Anemia As A Progression Promoter In Diabetic Nephropathy

Several studies have shown that anemia is an independent risk factor for progression in both diabetic and nondiabetic renal disease (22). For example, in the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan Study (RENAAL) study of patients with type 2 diabetes and nephropathy, anemia at the start of the study was a strong predictor of the rate of doubling of serum creatinine or development of ESRD (23). Similarly, the Canadian multicenter cohort study of 313 predialysis patients with CKD showed that a decrease in baseline Hb of 5 g/L over a median follow-up of 2 yr was associated with a 13% shorter time to initiation of renal replacement (24). The time to renal replacement shortened more than eightfold as Hb fell from 130 to less than 100 g/L.

However, it remains to be established whether patients with anemia simply have more severe renal disease. Anemia per se does not result in renal damage. As anemia may be considered a manifestation of renal injury, it is easy to imagine that damaged kidneys may be subject to more aggressive renal disease. Nonetheless, there are several potential mechanisms linking anemia with the progression of DN.

For instance, tissue hypoxia is a common mechanism for progression of various forms of renal disease in addition to high blood pressure and proteinuria (14). Anemia may induce mitogenic and fibrogenic stimuli by lowering the partial oxygen tension in the renal cortex. This could be mediated by HIF-1 which regulates genes involved in angiogenesis (such as the prosclerotic mitogen, VEGF), vasomotor response (inducible nitric oxide synthase), heme oxygenase-1 and endothelins, glycolysis (the glucose transporter GLUT-1 and glycolytic enzymes), matrix metabolism (transforming growth factor-Pj, collagens, and matrix metalloproteinases), and cell survival, all pathways implicated in the pathogenesis of progressive renal disease.

A major consequence of anemia is an increase in oxidative stress (25), a key mediator in the development and progression of diabetic renal disease. This may be mediated by the loss of antioxidant properties of erythrocytes including the enzymes superoxide dismutase, catalase, and other antioxidant proteins. In addition, renal anemia is associated with increased production of free radicals. It is conceivable that the combination of increased oxidative stress and tissue hypoxia associated with anemia may act to stimulate the production of extracellular matrix, increasing interstitial fibrosis and tubular apoptosis, and lead to tubular atrophy associated with progressive renal disease.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook


Post a comment