Prevalence and Associated Factors of Vitamin D Deficiency in High Altitude Region in Saudi Arabia: Three-Year Retrospective Study.

Background: Vitamin D has many functions in the human body, and its deficiency is associated with skeletal and non-skeletal diseases. Vitamin D deficiency (blood level of 25 (OH) vitamin D < 20 ng/mL) has been reported worldwide, including Kingdom of Saudi Arabia (KSA). Its prevalence and associated factors vary according to KSA region. Therefore, this study aimed to explore the prevalence and risk factors of vitamin D deficiency in the Taif region of KSA. Methods: This retrospective study included patients who attended outpatient clinics at the Alameen General Hospital from 2019 to 2021. Demographic, clinical, and laboratory data were collected using a hospital software system. Results: The study included 2153 patients and vitamin D deficiency was diagnosed in 900 (41.8%) of whom were diagnosed with vitamin D deficiency. It was more common in males (P=0.021), younger age (<0.001), and in patients without comorbidities. There was a positive correlation between 25 (OH) vitamin D levels and blood cholesterol, high-density lipoprotein, calcium, and vitamin B12 levels. In the binary logistic regression analysis, age was the most significant predictor (P<0.001), followed by the absence of thyroid disease (P=0.012) and asthma (P=0.030). Conclusion: Vitamin D deficiency is common in the Saudi population despite sunny weather in KSA. It is more prevalent among males, younger individuals, and those without comorbidities such as thyroid diseases and asthma.

Incidence of bone fractures among patients on maintenance hemodialysis.

BACKGROUND: Patients with chronic kidney disease, especially those undergoing hemodialysis (HD), have a higher risk of fragility fractures. However, the magnitude of the problem and risk factors associated with fracture incidence have not been well studied in the Kingdom of Saudi Arabia. METHODS: This multicenter retrospective study involved HD centers in Jeddah from 2015 to 2021. This study included all adult HD patients. Patient demographics, medication usage, and clinical and biochemical parameters were collected from the registry records. RESULTS: The study included 328 patients on HD, with a mean age of 53 years. The median duration of HD was 47 months. Osteoporosis was found in 9% of the patients, and 8% had a previous parathyroidectomy. Over the observation period, fractures occurred in 32 patients, with an incidence rate of 20 case/1000 end stage kidney disease patients-year. Patients with fractures had a higher rate of osteoporosis, underwent more parathyroidectomy, had longer HD vintage, and higher bone-specific alkaline phosphatase (BSAP) levels. BSAP was the most significant predictor of fracture incidence in the regression analysis. Using a BSAP cutoff value of 96.6 µg/L, the sensitivity and specificity to predict fractures were 81.8% and 49%, respectively. CONCLUSION: The main risk factors for incident fractures were osteoporosis, previous parathyroidectomy, longer HD vintage, and higher BSAP level. A higher BSAP score was the most significant predictor of incident fractures. This may highlight the importance of monitoring bone turnover markers and the negative impact of high bone turnover on patient health.

Is Adynamic Bone Always a Disease? Lessons from Patients with Chronic Kidney Disease.

Renal osteodystrophy (ROD) is a common complication of end-stage kidney disease that often starts early with loss of kidney function, and it is considered an integral part in management of patients with chronic kidney disease (CKD). Adynamic bone (ADB) is characterized by suppressed bone formation, low cellularity, and thin osteoid seams. There is accumulating evidence supporting increasing prevalence of ADB, particularly in early CKD. Contemporarily, it is not very clear whether it represents a true disease, an adaptive mechanism to prevent bone resorption, or just a transitional stage. Several co-players are incriminated in its pathogenesis, such as age, diabetes mellitus, malnutrition, uremic milieu, and iatrogenic factors. In the present review, we will discuss the up-to-date knowledge of the ADB and focus on its impact on bone health, fracture risk, vascular calcification, and long-term survival. Moreover, we will emphasize the proper preventive and management strategies of ADB that are pivotal issues in managing patients with CKD. It is still unclear whether ADB is always a pathologic condition or whether it can represent an adaptive process to suppress bone resorption and further bone loss. In this article, we tried to discuss this hard topic based on the available limited information in patients with CKD. More studies are needed to be able to clearly address this frequent ROD finding.

Low Turnover Renal Osteodystrophy With Abnormal Bone Quality and Vascular Calcification in Patients With Mild-to-Moderate CKD.

Introduction: Limited information is available on renal osteodystrophy (ROD) and vascular calcification (VC) during early chronic kidney disease (CKD). This study was designed to evaluate ROD and VC in 32 patients with CKD stages II to IV. Methods: Patients underwent dual-energy X-ray absorptiometry (DXA) for assessment of bone mineral density (BMD) and trabecular bone score (TBS), thoracic computed tomography for VC scoring using the Agatston method, and anterior iliac crest bone biopsy for mineralized bone histology, histomorphometry, and Fourier transform infrared spectroscopy (FTIR). Classical and novel bone markers were determined in the blood. Results: Mean estimated glomerular filtration rate (eGFR) was 44 ± 16 ml/min per 1.73 m2. Of the patients, 84% had low bone turnover. In Whites, eGFR correlated negatively with the turnover parameter activation frequency (Ac.f) (r -0.48, P = 0.019) and with parameters of bone formation. Most patients had VC (>80%) which correlated positively with levels of phosphorus, c-terminal fibroblast growth factor-23, and activin. Aortic calcifications (ACs) correlated negatively with bone formation rate (BFR) and Ac.f (rho -0.62, -0.61, P < 0.001). TBS correlated negatively with coronary calcification (rho -0.42, P = 0.019) and AC (rho -0.57, P = 0.001). These relationships remained after adjustment of age. The mineral-to-matrix ratio, an FTIR metric reflecting bone quality, was negatively related to Ac.f and positively related to AC. Conclusion: Low bone turnover and VC are predominant in early stages of CKD. This is the first study demonstrating mineral abnormalities indicating reduced bone quality in these stages of CKD.

Secondary Osteoporosis and Metabolic Bone Diseases.

Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by controlling minerals, electrolytes, acid-base, vitamin D and parathyroid function. Chronic kidney disease with its uremic milieu disturbs this balance, leading to renal osteodystrophy. Diabetes mellitus represents the most common secondary cause of osteoporosis. Thyroid and parathyroid disorders can dysregulate the osteoblast/osteoclast functions. Gastrointestinal disorders, malnutrition and malabsorption can result in mineral and vitamin D deficiencies and bone loss. Patients with chronic liver disease have a higher risk of fracture due to hepatic osteodystrophy. Proinflammatory cytokines in infectious, autoimmune, and hematological disorders can stimulate osteoclastogenesis, leading to osteoporosis. Moreover, drug-induced osteoporosis is not uncommon. In this review, we focus on causes, pathogenesis, and management of secondary osteoporosis.

Kidneys in SARS-CoV-2 era: A challenge of multiple faces.

INTRODUCTION: With the evolution of SARS-CoV-2 pandemic, it was believed to be a direct respiratory virus. But, its deleterious effects were observed on different body systems, including kidneys. AIM OF WORK: In this review, we tried as much as we can to summarize what has been discussed in the literature about the relation between SARS-CoV-2 infection and kidneys since December, 2019. METHODS: Each part of the review was assigned to one or two authors to search for relevant articles in three databases (Pubmed, Scopus, and Google scholar) and collected data were summarized and revised by two independent researchers. CONCLUSION: The complexity of COVID-19 pandemic and kidney could be attributed to the direct effect of SARS-CoV-2 infection on the kidneys, different clinical presentation, difficulties confronting dialysis patients, restrictions of the organ transplant programs, poor outcomes and bad prognosis in patients with known history of kidney diseases who got infected with SARS-CoV-2.

Characteristics and outcomes of prisoners hospitalized due to COVID-19 disease.

BACKGROUND: Correctional facilities have faced unique challenges during the COVID-19 pandemic. A COVID-19 outbreak was reported in the Federal Medical Center (FMC) in Lexington, Kentucky, a prison for inmates requiring medical and mental care. The main objective of this study was to examine clinical characteristics and outcomes of prisoners vs. non-prisoners admitted to the hospital due to COVID-19 disease. MATERIALS AND METHODS: We did a retrospective, comparative cohort study of 86 consecutive COVID-19 patients admitted to the University of Kentucky hospital between March 1 and June 1, 2020. Among these, 37 patients were inmates from a single local FMC and 49 were non-inmates. RESULTS: Mean (SD) age of the cohort was 59.1 (14.5) years, 68.6% were male and 61.6% white. All inmates were men. No significant differences in age or race were observed between inmates and non-inmates. Hypertension (81%), obesity (62%), COPD/asthma (43%), diabetes (41%), coronary artery diseases (38%), and chronic kidney disease (22%) were among the most common comorbidities prevalent in inmates. Inmates had overall higher serum creatinine and C-reactive protein, more proteinuria, and lower platelet counts at the time of hospital admission when compared to non-inmates. Incidence of acute kidney injury (AKI) was more frequent in inmates (68 vs. 38% in non-inmates, p = 0.008). Overall, patients who developed AKI had higher acuity of illness with more requirement of ICU care and mechanical ventilation. Kidney replacement therapy (KRT) was provided to 12.8% of patients. Inpatient mortality occurred in 15.1% of patients and was not different in inmates vs. non-inmates (13.5 vs. 16.3%, p = 0.862). All survivors became independent of KRT, and ~ 1 of 10 survivors had a reduction of eGFR ≥ 25% from baseline by the time of discharge, which was more frequent in inmates vs. non-inmates, 15.6 vs. 2.4%, p = 0.042, respectively. CONCLUSION: Inmates represent a vulnerable population with prevalent comorbidity and susceptibility to COVID-19. When compared to non-inmates with COVID-19, inmates exhibited higher incidence of AKI and, for survivors, less kidney recovery by the time of hospital discharge. Surveillance of long-term sequela of COVID-19 is warranted in this susceptible inmate population.

Relation of Wnt Signaling Pathway Inhibitors (Sclerostin and Dickkopf-1) to Left Ventricular Mass Index in Maintenance Hemodialysis Patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is common in hemodialysis (HD) patients. It predicts poor prognosis. Several inhibitors regulate Wnt canonical pathways like Dickkopf-related protein-1 (Dkk-1) and sclerostin. OBJECTIVES: To investigate the relationship between serum sclerostin, Dkk-1, left ventricular mass (LVM), and LVM index (LVMI) in HD patients. METHODS: This is a cross-sectional study including 65 HD patients in our HD unit. Patients were divided into two groups according to LVMI (group 1 with LVMI < 125 gm/m2 (N = 29) and group 2 with LVMI > 125 gm/m2 (N = 36)). Echocardiographic evaluation of the LVM, aortic, and mitral valves calcification (AVC and MVC) was done. Serum levels of sclerostin and Dkk-1 and patients' clinical and biochemical data were recorded. RESULTS: Group 2 showed significantly higher age, blood pressure, AVC, and MVC and significantly lower hemoglobin, sclerostin, and Dkk-1 levels. LVM and LVMI had a significant linear negative correlation to both serum sclerostin and Dkk-1 (r = -0.329 and -0.257, P=0.01 and 0.046 for LVM; r = -0.427 and -0.324, P=0.001 and 0.012 for LVMI, resp.). Serum Dkk-1 was an independent negative indicator for LVM and LVMI in multiple regression analyses (P=0.003 and 0.041 with 95% CI = -0.963 to -0.204 and -0.478 to -0.010, resp.). CONCLUSION: Serum sclerostin and Dkk-1 were significantly lower in HD patients with increased LVMI > 125 gm/m2, and both had a significant linear negative correlation with LVM and LVMI. Dkk-1 was a significant negative independent indicator for LVM and LVMI in HD patients.

Bone Quality in Chronic Kidney Disease Patients: Current Concepts and Future Directions - Part II.

BACKGROUND: Patients with chronic kidney disease (CKD) have an increased risk of osteoporotic fractures, which is due not only to low bone volume and mass but also poor microarchitecture and tissue quality. The pharmacological and nonpharmacological interventions detailed, herein, are potential approaches to improve bone health in CKD patients. Various medications build up bone mass but also affect bone tissue quality. Antiresorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the ability to repair bone microdamage and cause an increase in bone brittleness. On the other hand, some osteoporosis therapies may cause a redistribution of bone structure that may improve bone strength without noticeable effect on BMD. This may explain why some drugs can affect fracture risk disproportionately to changes in BMD. SUMMARY: An accurate detection of the underlying bone abnormalities in CKD patients, including bone quantity and quality abnormalities, helps in institution of appropriate management strategies. Here in this part II, we are focusing on advancements in bone therapeutics that are anticipated to improve bone health and decrease mortality in CKD patients. KEY MESSAGES: Therapeutic interventions to improve bone health can potentially advance life span. Emphasis should be given to the impact of various therapeutic interventions on bone quality.

Bone Quality in CKD Patients: Current Concepts and Future Directions - Part I.

BACKGROUND: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures independently of BMD in CKD patients. Bone quality and fracture risk in CKD patients can be better assessed by utilizing new technologies such as trabecular bone score and high-resolution imaging studies. Additionally, invasive assessments such as bone histology and micro-indentation are useful counterparts in the evaluation of bone quality. SUMMARY: A precise diagnosis of the underlying skeletal abnormalities in CKD patients is crucial to prevent further bone loss and fractures. We must consider bone quantity and quality abnormalities for management of CKD patients. Here in this part I, we are focusing on advances in bone quality diagnostics that are expected to help in proper understanding of the bone health in CKD patients. KEY MESSAGES: Assessment of bone quality and quantity in CKD patients is essential. Both noninvasive and invasive techniques for the assessment of bone quality are available.

Relation of protein energy wasting to carotid intima media thickness in hemodialysis patients.

Carotid intima media thickness (CIMT) can reflect the degree of atherosclerosis and cardiovascular risk in hemodialysis patients. Factors such as advanced age, male gender, family history, and smoking can increase the risk of CIMT. In hemodialysis (HD) patients, lower serum albumin level was found to be correlated with higher CIMT. This study aimed to evaluate the relation between CIMT and protein energy wasting (PEW) diagnosed according to the diagnostic criteria of International Society of Renal Nutrition and Metabolism (ISRNM) expert panel in HD patients. This study involved 45 HD patients who were divided into two groups according to the diagnostic criteria for PEW proposed by the ISRNM expert panel including group with PEW (11 patients) and group without PEW (34 patients). Caloric intake was evaluated by food frequency questionnaire for 3 days. Subjective global assessment (SGA) and malnutrition inflammation score (MIS) were fulfilled. Anthropometric measurements, as well as body composition, was evaluated by electrical bioimpedance analysis. Doppler ultrasonography was used to assess CIMT that was significantly higher in patients with PEW (p = 0.030). CIMT had significant positive correlation to age, SGA, and MIS (p = 0.008, 0.002, and 0.003, respectively). Significant negative correlation was observed between CIMT and serum albumin. Multiple linear regression analysis revealed that serum albumin was the only predictor of mean CIMT. In conclusion, CIMT seems to be related to malnutrition in HD patients. Low serum albumin was the only predictor of CIMT.

Diffusion Tensor Imaging in early prediction of renal fibrosis in patients with renal disease: Functional and histopathological correlations.

AIM: Renal fibrosis (RF) is a well-known marker of chronic kidney disease (CKD) progression. However, renal biopsy is an available tool for evaluation of RF, non-invasive tools are needed not only to detect but also to monitor the progression of fibrosis. The aim of this study is to evaluate the role of diffusion tensor imaging (DTI) in the assessment of renal dysfunction and RF in patients with renal disease. METHODS: Fifty-six patients with renal disorders and 22 healthy controls were recruited. All participants underwent DTI. Renal biopsy was performed for all patients. Mean renal medullary and cortical fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were compared between patients and healthy controls and correlated to serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24-h urinary protein (24h-UPRO) and renal histopathological scores. RESULTS: Cortical FA values were significantly higher (P = .001), while cortical ADC values were significantly lower in the patients' group (P = .002). Cortical FA values positively correlated to SCr (P = .006) and negatively correlated to eGFR (P = .03), while cortical ADC negatively correlated to percentage of sclerotic glomeruli, atrophic tubules and interstitial fibrosis (P = .001 for all variables). Medullary ADC negatively correlated to tubular atrophy (P = .02). The diagnostic performance of DTI for detecting RF was supported by ROC curve. Multiple linear regression analysis revealed that the mean cortex ADC was significantly decreased by 0.199 mg/dL for patients with >50% glomerulosclerosis in renal biopsy. CONCLUSION: DTI appears to represent a valuable tool for the non-invasive assessment of renal dysfunction and renal fibrosis.