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Current Diabetes Reports

, Volume 12, Issue 4, pp 440–446 | Cite as

Pathophysiology of Obesity-Related Renal Dysfunction Contributes to Diabetic Nephropathy

  • George BaylissEmail author
  • Larry A. Weinrauch
  • John A. D’Elia
Microvascular Complications—Nephropathy (B Roshan, Section Editor)

Abstract

Recent studies have demonstrated the role of insulin resistance in renal injury related to obesity, with hyperfiltration leading to glomerulomegaly in a pattern similar to that found in diabetic nephropathy. Similarities in the histologic patterns of damage from obesity and diabetes point to overlapping mechanisms of injury. In this review, we will examine the hormonal mechanisms, signaling pathways and injury patterns in renal injury resulting from obesity and attempt to draw conclusions on the reasons for these similarities.

Keywords

Obesity Obstructive sleep apnea Proteinuria Insulin resistance Podocyte Nephrin Adipocyte Diabetes Renal dysfunction Diabetic nephropathy 

Notes

Acknowledgments

The authors wish to thank Diane Young for her help in preparing this article.

Disclosure

Conflicts of interest: G. Bayliss: none; L.A. Weinrauch: none; J.A. D’Elia: has received grant support from the Pat Covelli Foundation, Amgen Corp., and Bayer Laboratories as investigator-initiated research.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Preble WE. Obesity: Observation on one thousand cases. Boston Med Surg J. 1923;188:617–21.CrossRefGoogle Scholar
  2. 2.
    Weisinger JR, Kempson RL, Eldridge FL, Swenson RS. The nephrotic syndrome: a complication of massive obesity. Ann Intern Med. 1974;81:440–7.PubMedGoogle Scholar
  3. 3.
    Cohen AH. Massive obesity and the kidney. A morphologic and statistical study. Am J Pathol. 1975;81:117–30.PubMedGoogle Scholar
  4. 4.
    Verani RR. Obesity-associated focal segmental glomerulosclerosis: pathological features of the lesion and relationship with cardiomegaly and hyperlipidemia. Am J Kidney Dis. 1992;20:629–34.PubMedGoogle Scholar
  5. 5.
    Kambham N, Markowitz GS, Valeri AM, et al. VD. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. 2001;59:1498–509.PubMedCrossRefGoogle Scholar
  6. 6.
    Fox CS, Larson MG, Leip EP, et al. Predictors of new-onset kidney disease in a community-based population. JAMA. 2004;291:844–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Morales E, Valero MA, Leon M, et al. Beneficial effects of weight loss in overweight patients with chronic proteinuric nephropathies. Am J Kidney Dis. 2003;41:319–27.PubMedCrossRefGoogle Scholar
  8. 8.
    Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA. 2004;291:2013–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Chaudhary BA, Sklar AH, Chaudhary TK, et al. Sleep apnea, proteinuria, and nephrotic syndrome. Sleep. 1988;11:69–74.PubMedGoogle Scholar
  10. 10.
    Sklar AH, Chaudhary BA. Reversible proteinuria in obstructive sleep apnea syndrome. Arch Intern Med. 1988;148:87–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Sklar AH, Chaudhary BA, Harp R. Nocturnal urinary protein excretion rates in patients with sleep apnea. Nephron. 1989;51:35–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Tsioufis C, Thomopoulos C, Dimitriadis K, et al. Association of obstructive sleep apnea with urinary albumin excretion in essential hypertension: a cross-sectional study. Am J Kidney Dis. 2008;52:285–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Casserly LF, Chow N, Ali S, et al. Proteinuria in obstructive sleep apnea. Kidney Int. 2001;60:1484–9.PubMedCrossRefGoogle Scholar
  14. 14.
    • Chou YT, Lee PH, Yang CT, et al. Obstructive sleep apnea: a stand-alone risk factor for chronic kidney disease. Nephrol Dial Transplant. 2011;26:2244–50. This article discusses the relationship of sleep apnea, insulin resistance and proteinuria.PubMedCrossRefGoogle Scholar
  15. 15.
    Hall JE. Mechanisms of abnormal renal sodium handling in obesity hypertension. Am J Hypertens. 1997;10:49S–55S.PubMedCrossRefGoogle Scholar
  16. 16.
    Chagnac A, Weinstein T, Korzets A, et al. Glomerular hemodynamics in severe obesity. Am J Physiol Ren Physiol. 2000;278:F817–22.Google Scholar
  17. 17.
    Chagnac A, Weinstein T, Herman M, et al. The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol: JASN. 2003;14:1480–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Chagnac A, Herman M, Zingerman B, et al. Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis of tubular sodium reabsorption. Nephrol Dial Transplant. 2008;23:3946–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Ix JH, Sharma K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol: JASN. 2010;21:406–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Hennige AM, Staiger H, Wicke C, et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One. 2008;3:e1765.PubMedCrossRefGoogle Scholar
  21. 21.
    Ix JH, Shlipak MG, Brandenburg VM, et al. Association between human fetuin-A and the metabolic syndrome: Data from the Heart and Soul Study. Circulation. 2006;113:1760–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Laughlin GA, Barrett-Connor E, May S, Langenberg C. Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study. Am J Epidemiol. 2007;165:164–74.PubMedCrossRefGoogle Scholar
  23. 23.
    Sharma K, Ramachandrarao S, Qiu G, et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest. 2008;118:1645–56.PubMedGoogle Scholar
  24. 24.
    Baumann M, von Eynatten M, Dan L, et al. Altered molecular weight forms of adiponectin in hypertension. J Clin Hypertens. 2009;11:11–6.CrossRefGoogle Scholar
  25. 25.
    Iwashima Y, Horio T, Kumada M, et al. Adiponectin and renal function, and implication as a risk of cardiovascular disease. Am J Cardiol. 2006;98:1603–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Pineiro R, Iglesias MJ, Gallego R, et al. Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett. 2005;579:5163–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Saginova EA, Galliamov MG, Severova MM, et al. The role of leptin, adiponectin and insulin-resistance markers in development of early stages of chronic kidney disease and atherosclerosis of carotid arteries in obese patients. Ter Arkh. 2011;83:47–53.PubMedGoogle Scholar
  28. 28.
    Ellington AA, Malik AR, Klee GG, et al. Association of plasma resistin with glomerular filtration rate and albuminuria in hypertensive adults. Hypertension. 2007;50:708–14.PubMedCrossRefGoogle Scholar
  29. 29.
    Coward R, Walsh GI, Koziell A, et al. Nephrin is critical for the action of insulin on human glomerular podocytes. Diabetes. 2007;56:1127–35.PubMedCrossRefGoogle Scholar
  30. 30.
    Jones N, Blasutig IM, Eremina V, et al. Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Nature. 2006;440:818–23.PubMedCrossRefGoogle Scholar
  31. 31.
    • Fornoni A, Jeon J, Varona Santos J, et al. Nephrin is expressed on the surface of insulin vesicles and facilitates glucose-stimulated insulin releases. Diabetes. 2010;59:190–9. This article discusses the role of nephrin, an important glomerular protein, in secretion of insulin vessicles in the pancreas.PubMedCrossRefGoogle Scholar
  32. 32.
    Hussain S, Romio L, Saleem M, et al. Nephrin deficiency activates NF-kappaB and promotes glomerular injury. J Am Soc Nephrol: JASN. 2009;20:1733–43.PubMedCrossRefGoogle Scholar
  33. 33.
    Nagase M, Yoshida S, Shibata S, et al. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. J Am Soc Nephrol: JASN. 2006;17:3438–46.PubMedCrossRefGoogle Scholar
  34. 34.
    Sharma R, Sharma M, Reddy S, et al. Chronically increased intrarenal angiotensin II causes nephropathy in an animal model of type 2 diabetes. Front Biosci. 2006;11:968–76.PubMedCrossRefGoogle Scholar
  35. 35.
    Callera GE, Touyz RM, Tostes RC, et al. Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension. 2005;45:773–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci U S A. 2003;100:14211–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Goodfriend TL, Ball DL, Egan BM, et al. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension. 2004;43:358–63.PubMedCrossRefGoogle Scholar
  38. 38.
    Fliser D, Schaefer F, Schmid D, et al. Angiotensin II affects basal, pulsatile, and glucose-stimulated insulin secretion in humans. Hypertension. 1997;30:1156–61.PubMedCrossRefGoogle Scholar
  39. 39.
    Blanco S, Bonet J, Lopez D, et al. ACE inhibitors improve nephrin expression in Zucker rats with glomerulosclerosis. Kidney Int Suppl. 2005;93:S10–4.PubMedCrossRefGoogle Scholar
  40. 40.
    Saitoh Y, Hongwei W, Ueno H, et al. Telmisartan attenuates fatty-acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells. Diabetes Metab. 2009;35:392–7.PubMedCrossRefGoogle Scholar
  41. 41.
    • Habibi J, Hayden MR, Sowers JR, et al. Nebivolol attenuates redox-sensitive glomerular and tubular mediated proteinuria in obese rats. Endocrinology. 2011;152:659–68. This article describes a possible nonhemodynamic mechanism by which a non-specific beta blocker may inhibit proteinuria.PubMedCrossRefGoogle Scholar
  42. 42.
    Ahima RS. Linking adiponectin to proteinuria. J Clin Invest. 2008;118(5):1619–22.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • George Bayliss
    • 1
    • 2
    Email author
  • Larry A. Weinrauch
    • 3
  • John A. D’Elia
    • 3
    • 4
  1. 1.Division of Kidney Diseases and HypertensionRhode Island and Miriam HospitalsProvidenceUSA
  2. 2.Alpert Medical SchoolBrown UniversityProvidenceUSA
  3. 3.Harvard Medical SchoolBostonUSA
  4. 4.Renal Unit, Joslin Diabetes CenterBeth Israel Deaconess Medical CenterBostonUSA

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