Role of Serum ADAM 17 (A Disintegrin And Metalloprotease 17) and Caspase 3 in Patients With Chronic Kidney Disease

Kidney diseases represent a global public health problem ,It is estimated that 10-15% of the population is affected by Chronic kidney disease.(1) Chronic kidney disease (CKD) is defined by persistent urine and structural abnormalities or impaired excretory renal function ( an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2, persisting for three months or more suggestive of a loss of functional nephrons) (2) the most common contributing factors to CKD include genetic abnormalities and ageing, while the most common underlying diseases associated with CKD are diabetes and hypertension However, CKD can be also due to infectious diseases, autoimmune diseases (such as lupus), and medications (3) A disintegrin and metalloproteinase (ADAM) 17, also known as tumour necrosis factor α-converting enzyme (TACE), is a metalloproteinase that releases the ectodomains of most growth factors, cytokines, receptors and enzymes and has been associated with the presence of chronic kidney disease (5) Clinical and experimental studies have shown that ADAM17 is involved in chronic kidney disease (CKD) with a proinflammatory and profibrotic role, suggesting that it could be an important mediator of CKD progression. ADAM17 inhibition attenuates fibrosis and inflammation, suggesting that its inhibition may be a possible new valuable therapeutic tool in fibrotic kidney disease treatment(6) Caspases (cysteine aspartases, cysteine-aspartic proteases) are protease enzymes which play a role in apoptotic pathway. Their name derives from their specific cysteine protease activity . Most cells have caspases in an inactive proenzyme form, which is activated and induces other pro-caspases, thus initiating a protease cascade. This process is able to amplify the apoptotic signaling pathway and to induce rapid cell death, ,Caspase-3 plays a dominant role in apoptosis, involved in the pathogenesis and progression of chronic kidney disease (CKD).(7)