Role of the Renal Microcirculation in Progression of Chronic Kidney Injury in Obesity

Abstract

Background: Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular and renal diseases. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity. Summary and Key Message: Microvascular (MV) disease plays a pivotal role in progressive kidney injury from different etiologies such as hypertension, diabetes, and atherosclerosis, which are all important consequences of chronic obesity. The MV networks are anatomical units that are closely adapted to specific functions of nutrition and removal of waste in every organ. Damage of the small vessels in several tissues and organs has been reported in obesity and may increase cardio-renal risk. However, the mechanisms by which obesity and its attendant cardiovascular and metabolic consequences interact to cause renal MV injury and chronic kidney disease are still unclear, although substantial progress has been made in recent years. This review addresses potential mechanisms and consequences of obesity-induced renal MV injury as well as current treatments that may provide protection of the renal microcirculation and slow progressive kidney injury in obesity.

The metabolic syndrome and chronic kidney disease

“…[19] Accumulation of visceral adipose and fat infiltration of the kidney may also induce inflammation-driven neovascularization through multiple cytokines that are enriched in adipose tissue, such as tumor necrosis factor (TNF)-α and interleukin-6. [20, 21]…”

“…[30] Uric acid, which is often elevated in MetS, also inhibits NO production, thus contributing to endothelial dysfunction. [18] Renal microvascular endothelial dysfunction increases glomerular capillary wall permeability and albuminuria, which may also promote glomerular capillary loss[21] in prolonged MetS and progression of renal injury. Indeed, MetS patients show a steeper decrease in kidney function over time compared to non-MetS patients, suggesting limited renal reserve, which might be the consequence of kidney vascular remodeling and parenchymal damage in MetS.…”

Small Vessels, Big Role

“…In the kidney, the glomerular and peritubular capillaries also command glomerular filtration, tubular reabsorption, and recirculation of body fluids, nutrients, hormones, and other substances to the body 6, 7 . Endothelial dysfunction as well as functional and structural rarefaction 8 of the renal microvessels play a prominent role in inducing renal injury associated with major cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, and atherosclerosis.…”

“…Endothelial dysfunction as well as functional and structural rarefaction 8 of the renal microvessels play a prominent role in inducing renal injury associated with major cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, and atherosclerosis. Furthermore, a defective renal microcirculation is a universal pathological feature in CKD that progresses as CKD evolves and compromise both the renal nutrition and renal function 6, 7 .…”

“…Although these comorbid conditions may develop separately, they often co-exist and may potentiate injury of target organs, including the kidneys, in an additive or synergistic fashion 7, 16, 17 .…”