Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function.

BACKGROUND Adiponectin, a newly discovered collagen-like protein of the collectin family exclusively produced by adipocytes, possesses anti-inflammatory properties. Plasma adiponectin is associated with a decreased cardiovascular risk in non-renal patients, and is reduced in obesity and insulin-resistant states. Although reports show an increase in the adiponectin level in maintenance haemodialysis, peritoneal dialysis and end-stage renal disease, there is no documentation of adiponectin levels and regulation in the early stages of chronic kidney disease (CKD). METHODS We prospectively measured glomerular filtration rate (GFR) in 48 patients with CKD using inulin clearance. Fasting blood was drawn to determine insulin, leptin, adiponectin and C-reactive protein (CRP) levels. Body fat mass was calculated using skinfold thickness measurements. RESULTS The patients' mean GFR was 53.5+/-24.9 (SD) ml/min/1.73 m2. Adiponectin was in the normal range in men (9.8+/-2.9 mg/l) and women (16.6+/-5.0 mg/l) with CKD, being significantly higher in women than men (P<0.001). Serum leptin was above normal (10.4+/-10.7 microg/l), whereas serum insulin and CRP were within their normal ranges (3.5+/-3.3 microU/ml and 2.6+/-5.0 mg/l, respectively). In linear regression analysis, adiponectin was negatively correlated with GFR (P = 0.02), fat mass (P = 0.03) and body mass index (P = 0.002), and strongly positively correlated with serum leptin (P = 0.003). A positive relationship was also found between plasma adiponectin and the urinary albumin/creatinine ratio (P = 0.007). No relationship was found between adiponectin and insulin or adiponectin and CRP. In multiple regression analysis, adiponectin was significantly positively correlated with leptin (P<0.0001), negatively with body mass index (P<0.0001) and only weakly with GFR (P = 0.04). CONCLUSIONS Despite an adverse metabolic environment in chronic renal insufficiency, serum adiponectin increases in non-obese patients when renal function deteriorates. Adiponectin is only weakly affected by renal function per se, but appears influenced by proteinuria, and more significantly by body mass index and the change in serum leptin that accompanies decline in renal function.

[1]  S. Maruoka,et al.  Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. , 2002, European journal of endocrinology.

[2]  T. Funahashi,et al.  Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. , 2001, Diabetes.

[3]  T Nakamura,et al.  Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. , 1999, Circulation.

[4]  F. Lönnqvist,et al.  Low leptin gene expression and hyperleptinemia in chronic renal failure. , 1998, Kidney international.

[5]  P. Vague,et al.  Increased Plasminogen Activator Inhibitor Activity in Non Insulin Dependent Diabetic Patients – Relationship with Plasma Insulin , 1989, Thrombosis and Haemostasis.

[6]  C. Yen,et al.  Adiponectin in peritoneal dialysis patients: a comparison with hemodialysis patients and subjects with normal renal function. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[7]  T. Tai,et al.  Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. , 2001, The Journal of clinical endocrinology and metabolism.

[8]  S. Kihara,et al.  Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors. , 2003, Kidney international. Supplement.

[9]  T Nakamura,et al.  Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[10]  W. Kraus,et al.  Adiponectin is not altered with exercise training despite enhanced insulin action. , 2002, American journal of physiology. Endocrinology and metabolism.

[11]  Y. Matsuzawa,et al.  Serum adiponectin and leptin levels in patients with lipodystrophies. , 2004, The Journal of clinical endocrinology and metabolism.

[12]  S. Kihara,et al.  Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. , 2002, Journal of the American Society of Nephrology : JASN.

[13]  Y. Halvorsen,et al.  Human adipocyte proteomics--a complementary way of looking at fat. , 2000, Pharmacogenomics.

[14]  NoriyukiOuchi,et al.  Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages , 2001 .

[15]  T Nakamura,et al.  Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. , 1999, Biochemical and biophysical research communications.

[16]  Philipp E. Scherer,et al.  A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes (*) , 1995, The Journal of Biological Chemistry.

[17]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[18]  K. Shimamoto,et al.  Blockade of the Renin-Angiotensin System Increases Adiponectin Concentrations in Patients With Essential Hypertension , 2003, Hypertension.

[19]  F. Schick,et al.  Relationship of serum adiponectin and leptin concentrations with body fat distribution in humans. , 2003, Obesity research.

[20]  C. Wanner,et al.  Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. , 1999, Kidney international.

[21]  B. Nicklas,et al.  Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity. , 2003, Diabetes care.

[22]  Arya M. Sharma,et al.  Association between adiponectin and mediators of inflammation in obese women. , 2003, Diabetes.

[23]  P. Stenvinkel,et al.  Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin. , 2004, Kidney international.

[24]  T. Funahashi,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance , 2022 .

[25]  J. Durnin,et al.  Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 Years , 1974, British Journal of Nutrition.