Современные представления о поражении почек при ожирении

Е.А. Сагинова, М.Г. Галлямов, М.M. Северова

Кафедра терапии и профболезней ММА им. И.М. Сеченова, Москва; Кафедра внутренних болезней факультета фундаментальной медицины МГУ им. М.В. Ломоносова, Москва
Обсуждаются механизмы развития, клинические варианты и прогностическое значение поражения почек при ожирении.


1. Hoefle G., Saely C.H., Aczel S. et al. Impact of central and total obesity on vascular mortality in patients undergoing coronary angiography. Int. J. Obes. 2005; 29: 785–791.
2. Rea D.J., Heimbach J.K., Grande J.P. et al. Glomerular volume and renal histology in obese and non-obese living kidney donors. Kidney Int. 2006; 70(9): 1636–1641.
3. Despres J.-P. Abdominal obesity: the most prevalent cause of the metabolic syndrome and related cardiometabolic risk. Eur. Heart J. 2006; 8 (Suppl. B): B4–B12.
4. Iseki K., Ikemiya Y., Kinjo K. et al. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int. 2004; 65 (5): 1870–1876.
5. Gelber R.P., Kurth T., Kausz A.T. et al. Association between body mass index and CKD in apparently healthy men. Am. J. Kidney Dis. 2005; 46: 871–880.
6. Kougias P., Chai H., Lin P.H. et al. Adipocyte-derived cytokine resistin causes endothelial dysfunction of porcine coronary arteries. J. Vasc. Surg. 2005; 41: 691–698.
7. Ford E.S., Giles W.H., Dietz W.H. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. J.A.M.A. 2002; 287 (3): 356–359.
8. Сhen J., Muntner P., Hamm L. et al. The metabolic syndrome and chronic kidney disease in U.S. Adults. Ann. Intern. Med. 2004; 140: 167–174.
9. Wang Y., Cheng Х. et al. Aassociation between obesity and kidney diseases: A systematic review and meta-analysis. Kidney Int. 2008; 73: 18–23.
10. Wolf G. Obesity and renal hemodynamics. Contrib Nephrol. 2006; 151: 184–202.
11. Сагинова Е.А., Федорова Е.Ю., Фомин В.В. и др. Формирование поражения почек у больных ожирением. Тер. архив 2006; 78 (5): 36–41.
12. Kasiske B.L., Crosson J.T. Renal disease in patients with massive obesity. Arch. Intern. Med. 1986; 146 (6): 1105–1109.
13. Praga M., Hernandez E., Morales E. Clinical features and long-term outcome of obesity- associated focal segmental glomerulosclerosis. Nephrol. Dial. Transplant 2001; 15: 1790–1798.
14. Kasiske B.L., Napier J. Glomerular sclerosis in patients with massive obesity. Am. J. Nephrol. 1985; 5 (1): 45–50.
15. Sasatomi Y., Tada M., Uesugi N. et al. Obesity associated with hypertension or hyperlipidemia accelerates renal damage. Pathobiology. 2001; 69 (2): 113–118.
16. Rea D.J., Heimbach J.K., Grande J.P. et al. Glomerular volume and renal histology in obese and non-obese living kidney donors. Kidney Int. 2006; 70(9): 1636–1641.
17. Orfila C., Lepert J.C., Modesto A. et al. IgA nephropathy complicating diabetic glomerulosclerosis. Nephron. 1998; 79(3):279–287.
18. Amore A., Roccatello D., Picciotto G., Emancipator S.N. Processing of IgA aggregates in a rat model of chronic liver disease. Clin Immunol Immunopathol. 1997; 84(2):107–114.
19. Despres J.-P., Lemieux I., Prud’homme D. Treatment of obesity: need to focus on high risk abdominally obese patients. B.M.J. 2001; 322: 716–720.
20. Hall J.E., Brands M.W., Henegar J.R. Mechanisms of hypertension and kidney disease in obesity. Ann. N. Y. Acad. Sci. 1999; 892: 91–107.
21. Wicek A., Kokot F., Chudek J. et al. The adipose tissue – a novel endocrine organ of interest to the nephrologist. Nephrol. Dial. Transplant. 2002; 17:191–195.
22. Gunter W., Sheldon C., Han D.C. et al. Leptin and renal disease. Am. J. Kidney Dis. 2002; 39: 1–11.
23. Wolf G., Ziyadeh F.N. Leptin and renal fibrosis. Contrib. Nephrol. 2006; 151: 175–183.
24. Han D.C., Isono M., Chen S. et al. Leptin stimulates type I collagen production in db/db mesangial cells, glucose uptake and TGF-b type II receptor expression. Kidney Int. 2001; 59: 1315–1323.
25. Wolf G., Hamann A., Han D.C. et al. Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int. 1999; 6(3): 860–872.
26. Stam F, van Guldener C, Becker A. et al. Endothelial dysfunction contributes to renal functionassociated cardiovascular mortality in a population with mild renal insufficiency: the Hoorn study. J. Am. Soc. Nephrol. 2006; 17: 537–545.
27. Quehenberger P., Exner M., Sunder-Plassmann R. et al. Leptin induces endothelin-1 in endothelial cells in vitro. Circ. Res. 2002; 90: 711–718.
28. Turner N.C., Morgan P.J., Haynes A.C. et al. Elevated renal endothelin-I clearance and mRNA levels associated with albuminuria and nephropathy in non-insulin-dependent diabetes mellitus: studies in obese fa/fa Zucker rats. Clin. Sci. (Lond). 1997; 93: 565–571.
29. Barton M., Carmona R., Morawietz H. et al. Obesity is associated with tissuespecific activation of renal angiotensin-converting enzyme in vivo: evidence for a regulatory role of endothelin. Hypertension. 2000; 35 (1 Pt. 2): 329–336.
30. Mather K.J., Lteif A., Steinberg H.O. et al. Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes. 2004; 53: 2060–2066.
31. Zoccali C. Asymmetric dimethylarginine (ADMA): a cardiovascular and renal risk factor on the move. J Hypertens. 2006; 24(4): 611–619.
32. Palm F., Onozato M.L., Luo Z. et al. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol. 2007; 293(6): H3227–H3245.
33. Masuda H., Goto M., Tamaoki S., Azuma H. Accelerated intimal hyperplasia and increased endogenous inhibitors for NO synthesis in rabbits with alloxaninduced hyperglycaemia. Br J Pharmacol. 1999; 126(1): 211–218.
34. Valkonen V.P., Tuomainen T.P., Laaksonen R. DDAH gene and cardiovascular risk. Vasc Med. 2005; 10 (Suppl 1):S45–S48.
35. Krzyzanowska K, Mittermayer F, Kopp HP et al. Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. J Clin Endocrinol Metab. 2004; 89(12): 6277–6281.
36. Ito A., Tsao P.S., Adimoolam S. et al. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation. 1999; 99(24): 3092–3095.
37. Caglar K., Yilmaz M.I., Sonmez A. et al. ADMA, proteinuria, and insulin resistance in non-diabetic stage I chronic kidney disease. Kidney Int. 2006; 70(4): 781–787.
38. Fliser D., Kronenberg F., Kielstein J.T. et al. Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study. J Am Soc Nephrol. 2005; 16(8): 2456–2461.
39. Nieuwdorp M., Meuwese M.C., Vink H. et al. The endothelial glycocalyx: a potential barrier between health and vascular disease. Curr Opin Lipidol. 2005; 16(5): 507–511.
40. Rana J.S., Nieuwdorp M., Jukema J.W. et al. Cardiovascular metabolic syndrome – an interplay of, obesity, inflammation, diabetes and coronary heart disease. Diabetes Obes. Metab. 2007; 9(3):218–232.
41. Wang W. Change in properties of the glycocalyx affects the shear rate and stress distribution on endothelial cells. J Biomech. Eng. 2007; 129(3):324–329.
42. Goligorsky M.S. Clinical assessment of endothelial dysfunction: combine and rule. Curr Opin Nephrol Hypertens. 2006; 15(6):617–624.
43. Rubio-Gayosso I., Platts S.H., Duling B.R. Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 2006; 290(6): H2247–H2256.
44. Мухин Н.А., Моисеев В.С. Кардиоренальные соотношения и риск сердечно-сосудистых заболеваний. Вестник РАМН. 2003; 11: 50–55.
45. Yuyun M., Alder A.I., Wareham N.J. What is the evidence that microalbuminuria is a predictor of cardiovascular disease events. Curr. Opin. Nephrol. Hypertens. 2005; 14: 271–276.
46. Schiffrin E.L., Touyz R.M. From bedside to bench to bedside: role of reninangiotensin-aldosterone system in remodeling of resistance arteries in hypertension. Am. J. Physiol Heart Circ. Physiol. 2004;287: H435–H446.
47. Touyz R.M., Schiffrin E.L. Reactive oxygen species in vascular biology: implications in hypertension. Histochem. Cell Biol. 2004;122:339–352.
48. Vendrell J., Broch M., Vilarrasa N. et al. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes. Res. 2004; 12(6): 962–971.
49. Wu Y., Liu Z., Xiang Z. et al. Obesity-related glomerulopathy: insights from gene expression profiles of the glomeruli derived from renal biopsy samples. Endocrinology. 2006; 147(1): 44–50.
50. Heimbach J.K., Taler S.J., Prieto M. et al. Obesity in living kidney donors: clinical characteristics and outcomes in the era of laparoscopic donor nephrectomy. Am. J. Transplant. 2005; 5(5): 1057–1064.
51. Pesavento T.E., Henry M.L., Falkenhain M.E. et al. Obese living kidney donors: short-term results and possible implications. Transplantation. 1999; 68(10): 1491–1496.
52. Espinoza R., Gracida C., Cancino J. et al. Effect of obese living donors on the outcome and metabolic features in recipients of kidney transplantation. Transplant. Proc. 2006; 38(3): 888–889.
53. Stevenson F.T., Wheeldon C.M., Gades M.D. et al. Hyperphagia as a mediator of renal disease initiation in obese Zucker rats. Obes. Res. 2001; 9(8): 492–499.
54. Eckel R.H., Grundy S.M., Zimmet P.Z. The metabolic syndrome. Lancet 2005; 365: 1415–1428.
55. Uribarri J., Katherine R. Tuttle Advanced Glycation End Products and Nephrotoxicity of High-Protein Diets, Clin. J. Am. Soc. Nephrol. 2006; 1: 1293–1299.
56. Wadden T.A., Berkowitz R.I., Womble L.G. et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N. Engl. J. Med. 2005; 353: 2111–2120.
57. Barbaro D., Orsini P., Pallini S. et al. Obesity in transplant patients: case report showing interference of orlistat with absorbtion of cyclosporine and review of literature. Endocr. Pract. 2002; 8(2): 124–126.
58. Errasti P., Garcia I., Lavilla J. et al. Reduction in blood cyclosporine concentration by orlistat in two renal transplant patients. Transplant Proc. 2002; 34(1): 137–139.
59. Evans S., Michael R., Wells. H. et al. Drug interaction in a renal transplant patient: cyclosporine-Neoral and orlistat. Am. J. Kidney Dis. 2003; 41(2): 493–496.
60. 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. 2003; 14: 1480–1486.
61. Sharma S.K., McCauley J., Cottam D. et al. Acute changes in renal function after laparoscopic gastric surgery for morbid obesity. Surg. Obes. Relat. Dis. 2006; 2(3): 389–392.
62. Parving H.H., Lenhert H., Brochner-Mortensen J. et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N. Engl. J. Med. 2001; 345: 870–878.
63. Praga M., Hernandez E., Morales E. et al. Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 2001; 16(9): 1790–1798.
64. Blanco S., Vaquero M., Gomez-Guerrero C. et al. Potential role of angiotensinconverting enzyme inhibitors and statins on early podocyte damage in a model of type 2 diabetes mellitus, obesity, and mild hypertension. Am. J. Hypertens. 2005; 18 (4 Pt. 1): 557–565.
65. Adelman R.D., Restaino I.G., Alon U.S. et al. Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. J. Pediatr. 2001; 138(4): 481–485.
66. Kurata A., Nishizawa H., Kihara S. et al. Blockade of angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation. Kidney Int. 2006; 70(10): 1717–1724.
67. Parving H, Persson F., Lewis J. et al. Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy. N Engl J Med. 2008; 358(23):2433–2446.
68. Kielstein J.T., Fliser D. Lowering asymmetric dimethylarginine-a new mechanism mediating the renoprotective effects of renin-angiotensin system inhibitors in proteinuric patients? Blood Purif. 2007;25(4):324–326.
69. Teplan V., Schuck O., Racek J. et al. Reduction of plasma asymmetric dimethylarginine in obese patients with chronic kidney disease after three years of a low-protein diet supplemented with keto-amino acids: a randomized controlled trial. Wien Klin. Wochenschr. 2008; 120(15-16):478–485.
70. Nathan D.M. Thiazolidinediones for initial treatment of type 2 diabetes? N. Engl. J. Med. 2006; 355(23): 2477–2480.

Об авторах / Для корреспонденции

Сагинова Е.А. – ассистент кафедры терапии и профболезней ММА им. И.М. Сеченова, к.м.н.
E-mail: med02@yandex.ru;
Галлямов М.Г. – аспирант кафедры внутренних болезней факультета фундаментальной медицины МГУ им. М.В. Ломоносова.
E-mail: mgtabib@gmail.com;
Северова М.М. – аспирант кафедры терапии и профболезней ММА им. И.М. Сеченова.
E-mail: mseverova@mail.ru

Похожие статьи

Бионика Медиа