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Figure 1. Putative mechanisms of action whereby obesity causes chronic kidney disease. 285 Perspectiva Obesity and kidney disease - C. P. Kovesdy et al The deleterious effect of obesity on the kidneys extends to other complications such as nephrolithiasis and kidney malignancies. Higher BMI is associated with an increased prevalence25 and incidence26,27 of nephrolithiasis. Furthermore, weight gain over time, and higher baseline WC were also associated with higher incidence of nephrolithiasis27. Obesity is associated with various types of malignancies, particularly cancers of the kidneys. In a population-based study of 5.24 million individuals from the UK, a 5 kg/m2 higher BMI was associated with a 25% higher risk of kidney cancers, with 10% of all kidney cancers attributable to excess weight28. Another large analysis examining the global burden of obesity on malignancies estimated that 17% and 26% of all kidney cancers in men and women, respectively, were attributable to excess weight29. The association between obesity and kidney cancers was consistent in both men and women, and across populations from different parts of the world in a meta-analysis that included data from 221 studies (of which 17 examined kidney cancers)30. Among the cancers examined in this meta-analysis, kidney cancers had the third highest risk associated with obesity (relative risk per 5 kg/m2 higher BMI: 1.24, 95%CI 1.20-1.28, p < 0.0001)30. Mechanisms of action underlying the renal effects of obesity Obesity results in complex metabolic abnormalities which have wide-ranging effects on diseases affecting the kidneys. The exact mechanisms whereby obesity may worsen or cause CKD remain unclear. The fact that most obese individuals never develop CKD, and the distinction of up to as many as 25% of obese individuals as “metabolically healthy” suggests that increased weight alone is not sufficient to induce kidney damage31. Some of the deleterious renal consequences of obesity may be mediated by downstream comorbid conditions such as diabetes mellitus or hypertension, but there are also effects of adiposity which could impact the kidneys directly, induced by the endocrine activity of the adipose tissue via production of (among others) adiponectin32, leptin33 and resistin34 (Figure 1). These include the development of inflammation35, oxidative stress36, abnormal lipid metabolism37, activation of the renin-angiotensin aldosterone system38, and increased production of insulin and insulin resistance39,40. These various effects result in specific pathologic changes in the kidneys41 which could underlie the higher risk of CKD seen in observational studies. These include ectopic lipid accumulation42 and increased deposition of renal sinus fat43,44, the development of glomerular hypertension and increased glomerular permeability caused by hyperfiltration-related glomerular filtration barrier injury45, and ultimately the development of glomerulomegaly46, and focal or segmental glomerulosclerosis41 (Figure 2). The incidence Figure 2. Obesity-related perihilar focal segmental glomerulosclerosis on a background of glomerulomegaly. Periodic Acid-Schiff stain, original magnification 400x. Courtesy of Dr. Patrick D. Walker, MD; Arkana Laboratories, Little Rock, AR. Rev Med Chile 2017; 145: 281-291


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