Overweight, obesity and metabolic alterations in chronic kidney disease

Abstract

There is now solid knowledge for associating overweight and obesity with CKD. The risk for ESRD is progressively higher at increasing body mass index (BMI) levels and in extremely obese individuals such risk is 5 times higher than that in persons with normal body mass. Visceral fat, insulin resistance and inflammation are nicely inter-correlated in cross sectional studies in CKD patients but it is still untested whether the association between waist circumference or waist-hip ratio and CKD underlies a causal connection. Notwithstanding knowledge on the quantitative relationship between risk factors implicated in kidney damage is still limited, evidence derived from clinical series in patients with various renal diseases (IgA nephropathy, renal agenesia or post-nephrectomy) supports the hypothesis that obesity is an important factor in the progression and perhaps even in the initiation of CKD. Hyperfiltration is commonly found in obese persons. Due to high sympathetic activity, high levels of angiotensin II and hyperinsulinemia, obese persons display enhanced sodium reabsorption in the proximal tubule and are unable to rapidly increase sodium excretion. Enhanced proximal salt reabsorption determines a reduced delivery of sodium to the macula densa and therefore promotes afferent vasodilatation and enhanced renin synthesis. As a result of high local angiotensin II levels, the efferent arteriole is constricted in the obese. Glomerulomegaly and focal glomerulosclerosis represent the anatomical counterparts of glomerular hyperfiltration-hypertension. Hyperfiltration apart, evidence is emerging that inflammatory cytokines produced by fat cells trigger inflammation in the kidney and that this mechanism contributes to reduce renal function in the obese.