Obesity and target organ damage: the kidney (original) (raw)
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Renal Disease in Obesity: The Need for Greater Attention
Journal of Renal Nutrition, 2006
Excess body weight may be associated with various functional/structural lesions of the kidney. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 mL/min/1.73 m2) is related to the increasing number of components of the metabolic syndrome, ie, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol, and hypertension. In the long run, end-stage renal failure may develop. An increased body mass index is particularly harmful in patients with reduced renal functional mass (unilateral renal agenesis or nephrectomy) and other renal diseases (immunoglobulin A nephritis and chronic graft dysfunction after kidney transplantation). In the pathogenesis of obesity-associated glomerulopathy, hyperfiltration is of fundamental importance. The factors involved are energy intake (high protein and salt), hyperinsulinemia, and enhanced tubuloglomerular feedback because of increased sodium reabsorption. The adrenergic and renin-angiotensin-aldosterone systems as well as glucocorticoids are stimulated. In addition, several active proteins generated in the central adipose tissue, such as leptin, proinflammatory cytokines, plasminogen activator inhibitor-1, angiotensinogen, and growth factors (transforming growth factor-beta1), as well as low levels of the protective adiponectin, may contribute to renal injury. Of greatest importance is the development of hypertension and of diabetes, which are directly related to the severity of central obesity. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise), or eventually by antiobesity medication or bariatric surgery. In the presence of glomerulopathy and/or hypertension, angiotensin converting enzyme inhibitors or angiotensin II type I receptor blockers are the drugs of choice to improve glomerular hyperfiltration.
Scope and mechanisms of obesity-related renal disease
Current Opinion in Nephrology and Hypertension, 2010
Purpose of review-Obesity is established as an important contributor of increased diabetes mellitus, hypertension, and cardiovascular disease, all of which can promote chronic kidney disease (CKD). Recently, there is a growing appreciation that even in the absence of these risks, obesity itself significantly increases CKD and accelerates its progression. Recent findings-Experimental and clinical studies reveal that adipose tissue, especially visceral fat, elaborates bioactive substances that contribute to the pathophysiologic renal hemodynamic and structural changes leading to obesity-related nephropathy. Adipocytes contain all the components of the renin-angiotensin-aldosterone system, plasminogen activator inhibitor, as well as adipocytespecific metabolites such as free fatty acids, leptin, and adiponectin which affect renal function and structure. In addition, fat is infiltrated by macrophages that can alter their phenotype and foster a proinflammatory milieu which advances pathophysiologic changes in the kidney associated with obesity. Summary-Obesity is an independent risk factor for development and progression of renal damage. While the current therapies aimed at slowing progressive renal damage include reduction in weight and rely on inhibition of the renin-angiotensin system, the approach will likely be supplemented by interventions aimed at obesity-specific targets including adipocyte-driven cytokines and inflammatory factors.
Pathophysiology of obesity-related renal dysfunction contributes to diabetic nephropathy
Current Diabetes Reports, 2012
Recent studies have demonstrated the role of insulin resistance in renal injury related to obesity, with hyperfiltration leading to glomerulomegaly in a pattern similar to that found in diabetic nephropathy. Similarities in the histologic patterns of damage from obesity and diabetes point to overlapping mechanisms of injury. In this review, we will examine the hormonal mechanisms, signaling pathways and injury patterns in renal injury resulting from obesity and attempt to draw conclusions on the reasons for these similarities.
Albuminuria in individuals whose body mass index exceeds 40 kg/m 2 is associated with the presence of large glomeruli, thickened basement membrane and epithelial cellular (podocyte) distortion. Obstructive sleep apnea magnifies glomerular injury as well, probably through a vasoconstrictive mechanism. Insulin resistance from excess fatty acids is exacerbated by decreased secretion of high molecular weight adiponectin from adipose cells in the obese state. Adiponectin potentiates insulin in its post-receptor signaling resulting in glucose oxidation in mitochondria. Recent studies of podocyte physiology have concentrated on the structural and functional requirements that prevent glomerular albumin leakage. The architecture of the podocyte involves nephrin and podocin, proteins that cooperate to keep slit pores between foot processes competent to retain albumin. Insulin and adiponectin are necessary for high-energy phosphate generation. When fatty acids bind to albumin, the toxicity to proximal renal tubules is magnified. Albumin and fatty acids are elevated in urine of individuals with obesity related nephrotic syndrome. Fatty acid accumulation and resistin inhibit insulin and adiponectin. Study of cytokines produced by adipose tissue (adiponectin and leptin) and macrophages (resistin) has led to a better understanding of the relationship between weight and hypertension. Leptin, is presumably secreted after food intake to inhibit the midbrain/ hypothalamic appetite centers. Resistance to leptin results in excess signaling to hypothalamic sympathetics leading to hypertension. Demonstration of the existence of a cerebral receptor mutation provide evidence for a role in hypertension of a central nervous reflex arc in humans. Further understanding of obesityrelated renal dysfunction has been accomplished recently using experimental models. Rapid weight loss following bariatric surgery may reverse renal pathology of obesity with restoration of normal blood pressure.
The role of obesity in kidney disease: recent findings and potential mechanisms
International Urology and Nephrology, 2011
Obesity epidemic is in rise in almost every industrialized country and continues to be a growing problem worldwide. In fact, obesity per se has been recognized as a chronic disease. Consequently, there has been a cascade of metabolic changes initiated by the markedly risen prevalence that contributes to the increased incidence of diabetes, hypertension, and cardiovascular disease. Moreover, obesity is also associated with an increased risk of chronic kidney disease (CKD). The majority of the studies indicate a direct relationship between body mass index (BMI) and CKD risk. Moreover, current evidence emphasized the fact that central obesity measurements, such as waist circumference, could be a better predictor of CKD progression and mortality than BMI. The detrimental effects of obesity on kidney outcome have been recognized in nondialysisdependent (NDD)-CKD patients. However, survival in overweight or obese CKD patients undergoing maintenance hemodialysis is paradoxically opposed compared with the general population. This ''reverse epidemiology,'' however, is valid mainly for the inflammated end-stage renal disease (ESRD) patients. In fact, renal transplant recipients with higher BMI have inferior patient and graft survival compared to patients with lower BMI. This review also provides perspectives concerning the mechanisms associated with obesity, such as the renin-angiotensin-aldosterone system (RAAS) activation, and the role of leptin, adiponectin, fetuin-A, and adipose tissue, as factors that contribute to the development of CKD. Prevention strategies for CKD patients are also discussed and should be considered by clinicians.
Adverse renal consequences of obesity
AJP: Renal Physiology, 2008
Emerging evidence indicates that obesity, even in the absence of diabetes contributes significantly to the development and progression of CKD. Glomerular hyperfiltration/hypertrophy in response to the increased metabolic needs of obesity are postulated to lead to the development of glomerulosclerosis (GS) in a manner analogous to that in reduced renal mass states. Nevertheless, the individual risk for developing GS with obesity is very low. It is proposed that glomerular hyperfiltration/hypertrophy are per se not pathogenic in the absence of an enhanced glomerular BP transmission and the modest preglomerular vasodilation that is likely present in the large majority of obese individuals is not sufficient to result in such increased BP transmission. However, in the small subset of obese individuals who are also born with a substantially reduced nephron number, there is a greater risk of enhanced glomerular BP transmission due to the substantially greater preglomerular vasodilation. Of perhaps greater clinical importance, similar additive deleterious effects of obesity on BP transmission would be expected in individuals with reduced renal mass, either congenital or acquired, or with concurrent renal disease, leading to accelerated progression. Of note, a low birth weight may be a risk factor for not only reduced nephron numbers at birth, but also for obesity and hypertension, resulting in a clustering of risk factors for progressive GS. Therefore, even though the individual risk for developing obesity GS is low, the cumulative impact of obesity on the public health burden of CKD is likely to be large because of its huge prevalence.
Renal injury in the extremely obese patients with normal renal function
Kidney International, 2008
We studied the glomerular architecture in renal biopsies of 95 patients undergoing bariatric surgery for extreme obesity but whose renal function was normal. The comparison group was 40 control patients having protocol biopsies. These latter patients had normal weight and renal function, were nondiabetic, non-hypertensive, and were undergoing nephrectomy or donating a kidney. Logistic regression models determined associations between the clinical and biochemical variables and glomerular lesions. Arterial hypertension, sleep apnea syndrome (SAS), and microalbuminuria were prevalent in the obese patients, as was hyperglycemia to a lesser extent. Focal and segmental glomerulosclerosis was present in only five extremely obese (EO) patients but absent in controls. Increased mesangial matrix, podocyte hypertrophy, mesangial cell proliferation, and glomerulomegaly were more frequent in the obese cohort than in the control group. Body mass index was a significant independent risk factor associated with glomerular lesions in all 135 patients and in the 95 EO patients, whereas SAS was associated with glomerulomegaly only in the EO. Our study shows that EO patients who lack overt clinical renal symptoms have a variety of glomerular abnormalities that correlate with body mass. Kidney International (2008) 73, 947-955 d Median values and interquartile ranges. e Mann-Whitney U-test.
Obesity and Chronic Kidney Disease
Journal of Renal Nutrition, 2010
This article summarizes the current hypotheses that link visceral obesity and kidney malfunction and provides information on the epidemiology and renal pathology resulting from visceral obesity.