Clinical features and long‐term outcome of obesity‐associated focal segmental glomerulosclerosis

Praga, Manuel; Hernández, Eduardo; Morales, Enrique; Campos, Ana Pérez; Valero, María Angeles; Martı́nez, Miguel Ángel; León, Miguel A Miranda de

doi:10.1093/ndt/16.9.1790

Cited by 253 publications

(225 citation statements)

References 27 publications

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“…Microalbuminuria was detected in 25 out of 207 non-diabetic obese patients in a study performed by Valensi et al 35 These findings suggest that obesityrelated renal damage should be defined as a special form of focalsegmental glomerulosclerosis slowly progressing to end-stage renal disease. 36 …”

Section: Structural Changes In the Kidneymentioning

confidence: 99%

Mechanisms of obesity-induced hypertension

et al. 2010

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The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies. Hypertension Research (2010) 33, 386-393; doi:10.1038/hr.2010.9Keywords: leptin; obesity; pressure natriuresis; rennin-angiotensin-aldosterone system; sympathetic nervous system INTRODUCTION Obesity is a common disorder that develops from the interaction between the genotype and the environment and involves social, behavioral, cultural, physiological, metabolic and genetic factors. A large number of studies have shown that obesity has an important negative impact on health in a population, leading to the recommendation for general practitioners to have an important function in the management of this condition and of its associated comorbidities such as hypertension, hyperlipidemia and hyperinsulinemia/insulin resistance. The relationship between obesity and hypertension is well established both in adults and children. 1,2 Obese individuals exhibit higher levels of office as well as ambulatory blood pressure (BP) from childhood to old age. Obese subjects display higher BP levels than non-obese individuals even in the normotensive range. The combination of obesity, hypertension and other cardiovascular risk factors significantly increases the probability of adverse cardiovascular outcomes, and raises considerations for aggressive treatment strategies. 3 The mechanisms through which obesity directly causes hypertension are still an area of research. Human and animal studies have elucidated the function of adipose tissue derivatives (adipokines and cytokines), neurohumoral pathways, metabolic functions and modulation of pressor/depressor mechanisms. Although obesity-related hypertension may be the result of a combinatio...

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Section: Structural Changes In the Kidneymentioning

confidence: 99%

Mechanisms of obesity-induced hypertension

et al. 2010

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“…Clinically, patients may present with the nephrotic syndrome (32), although, more often, they do not have nephrosis (27,29,30). In a series of 15 obese patients, Praga et al (30) reported the absence of features of nephrotic syndrome despite heavy proteinuria.…”

Section: Renal Structure and Function In Obesitymentioning

confidence: 99%

“…This likely occurs because of afferent arteriolar dilation as a result of proximal salt reabsorption, coupled with efferent renal arteriolar vasoconstriction as a result of elevated AngII. These effects may contribute to hyperfiltration, glomerulomegaly, and later focal glomerulosclerosis (29,30). Even though GFR is increased in obesity, urinary sodium excretion in response to a saline load is often delayed, and individuals exhibit an abnormal pressure natriuresis (135,136), indicating avid proximal tubular sodium reabsorption, likely as a result of both sympathetic activation and AngII effect.…”

Section: Other Potential Hemodynamic Factorsmentioning

confidence: 99%

Obesity and Obesity-Initiated Metabolic Syndrome

Wahba

Mak

2007

Clinical Journal of the American Society of Nephrology

461

343

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There is an epidemic of obesity and the metabolic syndrome in the United States and across the world. Both entities are associated with high mortality, mainly as a result of cardiovascular disease. The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease (CKD). Several recent epidemiologic studies have shown that obesity and the metabolic syndrome are independent predictors of CKD. In addition to diabetes and hypertension, several other mechanisms have been postulated to initiate and maintain kidney injury in patients with obesity and the metabolic syndrome. This article reviews the recent epidemiologic data linking obesity and the metabolic syndrome to CKD and summarizes the potential mechanisms of renal injury in this setting, with a focus on the role of inflammation, lipotoxicity, and hemodynamic factors. Potential preventive and therapeutic modalities based on the limited evidence available are discussed.Clin , and the increase occurred for both men and women and for all age groups (2). Since then, the trend for increased prevalence has continued, particularly for adolescents and men (1). Obesity is also on the rise in other industrialized countries (3-5). The metabolic syndrome, previously known as syndrome X and a major consequence of obesity, is also on the rise (6). According to the Third National Health and Nutrition Examination Survey (NHANES III), the prevalence of the metabolic syndrome in the United States is 23% in those who are 20 yr or older and Ͼ40% in those who are 60 yr or older (7). According to the Third Adult Treatment Panel of the National Cholesterol Education Program, the metabolic syndrome is defined as the presence of at least three of the following criteria, with or without diabetes: Central obesity (waist circumference in men Ͼ102 cm and in women Ͼ88 cm), hypertriglyceridemia (Ն150 mg/dl), low HDL cholesterol (men Ͻ40 mg/dl, women Ͻ50 mg/dl), elevated fasting glucose (Ͼ110 mg/dl), and hypertension (Ն130/85 mmHg) (8). A central feature of the metabolic syndrome is insulin resistance, which results in hyperglycemia and hyperinsulinemia, and eventually leads to the development of diabetes (9). Central obesity is the most important predisposing factor for insulin resistance (9). Chronic inflammation is another feature of the metabolic syndrome, which, together with insulin resistance, results in complex metabolic derangements that contribute to the pathogenesis of hypertension, lipoprotein abnormalities, atherosclerosis, coronary artery disease, and other organ dysfunction (10,11). Both obesity and the metabolic syndrome are associated with high mortality, mainly related to cardiovascular disease (12,13). Overweight, obesity, and the metabolic syndrome have recently emerged as strong independent risk factors for chronic kidney disease (CKD) and ESRD. This article reviews the epidemiology of CKD in relationship to obesity and the metabolic syndrome and the possible mechanisms of renal injury that is caused by obesity and obesity-initiated metab...

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“…9,10 Patients with normal numbers of nephrons may develop secondary FSGS as a result of morbid obesity, which causes an increased demand for glomerular filtration that parallels increased body mass. 11,12 Secondary forms of FSGS typically have a lower incidence of nephrotic syndrome and a better overall prognosis when compared with primary (idiopathic) FSGS. 13 Whereas the mainstay of treatment for primary FSGS is immunosuppression, secondary (postadaptive) forms of FSGS are treated with RAS blockade and treatment of the underlying cause whenever possible (e.g., weight loss in the obese patient).…”

Section: Introductionmentioning

confidence: 99%

Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse

Herlitz¹,

Markowitz²,

Farris³

et al. 2010

Journal of the American Society of Nephrology

163

111

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Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed Ն40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized. INDEX CASEThe index case (patient 1) is a 30-yr-old white male professional bodybuilder who had no significant medical history and presented to a local hospital with lower extremity edema. The patient was on no prescription medications, but as part of his bodybuilding regimen, he regularly consumed a highprotein diet (Ͼ550 g/d) and dietary supplements including 10 g/d creatine monohydrate, 1000 mg/d branched-chain amino acids, 10 g/d glutamine, and multivitamins. For more than a decade, he regularly used anabolic androgenic steroids (AASs), including injectable testosterone, methyl-1-testosterone (taken orally), growth hormone, and insulin to augment his bodybuilding. At the time of biopsy, his steroid regimen consisted of growth hormone 4 IU 5 d/wk and testosterone 500 mg intramuscularly twice weekly. In addition, he took 75 mg of ephedrine and 600 mg of caffeine before each workout session.Physical examination revealed a height of 71 inches (180 cm), a weight of 295 pounds (134 kg extremely muscular, highly toned physique (Figure 1). BP was 145/80 mmHg, and there was 2ϩ bilateral lower extremity edema. The patient was found to have a serum creatinine of 2.7 mg/dl, blood urea nitrogen of 24 mg/dl, serum albumin of 1.9 g/dl, total serum protein of 5.7 g/dl, serum cholesterol of 212 mg/dl, hematocrit of 45%, and white blood cell count of 10.3 ϫ 10 9 /L with a normal differential and platelet count of 254 ϫ...

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Clinical features and long‐term outcome of obesity‐associated focal segmental glomerulosclerosis

Cited by 253 publications

References 27 publications

Mechanisms of obesity-induced hypertension

Mechanisms of obesity-induced hypertension

Obesity and Obesity-Initiated Metabolic Syndrome

Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse

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