Arterial Stiffness and Dialysis Calcium Concentration

Arterial stiffness is the major determinant of isolated systolic hypertension and increased pulse pressure. Aortic stiffness is also associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease, hypertension, and general population. Hemodynamically, arterial stiffness results in earlier aortic pulse wave reflection leading to increased cardiac workload and decreased myocardial perfusion. Although the clinical consequence of aortic stiffness has been clearly established, its pathophysiology in various clinical conditions still remains poorly understood. The aim of the present paper is to review the studies that have looked at the impact of dialysis calcium concentration on arterial stiffness. Overall, the results of small short-term studies suggest that higher dialysis calcium is associated with a transient but significant increase in arterial stiffness. This calcium dependant increase in arterial stiffness is potentially explained by increased vascular smooth muscle tone of the conduit arteries and is not solely explained by changes in mean blood pressure. However, the optimal DCa remains to be determined, and long term studies are required to evaluate its impact on the progression of arterial stiffness

Temporal trends of aortic stenosis and comorbid chronic kidney disease in the province of Quebec, Canada

Objective: To investigate temporal trends of chronic kidney disease (CKD) among patients with incident aortic stenosis (AS) and to compare these trends with that of a matched control population. Methods: Using the Quebec Integrated Chronic Disease Surveillance System, we performed a population-based nested case-control study including 108 780 patients newly hospitalised with AS and 543 900 age-matched, sex-matched and fiscal year-matched patients without AS from 2000 to 2016 in Quebec (Canada). Three subgroups were considered. Dialysis subgroup had at least two outpatient billing codes of dialysis. The predialysis subgroup had at least one hospital or two billing diagnostic codes of CKD. The remaining individuals were included in the non-CKD subgroup. We estimated overall and sex-specific standardised annual proportions of CKD subgroups through direct standardisation using the 2016-2017 age structure of the incident AS cohort. The trends overtime were estimated through fitting robust Poisson regression models. Age-specific distribution of AS and control population were assessed for each subgroup. Results: From 2000 to 2016, age-standardised proportions of patients with AS with dialysis and predialysis increased by 41% (99% CI 12.0% to 78.1%) and by 45% (99% CI 39.1% to 51.6%), respectively. Inversely, age-standardised proportions of dialysis and pre-dialysis among non-AS patients decreased by 63% (99% CI 55.8% to 68.7%) and by 32% (99% CI 29.9% to 34.6%), respectively, during the same study period. In patients with and without AS, age-standardised annual proportions of males in predialysis were significantly higher than females in most of the study period. Patients with AS on dialysis and predialysis were younger than their respective controls (dialysis: 29.6% vs 45.1% had ≥80 years, predialysis: 60.8% vs 72.7% had ≥80 years). Conclusions: Over time, the proportion of patients with CKD increased significantly and remained consistently higher in incident AS individuals compared with controls. Our results highlight the need to investigate whether interventions targeting CKD risk factors may influence AS incidence in the future

Impact of an obesogenic diet program on bone densitometry, micro architecture and metabolism in male rat.

International audienceABSTRACT: Background The relationships between fat mass and bone tissue are complex and not fully elucidated. A high-fat/high-sucrose diet has been shown to induce harmful effects on bone micro architecture and bone biomechanics of rat. When such diet leads to obesity, it may induce an improvement of biomechanical bone parameters in rodent. Here, we examined the impact of a high-fat/high-sucrose diet on the body composition and its resulting effects on bone density and structure in male rats. Forty three Wistar rats aged 7 months were split into 3 groups: 1 sacrificed before diet (BD, n=14); 1 subjected to 16 weeks of high-fat/high-sucrose diet (HF/HS, n=14); 1 subjected to standard diet (Control, n=15). Abdominal circumference and insulin sensitivity were measured and visceral fat mass was weighed. The bone mineral density (BMD) was analyzed at the whole body and tibia by densitometry. Microcomputed tomography and histomorphometric analysis were performed at L2 vertebrae and tibiae to study the trabecular and cortical bone structures and the bone cell activities. Osteocalcin and CTX levels were performed to assess the relative balance of the bone formation and resorption. Differences between groups have been tested with an ANOVA with subsequent Scheffe post-hoc test. An ANCOVA with global mass and global fat as covariates was used to determine the potential implication of the resulting mechanical loading on bone. RESULTS: The HF/HS group had higher body mass, fat masses and abdominal circumference and developed an impaired glucose tolerance compared to Control group (p<0.001). Whole body bone mass (p<0.001) and BMD (p<0.05) were higher in HF/HS group vs. Control group. The trabecular thickness at vertebrae and the cortical porosity of tibia were improved (p<0.05) in HF/HS group. Bone formation was predominant in HF/HS group while an unbalance bone favoring bone resorption was observed in the controls. The HF/HS and Control groups had higher total and abdominal fat masses and altered bone parameters vs. BD group. Conclusions The HF/HS diet had induced obesity and impaired glucose tolerance. These changes resulted in an improvement of quantitative, qualitative and metabolic bone parameters. The fat mass increase partly explained these observations

Obesity and Bone Mineral Density Protection Paradox in Chronic Kidney Disease: Secreted Protein Acidic and Rich in Cysteine as a Piece of the Puzzle?

Obesity is a health condition that represents a risk factor for numerous diseases and complications. However, obesity might also have—to some extent—some “benefits” in certain situations. This includes potential bone protection in patients suffering from chronic kidney disease. In an attempt to explain such a paradox, we highlight secreted protein acidic and rich in cysteine (SPARC) as a hypothetical mediator of this protection. Indeed, SPARC properties provide a logical rationale to describe such bone protection via its overexpression combined with its calcium-binding and collagen-binding properties. We believe that exploring such hypotheses could open new doors to elucidate unknown pathways towards developing a new generation of molecular therapies

Role of the Wnt/ β

Vascular calcification and bone fragility are common and interrelated health problems that affect chronic kidney disease (CKD) patients. Bone fragility, which leads to higher risk of fracture and mortality, arises from the abnormal bone remodeling and mineralization that are seen in chronic kidney disease. Recently, sclerostin and Dickkopf-related protein 1 were suggested to play a significant role in CKD-related bone disease as they are known inhibitors of the Wnt pathway, thus preventing bone formation. This review focuses on new knowledge about the Wnt pathway in bone, how its function is affected by chronic kidney disease and how this affects bone structure. Expression of components and inhibitors of the Wnt pathway has been shown to be affected by the loss of kidney function, and a better understanding of the bone effects of Wnt pathway inhibitors could allow the development of new therapies to prevent bone fragility in this population

Giant osteoclasts in patients under bisphosphonates

BACKGROUND: Bisphosphonates have been widely used for treatment of high bone resorption states. It lowers bone turnover by inhibiting osteoclasts bone resorption with various mechanisms of actions: inhibition of osteoclast formation and attachment to the bone surface, induction of metabolic injury, alteration of vesicle trafficking and induction of osteoclast apoptosis. Bone biopsies studies from patients under bisphosphonates have shown that some resorption parameters are decreased as expected but the number of osteoclasts seems not to be necessarily decreased. The description of osteoclasts morphology from patients treated with bisphosphonates has rarely been reported in the literature. CASE PRESENTATION: We describe in this paper two patients treated with bisphosphonates from whom iliac crest bone biopsies have shown large, multinucleated and apoptotic osteoclasts that were not associated with bone resorption activities. The characteristics of these osteoclasts are described and the literature reviewed. CONCLUSION: The appropriate recognition of these giant osteoclasts in bone tissues from patients treated with bisphosphonates is of primary importance for bone pathologists and should not be interpreted as signs of increased bone resorption as seen in hyperparathyroidism, bone cancer or Paget’s disease of bone

Additional file 2: of Fracture risk in dialysis and kidney transplanted patients: a protocol for systematic review and meta-analysis

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

AbstractA 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

Pembrolizumab-Induced Anti-GBM Glomerulonephritis: A Case Report

Immune checkpoint inhibitors are known to have a wide range of autoimmune toxicities, such as acute interstitial nephritis. Immunotherapy induced glomerulonephritis has been described, but anti-glomerular basement membrane disease (anti-GBM) is rarely reported. We present a case report of a 60-year-old woman with squamous cell carcinoma of the cervix who was treated with pembrolizumab, an anti-programmed cell death protein 1, and who developed severe acute kidney injury 4 months after therapy initiation. The immune workup showed a positive serum anti-GBM antibody (24 U/mL). The kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G2 glomerular basement membrane staining, compatible with anti-GBM glomerulonephritis. The patient was treated with plasmapheresis, IV steroids, and cyclophosphamide, but she developed kidney failure, necessitating dialysis. Few case reports, such as the present case, provide a possible link between anti-GBM glomerulonephritis and immune checkpoint inhibitors, warranting early clinical suspicion and investigation in patients who are treated with these agents and subsequently develop acute kidney injury