Rola czynników hemodynamicznych i metabolicznych w powstawaniu nefropatii cukrzycowej
The role of haemodynamic and metabolic factors in the development of diabetic nephropathy
Overt diabetic nephropathy develops in 20-40% of diabetic patients (1-4). Although pathogenesis of diabetic nephropathy is not entirely elucidated, it is evident from numerous studies that hemodynamic as well as metabolic factors play an important role in its development. Diabetic nephropathy is thus a result of an interplay between those patophysiologic factors, although the basal pathogenetic factor is of course hyperglycemia.
Table 1. Chosen factors influencing intracapillary blood pressure (according to 13).
Similarly, as RAAS inhibiting agents seem to be effective in decreasing of proteinuria also in doses not lowering systemic blood pressure (11), their effectiveness must be dependent upon improvement of local hemodynamic, but also improvement of neural (decrease of adrenergic system activation) and other local factors (decrease of oxidative stress and of local proinflammatory and profibrotic factors) (12).
1. Krolewski AS, Warram JH, Christlieb AL et al.: The changing natural history of nephropathy in type 1 diabetes. A J Med 1985; 78: 785-794.
2. Hasslacher C, Ritz E, Wahl P, Michael C: Similar risk of nephropathy in patients with type I or type II diabetes mellitus. Nephrol Dialysis Transplant 1989; 4: 859-863.
3. Ravid M, Savin H, Jutrin I et al.: Long-term stabilizing effect of angiotensin converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 1993; 118: 577-581.
4. Adler A, Stevens RJ, Manley SE et al.: UKPDS Group Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003; 63: 225-232.
5. Rudberg S, Persson B, Dahlquist G: Increased glomerular filtration rate as a predictor of diabetic nephropathy – an 8-year prospective study. Kidney Int 1992; 41: 822-828.
6. Nelson DG, Benett PH, Beck GJ: Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. N Engl J Med 1991; 335: 1636-1642.
7. Stieger N, Worthmann K, Schiffer M: The role of metabolic and hemodynamic factors in podocyte injury in diabetes. Diabetes Metab Res 2011; 27: 207-215.
9. Bosh JP, Lew S, Glabman S, Lauer A: Renal hemodynamic changes in humans. Response to protein loading in normal and diseased kidneys. Am J Med 1986; 81: 809-815.
10. Hajashi K, Epstein M, Lountzelhiser R, Forster H: Impaired myogenic responsiveness of the afferent arteriole in streptozotocin-induced diabetic rats: role of eicosanoid derangements. J Am Soc Nephrol 1992; 2: 1578-1586.
11. Ruggenenti P, Cravedi P, Remuzzi G: The RAAS in the pathogenesis and treatment of diabetic nephropathy. Nat Rev Nephrol 2010; 6(6): 319-330.
12. Siragy HM, Carey RM: Role of intrarenal renin-angiotensin – aldosterone system in chronić kidney disease. Am J Nephrol 2010; 31: 541-550.
13. Grzeszczak W: Nefropatia cukrzycowa. [W:] Sieradzki J (red.): Cukrzyca. ViaMedica, Gdańsk 2006.
14. Alaveras A: Promotors of progression of diabetic nephropathy the relatives roles of blood glucose and blood pressure control. Nephrol Dial Transplant 1997; 12: 71-74.
15. Wolf G, Thaiss F: Hyperglyceamia – pathophysiological aspects of the cellular level. Nephrol Dial Transplant 1995; 10: 1109-1112.
16. The Diabetes Control and Complications Trial (DCCT) Research group Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complication. Trial Kidney Int 1995; 47: 1703-1720.
17. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853.
18. UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood – glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) (published erratum appears in Lancet). Lancet 1998; 352: 854-865.
19. Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin – dependent diabetes mellitus. N Engl J Med 1993; 329: 977-986.
20. Jackle-Meyer I, Szukics B, Neubauer K: Extracellural matrix proteins as early marker in diabetic nephropathy. Eur J Clin Chem Biochem 1995; 33: 211-219.
21. Shichiri M, Kishikawa H, OhkuboY, Wake N: Long-term results of the Kumamoto study on optimal diabetes control in type 2 diabetic patients. Diabetes Care 2000; 23: B21-B29.
22. Zoungas S, deGalan BE, Ninomiya T et al.: Combined effects of routine blood pressure lowering and intensive glucose control on macrovascular and microvascular outcomes in patients with diabetes: New results from the ADVANCE trial. Diabetes Care 2009; 32: 2068-2074.
23. The absence of glycemic treshold for the development of long – term complications: the perspective of Diabetes Control and Complications Trial. Diabetes 1996; 45: 1289-1298.
24. Eastman RC, Javitt JC, Herman WH: Model of complications of NIDDM. II. Analysis of the health benefits and cost – effectiveness of treating NIDDM with the goal of normoglycemia. Diabetes Care 1997; 20: 735-744.
25. Diabetes Control and Complications Trial Research Group. Lifetime benefits and costs of intensive therapy as practiced in the diabetes control and complications trial. JAMA 1996; 276: 1409-1415.
26. Eastman RC, Ritz E: Effect of control of diabetes mellitus on progression of renal failure. Kidney Int 1987; Suppl. 22: S53-S56.
27. Suzuki D, Miyazaki M, Jinde K: In situ hybridization studies of matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-1 and type IV collagen in diabetic nephropathy. Kidney Int 1997; 52: 11-119.
28. Reeves WB, Anohedi TE: Transforming growth factor beta contributes to progressive diabetic nephropathy. Proc Neth Acod Sci USA 2000; 97: 7667-7669.
29. McLennan SV, Mortell SKY, Ycle DK: Effect of mesangium glycation on matrix metaloproteinase activities: possible role in diabetic nephropathy. Diabetes 2002; 51: 2612-2618.
30. Czekalski S: Nefropatia cukrzycowa. [In:] Książek A, Rutkowski B: Nefrologia. Czelej, Lublin 2004: 346-371.
31. Viberti G: Diabetic nephropathy. [In:] Kahn CR, Weir GC (ed.): Joslins diabetes mellitus. Lea and Febiger 1994: 191-196.
32. Polizzi FC, Andican G, Cetin E et al.: Increased DNA glycation in type 2 diabetes mellitus: The effect of thiamine and pyridoxine therapy. Exp Clin Endocrinol Diabetol 2012 (epub ahead of print).
33. Lewis EJ, Greene T, Spitalewitz S et al.: Pyridorin in type 2 diabetic nephropathy. J Am Soc Nephr 2012; 23: 131-136.
34. Ishibashi Y, Matsui T, Takeuchi M, Yamagishi SI: Beneficial effect of metformin and irbesartan on advanced glycation end products (AGEs) – RAGE-induced proximal tubular cel injury. Pharmacol Res 2011 (epub ahead of print).
35. Alaveras A: Promotors of progression of diabetic nephropathy the relatives roles of blood glucose and blood pressure control. Nephrol Dial Transplant 1997; 12: 71-74.
36. Reeves WB, Rawal BB, Abdel-Rahman EM, Awad AS: Therapeutic Modalities in Diabetic Nephropathy: Future Approaches. Open J Nephrol 2012; 2(2): 5-18.
37. Chang SY, Chen YW, Chenier I et al.: Angiotensin II type II receptor deficiency accelerates the development of nephropathy in type 1 diabetes via oxidative stress and ACE2. Exp Diabetes Res 2011; 2011: 521076.
38. Kashihara N, Haruna Y, Kondeti VK, Kanwar YS: Oxidative stress in diabetic nephropathy. Curr Med Chem 2010; 17: 4256-4269.
39. Orchard TJ, Chang YF, Ferrell RE et al.: Nephropathy in type 1 diabetes: a manifestation of insulin resistance and multiple genetic susceptibilities? Further evidence from the Pittsburg Epidemiology of Diabetes Complication Study. Kidney Int 2002; 62: 963-970.
40. Wanner Ch, Zimmermann J, Quaschning T: Lipid disorders in diabetic nephropathy. [In:] Hasslacher Ch (ed.): Diabetic nephropathy, John Wileu & Sons 2001: 175-202.
41. Moorhead JF, El-Nahas M, Chan MK, Vorghese Z: Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 1982; 2: 1309-1311.
42. Schlöndorff D: Cellular mechanisms of lipid injury in the glomerulus. Am J Kidney Dis 1993; 22: 279-285.
43. Zoja C, Corna D, Gagliardini E et al.: Adding a statin to a combination of ACE inhibitor and ARB normalizes proteinuria in experimental diabetes, which translates into full renoprotection. Am J Physiol Renal Physiol 2010; 299: F1203-1211.
44. Mason JC: The statins – therapeutic diversity in renal disease? Curr Opin Nephrol Hypertens 2005; 14: 17-24.
45. Koya D, Haneda M, Inomata S et al.: Long-term effect of modification of dietary protein intake on the progression of diabetic nephropathy: a randomised controlled trial. Diabetologia 2009; 52: 2037-2045.