Denosumab-Induced Hypocalcemia and Hyperparathyroidism in de novo Kidney Transplant Recipients

2021 ◽  
pp. 1-9
Author(s):  
Giuseppe Cianciolo ◽  
Francesco Tondolo ◽  
Simona Barbuto ◽  
Francesca Iacovella ◽  
Guido Zavatta ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Bone Disease ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mineral Density

<b><i>Introduction:</i></b> Denosumab represents a realistic treatment option to increase bone mineral density in kidney transplant recipients (KTRs). It is still unknown how and at what extent posttransplantation bone disease and graft function influence the effects of denosumab on mineral metabolism indexes. In this study, we analyze risk factors of hypocalcemia and parathyroid hormone (PTH) increase after denosumab administration in eighteen de novo KTRs and its management before and after this treatment. <b><i>Methods:</i></b> We conducted a monocentric, observational, prospective study on de novo KTRs. All KTRs enrolled received a single 60 mg subcutaneous dose of denosumab every 6 months. Before kidney transplantation, no patients were treated with calcio-mimetic. After kidney transplantation and before antiresorptive therapy, no patients were treated with calcio-mimetic drugs and/or vitamin D receptor agonists, while all patients received nutritional vitamin D supplementation (from 1,000 IU to 1,500 IU daily). <b><i>Results:</i></b> Hypocalcemia was related to the degree of lumbar osteoporosis (<i>p</i> = 0.047); the increase in the PTH level was correlated to baseline bone turnover markers (bone alkaline phosphatase, serum osteocalcin, and β-C-terminal telopeptide), the 25 OH status, and eGFR. The introduction of calcitriol, after the PTH increase, in addition to cholecalciferol was necessary to ensure an adequate control of serum calcium and PTH during a follow-up of 15 months. Following the treatment with denosumab, it was observed an improvement of areal bone mineral density both at lumbar and femoral sites with a mean percentual increase of 1.74% and 0.25%, respectively. <b><i>Conclusions:</i></b> Denosumab is an effective treatment for bone disease in KTRs. In our study, the increase in PTH is not a transient event but prolonged throughout the follow-up period and requires continuous supplementation therapy with calcitriol.

scholarly journals Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients

2019 ◽  
Vol 95 (6) ◽  
pp. 1461-1470 ◽  
Author(s):  
Pieter Evenepoel ◽  
Kathleen Claes ◽  
Bjorn Meijers ◽  
Michaël R. Laurent ◽  
Bert Bammens ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Kidney Transplant ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mineral Density ◽  
Turnover Markers

FC 124PATTERNS OF RENAL OSTEODYSTROPHY ONE YEAR AFTER KIDNEY TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Kidney Transplantation ◽  
Bone Turnover ◽  
Kidney Transplant ◽  
Renal Osteodystrophy ◽  
Bone Disease ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Steroid Dose ◽  
Bone Biopsies

Abstract Background and Aims Bone disease after kidney transplantation is an issue of growing concern, as prolonged graft survival and older age of recipients necessitate focus on long-term health burdens such as osteoporosis and fractures. Pre-existing type of renal osteodystrophy, post-transplant immunosuppressive treatment, and de novo disturbances of mineral metabolism all contribute to bone disease in kidney transplant recipients. The current pattern of renal osteodystrophy after kidney transplantation is not well characterized. This study reports histomorphometric findings of protocolled bone biopsies in a large cohort of kidney transplant recipients 1 year post-transplant. Method Histomorphometric analysis of transiliac bone biopsies with prior tetracycline labelling was performed in 141 kidney transplant recipients. Biochemical measurements included bioactive parathyroid hormone (PTH), total calcium, phosphate, calcidiol, bicarbonate, and sclerostin. Kruskal-Wallis and Wilcoxon signed rank tests were used to evaluate differences across categories and between groups, respectively. Stepwise multivariate linear regression was performed to identify key demographic and biochemical determinants of bone turnover (bone formation rate, BFR), mineralization (mineralization lag time, Mlt), and volume (Bone area, BAr). Results Mean age was 57±11 years, 71% were men, and all were Caucasian. Mean eGFR was 49±16 (range 19 to 106) ml/min/1.73 m². Hyperparathyroidism (PTH &gt; 1.5xUNL) was seen in 48%, hypercalcemia (&gt;10.3 mg/dL) in 18%, hypophosphatemia (&lt;2.3 mg/dl) in 12%, and vitamin D deficiency (&lt;15 ng/mL) in 4% of patients. Categorization of bone turnover, mineralization, and volume is shown in Figure 1. Bone turnover was normal in the vast majority (71%). Patients with low turnover (26%) had received a higher cumulative steroid dose (2.78 vs 2.34g in low vs non-low turnover; p=0.02). Patients with delayed mineralization (16%) were younger (52 vs 58 yrs, p=0.02) and had received a higher cumulative steroid dose (2.85 vs 2.36g, p=0.003). They had higher levels of PTH (124 vs 53 ng/L, p&lt;0.001), and lower levels of phosphate (2.68 vs 3.18 mg/dL, p&lt;0.001), calcidiol (29 vs 37ug/L, p=0.02), bicarbonate (21.3 vs 23.3 mmol/L, p=0.004), and sclerostin (493 vs 594 pg/mL, p=0.03) compared to patients with normal mineralization. Patients with low bone volume tended to be older (61 vs 56 years, p=0.07). Independent determinants of BFR were PTH (β=0.68, p&lt;0.001) and cumulative steroid dose (β = -0.22, p=0.02). Determinants of Mlt were phosphate (β=-0.48, p=0.001) and cumulative steroid dose (β=0.18, p=0.004), and determinants of BAr were age (β=-0.15, p=0.002), and BMI (β=0.33, p=0.002). Conclusion Bone turnover is normal in the majority of kidney transplant recipients at 1 year post-transplant, despite a high prevalence of hyperparathyroidism. Low levels of bicarbonate, phosphate, and calcidiol may contribute to delayed bone mineralization in kidney transplant recipients.

scholarly journals Effect of denosumab on trabecular bone score in de novo kidney transplant recipients

2019 ◽  
Vol 34 (10) ◽  
pp. 1773-1780 ◽  
Author(s):  
Marco Bonani ◽  
Diana Frey ◽  
Nicole Graf ◽  
Rudolf P Wüthrich
Keyword(s):  
Lumbar Spine ◽  
Trabecular Bone ◽  
Kidney Transplant ◽  
De Novo ◽  
Trabecular Bone Score ◽  
Distal Tibia ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mineral Density ◽  
Total Hip

Abstract Background Kidney transplant recipients (KTR) are at risk to lose bone mass. The trabecular bone score (TBS) represents a recently developed parameter of lumbar spine trabecular bone texture that correlates with the occurrence of fractures. Methods We analysed the 1-year changes in TBS in 44 de novo KTR that were randomized 1:1 to denosumab or no treatment. TBS was derived from dual energy X-ray absorptiometry and was correlated with 1-year areal bone mineral density (aBMD) changes at the lumbar spine and total hip. Correlations were also performed with parameters of peripheral bone microarchitecture and bone strength at the distal tibia and distal radius, as assessed by high-resolution peripheral quantitative computed tomography (HRpQCT) and micro-finite element analysis. Results The baseline TBS in KTR amounted to 1.312 ± 0.101, which is lower than the TBS of an age-matched normal control population (range 1.364–1.471). The TBS correlated positively with aBMD at the lumbar spine (Spearman’s ρ = 0.56; P < 0.001) and total hip (ρ = 0.33; P < 0.05). The baseline TBS also correlated with HRpQCT-derived total (ρ = 0.49; P < 0.05) and trabecular volumetric BMD (ρ = 0.57; P < 0.01) and trabecular separation (ρ = −0.46; P < 0.05) at the tibia. Denosumab treatment led to an increase in TBS, paralleling the BMD changes at the lumbar spine. Conclusions The TBS is a useful additional score of bone health, which may help to better define fracture risk. Treatment with denosumab led to improved trabecular bone texture in de novo KTR in addition to its beneficial effect on BMD.

scholarly journals P1761SIDE EFFECTS OF MTOR INHIBITORS DEPEND ON THE BASELINE METABOLIC STATUS OF KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
David Cucchiari ◽  
Alicia Molina-Andujar ◽  
Enrique Montagud-Marrahi ◽  
Jordi Rovira ◽  
Fritz Diekmann
Keyword(s):  
Kidney Transplantation ◽  
Side Effects ◽  
Kidney Transplant ◽  
De Novo ◽  
Mtor Inhibitors ◽  
Metabolic Status ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background and Aims Biologically, the cellular activity of the mTOR complexes depends on the balance between the catabolic and the anabolic inputs. Hence, we hypothesized that the metabolic side effects of mTOR inhibitors (mTORi) in kidney transplantation depend on the baseline metabolic status of the patient. Method The analysis included all the patients that have been transplanted in our Center between June 2013 to December 2016, completed one year of follow-up and did not change medication during the first year after kidney transplantation (per-protocol population, n=298). Outcomes chosen include de novo diabetes, 1-year difference from baseline in glycated hemoglobin (HbA1c), triglycerides and total cholesterol. Kidney transplant recipients were treated either with an mTORi (either Sirolimus or Everolimus, n=134) or Mycophenolic Acid (MPA, n=164). Both drugs were always accompanied by tacrolimus and steroids. Patients were stratified according to the treatment received (mTORi versus MPA) and the baseline metabolic status (diabetes mellitus type 2 and obesity). Differences among groups were analyzed with exact Fisher test and ANOVA test with LSD post-hoc analysis. Results We observed a strong difference for 1-year change in HbA1c depending on the baseline metabolic status of the patients (P&lt;0.001 between groups, Figure 1a). The worst results were observed for patients with baseline diabetes. Among these, obese patients treated with mTORi had the higher increase in HbA1c (3.04 ± 1.18% from baseline, P&lt;0.01 with all groups at post-hoc analysis). De-novo diabetes was more frequent in patients taking mTORi (23.4 vs. 13.1%), albeit not significantly (P=0.100) and without differences taking into account obesity as a covariate. Triglycerides increased substantially in patients without baseline diabetes and treated with mTORi (P&lt;0.05). Surprisingly, in diabetic patients no differences were observed in triglycerides between mTORi and MPA groups (Figure 1b). There were no differences in the increase in total cholesterol among groups (P=0.155) (Figure 1c). Conclusion We observed that the 1-year increase in HbA1c and triglycerides attributable to mTORi after kidney transplantation depends on the baseline metabolic status of the patients. We propose that the metabolic side effects of mTORi depend on the balance between anabolic and catabolic inputs of every kidney transplant recipient.

scholarly journals Long‐term, prolonged‐release tacrolimus‐based immunosuppression in de novo kidney transplant recipients: 5‐year prospective follow‐up of the ADHERE study patients

2019 ◽  
Vol 33 (2) ◽  
pp. 161-173
Author(s):  
Oleg Rummo ◽  
Mario Carmellini ◽  
Nassim Kamar ◽  
Antoine Durrbach ◽  
Christiane Mousson ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Prolonged Release ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Effects of denosumab on hypercalcemia and bone mineral density loss in kidney transplant recipients

2019 ◽  
Vol 92 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Koji Nanmoku ◽  
Takahiro Shinzato ◽  
Taro Kubo ◽  
Toshihiro Shimizu ◽  
Takashi Yagisawa
Keyword(s):  
Bone Mineral Density ◽  
Kidney Transplant ◽  
Bone Mineral ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mineral Density ◽  
Bone Mineral Density Loss

scholarly journals Incidence and Impacts of Inflammatory Bowel Diseases among Kidney Transplant Recipients: A Meta-Analysis

2020 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Panupong Hansrivijit ◽  
Max M. Puthenpura ◽  
Charat Thongprayoon ◽  
Himmat S. Brar ◽  
Tarun Bathini ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Meta Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Adult Kidney ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background: The incidence of inflammatory bowel diseases (IBD) and its significance in kidney transplant recipients is not well established. We conducted this systematic review and meta-analysis to assess the incidence of and complications from IBD in adult kidney transplant recipients. Methods: Eligible articles were searched through Ovid MEDLINE, EMBASE, and the Cochrane Library from inception through April 2020. The inclusion criteria were adult kidney transplant patients with reported IBD. Effect estimates from the individual studies were extracted and combined using the fixed-effects model when I2 ≤ 50% and random-effects model when I2 > 50%. Results: of 641 citations, a total of seven studies (n = 212) were included in the systematic review. The mean age was 46.2 +/− 6.9 years and up to 51.1% were male. The mean duration of follow-up was 57.8 +/− 16.8 months. The pooled incidence of recurrent IBD was 27.6% (95% CI, 17.7–40.5%; I2 0%) while the pooled incidence of de novo IBD was 18.8% (95% CI, 10.7–31.0%; I2 61.3%). The pooled incidence of post-transplant IBD was similar across subgroup analyses. Meta-regression analyses showed no association between the incidence of IBD and age, male sex, and follow-up duration. For post-transplant complications, the pooled incidence of post-transplant infection was 4.7% (95% CI, 0.5–33.3%; I2 73.7%). The pooled incidence of graft rejection and re-transplantation in IBD patients was 31.4% (95% CI, 14.1–56.1%; I2 76.9%) and 30.4% (95% CI, 22.6–39.5%; I2 0%). Conclusion: Recurrent and de novo IBD is common among kidney transplant recipients and may result in adverse outcomes.

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