Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have significant cardiovascular morbidity and mortality that is in part due to the development of vascular calcification. Vascular calcification is an active, highly regulated process that shares many similarities with normal bone formation. New discoveries related to extracellular vesicles, microRNAs, and calciprotein particles continue to reveal the mechanisms that are involved in the initiation and progression of vascular calcification in CKD. Further innovations in these fields are critical for the development of biomarkers and therapeutic options for patients with CKD and ESRD.

Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease (CKD). The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of pro-calcific and anti-calcific factors. In the CKD population, an elevated phosphate burden is both highly prevalent and a known risk factor for ectopic calcification. Here we tested whether osteopontin, an inhibitor of calcification, protects against high phosphate load-induced nephrocalcinosis and vascular calcification. Osteopontin knockout mice were placed on a high phosphate diet for eleven weeks. Osteopontin deficiency together with phosphate overload caused uremia, nephrocalcinosis characterized by substantial renal tubular and interstitial calcium deposition, and marked vascular calcification when compared to controls. While the osteopontin-deficient mice did not exhibit hypercalcemia or hyperphosphatemia, they did show abnormalities in the mineral metabolism hormone fibroblast growth factor 23. Thus, endogenous osteopontin plays a critical role in the prevention of phosphate induced nephrocalcinosis and vascular calcification in response to high phosphate load. A better understanding of osteopontin’s role in phosphate induced calcification will hopefully lead to better biomarkers and therapies for this disease, especially in patients with CKD and other at risk populations.

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Glut1 deficiency syndrome is caused by SLC2A1 mutations on chromosome 1p34.2 that impairs glucose transport across the blood-brain barrier resulting in hypoglycorrhachia and decreased fuel for brain metabolism. Neuroglycopenia causes a drug-resistant metabolic epilepsy due to energy deficiency. Standard treatment for Glut1 deficiency syndrome is the ketogenic diet that decreases the demand for brain glucose by supplying ketones as alternative fuel. Treatment options are limited if patients fail the ketogenic diet. We present a case of successful diazoxide use with continuous glucose monitoring in a patient with Glut1 deficiency syndrome who did not respond to the ketogenic diet.

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