Circulating leptin levels predict the decline in renal function with age in a sample of adult men (The Olivetti Heart Study)

Leptin (LPT) is associated with a number of cardiovascular risk factors, such as high blood pressure (BP), insulin resistance and excess in body weight. Some studies find an unfavorable cross-sectional association between LPT and renal disease, in particular in patients with already known kidney dysfunction. There are few data on the relationship between LPT and changes in renal function over time in subjects without evidence of kidney dysfunction. Hence, the aim of this study is to estimate the predictive role of LPT on the decline in renal function occurring in an 8-year follow-up observation of a sample of adult apparently healthy men (The Olivetti Heart Study). The study includes 319 untreated normotensive and nondiabetic men without clinical evidence of renal dysfunction (creatinine clearance-CrCl > 60 mL/min/1.73 m2) at baseline. At baseline, LPT is significantly and positively associated with BMI, abdominal circumference, BP and Homa index, no relationship is found with CrCl. At the end of the 8-year follow-up, a significant association is detected between baseline LPT and changes occurring in BP. Moreover, an inverse correlation with changes in CrCl is found (r = − 0.12). This unfavorable relationship between baseline LPT and decline in renal function is also confirmed in the multivariate analyses, after adjustment for all potential confounders (R2 = 0.42, p < 0.01). The results of this prospective investigation suggest a predictive role of circulating LPT levels on decline in renal function over time, independently of main potential confounders, in normotensive and nondiabetic men with normal renal function at baseline.

[1]  L. Tartaglia,et al.  The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[2]  H. Yatsuya,et al.  Association between serum leptin concentration and white blood cell count in middle‐aged Japanese men and women , 2005, Diabetes/metabolism research and reviews.

[3]  B Lindholm,et al.  Soluble leptin receptors and serum leptin in end‐stage renal disease: relationship with inflammation and body composition , 2002, European journal of clinical investigation.

[4]  J. Zhen,et al.  Leptin promotes endothelial dysfunction in chronic kidney disease through AKT/GSK3β and β-catenin signals. , 2016, Biochemical and biophysical research communications.

[5]  M. Reilly,et al.  Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. , 2008, Journal of the American College of Cardiology.

[6]  K. Sharma,et al.  Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients. , 1997, Kidney international.

[7]  Paul M. Ridker,et al.  Prospective Study of C-Reactive Protein, Homocysteine, and Plasma Lipid Levels as Predictors of Sudden Cardiac Death , 2002, Circulation.

[8]  P. Strazzullo,et al.  Plasma leptin measurements in epidemiological investigation: comparison of two commonly used assays and estimate of regression dilution bias. , 2002, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[9]  Y. Kaneda,et al.  Leptin Induces Mitochondrial Superoxide Production and Monocyte Chemoattractant Protein-1 Expression in Aortic Endothelial Cells by Increasing Fatty Acid Oxidation via Protein Kinase A* , 2001, The Journal of Biological Chemistry.

[10]  M. Lane,et al.  Leptin regulates proinflammatory immune responses. , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  A. Więcek,et al.  Plasma leptin concentration in kidney transplant patients during the early post-transplant period. , 1998, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[12]  Jeroen J. Bax,et al.  2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). , 2007, Blood pressure.

[13]  A. Siani,et al.  High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study. , 2008, The Journal of clinical endocrinology and metabolism.

[14]  A. Dominiczak,et al.  2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) , 2007, European heart journal.

[15]  E. Ravussin,et al.  Relationship of the white blood cell count to body fat: role of leptin , 1997, British journal of haematology.

[16]  F. Cappuccio,et al.  Uric acid metabolism and tubular sodium handling. Results from a population-based study. , 1993, JAMA.

[17]  J. Coresh,et al.  Prevalence of chronic kidney disease in the United States. , 2007, JAMA.

[18]  C. Mélot,et al.  Leptin-Induced Endothelium-Independent Vasoconstriction in Thoracic Aorta and Pulmonary Artery of Spontaneously Hypertensive Rats: Role of Calcium Channels and Stores , 2017, PloS one.

[19]  F. Cappuccio,et al.  Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men. , 2012, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[20]  P. Brousset,et al.  High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects , 2000, International Journal of Obesity.

[21]  Liwei Lu,et al.  Role of leptin in immunity. , 2007, Cellular & molecular immunology.

[22]  V. Somers,et al.  Independent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans , 2004, Circulation.

[23]  Ose,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events* , 2002 .

[24]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[25]  L. Ferrucci,et al.  Longitudinal Association between Serum Leptin Concentration and Glomerular Filtration Rate in Humans , 2015, PloS one.

[26]  J. Friedman,et al.  Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. , 1996, The Journal of clinical investigation.

[27]  P. Ridker,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events☆ , 2003 .

[28]  J. Preželj,et al.  Adipocytokines are associated with renal function in patients with normal range glomerular filtration rate and type 2 diabetes. , 2009, Cytokine.

[29]  F. Cappuccio,et al.  Circulating leptin levels predict the development of metabolic syndrome in middle-aged men: an 8-year follow-up study , 2007, Journal of hypertension.

[30]  V. Somers,et al.  Leptin Induces C-Reactive Protein Expression in Vascular Endothelial Cells , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[31]  V. Sánchez-Margalet,et al.  Human leptin stimulates proliferation and activation of human circulating monocytes. , 1999, Cellular immunology.

[32]  M. Trevisan,et al.  Altered renal sodium handling in men with abdominal adiposity: a link to hypertension , 2001, Journal of hypertension.

[33]  P. Shepherd,et al.  Glucose-dependent Regulation of Cholesterol Ester Metabolism in Macrophages by Insulin and Leptin* , 2002, The Journal of Biological Chemistry.

[34]  A. Bitla,et al.  Adipokines and their Relation to Endothelial Dysfunction in Patients with Chronic Kidney Disease. , 2016, Journal of clinical and diagnostic research : JCDR.

[35]  E. Ortega,et al.  White blood cell count is associated with carotid and femoral atherosclerosis. , 2012, Atherosclerosis.