) compartment; Tb.N: trabecular number; Tb.Th: thickness; Tb.Sp: separation; Ct.Ar : cortical area ; Tt.Ar : trabecular area ; Ct.Th : cortical thickness ; R-Tx: Renal transplantation

Table 5: Tibial HR-pQCT

	At R-Tx		6 months post R-Tx		*Healthy controls*
Density
Tb.vBMD (mg/cm³)	203	(188-224)	204	(173-219)	190	(180-207)
Tt.vBMD (mg/cm³)	288	(264-320)	287	(264-321)	271	(252-335)
Ct.vBMD (mg/cm³)	797	(729-876)	791	(738-876)	781	(715-869)
Trabecular structure
Tb.N (mm⁻¹)	1.72	(1.54-2.01)	1.73	(1.54-1.93)	1.81	(1.68-1.94)
Tb.Th (mm)	0.1	(0.09-0.11)	0.1	(0.09-0.11)	0.09	(0.08-0.09)
Tb.Sp (mm)	0.47	(0.42-0.54)	0.47	(0.43-0.55)	0.46	(0.43-0.51)
Geometry
Ct.Ar (mm²)	83	(51-93)	81	(63-98)	104	(73-123)
Tt.Ar (mm²)	510	(396-613)	512	(380-617)	581	(473-653)
Ct.Th (mm)	0.84	(0.56-1.02)	0.85	(0.69-1.03)	1.02	(0.77-1.20)

Results expressed as median (Q1-Q3)

vBMD: volumetric bone mineral density for total (Tt.vBMD), trabecular (Tb.vBMD), and cortical (Ct.vBMD)compartment; Tb.N: trabecular number; Tb.Th: thickness; Tb.Sp: separation; Ct.Ar : cortical area ; Tt.Ar : trabecular area ; Ct.Th : cortical thickness ; R-Tx: Renal transplantation

* p<0.05 when comparing HC and patients at baseline

# p<0.05 when comparing patients at baseline and 6 months post RTx

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Changes in High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) in teenagers undergoing a first renal transplantation between baseline and 6 months

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Patients’ characteristics

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