Multimodality approach to treat calciphylaxis in end-stage kidney disease patients.

A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l'Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients (n = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes (n = 11), calcium-based phosphate binders use (n = 10), warfarin use (n = 9), obesity (n = 7), female gender (n = 8) and intravenous iron use (n = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51-143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables.

Comparison of Intranasal and Injectable Glucagon Administration Among Pediatric Population Responders.

Aims: Ease of use and acceptability of nasal versus injectable glucagon (IG) among pediatric responders have been little investigated. This study compared the performance of administering nasal and IG in parents of youth with type 1 diabetes (T1D) and in school workers. Enablers and barriers associated with each glucagon and preferred glucagon administration learning modality were also evaluated. Methods: Three months after watching short pedagogical videos, 30 parents and 30 school workers performed simulated scenarios where they administered both glucagon. Completion time and successful execution of critical steps were collected. Interviews assessed preferred learning modalities, barriers, and enablers associated with each glucagon. Results: Both groups administered nasal glucagon faster than IG (median [interquartile range]: parents 19 [12-29] vs. 97 [71-117] s, P < 0.001; school workers 24 [16-33] vs. 129 [105-165] s, P < 0.001). A lower proportion of participants successfully executed all critical steps for injectable versus nasal glucagon (significant difference for school workers [53% vs. 90%; P = 0.007] but not for parents [68% vs. 83%; P = 0.227]). Nasal glucagon was preferred for ease of use and acceptability. Preferred learning modalities were a combination of videos and workshops, but videos alone could suffice for nasal glucagon. Conclusions: Nasal glucagon is faster to use, more likely to be successfully administered, and more acceptable than IG for parents of children with T1D and school workers. Nasal glucagon training with videos could improve school workers' involvement in severe hypoglycemia management. Clinical Trial number, URL to the registration: NCT05395000, https://clinicaltrials.gov/ct2/show/NCT05395000.

Wnt/ß-catenin pathway inhibitors, bone metabolism and vascular health in kidney transplant patients.

BACKGROUND AND OBJECTIVES: Sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23) and α-klotho have been shown to play an important role in bone and vascular disease of chronic kidney disease. We aimed to evaluate the evolution of these bone markers in newly kidney transplanted patients, and whether they are associated with bone metabolism and vascular stiffness. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is a longitudinal single-center observational cohort study. Circulating levels of Wnt/ß-catenin pathway inhibitors (sclerostin, DKK1, FGF23 and α-klotho), arterial stiffness (carotid-femoral pulse-wave velocity (PWV), carotid-radial PWV, PWV ratio, augmented index) and bone parameters were assessed before (M0), and at 3 (M3) and 6 months (M6) after transplantation. Generalized estimating equations were conducted for comparative analyses between the three time points. We used a marginal structural model for repeated measures for the impact of changes in bone markers on the evolution of arterial stiffness. Multivariate linear regression analyses were performed for the associations between Wnt/ß-catenin pathway inhibitors and mineral metabolism parameters. RESULTS: We included 79 patients (70% male; median age of 53 (44-60) years old). The levels of sclerostin (2.06 ± 1.18 ng/mL at M0 to 0.88 ± 0.29 ng/mL at M6, p ≤ 0.001), DKK1 (364.0 ± 266.7 pg/mL at M0 to 246.7 ± 149.1 pg/mL at M6, p ≤ 0.001), FGF23 (5595 ± 9603 RU/mL at M0 to 137 ± 215 RU/mL at M6, p ≤ 0.001) and α-klotho (457.6 ± 148.6 pg/mL at M0 to 109.8 ± 120.7 pg/mL at M6, p < 0.05) decreased significantly after kidney transplant. Sclerostin and FGF23 were positively associated with carotid-femoral (standardized ß = 0.432, p = 0.037 and standardized ß = 0.592, p = 0.005) and carotid-radial PWV (standardized ß = 0.259, p = 0.029 and standardized ß = 0.242, p = 0.006) throughout the 6 months of follow-up. The nature of the associations between bone markers and bone metabolism parameters varies after kidney transplant. CONCLUSIONS: The circulating levels of Wnt/ß-catenin pathway inhibitors and α-klotho significantly decrease after kidney transplantation, while sclerostin and FGF23 levels might be associated with improvement of vascular stiffness and blood pressure.

Thiazide Diuretics and Fracture Risk: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Thiazide diuretics are commonly used antihypertensive agents. Until today, whether their use reduces fracture risk remains unclear. Our objective was to conduct a systematic review of thiazide diuretics' effects on fractures and bone mineral density (BMD) in randomized clinical trials (RCT) of adults. MEDLINE, EMBASE, CENTRAL, and the WHO's ICTRP registry were searched from inception to July 31, 2019. Two reviewers assessed studies for eligibility criteria: (i) RCTs; (ii) including adults; (iii) comparing thiazides, alone or in combination; (iv) to placebo or another medication; and (v) reporting fractures or BMD. Conference abstracts and studies comparing thiazides to antiresorptive or anabolic bone therapy were excluded. Bias was assessed using Cochrane Collaboration's Risk of Bias Tool-2. The primary outcome was fracture at any anatomical site. Secondary outcomes were osteoporotic fractures, hip fractures, and BMD at femoral neck, lumbar spine, and/or total hip. Fractures were pooled as risk ratios (RRs) using random-effect models. Prespecified subgroup analyses and post hoc sensitivity analyses were conducted. From 15,712 unique records screened, 32 trials (68,273 patients) met eligibility criteria. Thiazides were associated with decreased fractures at any site (RR = 0.87, 95% confidence interval [CI] 0.77-0.98; I 2  = 0%) and osteoporotic fractures (RR = 0.80; 95% CI 0.69-0.94; I 2  = 0%). Results were consistent in most subgroups and sensitivity analyses. Few studies reported hip fractures, and no association was found between thiazides and this outcome (RR = 0.84; 95% CI 0.67-1.04; I 2  = 0%). Only four studies reported BMD; a meta-analysis was not conducted because BMD reporting was inconsistent. Trials were deemed at low (3 studies, weight = 3%), some concerns (16 studies; 71%), or high (11 studies; 26%) risk of bias for the primary outcome. In conclusion, thiazide diuretics decreases the risk of fractures at any and at osteoporotic sites in a meta-analysis of RCTs. Additional studies are warranted in patients with high fracture risk. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone Marrow Adiposity, Bone Mineral Density and Wnt/ß-catenin Pathway Inhibitors Levels in Hemodialysis Patients.

BACKGROUND: Marrow adipose tissue (MAT) is known to accumulate in patients with chronic kidney disease. This pilot study aimed to evaluate bone mineral density (BMD), MAT, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) using computed tomography (CT) scans and to explore correlations between bone parameters, circulating Wnt/ß-catenin pathway inhibitor levels, and adipose tissue parameters. METHODS: Single-center cross-sectional pilot study conducted in hemodialysis patients at the Centre Universitaire de Québec, Hôtel-Dieu de Québec hospital, Canada. CT-scan slices were acquired at the levels of the hip, L3 vertebra, and tibia. Volumetric and areal BMD, tibia cortical thickness, VAT and SAT area, and fat marrow index (FMI) were analyzed using the Mindways QCT Pro software. Blood levels of sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor 23, and α-Klotho were assessed. Spearman's rho test was used to evaluate correlations. RESULTS: Fifteen hemodialysis patients (median age, 75 [66-82] years; 80% male; dialysis vintage, 39.3 [27.4-71.0] months) were included. While inverse correlations were obtained between L3 FMI and BMD, positive correlations were found between proximal tibial FMI and vertebral and tibial BMD, as well as with tibial (proximal and distal) cortical thickness. VAT had a positive correlation with α-Klotho levels, whereas L3 FMI had a negative correlation with DKK1 levels. CONCLUSIONS: CT-scan allows simultaneous evaluation of bone and marrow adiposity in dialysis patients. Correlations between MAT and BMD vary depending on the bone site evaluated. DKK1 and α-Klotho levels correlate with adipose tissue accumulation in dialysis patients.

Type of subtotal parathyroidectomy and evolution of parathyroid hormone levels in end-stage renal disease patients: a retrospective cohort study.

PURPOSE: Parathyroidectomy (PTX) is performed in end-stage renal disease (ESRD) for the treatment of secondary hyperparathyroidism. Whether and how the number of glands removed affects parathyroid hormone (PTH) levels remain controversial. The objective of this study is to compare the biochemical and pharmacological evolution after subtotal PTX according to the number of glands removed in ESRD. METHODS: This is a unicenter longitudinal retrospective cohort study of ESRD patients who have undergone PTX [< 3 glands (group 1) vs ≥ 3 glands (group 2)] from April 2006 to October 2014 at CHU de Québec, Canada. Demographic data, comorbidities, pharmacological and biochemical parameters were collected before, 3, 6, 12 and 24 months after PTX. Linear mixed model was performed to compare the biochemical and pharmacological evolution. RESULTS: We included 37 (13 in group 1, 24 in group 2) ESRD patients with a median age of 53 (46-58) years. The population is 68% male with a median dialysis vintage of 30.7 (18.0-61.2) months. The two groups were similar in terms of demographics and comorbidities. Compared to baseline, PTH levels in groups 1 and 2 dropped significantly at 2 years (1239-361 ng/L and 1542-398 ng/L, p < 0.05) but the evolution was comparable between the two groups. CONCLUSIONS: Our results show the efficacy of subtotal PTX in lowering PTH levels in our ESRD cohort. However, the results were not different according to the number of glands removed.

Fracture Risk in Dialysis and Kidney Transplanted Patients: A Systematic Review.

Chronic kidney disease is associated with an increased risk of fracture and cardiovascular mortality. The risk of fracture in hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) patients is higher when compared with the general population. However, there exists a knowledge gap concerning which group has the highest risk of fracture. We aimed to compare the risk of fracture in HD, PD, and KT populations. We conducted a systematic review of observational studies evaluating the risk of fracture in HD, PD, or KT patients. Eligible studies were searched using MEDLINE, Embase, Web of Science, and Cochrane Library from their inception to January 2016, and in grey literature. Incidences (cumulative and rate) of fracture were described together using the median, according to fracture sites, the data source (administrative database or cohort and clinical registry), and fracture diagnosis method. Prevalence estimates were described separately. We included 47 studies evaluating the risk of fracture in HD, PD, and KT populations. In administrative database studies, incidence of hip fracture in HD (median 11.45 per 1000 person-years [p-y]), range: 9.3 to 13.6 was higher than in KT (median 2.6 per 1000 p-y; range 1.5 to 3.8) or in PD (median 5.2 per 1000 p-y; range 4.1 to 6.3). In dialysis (HD+PD), three studies reported a higher incidence of hip fracture than in KT. Prevalent vertebral fracture (assessed by X-rays or questionnaire) reported in HD was in a similar range as that reported in KT. Incidence of overall fracture was similar in HD and KT, from administrative databases studies, but lower in HD compared with KT, from cohorts or clinical registry studies. This systematic review suggests an important difference in fracture risk between HD, PD, and KT population, which vary according to the diagnosis method for fracture identification. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.