Abstract
Obesity is an independent risk factor for chronic kidney disease (CKD). The mechanisms linking obesity and CKD include systemic changes such as high blood pressure and hyperglycemia, and intrarenal effects relating to lipid accumulation. Normal lipid metabolism is integral to renal physiology and disturbances of renal lipid and energy metabolism are increasingly being linked with kidney disease. AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) are important regulators of fatty acid oxidation, which is frequently abnormal in the kidney with CKD. A high fat diet reduces renal AMPK activity, thereby contributing to reduced fatty acid oxidation and energy imbalance, and treatments to activate AMPK are beneficial in animal models of obesity-related CKD. Studies have found that the specific cell types affected by excessive lipid accumulation are proximal tubular cells, podocytes, and mesangial cells. Targeting disturbances of renal energy metabolism is a promising approach to addressing the current epidemic of obesity-related kidney disease.
Highlights
Obesity is an important and independent risk factor for the development and progression of chronic kidney disease (CKD) [1,2]
A remaining question, is that whilst this may explain the association of various causes of CKD with lipid accumulation, it does not seem to explain the association between obesity and CKD, that is seen in both humans and animal models
Obesity is established as an important and independent risk factor for CKD. The mechanisms underlying this association involve systemic effects such as hypertension, hyperglycemia, and dyslipidemia. Intrarenal effects such as impaired fatty acid oxidation and lipid accumulation may further contribute to CKD pathogenesis (Figure 3)
Summary
Obesity is an important and independent risk factor for the development and progression of chronic kidney disease (CKD) [1,2]. While it is well known that obesity increases the risk of high blood pressure (hypertension) and diabetes, themselves both major risk factors for CKD [3], studies indicate that hypertension and diabetes only partly explain the association between obesity and CKD, suggesting the involvement of other pathways [4,5]. The mechanisms underlying the strong epidemiological link between excess adiposity and kidney disease are not well understood. Both systemic changes and processes within the kidney appear to contribute. Whilst the observed association between the accumulation of excessive lipids and CKD is well known, there is disagreement as to whether this lipid accumulation is directly toxic, or whether the primary impairment is defective lipid metabolism [8,9,10,11,12]
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