Application of artificial intelligence to chronic kidney disease mineral bone disorder.

The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed towards secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. We describe in this review a novel approach to CKD-MBD combining mathematical modelling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals.

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.

Role of detached podocytes in differentiating between minimal change disease and early focal segmental glomerulosclerosis, can we rely on routine light microscopy?

BACKGROUND: Detachment of podocytes represents a turning point in the development of glomerular sclerosis and consequently, of CKD progression. Furthermore, detachment may differentiate minimal change disease (MCD) cases-which have only podocyte effacement-from early focal segmental glomerulosclerosis (FSGS) in which effacement and detachment are observed by electron microscopy. Noteworthy, it is not uncommon for early FSGS to present with clinical presentation and light microscopy (LM) pictures identical to MCD. In our routine practice, we often find cells that lie freely in Bowman's space by LM. In this study, we try to determine whether these cells are detached podocytes that are worth reporting or just an artifact that can be ignored. METHODS: To the best of our knowledge, no study has discussed the accuracy of LM in detecting detached podocytes by the routinely used stains. We retrospectively selected 118 cases that were diagnosed as MCD by LM, and searched for detached cells in Bowman's space in their archived, routinely stained LM slides. After that, we tried to find any correlation between the clinical course, detached cells in LM picture and the EM reports. RESULTS: LM can significantly detect detached podocytes with a positive predictive value of 93%, specificity of 85%, and sensitivity of 46%. Significant correlations were found between detached cells and degree of proteinuria and late steroid resistance. CONCLUSION: Detecting detached podocytes by LM is a specific finding that must be reported whenever detected, as it predicts response to steroids and may be able to differentiate MCD from early FSGS by identifying patients who could have podocytopenia.

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.

Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5×105 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders.