cholecalciferol and Ischemia

Acute kidney injury (AKI) is a common complication in patients with potentially life-threatening diseases, and it is also usually associated with unacceptable morbidity and mortality rates. Therefore, new and efficient therapies are urgently required to relieve AKI. It is well known that, reactive oxygen species (ROS), the NF-κB signaling pathways and pyroptosis are involved in AKI induced by ischemia/reperfusion (I/R). The present study seeks to further confirm the internal relationship between vitamin D deficiency and I/R-induced AKI in patients, and to explore the underlying mechanisms of ROS, NF-κB signaling pathways and pyroptosis in the renal ischemia-reperfusion injury, as well as investigating the protective role of cholecalciferol. Patients with vitamin D deficiency show worse renal function reflected by postoperative glomerular filtration rate (GFR) and more release of proinflammatory cytokine IL-1β and IL-18. Renal cell injury and renal dysfunction induced by I/R surgery were attenuated in the ICR mice administered with cholecalciferol. Cholecalciferol reduced ROS production, suppressed activated NF-κB signaling, and inhibited gasdermin D (GSDMD, a pyroptosis execution protein)-mediated pyroptosis. Cholecalciferol therefore has potential, as a clinical drug, to protect renal function in I/R-induced AKI through reducing ROS production, NF-κB activation and GSDMD-mediated pyroptosis.

Topics: Acute Kidney Injury; Animals; Cholecalciferol; Humans; Ischemia; Kidney; Mice; Mice, Inbred ICR; NF-kappa B; Pyroptosis; Reactive Oxygen Species; Reperfusion; Reperfusion Injury; Vitamin D Deficiency

Calciphylaxis occurred in a 40-year old female patient with end-stage renal failure. The patient developed livedo racemosa ("livedo reticularis") with painful skin necrosis and ulcers involving multiple areas of the hip and legs after 22 years of hemodialysis. X-ray-examinations revealed calcinosis of peripheral arteries, especially of the pelvis, thigh and hands, while histological examinations showed a fibrosis and calcinosis of small subcutaneous arteries. A generalized cutaneous microangiopathy could be demonstrated by transcutaneous oxygen pressure measurements. Laboratory data showed a moderate secondary hyperparathyroidism with mild elevation of calcium-phosphate product. In addition to the hemodialysis an attempt was made to improve the microcirculation by vasoactive drugs. The clinical course was characterized by slow healing of the ulcers and occurrence of new areas of cutaneous necrosis. Calciphylaxis is a rare late complication in patients with advanced, often end-stage renal failure. It has characteristic histopathological features and is frequently, but not always, associated with a disturbed calcium and phosphorus metabolism and mildly elevated levels of parathyroid hormone. Calciphylaxis is classified as a special type of metastatic calcinosis.

Topics: Adult; Aluminum Hydroxide; Calciphylaxis; Calcium; Cholecalciferol; Disseminated Intravascular Coagulation; Ergocalciferols; Erythropoietin; Female; Humans; Ischemia; Kidney Failure, Chronic; Long-Term Care; Necrosis; Parathyroid Hormone; Renal Dialysis; Skin Diseases, Vascular

Topics: Calcium; Cholecalciferol; Forearm; Glucose; Humans; Hypoparathyroidism; Insulin; Ischemia; Muscles; Muscular Diseases; Phosphates; Physical Exertion; Uric Acid