elastin and Kidney-Diseases

Disturbances in bone and mineral metabolism in patients with chronic kidney disease (CKD) affect not only the bone diseases but also other organ disorders in the whole body and deteriorate the survival of these patients. The term CKD-Mineral and Bone Disorder (CKD-MBD) has been established describing a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD. Vascular calcification and secondary hyperparathyroidism are major diseases in CKD-MBD.

Topics: Apoptosis; Bone Density; Bone Diseases, Metabolic; Calcinosis; Chronic Disease; Elastin; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Muscle, Smooth, Vascular; Receptors, Calcitriol; Receptors, Calcium-Sensing; Vascular Diseases

Topics: Elastin; Fibrosis; Humans; Kidney Diseases; Magnetic Resonance Imaging

Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastin was hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agent ESMA specifically detected elastin expression in multiple mouse models of renal fibrosis and also in fibrotic human kidneys. Elastin imaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastin imaging detected ensuing fibrosis not identifiable via routine assessment of kidney function. Elastin imaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis.

Topics: Adult; Aged; Animals; Disease Progression; Elastin; Female; Fibrosis; Humans; Kidney; Kidney Diseases; Magnetic Resonance Imaging; Male; Mice, Inbred C57BL; Middle Aged; Molecular Imaging; Rats, Wistar

Topics: Biopsy; Elastin; Fibrosis; Humans; Kidney Diseases

Vascular calcification is the most important cause of cardiovascular disease in patients with chronic kidney disease (CKD). Medial layer vascular calcification, which is recognized to be an active process (i.e. the transformation of vascular smooth muscle cells into osteoblast-like cells), is common in CKD patients. We have recently reported the possibility of an interaction between elastin degradation and medial layer vascular calcification. Matrix metalloproteinase-2 (MMP-2), which induces the degradation of elastin, has been implicated in the elastic calcification in arteries of dialysis patients; however, the precise mechanisms by which elastin degradation interacts with the development of vascular calcification remain to be studied. To clarify the mechanisms by which elastin degradation is involved in the development of medial layer vascular calcification in the uremic milieu, we induced aortic medial layer calcification in 5/6 nephrectomized uremic rats (male Sprague-Dawley rats) fed a diet containing high phosphate (1.2%) and lactate (20%). After 10 weeks, the rats were euthanized for the measurement of serum chemistry profiles and histological analyses. The uremic rats showed significant increases in blood pressure, serum creatinine, phosphate, and parathyroid hormone levels compared with normal rats. Von Kossa staining showed medial layer aortic calcification in the uremic rats. In calcified lesions, thin elastic lamellae were observed by elastin staining, indicating that elastin degradation could occur in the area. Furthermore, MMP-2 expression determined by immunohistochemistry was also observed in the same area. Elastin degradation accompanied by MMP-2 expression might be involved in the development of medial layer vascular calcification in uremic rats.

Topics: Animals; Aorta; Blood Pressure; Calcinosis; Cardiovascular Diseases; Chronic Disease; Creatinine; Elastin; Kidney Diseases; Male; Matrix Metalloproteinase 2; Parathyroid Hormone; Phosphates; Rats; Rats, Sprague-Dawley; Uremia

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Calcium; Carbon Isotopes; Elastin; Glycine; Heart Diseases; Kidney Diseases; Magnesium Deficiency; Male; Rats