Chronic kidney disease: Definition, updated epidemiology, staging, and mechanisms of increased cardiovascular risk

According to the CDC, 1 in 3 adults with diabetes and 1 in 5 adults with hypertension may have CKD. According to the current CDC statistics, CKD is more common in people aged 65 years or older (38%) than in people aged 45-64 years (13%) or 18-44 years (7%), and is slightly more common in women (15%) than men (12%); moreover, African Americans are about 3 times more likely than whites to develop ESKD. 5 MECHANISMS LEADING TO CKD In the Western world, the main risk factor for CKD development is diabetes, which is present in 30%–50% of CKD patients. 6 Hypertension and smoking are other strong factors increasing the risk of CKD as well as the speed of its progression. 6 Instead, in India, Asia, and Sub-Saharan Africa, the leading cause of CKD is glomerulonephritis, followed by CKD of unknown genesis, probably prompted by soil pollution with heavy metals and pesticides and excessive use of herbal-based traditional medicines. 7 HIV contributes significantly to CKD due to the direct glomerular interstitial damage caused by HIV per se and to the significant nephrotoxicity of antiretroviral therapies. 6 Despite the diverse etiologies, the main mechanism of CKD is believed to heavily rely on microvasculature dysfunction. [...]proteinuria develops and tubular epithelium becomes exposed to proteins such as albumin, compliment system components, and cytokines which further exacerbate the inflammatory response. 8 Accumulation of damaged DNA in tubular epithelium through the chronic inflammation produces cell cycle arrest, accompanied by a switch to a specific type of secretory phenotype, which further facilitates pro-fibrotic modifications. 8 Uncontrolled accumulation of extracellular matrix decreases the capillary density, thus obstructing oxygen and nutrient supply to tubular cells. Other parameters to measure arterial stiffness include the augmentation index at heart rate 75 bpm (AIx@75) 25 and the ambulatory arterial stiffness index. 26 Changes in arterial stiffness may be hastened in hypertensive patients whose treatments fail to reduce their PWV. [...]failure to reduce PWV in hypertensive patients was a significant predictor of cardiovascular death in ESKD despite reasonable blood pressure control. 27 There is conflicting evidence that early atherosclerosis is linked to increased arterial stiffness.