Immunologic and endocrine functions of adipose tissue: implications for kidney disease (original) (raw)

• Jha, V. et al. Chronic kidney disease: global dimension and perspectives. Lancet 382, 260–272 (2013).
  PubMed Google Scholar
• Hall, M. E. et al. Obesity, hypertension, and chronic kidney disease. Int. J. Nephrol. Renovasc. Dis. 7, 75–88 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Maric-Bilkan, C. Obesity and diabetic kidney disease. Med. Clin. North Am. 97, 59–74 (2013).
  Article PubMed Google Scholar
• Wickman, C. & Kramer, H. Obesity and kidney disease: potential mechanisms. Semin. Nephrol. 33, 14–22 (2013).
  Article CAS PubMed Google Scholar
• Satirapoj, B. et al. Obesity and its relation to chronic kidney disease: a population-based, cross-sectional study of a Thai army population and relatives. Nephrology (Carlton) 18, 229–234 (2013).
  Article CAS Google Scholar
• Wang, Y., Chen, X., Song, Y., Caballero, B. & Cheskin, L. J. Association between obesity and kidney disease: a systematic review and meta-analysis. Kidney Int. 73, 19–33 (2008). The findings of this meta-analysis suggest overweight and obesity are associated with a high risk of kidney disease.
  Article CAS PubMed Google Scholar
• World Health Organization. Obesity and overweight — fact sheet. WHO http://www.who.int/mediacentre/factsheets/fs311/en (2017).
• D'Agati, V. D. et al. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat. Rev. Nephrol. 12, 453–471 (2016).
  Article CAS PubMed Google Scholar
• Tran, M.-H., Foster, C. E., Kalantar-Zadeh, K. & Ichii, H. Kidney transplantation in obese patients. World J. Transplant. 6, 135–143 (2016).
  Article PubMed PubMed Central Google Scholar
• Chagnac, A. et al. The effects of weight loss on renal function in patients with severe obesity. J. Am. Soc. Nephrol. 14, 1480–1486 (2003).
  Article PubMed Google Scholar
• Tirosh, A. et al. Renal function following three distinct weight loss dietary strategies during 2 years of a randomized controlled trial. Diabetes Care 36, 2225–2232 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Morales, E. & Praga, M. The effect of weight loss in obesity and chronic kidney disease. Curr. Hypertens. Rep. 14, 170–176 (2012).
  Article PubMed Google Scholar
• Teta, D. Weight loss in obese patients with chronic kidney disease: who and how? J. Ren. Care 36 (Suppl. 1), 163–171 (2010).
  Article PubMed Google Scholar
• Wu, J. et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366–376 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Cohen, P. & Spiegelman, B. M. Brown and beige fat: molecular parts of a thermogenic machine. Diabetes 64, 2346–2351 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Giordano, A., Smorlesi, A., Frontini, A., Barbatelli, G. & Cinti, S. White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ. Eur. J. Endocrinol. 170, R159–R171 (2014).
  Article CAS PubMed Google Scholar
• Hausman, D. B., DiGirolamo, M., Bartness, T. J., Hausman, G. J. & Martin, R. J. The biology of white adipocyte proliferation. Obes. Rev. 2, 239–254 (2001).
  Article CAS PubMed Google Scholar
• Cinti, S. The adipose organ. Prostaglandins Leukot. Essent. Fatty Acids 73, 9–15 (2005).
  Article CAS PubMed Google Scholar
• Ussar, S. et al. ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. Sci. Transl Med. 6, 247ra103 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• de Jong, J. M. A., Larsson, O., Cannon, B. & Nedergaard, J. A stringent validation of mouse adipose tissue identity markers. Am. J. Physiol. Endocrinol. Metab. 308, E1085–E1105 (2015).
  Article CAS PubMed Google Scholar
• Rosen, E. D. & Spiegelman, B. M. What we talk about when we talk about fat. Cell 156, 20–44 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Dadson, P. et al. Effect of bariatric surgery on adipose tissue glucose metabolism in different depots in patients with or without type 2 diabetes. Diabetes Care 39, 292–299 (2016).
  CAS PubMed Google Scholar
• O'Rourke, R. W. et al. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-γ in inflammation in human adipose tissue. Int. J. Obes. (Lond.). 33, 978–990 (2009).
  Article CAS PubMed Central Google Scholar
• Wijayatunga, N. N. et al. Adipose depot-specific differences in transcriptome and microRNA expression in high fat diet induced obese mice. FASEB J. 30, 622–626 (2016).
  Google Scholar
• Wang, Q. A., Tao, C., Gupta, R. K. & Scherer, P. E. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat. Med. 19, 1338–1344 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Jeffery, E. et al. The adipose tissue microenvironment regulates depot-specific adipogenesis in obesity. Cell Metab. 24, 142–150 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Ferrante, A. W. Jr. The immune cells in adipose tissue. Diabetes. Obes. Metab. 15 (Suppl. 3), 34–38 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Huh, J. Y., Park, Y. J., Ham, M. & Kim, J. B. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol. Cells 37, 365–371 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Cipolletta, D. Adipose tissue-resident regulatory T cells: phenotypic specialization, functions and therapeutic potential. Immunology 142, 517–525 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Becker, M., Levings, M. K. & Daniel, C. Adipose-tissue regulatory T cells: critical players in adipose-immune crosstalk. Eur. J. Immunol. http:dx.doi.org/10.1002/eji.201646739 (2017).
• Weisberg, S. P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).
  CAS PubMed PubMed Central Google Scholar
• Murano, I. et al. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J. Lipid Res. 49, 1562–1568 (2008).
  Article CAS PubMed Google Scholar
• Amano, S. U. et al. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab. 19, 162–171 (2014).
  Article CAS PubMed Google Scholar
• Oh, D. Y., Morinaga, H., Talukdar, S., Bae, E. J. & Olefsky, J. M. Increased macrophage migration into adipose tissue in obese mice. Diabetes 61, 346–354 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Zheng, C. et al. Local proliferation initiates macrophage accumulation in adipose tissue during obesity. Cell Death Dis. 7, e2167 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Zamarron, B. F. et al. Macrophage proliferation sustains adipose tissue inflammation in formerly obese mice. Diabetes 66, 392–406 (2017).
  CAS PubMed Google Scholar
• Magkos, F. et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 23, 591–601 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Bradley, D. et al. Gastric bypass and banding equally improve insulin sensitivity and β cell function. J. Clin. Invest. 122, 4667–4674 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Haase, J. et al. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia 57, 562–571 (2014).
  Article CAS PubMed Google Scholar
• Tardelli, M. et al. Osteopontin is a key player for local adipose tissue macrophage proliferation in obesity. Mol. Metab. 5, 1131–1137 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Lumeng, C. N., Bodzin, J. L. & Saltiel, A. R. Obesity induces a phenotypic switch in adipose tissuemacrophage polarization. J. Clin. Invest. 117, 175–184 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Lesna, I. K. et al. Human adipose tissue accumulation is associated with pro-inflammatory changes in subcutaneous rather than visceral adipose tissue. Nutr. Diabetes 7, e264 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Kralova Lesna, I. et al. Characterisation and comparison of adipose tissue macrophages from human subcutaneous, visceral and perivascular adipose tissue. J. Transl Med. 14, 208 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Shankar, A., Syamala, S., Xiao, J. & Muntner, P. Relationship between plasma leptin level and chronic kidney disease. Int. J. Nephrol. 2012, 269532 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Bluher, M. Adipokines — removing road blocks to obesity and diabetes therapy. Mol. Metab. 3, 230–240 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Fasshauer, M. & Bluher, M. Adipokines in health and disease. Trends Pharmacol. Sci. 36, 461–470 (2015).
  Article CAS PubMed Google Scholar
• Wang, G.-X., Zhao, X.-Y. & Lin, J. D. The brown fat secretome: metabolic functions beyond thermogenesis. Trends Endocrinol. Metab. 26, 231–237 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Villarroya, F., Cereijo, R., Villarroya, J. & Giralt, M. Brown adipose tissue as a secretory organ. Nat. Rev. Endocrinol. 13, 26–35 (2017).
  Article CAS PubMed Google Scholar
• Pajvani, U. B. et al. Fat apoptosis through targeted activation of caspase 8: a new mouse model of inducible and reversible lipoatrophy. Nat. Med. 11, 797–803 (2005). This study uses inducible fatless mice to study the roles of adipocytes in the regulation of multiple pathophysiological functions.
  Article CAS PubMed Google Scholar
• Wernstedt Asterholm, I. et al. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab. 20, 103–118 (2014). This paper establishes the important beneficial roles of inflammation on adipose tissues.
  Article CAS PubMed Google Scholar
• Virtue, S. et al. Prostaglandin profiling reveals a role for haematopoietic prostaglandin D synthase in adipose tissue macrophage polarisation in mice and humans. Int. J. Obes. (Lond.) 39, 1151–1160 (2015).
  Article CAS Google Scholar
• Ricciotti, E. & FitzGerald, G. A. Prostaglandins and inflammation. Arterioscler. Thromb. Vasc. Biol. 31, 986–1000 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Nasrallah, R., Hassouneh, R. & Hebert, R. L. Chronic kidney disease: targeting prostaglandin E2 receptors. Am. J. Physiol. Renal Physiol. 307, F243–F250 (2014).
  Article CAS PubMed Google Scholar
• Mothe-Satney, I. et al. Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice. Diabetes 61, 2311–2319 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Sharma, J. N. & Mohammed, L. A. The role of leukotrienes in the pathophysiology of inflammatory disorders: is there a case for revisiting leukotrienes as therapeutic targets? Inflammopharmacology 14, 10–16 (2006).
  Article CAS PubMed Google Scholar
• Ying, W. et al. Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling. J. Clin. Invest. 127, 1019–1030 (2017).
  Article PubMed PubMed Central Google Scholar
• Mehmood, Z. H. & Papandreou, D. An updated mini review of vitamin D and obesity: adipogenesis and inflammation state. Open Access Maced. J. Med. Sci. 4, 526–532 (2016).
  Article PubMed PubMed Central Google Scholar
• Abbas, M. A. Physiological functions of Vitamin D in adipose tissue. J. Steroid Biochem. Mol. Biol. 165, 369–381 (2017).
  Article CAS PubMed Google Scholar
• Mittendorfer, B. Origins of metabolic complications in obesity: adipose tissue and free fatty acid trafficking. Curr. Opin. Clin. Nutr. Metab. Care 14, 535–541 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Stern, J. H., Rutkowski, J. M. & Scherer, P. E. Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk. Cell Metab. 23, 770–784 (2016). This is a timely overview of the importance of adipocyte-derived factors.
  Article CAS PubMed PubMed Central Google Scholar
• Erion, D. M. & Shulman, G. I. Diacylglycerol-mediated insulin resistance. Nat. Med. 16, 400–402 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Bikman, B. T. & Summers, S. A. Ceramides as modulators of cellular and whole-body metabolism. J. Clin. Invest. 121, 4222–4230 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Mitsnefes, M. et al. Ceramides and cardiac function in children with chronic kidney disease. Pediatr. Nephrol. 29, 415–422 (2014).
  Article PubMed PubMed Central Google Scholar
• Afshinnia, F. et al. Lipidomic signature of progression of chronic kidney disease in the chronic renal insufficiency cohort. Kidney Int. Rep. 1, 256–268 (2016).
  Article PubMed PubMed Central Google Scholar
• Deng, Y. et al. An adipo-biliary-uridine axis that regulates energy homeostasis. Science 355, eaaf5375 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Kimura, T. et al. Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling. Sci. Rep. 6, 26138 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Sun, K., Tordjman, J., Clement, K. & Scherer, P. E. Fibrosis and adipose tissue dysfunction. Cell Metab. 18, 470–477 (2013). This is an important overview summarizing the pathophysiological consequences of adipose tissue fibrosis.
  Article CAS PubMed PubMed Central Google Scholar
• Spencer, M. et al. Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance. J. Clin. Endocrinol. Metab. 96, E1990–E1998 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Chun, T.-H. et al. A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Cell 125, 577–591 (2006).
  Article CAS PubMed Google Scholar
• Lee, J.-T. et al. Macrophage metalloelastase (MMP12) regulates adipose tissue expansion, insulin sensitivity, and expression of inducible nitric oxide synthase. Endocrinology 155, 3409–3420 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Niu, H. et al. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity. Sci. Rep. 6, 20171 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Borgeson, E. et al. Lipoxin A4 attenuates adipose inflammation. FASEB J. 26, 4287–4294 (2012).
  Article CAS PubMed Google Scholar
• Borgeson, E. et al. Lipoxin A4 attenuates obesity-induced adipose inflammation and associated liver and kidney disease. Cell Metab. 22, 125–137 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Ambarkar, M. et al. Adipokines and their relation to endothelial dysfunction in patients with chronic kidney disease. J. Clin. Diagn. Res. 10, BC04-8 (2016).
  PubMed Google Scholar
• Zhao, H.-L. et al. Fat redistribution and adipocyte transformation in uninephrectomized rats. Kidney Int. 74, 467–477 (2008). This study demonstrates fat redistribution and beiging phenotypes in the progression of renal injury, indicating the adiporenal crosstalk and therapeutic interventions that prevent fat redistribution might ameliorate chronic renal dysfunction.
  Article CAS PubMed Google Scholar
• Kir, S. et al. PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer. Cell Metab. 23, 315–323 (2016).
  Article CAS PubMed Google Scholar
• Xiang, D. M. et al. Chronic kidney disease promotes chronic inflammation in visceral white adipose tissue. Am. J. Physiol. Renal Physiol. 312, F689–F701 (2017).
  Article CAS PubMed Google Scholar
• D'Apolito, M. et al. Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure. J. Clin. Invest. 120, 203–213 (2010).
  Article PubMed Google Scholar
• Engeli, S., Negrel, R. & Sharma, A. M. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 35, 1270–1277 (2000).
  Article CAS PubMed Google Scholar
• Yvan-Charvet, L. & Quignard-Boulange, A. Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity. Kidney Int. 79, 162–168 (2011).
  Article CAS PubMed Google Scholar
• Yiannikouris, F. et al. Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 302, R244–R251 (2012).
  Article CAS PubMed Google Scholar
• Massiera, F. et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J. 15, 2727–2729 (2001).
  Article CAS PubMed Google Scholar
• Kihara, M. et al. Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice. Kidney Int. 53, 548–555 (1998).
  Article CAS PubMed Google Scholar
• Cole, B. K. et al. Valsartan protects pancreatic islets and adipose tissue from the inflammatory and metabolic consequences of a high-fat diet in mice. Hypertension 55, 715–721 (2010).
  Article CAS PubMed Google Scholar
• Guo, H. et al. Protective effects of glucagon-like peptide-1 analog on renal tubular injury in mice on high-fat diet. Cell. Physiol. Biochem. 41, 1113–1124 (2017).
  Article CAS PubMed Google Scholar
• Ma, L.-J. et al. Angiotensin type 1 receptor modulates macrophage polarization and renal injury in obesity. Am. J. Physiol. Renal Physiol. 300, F1203–F1213 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Azushima, K. et al. Adipocyte-specific enhancement of angiotensin II type 1 receptor-associated protein ameliorates diet-induced visceral obesity and insulin resistance. J. Am. Heart Assoc. 6, e004488 (2017).
  Article PubMed PubMed Central Google Scholar
• Maeda, A. et al. Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity. J. Am. Heart Assoc. 2, e000312 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Uneda, K. et al. Angiotensin II type 1 receptor-associated protein regulates kidney aging and lifespan independent of angiotensin. J. Am. Heart Assoc. 6, e006120 (2017).
  Article PubMed PubMed Central Google Scholar
• Kobayashi, R. et al. An angiotensin II type 1 receptor binding molecule has a critical role in hypertension in a chronic kidney disease model. Kidney Int. 91, 1115–1125 (2017).
  Article CAS PubMed Google Scholar
• AbdAlla, S., Lother, H., Abdel-tawab, A. M. & Quitterer, U. The angiotensin II AT2 receptor is an AT1 receptor antagonist. J. Biol. Chem. 276, 39721–39726 (2001).
  Article CAS PubMed Google Scholar
• Benndorf, R. A. et al. Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice. Kidney Int. 75, 1039–1049 (2009).
  Article CAS PubMed Google Scholar
• Ali, Q., Dhande, I., Samuel, P. & Hussain, T. Angiotensin type 2 receptor null mice express reduced levels of renal angiotensin II type 2 receptor/angiotensin (1–7)/mas receptor and exhibit greater high-fat diet-induced kidney injury. J. Renin Angiotensin Aldosterone Syst. http:dx.doi.org/10.1177/1470320316661871 (2016).
• Yvan-Charvet, L. et al. Deficiency of angiotensin type 2 receptor rescues obesity but not hypertension induced by overexpression of angiotensinogen in adipose tissue. Endocrinology 150, 1421–1428 (2009).
  Article CAS PubMed Google Scholar
• Li, H. et al. Telmisartan ameliorates nephropathy in metabolic syndrome by reducing leptin release from perirenal adipose tissue. Hypertension 68, 478–490 (2016).
  Article CAS PubMed Google Scholar
• Patel, S. N., Ali, Q. & Hussain, T. Angiotensin II type 2-receptor agonist C21 reduces proteinuria and oxidative stress in kidney of high-salt-fed obese zucker rats. Hypertension 67, 906–915 (2016).
  Article CAS PubMed Google Scholar
• Pandey, A. et al. H2AK119 monoubiquitination regulates angiotensin II receptor mediated macrophage infiltration and renal fibrosis in type 2 diabetic rats. Biochimie 131, 68–76 (2016).
  Article CAS PubMed Google Scholar
• Reddy, M. A. et al. Losartan reverses permissive epigenetic changes in renal glomeruli of diabetic db/db mice. Kidney Int. 85, 362–373 (2014).
  Article CAS PubMed Google Scholar
• Wolf, G., Chen, S., Han, D. C. & Ziyadeh, F. N. Leptin and renal disease. Am. J. Kidney Dis. 39, 1–11 (2002).
  Article CAS PubMed Google Scholar
• Serradeil-Le Gal, C. et al. Characterization and localization of leptin receptors in the rat kidney. FEBS Lett. 404, 185–191 (1997).
  Article CAS PubMed Google Scholar
• Hudkins, K. L. et al. BTBR ob/ob mutant mice model progressive diabetic nephropathy. J. Am. Soc. Nephrol. 21, 1533–1542 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Chua, S. J. et al. A susceptibility gene for kidney disease in an obese mouse model of type II diabetes maps to chromosome 8. Kidney Int. 78, 453–462 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Lim, C. C. et al. Elevated serum leptin, adiponectin and leptin to adiponectin ratio is associated with chronic kidney disease in Asian adults. PLoS ONE 10, e0122009 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Menon, V. et al. Factors associated with serum leptin in patients with chronic kidney disease. Clin. Nephrol. 61, 163–169 (2004).
  Article CAS PubMed Google Scholar
• Cumin, F., Baum, H. P. & Levens, N. Leptin is cleared from the circulation primarily by the kidney. Int. J. Obes. Relat. Metab. Disord. 20, 1120–1126 (1996).
  CAS PubMed Google Scholar
• Sharma, K. et al. Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients. Kidney Int. 51, 1980–1985 (1997).
  Article CAS PubMed Google Scholar
• Pedone, C. et al. Longitudinal association between serum leptin concentration and glomerular filtration rate in humans. PLoS ONE 10, e0117828 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Cui, H., Lopez, M. & Rahmouni, K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat. Rev. Endocrinol. 13, 338–351 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Alhasson, F. et al. 90 — High circulatory leptin mediated NOX-2 promotes kidney inflammation in nonalcoholic fatty liver disease via MiR21-dependent mesangial cell activation. Free Radical Biol. Med. 100, S51 (2016).
  Article Google Scholar
• Wolf, G. et al. Leptin stimulates proliferation and TGF-β expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int. 56, 860–872 (1999).
  Article CAS PubMed Google Scholar
• Ding, N. et al. Leptin promotes endothelial dysfunction in chronic kidney disease through AKT/GSK3β and β-catenin signals. Biochem. Biophys. Res. Commun. 480, 544–551 (2016).
  Article CAS PubMed Google Scholar
• Kriz, W., Kaissling, B. & Le Hir, M. Epithelial-mesenchymal transition (EMT) in kidney fibrosis: fact or fantasy? J. Clin. Invest. 121, 468–474 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Guerrot, D. et al. Progression of renal fibrosis: the underestimated role of endothelial alterations. Fibrogenesis Tissue Repair 5, S15 (2012).
  Article PubMed PubMed Central Google Scholar
• Mou, X. et al. Serum TGF-β1 as a biomarker for type 2 diabetic nephropathy: a meta-analysis of randomized controlled trials. PLoS ONE 11, e0149513 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Lan, H. Y. & Chung, A. C.-K. TGF-β/Smad signaling in kidney disease. Semin. Nephrol. 32, 236–243 (2012).
  Article CAS PubMed Google Scholar
• Cui, W., Maimaitiyiming, H., Qi, X., Norman, H. & Wang, S. Thrombospondin 1 mediates renal dysfunction in a mouse model of high-fat diet-induced obesity. Am. J. Physiol. Renal Physiol. 305, F871–F880 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Kumpers, P. et al. Leptin is a coactivator of TGF-β in unilateral ureteral obstructive kidney disease. Am. J. Physiol. Renal Physiol. 293, F1355–F1362 (2007).
  Article CAS PubMed Google Scholar
• Briffa, J. F. et al. Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells. Mol. Cell. Endocrinol. 401, 25–34 (2015).
  Article CAS PubMed Google Scholar
• Chen, K.-H. et al. The AMPK agonist AICAR inhibits TGF-β1 induced activation of kidney myofibroblasts. PLoS ONE 9, e106554 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Lim, A. K. H. et al. Role of MKK3-p38 MAPK signalling in the development of type 2 diabetes and renal injury in obese db/db mice. Diabetologia 52, 347–358 (2009).
  Article CAS PubMed Google Scholar
• Blanca, A. J. et al. Leptin induces oxidative stress through activation of NADPH oxidase in renal tubular cells: antioxidant effect of L-carnitine. J. Cell. Biochem. 117, 2281–2288 (2016).
  Article CAS PubMed Google Scholar
• Paz-Filho, G., Mastronardi, C. A. & Licinio, J. Leptin treatment: facts and expectations. Metabolism 64, 146–156 (2015).
  Article CAS PubMed Google Scholar
• Liu, J., Lee, J., Salazar Hernandez, M. A., Mazitschek, R. & Ozcan, U. Treatment of obesity with celastrol. Cell 161, 999–1011 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, J. et al. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice. Nat. Med. 22, 1023–1032 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Crunkhorn, S. Metabolic disease: leptin sensitizer reverses obesity. Nat. Rev. Drug Discov. 15, 601 (2016).
  Article CAS PubMed Google Scholar
• Greenhill, C. Obesity: new leptin sensitizer identified. Nat. Rev. Endocrinol. 12, 558 (2016).
  Article CAS PubMed Google Scholar
• Cheung, W. W. et al. A pegylated leptin antagonist ameliorates CKD-associated cachexia in mice. J. Am. Soc. Nephrol. 25, 119–128 (2014). This study reveals that blocking leptin signalling by leptin antagonists would benefit CKD.
  Article CAS PubMed Google Scholar
• Lourenco, E. V., Liu, A., Matarese, G. & La Cava, A. Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation. Proc. Natl Acad. Sci. USA 113, 10637–10642 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Simonds, S. E. et al. Leptin mediates the increase in blood pressure associated with obesity. Cell 159, 1404–1416 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Scholze, A., Rattensperger, D., Zidek, W. & Tepel, M. Low serum leptin predicts mortality in patients with chronic kidney disease stage 5. Obesity (Silver Spring) 15, 1617–1622 (2007).
  Article CAS Google Scholar
• Scherer, P. E., Williams, S., Fogliano, M., Baldini, G. & Lodish, H. F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 270, 26746–26749 (1995).
  Article CAS PubMed Google Scholar
• Bouskila, M., Pajvani, U. B. & Scherer, P. E. Adiponectin: a relevant player in PPARγ-agonist-mediated improvements in hepatic insulin sensitivity? Int. J. Obes. (Lond.) 29, S17–S23 (2005).
  Article CAS Google Scholar
• Hyun, Y. Y. et al. Serum adiponectin and protein-energy wasting in predialysis chronic kidney disease. Nutrition 33, 254–260 (2016).
  Article CAS PubMed Google Scholar
• Rovin, B. H. et al. Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus. Kidney Int. 68, 1825–1833 (2005).
  Article CAS PubMed Google Scholar
• Zoccali, C. et al. Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors. Kidney Int. Suppl. 63, S98–S102 (2003).
  Article Google Scholar
• Zoccali, C. et al. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J. Am. Soc. Nephrol. 13, 134–141 (2002).
  Article CAS PubMed Google Scholar
• Georgoulidou, A. et al. Adiponectin plasma levels and albuminuria in patients with type 2 diabetes and different stages of diabetic kidney disease. J. Nephrol. Ther. 7, 2–7 (2017).
  Article Google Scholar
• Kim, H. Y. et al. Association of serum adiponectin level with albuminuria in chronic kidney disease patients. Clin. Exp. Nephrol. 20, 443–449 (2016).
  Article CAS PubMed Google Scholar
• Menon, V. et al. Adiponectin and mortality in patients with chronic kidney disease. J. Am. Soc. Nephrol. 17, 2599–2606 (2006).
  Article CAS PubMed Google Scholar
• Sharma, K. et al. Adiponectin regulates albuminuria and podocyte function in mice. J. Clin. Invest. 118, 1645–1656 (2008).
  CAS PubMed PubMed Central Google Scholar
• Halberg, N. et al. Systemic fate of the adipocyte-derived factor adiponectin. Diabetes 58, 1961–1970 (2009).
  Article PubMed PubMed Central Google Scholar
• von Eynatten, M. et al. Urinary adiponectin excretion: a novel marker for vascular damage in type 2 diabetes. Diabetes 58, 2093–2099 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Panduru, N. M. et al. Urinary adiponectin is an independent predictor of progression to end-stage renal disease in patients with type 1 diabetes and diabetic nephropathy. Diabetes Care 38, 883–890 (2015).
  Article CAS PubMed Google Scholar
• Perri, A. et al. Adiponectin is expressed and secreted by renal tubular epithelial cells. J. Nephrol. 26, 1049–1054 (2013).
  Article CAS PubMed Google Scholar
• Perri, A. et al. Adiponectin secreted by tubular renal cells during LPS exposure worsens the cellular inflammatory damage. J. Nephrol. 29, 185–194 (2016).
  Article CAS PubMed Google Scholar
• Rutkowski, J. M. et al. Adiponectin alters renal calcium and phosphate excretion through regulation of klotho expression. Kidney Int. 91, 324–337 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Cammisotto, P. G., Londono, I., Gingras, D. & Bendayan, M. Control of glycogen synthase through ADIPOR1-AMPK pathway in renal distal tubules of normal and diabetic rats. Am. J. Physiol. Renal Physiol. 294, F881–F889 (2008).
  Article CAS PubMed Google Scholar
• Park, H. S. et al. Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathy. J. Transl Med. 14, 176 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Sopic´, M. et al. Downregulation of AdipoR1 is associated with increased circulating adiponectin levels in serbian chronic kidney disease patients. J. Med. Biochem. 35, 436–442 (2016).
• Shen, Y. Y., Charlesworth, J. A., Kelly, J. J., Loi, K. W. & Peake, P. W. Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney disease. Nephrol. Dial. Transplant. 22, 171–178 (2007).
  Article CAS PubMed Google Scholar
• Martinez Cantarin, M. P., Keith, S. W., Waldman, S. A. & Falkner, B. Adiponectin receptor and adiponectin signaling in human tissue among patients with end-stage renal disease. Nephrol. Dial. Transplant. 29, 2268–2277 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Yamada-Obara, N. et al. Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring. Clin. Exp. Nephrol. 20, 853–861 (2016).
  Article CAS PubMed Google Scholar
• Ohashi, K. et al. Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler. Thromb. Vasc. Biol. 27, 1910–1917 (2007).
  Article CAS PubMed Google Scholar
• Rutkowski, J. M. et al. Adiponectin promotes functional recovery after podocyte ablation. J. Am. Soc. Nephrol. 24, 268–282 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Nakamaki, S. et al. Adiponectin reduces proteinuria in streptozotocin-induced diabetic Wistar rats. Exp. Biol. Med. (Maywood) 236, 614–620 (2011).
  Article CAS Google Scholar
• Guo, X. et al. Adiponectin retards the progression of diabetic nephropathy in db/db mice by counteracting angiotensin II. Physiol. Rep. 2, e00230 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Bijland, S., Mancini, S. J. & Salt, I. P. Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clin. Sci. (Lond.) 124, 491–507 (2013).
  Article CAS Google Scholar
• Smith, B. K. & Steinberg, G. R. AMP-activated protein kinase, fatty acid metabolism, and insulin sensitivity. Curr. Opin. Clin. Nutr. Metab. Care 20, 248–253 (2017).
  Article CAS PubMed Google Scholar
• Zhu, Q. et al. Adipocyte-deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis. J. Clin. Invest. 126, 4273–4288 (2016).
  Article PubMed PubMed Central Google Scholar
• Gauthier, M.-S. et al. Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans. Biochem. Biophys. Res. Commun. 404, 382–387 (2011).
  Article CAS PubMed Google Scholar
• Dugan, L. L. et al. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J. Clin. Invest. 123, 4888–4899 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Decleves, A.-E., Mathew, A. V., Cunard, R. & Sharma, K. AMPK mediates the initiation of kidney disease induced by a high-fat diet. J. Am. Soc. Nephrol. 22, 1846–1855 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Decleves, A.-E. et al. Regulation of lipid accumulation by AMP-activated kinase in high fat diet-induced kidney injury. Kidney Int. 85, 611–623 (2014).
  Article CAS PubMed Google Scholar
• Wu, U. et al. Protective effects of berberine on high fat-induced kidney damage by increasing serum adiponectin and promoting insulin sensitivity. Int. J. Clin. Exp. Pathol. 8, 14486–14492 (2015).
  CAS PubMed PubMed Central Google Scholar
• Cameron, K. O. et al. Discovery and preclinical characterization of 6-chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid (PF-06409577), a direct activator of adenosine monophosphate-activated protein kinase (AMPK), for the potential treatment of diabetic nephropathy. J. Med. Chem. 59, 8068–8081 (2016).
  Article CAS PubMed Google Scholar
• Salatto, C. T. et al. Selective activation of AMPK β1-containing isoforms improves kidney function in a rat model of diabetic nephropathy. J. Pharmacol. Exp. Ther. 361, 303–311 (2017).
  Article CAS PubMed Google Scholar
• Sas, K. M. et al. Targeted lipidomic and transcriptomic analysis identifies dysregulated renal ceramide metabolism in a mouse model of diabetic kidney disease. J. Proteomics Bioinform. http:dx.doi.org/10.4172/jpb.S14-002 (2015).
• Holland, W. L. et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat. Med. 17, 55–63 (2011).
  Article CAS PubMed Google Scholar
• Holland, W. L. et al. Inducible overexpression of adiponectin receptors highlight the roles of adiponectin-induced ceramidase signaling in lipid and glucose homeostasis. Mol. Metab. 6, 267–275 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Vasiliauskaite-Brooks, I. et al. Structural insights into adiponectin receptors suggest ceramidase activity. Nature 544, 120–123 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Holland, W. L. & Scherer, P. E. Structural biology: receptors grease the metabolic wheels. Nature 544, 42–44 (2017).
  Article CAS PubMed Google Scholar
• Park, J. et al. Obesity paradox in end-stage kidney disease patients. Prog. Cardiovasc. Dis. 56, 415–425 (2014).
  Article PubMed Google Scholar
• Kalantar-Zadeh, K. et al. The obesity paradox in kidney disease: how to reconcile it with obesity management. Kidney Int. Rep. 2, 271–281 (2017).
  Article PubMed PubMed Central Google Scholar
• Kim, J.-Y. et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest. 117, 2621–2637 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Cooper, R. et al. ACE, angiotensinogen and obesity: a potential pathway leading to hypertension. J. Hum. Hypertens. 11, 107–111 (1997).
  Article CAS PubMed Google Scholar
• Ernst, M. C. & Sinal, C. J. Chemerin: at the crossroads of inflammation and obesity. Trends Endocrinol. Metab. 21, 660–667 (2010).
  Article CAS PubMed Google Scholar
• Zylla, S. et al. Serum chemerin levels are inversely associated with renal function in a general population. Clin. Endocrinol. (Oxf.) http://dx.doi.org/10.1111/cen.13449 (2017).
• Ebert, T. et al. Circulating adipocyte fatty acid binding protein is increased in chronic and acute renal dysfunction. Nutr. Metab. Cardiovasc. Dis. 24, 1027–1034 (2014).
  Article CAS PubMed Google Scholar
• Furuhashi, M. et al. Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease. PLoS ONE 6, e27356 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Furuhashi, M., Saitoh, S., Shimamoto, K. & Miura, T. Fatty acid-binding protein 4 (FABP4): pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases. Clin. Med. Insights Cardiol. 8, 23–33 (2014).
  PubMed Google Scholar
• Hashizume, M. & Mihara, M. Atherogenic effects of TNF-α and IL-6 via up-regulation of scavenger receptors. Cytokine 58, 424–430 (2012).
  Article CAS PubMed Google Scholar
• Su, H., Lei, C.-T. & Zhang, C. Interleukin-6 signaling pathway and its role in kidney disease: an update. Front. Immunol. 8, 405 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, B. T. et al. Association of C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 with chronic kidney disease. BMC Nephrol. 16, 77 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Lin, Z. et al. Circulating FGF21 levels are progressively increased from the early to end stages of chronic kidney diseases and are associated with renal function in Chinese. PLoS ONE 6, e18398 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Crasto, C., Semba, R. D., Sun, K. & Ferrucci, L. Serum fibroblast growth factor 21 is associated with renal function and chronic kidney disease in community-dwelling adults. J. Am. Geriatr. Soc. 60, 792–793 (2012).
  Article PubMed PubMed Central Google Scholar
• Boucher, J. et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology 146, 1764–1771 (2005).
  Article CAS PubMed Google Scholar
• Bertrand, C., Valet, P. & Castan-Laurell, I. Apelin and energy metabolism. Front. Physiol. 6, 115 (2015).
  Article PubMed PubMed Central Google Scholar
• Chandrasekaran, B., Dar, O. & McDonagh, T. The role of apelin in cardiovascular function and heart failure. Eur. J. Heart Fail. 10, 725–732 (2008).
  Article CAS PubMed Google Scholar
• Lacquaniti, A. et al. Apelin and copeptin as biomarkers of kidney disease. Springer Nature https://link.springer.com/content/pdf/10.1007%2F978-94-007-7699-9\_43.pdf (2015).
• Szczepanska, M. et al. Evaluation of adipocytokines in children with chronic kidney disease. Endokrynol. Pol. 66, 100–107 (2015).
  Article CAS PubMed Google Scholar
• Axelsson, J. et al. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int. 69, 596–604 (2006).
  Article CAS PubMed Google Scholar
• Azuma, K. et al. Correlation between serum resistin level and adiposity in obese individuals. Obes. Res. 11, 997–1001 (2003).
  Article CAS PubMed Google Scholar
• Feng, R. et al. Higher vaspin levels in subjects with obesity and type 2 diabetes mellitus: a meta-analysis. Diabetes Res. Clin. Pract. 106, 88–94 (2014).
  Article CAS PubMed Google Scholar
• Sengul, E., Duygulu, G., Dindar, S. & Bunul, F. Serum omentin-1, inflammation and carotid atherosclerosis in patients with non-diabetic chronic kidney disease. Ren. Fail. 35, 1089–1093 (2013).
  Article CAS PubMed Google Scholar
• Qasem, A., Farage, S., Elmesallamy, F. A. & Elsaid, H. H. Association of plasma omentin-1 level with insulin resistance in chronic kidney disease patients. Egypt. J. Obes. Diabetes Endocrinol. 1, 72–76 (2015).
  Article Google Scholar
• Alcelik, A. et al. Serum levels of omentin in end-stage renal disease patients. Kidney Blood Press. Res. 35, 511–516 (2012).
  Article CAS PubMed Google Scholar
• Catoi, A. F. et al. Increased chemerin and decreased omentin-1 levels in morbidly obese patients are correlated with insulin resistance, oxidative stress and chronic inflammation. Clujul Med. 87, 19–26 (2014).
  Article PubMed PubMed Central Google Scholar
• Watanabe, T., Watanabe-Kominato, K., Takahashi, Y., Kojima, M. & Watanabe, R. Adipose tissue-derived omentin-1 function and regulation. Compr. Physiol. 7, 765–781 (2017).
  Article PubMed Google Scholar
• Frey, S. K. et al. Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver. Lipids Health Dis. 7, 29 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Graham, T. E. et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N. Engl. J. Med. 354, 2552–2563 (2006).
  Article CAS PubMed Google Scholar
• Chang, Y.-H., Chang, D.-M., Lin, K.-C., Shin, S.-J. & Lee, Y.-J. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab. Res. Rev. 27, 515–527 (2011).
  Article CAS PubMed Google Scholar
• Mahmood, N., Junejo, A. M., Jamal, Q. & Awan, R. Association of visfatin with chronic kidney disease in a cohort of patients with and without diabetes. J. Pak. Med. Assoc. 60, 922–926 (2010).
  PubMed Google Scholar
• Adeghate, E. Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions. Curr. Med. Chem. 15, 1851–1862 (2008).
  Article CAS PubMed Google Scholar
• Yan, Q.-W. et al. The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes 56, 2533–2540 (2007).
  Article CAS PubMed Google Scholar
• Bolignano, D. et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin. J. Am. Soc. Nephrol. 4, 337–344 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hasegawa, M. et al. Plasma neutrophil gelatinase-associated lipocalin as a predictor of cardiovascular events in patients with chronic kidney disease. Biomed. Res. Int. 2016, 8761475 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Saldanha, J. F. et al. The newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: are there associations with food intake, body composition and inflammation? Regul. Pept. 173, 82–85 (2012).
  Article CAS PubMed Google Scholar
• Richter, J. et al. Serum levels of the adipokine progranulin depend on renal function. Diabetes Care 36, 410–414 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Korolczuk, A. & Beltowski, J. Progranulin, a new adipokine at the crossroads of metabolic syndrome, diabetes, dyslipidemia and hypertension. Curr. Pharm. Des. 23, 1533–1539 (2017).
  Article CAS PubMed Google Scholar
• Gomez-Ambrosi, J. et al. Plasma osteopontin levels and expression in adipose tissue are increased in obesity. J. Clin. Endocrinol. Metab. 92, 3719–3727 (2007).
  Article CAS PubMed Google Scholar
• Kahles, F., Findeisen, H. M. & Bruemmer, D. Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol. Metab. 3, 384–393 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Barreto, D. V. et al. Prognostic implication of plasma osteopontin levels in patients with chronic kidney disease. Nephron Clin. Pract. 117, c363–c372 (2011).
  Article CAS PubMed Google Scholar
• Lorenzen, J. et al. Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease. Eur. J. Clin. Invest. 40, 294–300 (2010).
  Article CAS PubMed Google Scholar
• Nomura, I., Kato, J., Tokashiki, M. & Kitamura, K. Increased plasma levels of the mature and intermediate forms of adrenomedullin in obesity. Regul. Pept. 158, 127–131 (2009).
  Article CAS PubMed Google Scholar
• Dieplinger, B. et al. Pro-A-type natriuretic peptide and pro-adrenomedullin predict progression of chronic kidney disease: the MMKD Study. Kidney Int. 75, 408–414 (2009).
  Article CAS PubMed Google Scholar