Effect of vitamin D sterols on bone histology in pre-dialysis patients: A prospective controlled study.

BACKGROUND: Abnormalities related to mineral and bone metabolism are a common finding in chronic kidney disease (CKD). Vitamin D compounds are often prescribed to CKD patients with the purpose to control secondary hyperparathyroidism and reduce the risk of high-turnover bone disease. However, data on the effect of vitamin D sterols on bone histology in non-dialysis CKD is limited. MATERIALS AND METHODS: A prospective controlled study was conducted on a cohort of 56 patients with CKD stages 3 and 4. 19 patients on calcitriol and 12 patients on cholecalciferol were compared to a group of 25 age- and sex-matched controls. Participants underwent a tetracycline double-labelled transiliac bone biopsy before starting therapy and again 12 months later. Changes from baseline in circulating biomarkers and bone histomorphometric parameters were analyzed. RESULTS: Low-turnover bone disease was the most common pattern of renal osteodystrophy on the initial biopsy. There was no difference in biochemical or histomorphometric values between the three study groups at baseline. Serum intact parathormone (iPTH) and bone formation rate decreased significantly in calcitriol-treated patients, with prevalence of low-turnover bone disease doubling from baseline. In contrast, no significant changes were noted in cholecalciferol-treated and control subjects. CONCLUSION: Calcitriol was effective in preventing secondary hyperparathyroidism and high-turnover bone disease. However, it was associated with an increased risk of developing or aggravating low-turnover bone disease. In the absence of a bone biopsy, calcitriol use in pre-dialysis CKD should be reserved for patients with a progressive rise in iPTH levels, in whom high-turnover bone disease is suspected.

Lung ultrasound as a tool to guide respiratory physiotherapy.

Lung ultrasound (LUS) is becoming an invaluable tool in the management of critically ill patients. We report two cases showing the importance of LUS as a guide to optimize respiratory physiotherapy in the intensive care unit, allowing a successful lung donation process and to redirect the physiotherapist's approach. The use of LUS requires an adequate training but it is becoming an important tool in management algorithms for critically ill patients.

Evolution of bone disease after kidney transplantation: A prospective histomorphometric analysis of trabecular and cortical bone.

AIM: Post-transplant bone disease results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. Bone biopsy remains the gold-standard diagnostic tool. METHODS: We aimed to prospectively evaluate trabecular and cortical bone by histomorphometry after kidney transplantation. Seven patients, willing to perform follow-up bone biopsy, were included in the study. Dual-X-ray absorptiometry and trans-iliac bone biopsy were performed within the first 2 months after renal transplantation and repeated after 2-5 years of follow-up. RESULTS: Follow-up biopsy revealed a significant decrease in osteoblast surface/bone surface (0.91 ± 0.81 to 0.47 ± 0.12%, P = 0.036), osteoblasts number/bone surface (0.45 (0.23, 0.94) to 0.00/mm(2) , P = 0.018) and erosion surface/bone surface (3.75 ± 2.02 to 2.22 ± 1.38%, P = 0.044). A decrease in trabecular number (3.55 (1.81, 2.89) to 1.55/mm (1.24, 2.06), P = 0.018) and increase in trabecular separation (351.65 ± 135.04 to 541.79 ± 151.91 µm, P = 0.024) in follow-up biopsy suggest loss in bone quantity. We found no significant differences in cortical analysis, except a reduction in external cortical osteonal eroded surface (5.76 (2.94, 13.97) to 3.29% (0.00, 6.67), P = 0.043). Correlations between bone histomorphometric and dual-X-ray absorptiometry parameters gave inconsistent results. CONCLUSIONS: The results show a reduction in bone activity, suggesting increased risk of adynamic bone and loss of bone volume. Cortical bone seems less affected by post-transplant biological changes in the first years after kidney transplantation.

Convergent QSAR studies on a series of NK3 receptor antagonists for schizophrenia treatment.

The dopamine hypothesis states that decreased dopaminergic neurotransmission reduces schizophrenia symptoms. Neurokinin-3 receptor (NK3) antagonists reduce dopamine release and have shown positive effects in pre-clinical and clinical trials. We employed 2D and 3D-QSAR analysis on a series of 40 non-peptide NK3 antagonists. Multivariate statistical analysis, PCA and HCA, were performed to rational training/test set splitting and PLS regression was employed to construct all QSAR models. We constructed one highly predictive CoMFA model (q(2)= 0.810 and r(2)= 0.929) and acceptable HQSAR and CoMSIA models (HQSAR q(2)= 0.644 and r(2)= 0.910; CoMSIA q(2)= 0.691, r(2)= 0.911). The three different techniques provided convergent physicochemical results. All models indicate cyclopropane, piperidine and di-chloro-phenyl ring attached to cyclopropane ring and also the amide group attached to the piperidine ring could play an important role in ligand-receptor interactions. These findings may contribute to develop potential NK3 receptor antagonists for schizophrenia.

Comparison of two visual methods for detecting caries among obese and non-obese children.

OBJECTIVE: The study aimed to compare two visual methods for detecting caries among obese and non-obese children in Salvador, Brazil. MATERIALS AND METHODS: A cross-sectional study was conducted from 2011-2012, which evaluated 180 paediatric patients, 6-14 years old, girls and boys, categorized into two groups: obese and non-obese (healthy weight), according to the body mass index. For the evaluation of dental caries, the decayed, missing or filled teeth index (DMFT/dmft) and International Caries Detection and Assessment System II (ICDAS II) visual criteria were used. RESULTS: The mean DMFT value was 0.98 in obese children and 0.57 in the non-obese children, without significant differences between groups (p = 0.206). The mean dmft value in the non-obese children (1.66) was higher than in obese children (0.95), with significant differences between groups (p = 0.021). According to ICDAS II criteria, there was a higher prevalence of non-cavitated enamel lesions (D1-3) in obese children (n = 156, 10.5%) compared to the non-obese children (n = 55, 1.9%), with significant differences between the groups (p < 0.001). CONCLUSIONS: The inclusion of non-cavitated lesions during the caries evaluation represents a challenge in diagnosis, which allows for control of this process before the evolution of these lesions to cavitation.

Anthropometric and biochemical profile of children and adolescents with chronic kidney disease in a predialysis pediatric interdisciplinary program.

This is longitudinal retrospective observational cohort study that evaluated anthropometric and biochemical variables of children and adolescents admitted to a Predialysis Interdisciplinary Management Program (PDIMP) responsible for the follow-up of children and adolescents at stages 2 to 4 of chronic kidney disease (CKD) at a tertiary center. One hundred thirty-eight patients with CKD on predialysis treatment with median age at admission of 9 years and the median follow-up time of 5 years were evaluated. Seventy-four (53%) had CKD stage 3 at admission and 70 (51%) reached CKD stage 5 at the end of the follow-up. There was no significant difference between the mean initial and final hemoglobin and serum albumin. However, the final serum bicarbonate presented a significant improvement. Analyses stratified according to clinical variables of interest showed a significant improvement in body mass index (BMI) Z score, especially in the subgroup of children admitted under two years of age. In relation to stature-for-age Z score, data show a significant improvement in stature SD at the end of the study. In conclusion, the present study showed improvement of nutritional status of CKD patients and that the deterioration of renal function was not correlated with BMI-for-age Z score.

Assistance time and peripheral oxygen saturation in prehospital emergency data as predictors of COVID19 hospital outcomes.

To verify if data obtained in the prehospital evaluation of patients with severe acute respiratory syndrome (SARS) during the initial response to the COVID-19 pandemic is associated with clinical outcomes: mechanical ventilation, hospital discharge, and death. This is a retrospective analysis involving secondary data from the Emergency Medical Service (EMS) records and the Health Surveillance Information System of patients assisted by the EMS in Manaus, from January to June 2020, the period of the first peak of COVID-19 cases. The combination of the two databases yielded a total of 1.190 patients, who received a first EMS response and were later admitted to hospital with SARS and had data on clinical outcomes of interest available. Patients were predominantly male (754, 63.4%), with a median age of 66 (IQR: 54.0-78.0) years. SARS illness before medical assistance was associated to need for invasive mechanical ventilation (IMV, p < 0.001). Lower pre-hospital SpO2 was associated to death (p = 0.025). Death was more common among patients with respiratory support needs, especially in the invasive ventilation group (262/287; 91.3%) (p < 0.001). In addition, IMV was more common among elderly individuals (p < 0.001). Patients admitted to ICU had a greater chance of dying when compared to non-ICU admitted patients (p < 0.001), and closely related to IMV (p < 0.001). Patients in ICU were also older (p = 0.003) and had longer hospital stay (p < 0.001). Mortality was associated with mechanical ventilation (p < 0.001), ICU admission (p < 0.001), and older age (p < 0.001). Patients who died had a shorter length of both ICU and total hospital stay (p < 0.001). Prehospital EMS may provide feasible and early recognition of critical patients with SARS in strained healthcare systems, such as in low-resource settings and pandemics.

Alkylphospholipids - a promising class of chemotherapeutic agents with a broad pharmacological spectrum.

PURPOSE: Since when alkylphospholipds (ALPs) were discovered and, even further after miltefosine's approval for the treatment of cutaneous metastasis of breast cancer and leishmaniasis, their activity against many other diseases have been extensively studied. This review aims to provide a summary of the alkylphospholipids' applications investigated so far. RESULTS: The mechanism of action of ALPs is not fully understood, however it is believed that they interfere with lipid homeostasis leading to cell apoptosis. Due to ALPs cytotoxic activity, this class of molecules has shown to be effective against many diseases and conditions. Besides the approval of miltefosine for application in cutaneous metastasis of breast cancer and visceral and cutaneous leishmaniasis, several other analogs have proved efficacy and are promising as less toxic alternatives. ALPs have also shown in vitro and in vivo activity against Trypanosoma spp., amoebae, Tricomonas vaginalis, Schistosoma mansoni, HIV, and some fungi and bacteria species. The use of ALPs for intraocular lens coating is also under investigation. In addition, a clinical trial comparing miltefosine with usual treatments to spontaneous urticaria is also being conducted. CONCLUSIONS: Alkylphospholipids present such a broad pharmacological spectrum that justifies the need for further investigations of the drug class mechanisms of action, as well as the search for new analogs with improved activity and toxicological profiles.

Closing the Gap: A Case Report on a Blood Patch Solution for Cerebrospinal Fluid Leak.

Spontaneous intracranial hypotension is a condition resulting from cerebrospinal fluid leaks at the spinal level that disrupt the regulation of intracranial pressure. This disorder is an uncommon cause of debilitating headaches but can have variable clinical manifestations, which contributes to delayed diagnosis and potentially severe consequences. The standard treatment consists of conservative measures such as bed rest, hydration, and a pharmacological approach with paracetamol, caffeine, ergotamine, and dexamethasone. When conservative measures fail, an epidural blood patch is the gold standard treatment, where a small amount of blood is injected into the epidural space to form a clot to seal any existing leak. Recent studies showed a success rate of 64% without the need for further intervention. The authors report a case of a 55-year-old woman with a three-month history of daily severe headaches. Imaging exams showed subdural collections, suggesting the hypothesis of cerebrospinal fluid hypotension. After the failure of conservative measures, an epidural blood patch was performed with progressive clinical improvement.  This case demonstrates the potential effectiveness of an epidural blood patch in the management of spontaneous intracranial hypotension and its complications, offering an encouraging option for those unresponsive to conservative measures. It also highlights the importance of a multidisciplinary approach involving neurologists and anesthesiologists.

Vascular calcification in peritoneal dialysis patients and its association with bone-derived molecules and bone histomorphometry.

INTRODUCTION: Data regarding vascular calcification (VC) in contemporary peritoneal dialysis (PD) patients is scarce. Bone-vascular axis has been demonstrated in hemodialysis (HD). However, studies showing the link between bone disease and VC in PD patients are lacking. The role of sclerostin, dickkopf-related protein 1 (DKK-1), receptor activator for nuclear factor kB ligand and osteoprotegerin (OPG) in VC in PD remains to clarify. MATERIALS AND METHODS: Bone biopsy was performed in 47 prevalent PD patients with histomorphometric analysis. Patients were submitted to pelvis and hands X-ray to evaluate VC using the Adragão score (AS). Relevant clinical and biochemical data was collected. RESULTS: Thirteen patients (27.7%) had positive AS (AS≥1). Patients with VC were significantly older (58.9 vs. 50.4 years, p=0.011), had a lower dialysis dose (KT/V 2.0 vs. 2.4, p=0.025) and a higher glycosylated hemoglobin (7.2 vs. 5.4%, p=0.001). There was not any laboratorial parameter of mineral and bone disease used in clinical practice different between patients with or without VC. All diabetic patients had VC but only 8.1% of non-diabetic had VC (p<0.001). Patients with VC showed significantly higher erythrocyte sedimentation rate (ESR) (91.1 vs. 60.0mm/h, p=0.001), sclerostin (2250.0 vs. 1745.8pg/mL, p=0.035), DKK-1 (1451.6 vs. 1042.9pg/mL, p=0.041) and OPG levels (2904.9 vs. 1518.2pg/mL, p=0.002). On multivariate analysis, only ESR remained statistically significant (OR 1.07; 95% CI 1.01-1.14; p=0.022). Bone histomorphometric findings were not different in patients with VC. There was no correlation between bone formation rate and AS (r=-0.039; p=0.796). CONCLUSION: The presence of VC was not associated with bone turnover and volume evaluated by bone histomorphometry. Inflammation and diabetes seem to play a more relevant role in VC in PD.

Miconazole-loaded nanoparticles coated with hyaluronic acid to treat vulvovaginal candidiasis.

Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.

Trichuris sp. from 1,040 +/- 50-year-old Cervidae coprolites from the archaeological site Furna do Estrago, Pernambuco, Brazil.

We present results of the paleoparasitological analysis of Cervidae coprolites that were recovered from the archaeological site Furna do Estrago, Pernambuco, Brazil. Trichuris sp. eggs were recovered from the coprolite samples dated 1,040 ± 50 years before present. This is the first record of Trichuris sp. in semiarid Cervidae, unexpectedly recorded in archaeological material.

Microhardness change of enamel due to bleaching with in-office bleaching gels of different acidity.

OBJECTIVE: The aim of this study was to assess the enamel microhardness treated with three in-office bleaching agents, containing 35% hydrogen peroxide with different acidity. MATERIALS AND METHODS: Bovine incisors were divided into three groups that received the following bleaching agents: Whiteness HP, Total Bleach and Opalescence Xtra. Three gel applications/10-min each, totaling 30-min of bleaching treatment, were made on the teeth and activated with a blue LED (1000 mW/470 nm) combined to a LASER (120 mW/795 nm) device (Easy Bleach-Clean Line). Vickers hardness (VH) was evaluated at baseline and after the bleaching procedure. The values of Hardness loss [HNL] (% reduction) were calculated. The two-sample t-test was used for comparison of the HNL of the three bleaching products (5% level of significance). RESULTS: The Opalescence Xtra, which had the lowest pH value (pH = 4.30), showed a significant increase of HNL when compared with Total Bleach bleaching agent, which had the highest pH value (pH = 6.62). CONCLUSIONS: The 35% hydrogen peroxide bleaching agents resulted in a reduction in surface enamel microhardness and bleaching with the most acid agent resulted in a significant enamel hardness loss compared to the less acid agent (4.30 vs 6.62). Strategies proposed to reduce the enamel loss after bleaching treatment may include the use of daily fluoride therapy, mouth rinsing (fluoride, milk and sodium bicarbonate solution), fluoride/bicarbonate dentifrices without abrasives, do not toothbrush immediately after bleaching, fluorides and calcium add to bleaching agents.

General versus regional anaesthesia for hip fracture surgery - impact on mortality and length of stay.

BACKGROUND: Hip fractures are extremely common and are considered a public health problem. The best anaesthetic technique for this surgery remains controversial. The aim of this study is to determine the impact of anaesthesia on perioperative and 30-day mortality and length of stay, in patients undergoing hip fracture surgery. MATERIAL: Adults undergoing hip fracture surgery, between January 1st, 2017 and December 31st, 2018, were retrospectively identified and categorized according to the anaesthetic technique. Perioperative and 30-day mortality rates and the length of stay were analysed. RESULTS: We identified 562 patients who underwent hip fracture surgery, 361 of whom were submitted to general anaesthesia and 201 to regional anaesthesia. The adjusted analysis showed no statistically significant difference in the risk of perioperative and 30-day mortality (odds ratio 1.12, 95% CI: 0.62-2.03; odds ratio 1.17, 95% CI: 0.72-1.92) or length of stay (0, 9 days [-1.6 to 3.4], P = 0.301). CONCLUSIONS: Our results were similar to those of studies already published in other countries. Within the limitations of our study, we concluded that there is no impact of the anaesthetic technique on perioperative and 30-day mortality rates and on the length of stay, for hip fracture surgery. In future studies, it will be opportune to investigate factors that influence the safety of anaesthetic techniques and that are subject to intervention by the anaesthesiologist.

The Acute Impact of the Early Stages of COVID-19 Pandemic in People with Pre-Existing Psychiatric Disorders: A Systematic Review.

People with pre-pandemic health conditions are more vulnerable and more likely to suffer greater psychosocial impact due to the current COVID-19 pandemic and the lockdown measures. Thus, the objective of this work was to systematically review the impact of the early stages COVID-19 pandemic on people with pre-existing psychiatric disorders. The search was performed between 23 January and 2 September 2021 in PubMed, PsycINFO, and EMBASE. A total of 4167 published results were identified; however, only 49 were included in this review. Results show that there was considerable heterogeneity among studies, which resulted in a low consensus. However, it seems that the impact of the first stage of the COVID-19 pandemic on psychiatric disorders was two-fold: (1) an overall effect, in which people suffering from psychiatric disorders in general experienced more psychological distress and anxiety when compared to people who had no psychiatric diagnosis, and (2) a condition-specific effect, namely in people suffering from eating disorders and obsessive compulsive disorders. Moreover, the current work highlights that there were also some external factors that were related to worsening symptoms. For instance, unemployment or experiencing work and financial difficulties can be a trigger for greater distress during the pandemic for people with mood disorders, and being alone and in social isolation during the COVID-19 pandemic may actually increase substance use and relapse rates. Further studies are needed to prospectively investigate the long-term effects of the current COVID-19 pandemic on people with (pre)-existing psychiatric conditions and on the onset or deterioration of psychiatric-related symptoms in a larger number of participants, as well as exploring the long-term effects of the current pandemic on mental health.

Minute Zero: an essential assessment in peri-operative ultrasound for anaesthesia.

In recent years, ultrasonography has gained unmatched importance in medical practice. After the initial use for central vascular access placement and regional anaesthesia, its application has expanded to airway, ocular, abdominal, lung and cardiac ultrasound, with the concept of point of care ultrasound (POCUS) gaining acceptability and applicability in the most diverse situations. In fact, it has recently been acclaimed as the fifth pillar to bedside evaluation [1]. Performing a POCUS-guided eva-luation has proved to be of value in emergency medicine, with studies demonstrating improved diagnosis and better outcomes [2]. Similarly, in critical care, systematic ultrasound evaluation has been shown to decrease the use of conventional diagnostic imaging tools and time on mechanical ventilation and improve the management of fluid therapy [3]. Recognition of the benefit of ultrasound evaluation in the perioperative period has been increasing. In fact, the need to master clinical ultrasound evaluation has led the Canadian anaesthesiology academic centres to issue recommendations regarding the scope of practice and required training for perioperative POCUS [4].

Evaluation of Renal Osteodystrophy and Serum Bone-Related Biomarkers in a Peritoneal Dialysis Population.

The spectrum of renal osteodystrophy (ROD) in peritoneal dialysis (PD) patients remains to be clarified. Ideal intact parathormone (iPTH) levels range is still not defined. The role of sclerostin, dickkopf-related protein 1, osteoprotegerin, and receptor activator for nuclear factor κB ligand for the diagnosis of ROD needs to be elucidated. In this cross-sectional study, tetracycline double-labeled bone biopsy was performed in 49 patients with histomorphometric analysis according Kidney Disease Improving Global Outcomes (KDIGO) guidelines. All patients were treated with biocompatible PD solutions, with calcium concentration of 1.25 mmol/L. Adynamic bone was the most frequent diagnosed pattern (42.9%) followed by hyperparathyroid-related bone disease (28.6%). Twenty-two percent of patients had normal bone. In patients with iPTH within the KDIGO recommended range for dialysis patients, adynamic bone was found in 59% of cases. Median (range) iPTH in patients with adynamic bone was 312 (60-631) pg/mL. Median (range) levels of sclerostin varied from 1511.64 (458.84-6387.70) pg/mL in patients with hyperparathyroid bone disease to 2433.1 (1049.59-11354.52) pg/mL in patients with adynamic bone. Sclerostin/iPTH ratio was the best marker of low turnover disease but iPTH performed best in the diagnosis of high turnover disease. Calcium mass transfer was positive in patients with low bone volume. Adynamic bone is the most frequent ROD pattern in contemporary PD. Our results suggest the need to review the iPTH target range for this population. The sclerostin/iPTH ratio showed improved performance compared to iPTH for the diagnosis of low turnover bone. © 2022 American Society for Bone and Mineral Research (ASBMR).

Could Bone Biomarkers Predict Bone Turnover after Kidney Transplantation?-A Proof-of-Concept Study.

AIM: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects of transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD). These include sclerostin and the soluble receptor activator of nuclear factor-kB ligand (sRANKL). METHODS: To better understand the role of biomarkers in post-transplant bone disease, this study was designed to prospectively evaluate and correlate results from the histomorphometric analysis of bone biopsies after KT with emerging serum biomarkers of the CKD-MBD: sclerostin, Dickkopf-related protein 1 (Dkk-1), sRANKL and osteo-protegerin (OPG). RESULTS: Our data shows a significant increase in plasma levels of bioactive sclerostin after KT accompanied by a significant reduction in plasma levels of Dkk-1, suggesting a promotion of the inhibition of bone formation by osteoblasts through the activation of these inhibitors of the Wnt signaling pathway. In addition, we found a significant increase in plasma levels of free sRANKL after KT accompanied by a significant reduction in plasma levels of its decoy receptor OPG, suggesting an enhanced bone resorption by osteoclasts mediated by this mechanism. CONCLUSIONS: Taken together, these results suggest that the loss of bone volume observed after KT could be explain mainly by the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone resorption mediated by sRANKL.

Low bone turnover is associated with plain X-ray vascular calcification in predialysis patients.

BACKGROUND: Vascular calcification (VC) is a common finding in chronic kidney disease (CKD) patients and predicts subsequent cardiovascular morbidity and mortality in this population. Vascular calcification is linked to disordered mineral metabolism and has been associated with bone histomorphometry changes in CKD. However, data on predialysis patients is scarce. METHODS: A cross-sectional study was conducted on a cohort of 56 CKD patients not yet on dialysis, who underwent a transiliac bone biopsy for histomorphometric evaluation after double tetracycline labeling. Patients had no previous exposure to calcium salts, vitamin D agents, steroids or bisphosphonates. Vascular calcification was assessed at the time of biopsy, using Kauppila (plain X-ray of the lateral lumbar spine) and Adragão (plain X-ray of the pelvis and hands) scores. RESULTS: Vascular calcification was seen in two-thirds of the cohort. Subjects with VC were more likely to be male and have diabetes, and had significantly higher sclerostin and osteoprotegerin circulating levels than those without VC. The histomorphometric analysis showed that bone formation rate was significantly lower in VC compared to non-VC patients. In the multivariable logistic regression analysis, bone formation rate was independently associated with the presence of VC. CONCLUSIONS: Vascular calcification is highly prevalent in predialysis patients, especially in those with diabetes. The independent association between bone formation rate and VC provides evidence of an important interaction between bone and vessel in CKD. Our results suggest that low bone turnover is a non-traditional risk factor for cardiovascular disease in predialysis patients.

Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4.

BACKGROUND: Disordered mineral and bone metabolism is a common complication of chronic kidney disease (CKD). Bone biopsy remains the gold standard tool for evaluating renal osteodystrophy (ROD), but it is an invasive procedure. Despite a growing interest in the ability of newer bone biomarkers to discriminate between different forms of ROD, data on pre-dialysis patients are scarce. METHODS: A cross-sectional study was conducted in a cohort of 56 patients with CKD Stages 3 and 4. Participants underwent a transiliac bone biopsy after a course of double tetracycline labelling. Circulating levels of Wnt signalling inhibitors sclerostin and Dickkopf-1 (DKK1), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin were measured and correlated with histomorphometric analysis results. RESULTS: Most patients had abnormal bone histology and low-turnover bone disease was the predominant form of ROD. Characteristics associated with high bone turnover were worse renal function, lower serum calcium and higher intact parathyroid hormone and fibroblast growth factor-23 levels. Patients with low bone turnover, on the other hand, presented with higher sclerostin along with lower DKK1 and sRANKL levels. In the multivariable logistic regression analysis, sclerostin and DKK1 levels were independently associated with low-turnover bone disease. CONCLUSIONS: Our results suggest that circulating levels of Wnt signalling inhibitors sclerostin and DKK1 are predictive of low-turnover bone disease in patients not yet on dialysis. Further research is needed to assess the performance of these bone turnover biomarkers, compared with histomorphometric analysis, in the diagnosis and treatment monitoring of ROD.