Integrated home dialysis model: facilitating home-to-home transition.

Peritoneal dialysis (PD) and home hemodialysis (HHD) are the two home dialysis modalities offered to patients. They promote patient autonomy, enhance independence, and are generally associated with better quality of life compared to facility hemodialysis. PD offers some advantages (enhanced flexibility, ability to travel, preservation of residual kidney function, and vascular access sites) but few patients remain on PD indefinitely due to peritonitis and other complications. By contrast, HHD incurs longer and more intensive training combined with increased upfront health costs compared to PD, but is easier to sustain in the long term. As a result, the integrated home dialysis model was proposed to combine the advantages of both home-based dialysis modalities. In this paradigm, patients are encouraged to initiate dialysis on PD and transfer to HHD after PD termination. Available evidence demonstrates the feasibility and safety of this approach and some observational studies have shown that patients who undergo the PD-to-HHD transition have clinical outcomes comparable to patients who initiate dialysis directly on HHD. Nevertheless, the prevalence of PD-to-HHD transfers remains low, reflecting the multiple barriers that prevent the full uptake of home-to-home transitions, notably a lack of awareness about the model, home-care "burnout," clinical inertia after a transfer to facility HD, suboptimal integration of PD and HHD centers, and insufficient funding for home dialysis programs. In this review, we will examine the conceptual advantages and disadvantages of integrated home dialysis, present the evidence that underlies it, identify challenges that prevent its success and finally, propose solutions to increase its adoption.

Differences in Antihypertensive Medication Prescription Profiles Between 2009 and 2021: A Retrospective Cohort Study of CARTaGENE.

Background: Although blood pressure (BP) control is critical to prevent cardiovascular diseases, hypertension control rates in Canada are in decline. Objective: To assess this issue, we sought to evaluate the differences in antihypertensive medication prescription profiles in the province of Quebec between 2009 and 2021. Design: This is a retrospective cohort study. Setting: We used data from the CARTaGENE population-based cohort linked to administrative health databases. Patients: Participants with any drug claim in the 6 months prior to the end of follow-up were included. Measurements: Guideline-recommended antihypertensive drug prescription profiles were assessed at the time of enrollment (2009-2010) and end of follow-up (March 2021). Methods: Prescriptions practices from the 2 time periods were compared using Pearson's chi-square tests. A sensitivity analysis was performed by excluding participants in which antihypertensive drugs may not have been prescribed solely to treat hypertension (presence of atrial fibrillation/flutter, ischemic heart disease, heart failure, chronic kidney disease, or migraines documented prior to or during follow-up). Results: Of 8447 participants included in the study, 31.4% and 51.3% filled prescriptions for antihypertensive drugs at the beginning and end of follow-up. In both study periods, guideline-recommended monotherapy was applied in most participants with hypertension (77.9% vs 79.5%, P = .3), whereas optimal 2 and 3-drug combinations were used less frequently (62.0% vs 61.4%, P = .77, 51.9% vs 46.7%, P = .066, respectively). Only the use of long-acting thiazide-like diuretics (9.5% vs 27.7%, P < .001) and spironolactone as a fourth-line agent (8.3% vs 15.9%, P = .054) increased with time but nonetheless remained infrequent. Results were similar in the sensitivity analysis. Limitations: Specific indication of the prescribed antihypertensive medications and follow-up BP data was not available. Conclusions: Application of hypertension guidelines for the choice of antihypertensive drugs remains suboptimal, highlighting the need for education initiatives. This may be an important step to raise BP control rates in Canada.

Contexte: Bien que le contrôle de la pression artérielle (PA) soit essentiel pour prévenir les maladies cardiovasculaires, les taux de maitrise de l'hypertension artérielle sont en déclin au Canada. Objectifs: Pour traiter cette problématique, nous avons cherché à évaluer les différences dans les profils de prescription de médicaments antihypertenseurs dans la province de Québec entre 2009 et 2021. Conception: Étude de cohorte rétrospective. Cadre: Nous avons utilisé les données de la cohorte populationnelle CARTaGENE reliées aux bases de données administratives en santé. Sujets: Ont été inclus les participants qui ont présenté une demande de remboursement de médicament dans les six mois précédant la fin du suivi. Mesures: Les profils de prescription de médicaments antihypertenseurs recommandés dans les lignes directrices ont été évalués au moment de l'inclusion (2009-2010) et à la fin du suivi (mars 2021). Méthodologie: Les profils de prescription des deux périodes ont été comparés à l'aide des tests Chi-Square de Pearson. Une analyse de sensibilité a été réalisée en excluant les participants pour lesquels les antihypertenseurs n'avaient possiblement pas été prescrits uniquement pour traiter l'hypertension (présence de fibrillation auriculaire, cardiopathie ischémique, insuffisance cardiaque, insuffisance rénale chronique ou migraines documentées avant ou pendant le suivi). Résultats: Des 8 447 participants inclus dans l'étude, 31,4 % avait rempli des prescriptions de médicaments antihypertenseurs au début du suivi et 51,3 % à la fin du suivi. Dans les deux périodes à l'étude, la monothérapie recommandée par les directives a été appliquée chez la plupart des participants avec hypertension artérielle (77,9 % c. 79,5 %; P = 0,3), tandis que les combinaisons optimales de deux médicaments (62,0 % c. 61,4 %; P = 0,77) et de trois médicaments (51,9 % c. 46,7 % P = 0,066) ont été utilisées moins fréquemment. Seules les utilisations de diurétiques thiazidiques à action prolongée (9,5 % c. 27,7 %; P < 0,001) et de spironolactone en quatrième intention (8,3 % c. 15,9 %; P = 0,054) ont augmenté avec le temps, mais sont demeurées néanmoins peu fréquentes. Les résultats étaient similaires dans l'analyse de sensibilité. Limites: L'indication précise pour la prescription de médicaments antihypertenseurs et les données de suivi sur la pression artérielle n'étaient pas disponibles. Conclusion: L'application des lignes directrices sur l'hypertension artérielle pour le choix des médicaments antihypertenseurs reste sous-optimale, ce qui souligne un besoin pour des initiatives en matière d'éducation. Cela pourrait constituer une étape importante d'une stratégie visant l'augmentation des taux de contrôle de la PA au Canada.

Activation of mGlu 2/3 receptors with the orthosteric agonist LY-404,039 alleviates dyskinesia in experimental parkinsonism.

LY-404,039 is an orthosteric agonist at metabotropic glutamate 2 and 3 (mGlu 2/3 ) receptors, with a possible additional agonist effect at dopamine D 2 receptors. LY-404,039 and its pro-drug, LY-2140023, have previously been tested in clinical trials for psychiatric indications and could therefore be repurposed if they were shown to be efficacious in other conditions. We have recently demonstrated that the mGlu 2/3 orthosteric agonist LY-354,740 alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat without hampering the anti-parkinsonian action of L-DOPA. Here, we seek to take advantage of a possible additional D 2 -agonist effect of LY-404,039 and see if an anti-parkinsonian benefit might be achieved in addition to the antidyskinetic effect of mGlu 2/3 activation. To this end, we have administered LY-404,039 (vehicle, 0.1, 1 and 10 mg/kg) to 6-OHDA-lesioned rats, after which the severity of axial, limbs and oro-lingual (ALO) AIMs was assessed. The addition of LY-404,039 10 mg/kg to L-DOPA resulted in a significant reduction of ALO AIMs over 60-100 min (54%, P  < 0.05). In addition, LY-404,039 significantly enhanced the antiparkinsonian effect of L-DOPA, assessed through the cylinder test (76%, P  < 0.01). These results provide further evidence that mGlu 2/3 orthosteric stimulation may alleviate dyskinesia in PD and, in the specific case of LY-404,039, a possible D 2 -agonist effect might also make it attractive to address motor fluctuations. Because LY-404,039 and its pro-drug have been administered to humans, they could possibly be advanced to Phase IIa trials rapidly for the treatment of motor complications in PD.

Individual versus integration of multiple components of central blood pressure and aortic stiffness in predicting cardiovascular mortality in end-stage renal diseases.

Aortic stiffness, measured by carotid-femoral pulse wave velocity (PWV), is a predictor of cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD). Aortic stiffness increases aortic systolic and pulse pressures (cSBP, cPP) and augmentation index adjusted for a heart rate of 75 beats per minute (AIx@75). In this study, we examined if the integration of multiple components of central blood pressure and aortic stiffness (ICPS) into risk score categories could improve CV mortality prediction in ESRD. In a prospective cohort of 311 patients with ESRD on dialysis who underwent vascular assessment at baseline, 118 CV deaths occurred after a median follow-up of 3.1 years. The relationship between hemodynamic parameters and CV mortality was analyzed through Kaplan-Meier and Cox survival analysis. ICPS risk score from 0 to 5 points were calculated from points given to tertiles, and were regrouped into three risk categories (Average, High, Very-High). A strong association was found between the ICPS risk categories and CV mortality (High risk HR = 2.20, 95% CI: 1.05-4.62, P = 0.036); Very-High risk (HR = 4.44, 95% CI: 2.21-8.92, P < 0.001) as compared to the Average risk group. The Very-High risk category remained associated with CV mortality (HR = 3.55, 95% CI: 1.37-9.21, P = 0.009) after adjustment for traditional CV risk factors as compared to the Average risk group. While higher C-statistics value of ICPS categories (C: 0.627, 95% CI: 0.578-0.676, P = 0.001) was not statistically superior to PWV, cPP or AIx@75, the use of ICPS categories resulted in a continuous net reclassification index of 0.56 (95% CI: 0.07-0.99). In conclusion, integration of multiple components of central blood pressure and aortic stiffness may potentially be useful for better prediction of CV mortality in this cohort.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Impact of Successive Office Blood Pressure Measurements During a Single Visit on Cardiovascular Risk Prediction: Analysis of CARTaGENE.

BACKGROUND: Multiple office blood pressure (BP) readings correlate more closely with ambulatory BP than single readings. Whether they are associated with long-term outcomes and improve cardiovascular risk prediction is unknown. Our objective was to assess the long-term impact of multiple office BP readings. METHODS: We used data from CARTaGENE, a population-based survey comprising individuals aged 40 to 70 years. Three BP readings (BP1, BP2, and BP3) at 2-minute intervals were obtained using a semiautomated device. They were averaged to generate BP1-2, BP2-3, and BP1-2-3 for systolic BP (SBP) and diastolic BP. Cardiovascular events (major adverse cardiovascular event [MACE]: cardiovascular death, stroke, and myocardial infarction) during a 10-year follow-up were recorded. Associations with MACE were obtained using adjusted Cox models. Predictive performance was assessed with 10-year atherosclerotic cardiovascular disease scores and their associated C statistics. RESULTS: In the 17 966 eligible individuals, 2378 experienced a MACE during follow-up. Crude SBP values ranged from 122.5 to 126.5 mm Hg. SBP3 had the strongest association with MACE incidence (hazard ratio, 1.10 [1.05-1.15] per SD) and SBP1 the weakest (hazard ratio, 1.06 [1.01-1.10]). All models including SBP1 (SBP1, SBP1-2, and SBP1-2-3) were underperformed. At a given SBP value, the excess MACE risk conferred by SBP3 was 2× greater than SBP1. In atherosclerotic cardiovascular disease scores, SBP3 yielded the highest C statistic, significantly higher than most other SBP measures. In contrast to SBP, all diastolic BP readings yielded similar results. CONCLUSIONS: Cardiovascular risk prediction is improved by successive office SBP values, especially when the first reading is discarded. These findings reinforce the necessity of using multiple office BP readings.

Enhancing central blood pressure accuracy through statistical modeling: A proof-of-concept study.

Background: Non-invasive estimation of central blood pressure (BP) may have better prognostic value than brachial BP. The accuracy of central BP is limited in certain populations, such as in females and the elderly. This study aims to examine whether statistical modeling of central BP for clinical and hemodynamic parameters results in enhanced accuracy. Methods: This study is a cross-sectional analysis of 500 patients who underwent cardiac catheterization. Non-invasive brachial cuff and central BP were measured simultaneously to invasive aortic systolic BP (AoSBP). Central BP was calibrated for brachial systolic (SBP) and diastolic BP (Type I calibration; C1SBP) or brachial mean and diastolic BP (Type II calibration; C2SBP). Differences between central SBP and the corresponding AoSBP were assessed with linear regression models using clinical and hemodynamic parameters. These parameters were then added to C1SBP and C2SBP in adjusted models to predict AoSBP. Accuracy and precision were computed in the overall population and per age or sex strata. Results: C1SBP underestimated AoSBP by 11.2 mmHg (±13.5) and C2SBP overestimated it by 6.2 mmHg (±14.8). Estimated SBP amplification and heart rate were the greatest predictors of C1- and C2-AoSBP accuracies, respectively. Statistical modeling improved both accuracy (0.0 mmHg) and precision (±11.4) but more importantly, eliminated the differences of accuracy seen in different sex and age groups. Conclusion: Statistical modeling greatly enhances the accuracy of central BP measurements and abolishes sex- and age-based differences. Such factors could easily be implemented in central BP devices to improve their accuracy.

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.

Prediction of Cardiovascular Events by Pulse Waveform Parameters: Analysis of CARTaGENE.

Background Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population-based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10-year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c-index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow-up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores. Conclusions Some waveform parameters are independently associated with MACEs in a population-based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

Accuracy Difference of Noninvasive Blood Pressure Measurements by Sex and Height.

Importance: Women are at higher risk of cardiovascular events than men with similar blood pressure (BP). Whether this discrepancy in risk is associated with the accuracy of brachial cuff BP measurements is unknown. Objectives: To examine the difference in brachial cuff BP accuracy in men and women compared with invasively measured aortic BP and to evaluate whether noninvasive central BP estimation varies with sex. Design, Setting, and Participants: This cross-sectional study enrolled 500 participants without severe aortic stenosis or atrial fibrillation from January 1 to December 31, 2019, who were undergoing nonurgent coronary angiography at a tertiary care academic hospital. Exposures: Simultaneous measurements of invasive aortic BP and noninvasive BP. Main Outcomes and Measures: Sex differences in accuracy were determined by calculating the mean difference between the noninvasive measurements (brachial and noninvasive central BP) and the invasive aortic BP (reference). Linear regression and mediation analyses were performed to identify mediators between sex and brachial cuff accuracy. Results: This study included 500 participants (145 female [29%] and 355 male [71%]; 471 [94%] White; mean [SD] age, 66 [10] years). Baseline characteristics were similar for both sexes apart from body habitus. Despite similar brachial cuff systolic BP (SBP) (mean [SD], 124.5 [17.7] mm Hg in women vs 124.4 [16.4] in men; P = .97), invasive aortic SBP was higher in women (mean [SD], 130.9 [21.7] in women vs 124.7 [20.1] mm Hg in men; P < .001). The brachial cuff was relatively accurate compared with invasive aortic SBP estimation in men (mean [SD] difference, -0.3 [11.7] mm Hg) but not in women (mean [SD] difference, -6.5 [12.1] mm Hg). Noninvasive central SBP (calibrated for mean and diastolic BP) was more accurate in women (mean [SD] difference, 0.6 [15.3] mm Hg) than in men (mean [SD] difference, 8.3 [14.2] mm Hg). This association of sex with accuracy was mostly mediated by height (3.4 mm Hg; 95% CI, 1.1-5.6 mm Hg; 55% mediation). Conclusions and Relevance: In this cross-sectional study, women had higher true aortic SBP than men with similar brachial cuff SBP, an association that was mostly mediated by a shorter stature. This difference in BP measurement may lead to unrecognized undertreatment of women and could partly explain why women are at greater risk for cardiovascular diseases for a given brachial cuff BP than men. These findings may justify the need to study sex-specific BP targets or integration of sex-specific parameters in BP estimation algorithms.

Vitamin D Analogues and Fracture Risk in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Vitamin D receptor agonists (VDRAs) are commonly prescribed in chronic kidney disease (CKD). However, their protective effects on bone remain controversial. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of VDRAs on fracture risk and bone mineral density (BMD) in adult patients with CKD. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the WHO's International Clinical Trials Registry Platform databases from inception to June 19, 2021. We included RCTs comparing VDRAs, to placebo or another medication, in adults with CKD requiring or not dialysis. Conference abstracts and trials involving kidney transplant recipients and/or comparing VDRAs to antiresorptive or anabolic bone therapy were excluded. Primary outcome was fracture at any anatomical site. Secondary outcomes were BMD at femoral neck, lumbar spine, and/or total hip. Prespecified subgroup analyses were conducted according to baseline demographics, overall risk of bias, and follow-up time. From 6868 references retrieved, eight RCTs were eligible: five reported fracture, two reported BMD, and one reported both outcomes. As comparator, one study used no VDRAs, one used nutritional intervention and no medication, and six used placebo. In meta-analysis, VDRAs were not associated with a significant reduction in total fractures in overall (risk ratio = 0.79, 95% confidence interval 0.38-1.65, I2 = 0%, six trials, 1507 participants, 27 fractures) or in prespecified subgroup analyses. Three trials reported BMD at different sites and with different BMD measurements; thus, a meta-analysis could not be performed. Two RCTs were at high risk of bias, notably because of deviations from the intended interventions. As limitation, we have to mention the low total number of fractures included in our meta-analysis. In conclusion, current evidence from RCTs is insufficient to associate VDRAs with bone protection in CKD. Further large and long-term studies specifically designed to evaluate the efficacy of VDRAs on bone outcomes are thus required. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

FGF23-Klotho Axis and Fractures in Patients Without and With Early CKD: A Case-Cohort Analysis of CARTaGENE.

CONTEXT: Whether fibroblast growth factor-23 (FGF23) and α-Klotho are associated with fractures, especially in chronic kidney disease (CKD), remains controversial. OBJECTIVE: We evaluated how FGF23, α-Klotho, and traditional mineral parameters predict fractures in individuals with and without early CKD. METHODS: We conducted a stratified case-cohort analysis using CARTaGENE, a population-based survey from Quebec, Canada. Individuals aged 40 to 69 years were selected according to outcome and CKD status (non-CKD: eGFR > 60 mL/min/1.73 m2; CKD stage 3: eGFR 30-60 mL/min/1.73 m2]). Baseline levels of c-terminal FGF23 (cFGF23), α-Klotho, parathyroid hormone (PTH), phosphate, and calcium were analyzed for associations with osteoporotic fracture incidence from recruitment (2009-2010) through March 2016. Adjusted Cox models were used, and predictors were treated linearly or flexibly using splines. RESULTS: A total of 312 patients (159 non-CKD; 153 CKD) were included; 98 had ≥ 1 fracture at any site during a median follow up of 70 months. Compared with non-CKD, CKD patients had increased levels of cFGF23 but similar levels of α-Klotho. cFGF23 was linearly associated with increased fracture incidence (adjusted HR = 1.81 [1.71, 1.93] per doubling for all participants). The association of α-Klotho with fracture followed a U-curve (overall P = 0.019) but was attenuated by adjustment for potential mediators (bone mineral density, phosphate, PTH). PTH and phosphate also had U-shaped associations with fracture. Associations were mostly similar between non-CKD and CKD. Adjustment for cFGF23 strongly attenuated the association between CKD status and fractures. CONCLUSION: cFGF23 is associated linearly with fracture incidence while α-Klotho, PTH, and phosphate levels have a U-shaped association.

Iliac crest bone biopsy by interventional radiologists to improve access to bone biopsy in chronic kidney disease populations: technical note and a case series.

INTRODUCTION: Chronic kidney disease-mineral and bone disorder (CKD-MBD) leads to increased fracture risk. Iliac crest biopsy remains the gold standard for diagnosing bone disease in CKD. Unfortunately, bone biopsy is rarely performed which is mainly due to the inability of clinicians to perform the procedure. In this paper, we propose a fluoroscopy-guided procedure performed by interventional radiologists as a novel approach to iliac crest biopsy in adult population. We describe the implementation of the procedure and present the first 11 cases of CKD patients who underwent iliac crest biopsy with this new approach. METHODS: A nephrologist already trained in performing iliac crest biopsy initiated the creation of a fluoroscopy-based iliac crest biopsy program. Two interventional radiologists underwent a short training. Patients' demographical, clinical and biochemical data were collected on the day of the biopsy. Complications within the first three months after the procedure were collected from electronical records. RESULTS: IR rapidly mastered the procedure. The use of fluoroscopy allowed a precise localisation of the biopsy site and standardization of the intervention, which ensured specimen quality. The new approach allowed CKD patients to access iliac crest biopsy, which resulted in precise bone disease diagnosis (levels of bone turnover and mineralization) and targeted therapy for each case. There were no complications during, nor within 3 months after the intervention. CONCLUSIONS: We believe this approach will increase the access to iliac crest biopsy for diagnosing bone disease in CKD population. Studies are now needed to evaluate whether CKD patients will benefit from anti-osteoporotic therapy based on the results of iliac crest biopsy.

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.

Comparison of Fracture Prediction Tools in Individuals Without and With Early Chronic Kidney Disease: A Population-Based Analysis of CARTaGENE.

Whether fracture prediction tools developed for the management of osteoporosis can be used in chronic kidney disease (CKD) is poorly known. We aimed to compare the performance of fracture prediction tools in non-CKD and CKD. We analyzed CARTaGENE, a population-based survey of 40-year-old to 69-year-old individuals recruited between 2009 and 2010. Renal function was assessed using baseline creatinine and categorized according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines (non-CKD, stage 2, stage 3). Individuals without creatinine measurements or with advanced CKD (stage 4 or 5; prevalence <0.25%) were excluded. Predicted 5-year fracture probabilities (using Fracture Risk Assessment Tool [FRAX], QFracture, and Garvan) were computed at baseline. Fracture incidence (major fracture [MOF] or any fracture) was evaluated in administrative databases from recruitment to March 2016. Discrimination (hazard ratios [HRs] per standard deviation [SD] increase in Cox models; c-statistics) and calibration (standardized incidence ratios [SIRs] before and after recalibration) were assessed in each CKD strata. We included 19,393 individuals (9522 non-CKD; 9114 stage 2; 757 stage 3). A total of 830 patients had any fracture during follow-up, including 352 MOF. FRAX (HR = 1.89 [1.63-2.20] non-CKD; 1.64 [1.41-1.91] stage 2; 1.76 [1.10-2.82] stage 3) and QFracture (HR = 1.90 [1.62-2.22] non-CKD; 1.57 [1.35-1.82] stage 2; 1.86 [1.19-2.91] stage 3) discriminated MOF similarly in non-CKD and CKD. In contrast, the discrimination of Garvan for any fracture tended to be lower in CKD stage 3 compared to non-CKD and CKD stage 2 (HR = 1.36 [1.22-1.52] non-CKD; 1.34 [1.20-1.50] stage 2; 1.11 [0.79-1.55] stage 3). Before recalibration, FRAX globally overestimated fracture risk while QFracture and Garvan globally underestimated fracture risk. After recalibration, FRAX and QFracture were adequately calibrated for MOF in all CKD strata whereas Garvan tended to underestimate any fracture risk in CKD stage 3 (SIR = 1.31 [0.95-1.81]). In conclusion, the discrimination and calibration of FRAX and QFracture is similar in non-CKD and CKD. Garvan may have a lower discrimination in CKD stage 3 and underestimate fracture risk in these patients. © 2020 American Society for Bone and Mineral Research.

Incidence of fractures in middle-aged individuals with early chronic kidney disease: a population-based analysis of CARTaGENE.

BACKGROUND: Previous studies evaluating fractures in chronic kidney disease (CKD) have mostly focused on hip or major fractures in aged populations with moderate to advanced CKD. We aimed at evaluating the association between early CKD and fracture incidence at all sites across age and sex in middle-aged individuals. METHODS: We analyzed CARTaGENE, a prospective population-based survey of 40- to 69-year-old individuals from Quebec (Canada). Estimated glomerular filtration rate (eGFR) at baseline was evaluated categorically or continuously using restricted cubic splines. Fractures at any site (except toes, hand and craniofacial) for up to 7 years of follow-up were identified through administrative databases using a validated algorithm. Adjusted Cox models were used to evaluate the association of CKD with fracture. Interaction terms for age and sex were also added. RESULTS: A total of 19 391 individuals (756 CKD Stage 3; 9114 Stage 2; 9521 non-CKD) were included and 829 fractures occurred during a median follow-up of 70 months. Compared with the median eGFR of 90 mL/min/1.73 m2, eGFRs of ≤60 mL/min/1.73 m2 were associated with increased fracture incidence in unadjusted and adjusted models [adjusted hazard ratio (HR) = 1.25 (95% confidence interval 1.05-1.49) for 60 mL/min/1.73 m2; 1.65 (1.14-2.37) for 45 mL/min/1.73 m2]. The eGFR was linearly associated with fracture incidence <75 mL/min/1.73 m2 [HR = 1.18 (1.04-1.34) per 10 mL/min/1.73 m2 decrease] but not above [HR = 0.98 (0.91-1.06) per 10 mL/min/1.73 m2 decrease). The effect of decreased eGFR on fracture incidence was more pronounced in younger individuals [HR = 2.45 (1.28-4.67) at 45 years; 1.11 (0.73-1.67) at 65 years] and in men. CONCLUSIONS: Even early CKD increases fracture incidence, especially in younger individuals and in men.

Predictive value of quantitative ultrasound parameters in individuals with chronic kidney disease: A population-based analysis of CARTaGENE.

BACKGROUND: The use of calcaneal quantitative ultrasound (QUS) to predict fractures has not been well studied in early CKD populations. We compared the association of QUS with incidental fractures and its predictive properties in non-CKD and CKD individuals. METHODS: Analysis of a prospective population-based survey of 40- to 69-year-old individuals recruited between 2009 and 2010. QUS parameters (stiffness index [SI], speed of sound [SOS], broadband attenuation [BUA]) were measured at baseline. Renal function was measured using baseline creatinine and was classified into CKD stages (non-CKD, stage 2, stage 3). Fracture incidence at any site or at major osteoporotic fracture sites for up to 7 years of follow-up was identified in administrative databases using a validated algorithm. The association (age-adjusted hazard ratio per standard deviation decrease in Cox models), discrimination (c-statistic) and calibration (standardized incidence ratio [SIR]) of QUS parameters with fracture outcomes was computed in each CKD stratum. RESULTS: We included 18,306 individuals (9,011 non-CKD; 8,595 CKD stage 2; 700 CKD stage 3). During a median follow-up of 70 months, we identified 782 fractures at any site and 326 major osteoporotic fractures. Although all QUS parameters (SI, SOS and BUA) were associated with any or major fracture incidence in non-CKD and CKD patients, the magnitude of these associations was lower for any fracture and for BUA. QUS parameters moderately discriminated incidental fractures across CKD strata but underestimated fracture incidence in CKD stage 3 even after adjustment for demographics and clinical risk factors. At a given QUS value, CKD stage 3 patients had higher fracture risk than non-CKD and CKD stage 2 patients. CONCLUSIONS: QUS parameters are associated with fracture incidence in both non-CKD and CKD but underestimate fracture incidence in individuals with early CKD.

Programmable deep-UV laser platform for inspection and metrology.

This Letter reports on a high-power, narrow-linewidth deep-UV laser platform built upon a frequency-quintupled, Yb-fiber master-oscillator and power-amplifier system. The source, emitting at a pulse repetition rate of 120 MHz with a linewidth of 90 GHz and beam quality of MX/Y2∼2.1/1.5, has been stably maintained over two weeks by successively changing positions and temperatures of nonlinear crystals in parallel, while outputting a 0.5-W average power at 213 nm.