Endogenous Sex Steroid Hormones and Measures of Chronic Kidney Disease
Endogenous Sex Steroid Hormones and Measures of Chronic Kidney Disease
Context Sex steroid hormones may play a role in the pathogenesis of chronic kidney disease (CKD).
Objective To determine whether sex steroid hormone concentrations are associated with kidney function or kidney damage in men in the general US population. We hypothesized that lower serum testosterone and E2 concentrations are associated with CKD.
Design patients and measurements Serum sex steroid hormones were measured by electrochemiluminescence immunoassays for 1470 men who attended the morning session of Phase I of the Third National Health and Nutrition Examination Survey (NHANES III). We used two measures of CKD, estimated glomerular filtration rate (eGFR) < 60 ml/min/1·73 m calculated using serum creatinine or cystatin C levels and the abbreviated Modification of Diet in Renal Disease Study formulae and urinary albumin : creatinine ratio (UACR) ≥ 17 mg/g.
Results Mean free testosterone concentration was higher in men with an eGFR < 60 ml/min/1·73 m than in men with a higher eGFR. In multivariable adjusted models, the odds of an eGFR < 60 ml/min/1·73 m or UACR ≥ 17 mg/g did not differ across tertiles of hormones with the exception of free E2; those in the highest vs. lowest tertile had an elevated odds of decreased eGFR (OR: 3·04, 95% CI (1·22, 7·57); P-trend = 0·02).
Conclusions In a nationally representative sample of US adult men, higher free E2 concentration was significantly associated with an eGFR < 60 ml/min/1·73 m as assessed by serum creatinine or cystatin C even after multivariable adjustment. These findings are in contrast to the hypothesis that oestrogens may protect against CKD, though reverse causation cannot be ruled out. Longitudinal investigation of the role of oestrogens in kidney haemodynamics, function, and pathophysiology is warranted.
An estimated 26·3 million individuals in the United States have chronic kidney disease (CKD), and of these, the majority suffer from mild to moderate kidney dysfunction. The major risk factors for CKD include diabetes, hypertension, obesity, older age and smoking, however, our understanding of the pathophysiology of CKD is yet incomplete. Due to the population burden of CKD and its sequelae, increasing focus has been placed on understanding the pathways and mechanisms leading to CKD.
Sex steroid hormones may play a role in the development of CKD, as they affect sodium handling and renal haemodynamics, and may be a contributory factor in the more pronounced rates of kidney decline, age-related kidney disease and end stage renal disease observed in men vs. women. Animal studies have shown higher endogenous testosterone to be detrimental to overall kidney function and vasculature, and that lower levels are protective against hypertension. In contrast, studies in humans (males) have found low levels of circulating testosterone to be associated with hypertension and elevated serum cholesterol and glucose, as well as with diabetes. Endogenous oestrogens are believed to protect the kidneys and the vascular wall against damage in both men and women in human and animal studies. Sex steroid hormones may also mediate the effect of some of the risk factors (e.g. smoking) for CKD. Elucidation of the effect of sex steroid hormones on the development of CKD is further complicated by reverse causation; that is, men with CKD have been found to have disturbances in sex steroid hormone levels. More specifically, total and free testosterone concentrations are reduced while total plasma oestrogen levels are elevated, and SHBG levels are normal.
The relation between sex steroid hormones and kidney disease has not been well-explored in epidemiological studies. The purpose of the current investigation was to determine whether sex steroid hormone concentrations are associated with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1·73 m or a urinary albumin : creatinine ratio (UACR) ≥ 17 mg/g, both indicators of CKD, in men in the general US population. We hypothesized that lower serum testosterone and E2 concentrations are associated with worse kidney function and a high prevalence of kidney damage.
Abstract and Introduction
Abstract
Context Sex steroid hormones may play a role in the pathogenesis of chronic kidney disease (CKD).
Objective To determine whether sex steroid hormone concentrations are associated with kidney function or kidney damage in men in the general US population. We hypothesized that lower serum testosterone and E2 concentrations are associated with CKD.
Design patients and measurements Serum sex steroid hormones were measured by electrochemiluminescence immunoassays for 1470 men who attended the morning session of Phase I of the Third National Health and Nutrition Examination Survey (NHANES III). We used two measures of CKD, estimated glomerular filtration rate (eGFR) < 60 ml/min/1·73 m calculated using serum creatinine or cystatin C levels and the abbreviated Modification of Diet in Renal Disease Study formulae and urinary albumin : creatinine ratio (UACR) ≥ 17 mg/g.
Results Mean free testosterone concentration was higher in men with an eGFR < 60 ml/min/1·73 m than in men with a higher eGFR. In multivariable adjusted models, the odds of an eGFR < 60 ml/min/1·73 m or UACR ≥ 17 mg/g did not differ across tertiles of hormones with the exception of free E2; those in the highest vs. lowest tertile had an elevated odds of decreased eGFR (OR: 3·04, 95% CI (1·22, 7·57); P-trend = 0·02).
Conclusions In a nationally representative sample of US adult men, higher free E2 concentration was significantly associated with an eGFR < 60 ml/min/1·73 m as assessed by serum creatinine or cystatin C even after multivariable adjustment. These findings are in contrast to the hypothesis that oestrogens may protect against CKD, though reverse causation cannot be ruled out. Longitudinal investigation of the role of oestrogens in kidney haemodynamics, function, and pathophysiology is warranted.
Introduction
An estimated 26·3 million individuals in the United States have chronic kidney disease (CKD), and of these, the majority suffer from mild to moderate kidney dysfunction. The major risk factors for CKD include diabetes, hypertension, obesity, older age and smoking, however, our understanding of the pathophysiology of CKD is yet incomplete. Due to the population burden of CKD and its sequelae, increasing focus has been placed on understanding the pathways and mechanisms leading to CKD.
Sex steroid hormones may play a role in the development of CKD, as they affect sodium handling and renal haemodynamics, and may be a contributory factor in the more pronounced rates of kidney decline, age-related kidney disease and end stage renal disease observed in men vs. women. Animal studies have shown higher endogenous testosterone to be detrimental to overall kidney function and vasculature, and that lower levels are protective against hypertension. In contrast, studies in humans (males) have found low levels of circulating testosterone to be associated with hypertension and elevated serum cholesterol and glucose, as well as with diabetes. Endogenous oestrogens are believed to protect the kidneys and the vascular wall against damage in both men and women in human and animal studies. Sex steroid hormones may also mediate the effect of some of the risk factors (e.g. smoking) for CKD. Elucidation of the effect of sex steroid hormones on the development of CKD is further complicated by reverse causation; that is, men with CKD have been found to have disturbances in sex steroid hormone levels. More specifically, total and free testosterone concentrations are reduced while total plasma oestrogen levels are elevated, and SHBG levels are normal.
The relation between sex steroid hormones and kidney disease has not been well-explored in epidemiological studies. The purpose of the current investigation was to determine whether sex steroid hormone concentrations are associated with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1·73 m or a urinary albumin : creatinine ratio (UACR) ≥ 17 mg/g, both indicators of CKD, in men in the general US population. We hypothesized that lower serum testosterone and E2 concentrations are associated with worse kidney function and a high prevalence of kidney damage.
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