Pathogenesis of Diabetic Glomerulopathy: The Role of Glomerular Hemodynamic Factors

  • Sharon Anderson


Glomerular hyperfiltration in insulin-dependent (Type 1) diabetes mellitus of short duration has been recognized for many years [1–3], with increments in renal plasma flow (RPF) and nephromegaly [3]. With the finding of early hyperfiltration, Stalder and Schmid proposed that these early functional changes may predispose the subsequent development of diabetic glomerulopathy [1]. Early support for the hypothesis that renal hyperperfusion and hyperfiltration contribute to diabetic glomerulopathy emanated from the finding of diabetic glomerulopathy only in the non-stenosed kidney in the setting of unilateral renal artery stenosis [4].


Diabetic Nephropathy Atrial Natriuretic Peptide Experimental Diabetes Renal Plasma Flow Renal Hemodynamic 
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  1. 1.
    Stalder G, Schmid R. Severe functional disorders of glomerular capillaries and renal hemodynamics in treated diabetes mellitus during childhood. Ann Paediatr 1959; 193: 129–138.PubMedGoogle Scholar
  2. 2.
    Ditzel J, Junker K. Abnormal glomerular filtration rate, renal plasma flow and renal protein excretion in recent and short-term diabetes. BMJ 1972; 2: 13–19.PubMedCrossRefGoogle Scholar
  3. 3.
    Mogensen CE, Andersen MJF. Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 1973; 22: 706–712.PubMedGoogle Scholar
  4. 4.
    Berkman J, Rifkin H. Unilateral nodular diabetic glomerulosclerosis (Kimmelstiel-Wilson). Metabolism 1973; 22: 715–722.PubMedCrossRefGoogle Scholar
  5. 5.
    Vora J, Dolben J, Dean J, Williams JD, Owens DR, Peters JR. Renal hemodynamics in newly presenting non-insulin-dependent diabetics. Kidney Int 1992; 41: 829–835.PubMedCrossRefGoogle Scholar
  6. 6.
    Myers BD, Nelson RG, Williams GW, et al. Glomerular function in Pima Indian with non-insulin-dependent diabetes mellitus of recent origin. J Clin Invest 1991; 88: 524–530.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Palmisano JJ, Lebovitz HE. Renal function in Black Americans with type II diabetes. J Diabetic Compl 1989; 3: 40–44.CrossRefGoogle Scholar
  8. 8.
    Nelson RG, Beck GJ, Bennett PH, Knowler WC, Mitch WE, Myers BD. Changes in glomerular function with the onset of non-insulin-dependent diabetes in Pima Indians (Abstract). Diabetologia 1993; 36: A27.Google Scholar
  9. 9.
    Nowack R, Raum E, Blum W, Ritz E. Renal hemodynamics in recent-onset Type II diabetes. Am J Kidney Dis 1992; 20: 342–347.PubMedGoogle Scholar
  10. 10.
    Ritz E, Stefanski A. Diabetic nephropathy in Type II diabetes. Am J Kidney Dis 1996; 27: 167–194.PubMedCrossRefGoogle Scholar
  11. 11.
    Mogensen CE. Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. Scand J Clin Lab Inv 1986; 46: 201–206.CrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    Lervang H-H, Jensen S, Borchner-Mortensen J, Ditzel J. Early glomerular hyperfiltration and the development of late nephropathy in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1988; 31: 723–729.PubMedCrossRefGoogle Scholar
  14. 14.
    Messent J, Jones SL, Wiseman M, Viberti GC. Glomerular hyperfiltration and albuminuria: an 8 year prospective study (Abstract). Diabetologia 1991; 34: Suppl. 2: 3A.Google Scholar
  15. 15.
    Vora JP, Peters JR, Williams JD. Evolution of renal hemodynamics in non-insulin-dependent diabetics (NIDDMs): a 2 year study (Abstract). J Am Soc Nephrol 1993; 4: 310.Google Scholar
  16. 16.
    Anderson S. Antihypertensive therapy in experimental diabetes. J Am Soc Nephrol 1992; 3: Suppl. 1: S86–S90.PubMedGoogle Scholar
  17. 17.
    O’Donnell MP, Kasiske BL, Keane WF. Glomerular hemodynamics and structural alterations in experimental diabetes. FASEB J 1986; 2: 2339–2347.Google Scholar
  18. 18.
    Park SK, Meyer TW. The effect of hyperglycemia on glomerular function in obese Zucker rats. J Lab Clin Med 1995; 125: 501–507.PubMedGoogle Scholar
  19. 19.
    Hostetter TH, Troy JL, Brenner BM. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int 1981; 19:410–415.PubMedCrossRefGoogle Scholar
  20. 20.
    Reubi FC. Glomerular filtration rate, renal blood flow, and blood viscosity during and after diabetic coma. Circ Res 1953; 1: 410–413.PubMedCrossRefGoogle Scholar
  21. 21.
    Zatz R, Meyer TW, Rennke HG, Brenner BM. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci (USA) 1985; 82: 5963–5967.CrossRefGoogle Scholar
  22. 22.
    Zatz R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 1986; 77: 1925–1930.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Seyer-Hansen K. Renal hypertrophy in experimental diabetes mellitus. Kidney Int 1983; 23: 643–646.PubMedCrossRefGoogle Scholar
  24. 24.
    Seyer-Hansen K, Hansen J, Gundersen HJG. Renal hypertrophy in experimental diabetes. A morphometry study. Diabetologia 1980; 18: 501–505.PubMedCrossRefGoogle Scholar
  25. 25.
    Steffes MW, Brown DM, Basgen JM, Mauer SM. Amelioration of mesangial volume and surface alterations following islet transplantation in diabetic rats. Diabetes 1980; 29: 509–515.PubMedCrossRefGoogle Scholar
  26. 26.
    Mauer SM, Michael AF, Fish AJ, Brown DM. Spontaneous immunoglobulin and complement deposition in glomeruli of diabetic rats. Lab Invest 1972; 27: 488–494.PubMedGoogle Scholar
  27. 27.
    O’Donnell MP, Kasiske BL, Daniels FX, Keane WF. Effect of nephron loss on glomerular hemodynamics and morphology in diabetic rats. Diabetes 1986; 35: 1011–1015.PubMedCrossRefGoogle Scholar
  28. 28.
    Mauer SM, Steffes MW, Azar S, Sandberg SK, Brown DM. The effect of Goldblatt hypertension on development of the glomerular lesions of diabetes mellitus in the rat. Diabetes 1978; 27: 738–744.PubMedCrossRefGoogle Scholar
  29. 29.
    Christiansen JS, Gammelgaard J, Tronier B, Svendsen PA, Parving H-H. Kidney function and size in diabetics before and during initial insulin treatment. Kidney Int 1982; 21: 683–688.PubMedCrossRefGoogle Scholar
  30. 30.
    Parving H-H, Christiansen JS, Noer I, Tronier B, Mogensen CE. The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics. Diabetologia 1980; 19: 350–354.PubMedCrossRefGoogle Scholar
  31. 31.
    Christiansen JS, Gammelgaard J, Orskov H, Andersen AR, Telmer S, Parving H-H. Kidney function and size in normal subjects before and during growth hormone administration for one week. Eur J Clin Invest 1980; 11:487–490.CrossRefGoogle Scholar
  32. 32.
    Vora J, Dolben J, Williams JD, Peters JR, Owens DR. Impact of initial treatment on renal function in newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1993; 36: 734–740.PubMedCrossRefGoogle Scholar
  33. 33.
    Stackhouse S, Miller PL, Park SK, Meyer TW. Reversal of glomerular hyperfiltration and renal hypertrophy by blood glucose normalization in diabetic rats. Diabetes 1990; 39: 989–995.PubMedCrossRefGoogle Scholar
  34. 34.
    Scholey JW, Meyer TW. Control of glomerular hypertension by insulin administration in diabetic rats. J Clin Invest 1989; 83: 1384–1389.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Tucker BJ, Anderson CM, Thies RS, Collins RC, Blantz RC. Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats. Kidney Int 1992; 42: 1160–1168.PubMedCrossRefGoogle Scholar
  36. 36.
    Sabbatini M, Sansone G, Uccello F, Giliberti A, Conte G, Andreucci VE. Early glycosylation products induce glomerular hyperfiltration in normal rats. Kidney Int 1992; 42: 875–881.PubMedCrossRefGoogle Scholar
  37. 37.
    Ortola FV, Ballermann BJ, Anderson S, Mendez RE, Brenner BM. Elevated plasma atrial natriuretic peptide levels in diabetic rats. J Clin Invest 1987; 80: 670–674.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Mattar AL, Ribeiro MO, Fujihara CK, Padilha RM, DeNucci G, Zatz R. Effects of acute and chronic nitric oxide blockade on renal function of diabetic rats (Abstract). J Am Soc Nephrol 1993; 4: 799.Google Scholar
  39. 39.
    Komers R, Allen TJ, Cooper ME. Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes. Diabetes 1994; 43: 1190–1197.PubMedCrossRefGoogle Scholar
  40. 40.
    Ballermann BJ, Skorecki KL, Brenner BM. Reduced glomerular angiotensin II receptor density in early untreated diabetes mellitus in the rat. Am J Physiol 1984; 247: F110–F116.PubMedGoogle Scholar
  41. 41.
    Wilkes BM, Kaplan R, Mento PF, Aynedjian H Macica CM, Schlondorff D, Bank N. Reduced glomerular thromboxane receptor sites and vasoconstrictor responses in diabetic rats. Kidney Int 1992; 41: 992–999.PubMedCrossRefGoogle Scholar
  42. 42.
    Christlieb AR. Renin, angiotensin and norepinephrine in alloxan diabetes. Diabetes 1974; 23: 962–970.PubMedGoogle Scholar
  43. 43.
    Kennefick TM, Oyama TT, Thompson MM, Anderson S. Increased sensitivity to angiotensin action in the diabetic rat kidney (Abstract). J Am Soc Nephrol 1994; 5: 967.Google Scholar
  44. 44.
    Ohishi K, Okwueze MI, Vari RC, Carmines PK. Juxtamedullary microvascular dysfunction during the hyperfiltration stage of diabetes mellitus. Am J Physiol 1994; 267: F99–F105.PubMedGoogle Scholar
  45. 45.
    Blantz RC, Peterson OW, Gushwa L, Tucker BJ. Effect of modest hyperglycemia on tubuloglomerular feedback activity. Kidney Int 1982; 22: Suppl. 12: S206–S212.Google Scholar
  46. 46.
    Vallon V, Blantz RC, Thomson S. Homeostatic efficiency of tubuloglomerular feedback is reduced in established diabetes mellitus in rats. Am J Physiol 1995; 269: F876–F883.PubMedGoogle Scholar
  47. 47.
    Zhang PL, Mackenzie HS, Troy JL, Brenner BM. Effects of an atrial natriuretic peptide receptor antagonist on glomerular hyperfiltration in diabetic rats. J Am Soc Nephrol 1994; 4: 1564–1570.PubMedGoogle Scholar
  48. 48.
    Jensen PK, Steven K, Blaehr H, Christiansen JS, Parving H-H. Effects of indomethacin on glomerular hemodynamics in experimental diabetes. Kidney Int 1986; 29: 490–495.PubMedCrossRefGoogle Scholar
  49. 49.
    Mayfield RK, Margolius HS, Levine JH, Wohltmann HJ, Loadholt CB, Colwell JA. Urinary kallikrein excretion in insulin-dependent diabetes mellitus and its relationship to glycemic control. J Clin Endocrinol Metab 1984; 59: 278–286.PubMedCrossRefGoogle Scholar
  50. 50.
    Jaffa AA, Rust PF, Mayfield RK. Kinin, a mediator of diabetes-induced glomerular hyperfiltration. Diabetes 1995; 44: 156–160.PubMedCrossRefGoogle Scholar
  51. 51.
    Vora JP, Oyama TT, Thompson MM, Anderson S. Interactions of the renin-angiotensin system and kallikrein-kinin system in the diabetic kidney (Abstract). J Am Soc Nephrol 1995; 6: 1051.Google Scholar
  52. 52.
    Goldfarb S, Ziyadeh FN, Kern EFO, Simmons DA. Effects of polyol-pathway inhibition and dietary myo-inositol on glomerular hemodynamic function in experimental diabetes mellitus in rats. Diabetes 1991; 40: 465–471.PubMedCrossRefGoogle Scholar
  53. 53.
    Daniels BS, Hostetter TH. Aldose reductase inhibition and glomerular abnormalities in diabetic rats. Diabetes 1989; 38: 981–986.PubMedCrossRefGoogle Scholar
  54. 54.
    Anderson S, Brenner BM. »The critical role of nephron mass and of intraglomerular pressure for initiation and progression of experimental hypertensive-renal disorders.« In Hypertension: Pathophysiology, Diagnosis, and Management, Ch. 93. 2nd ed, Laragh JH, Brenner BM, eds. New York: Raven Press, 1995; pp 1553–1568.Google Scholar
  55. 55.
    Kuchan MJ, Frangos JA. Shear stress regulates endothelin-1 release via protein kinase C and cGMP in cultured endothelial cells. Am J Physiol 1993; 264: H150–H156.PubMedGoogle Scholar
  56. 56.
    Buga GM, Gold ME, Fukuto JM, Ignarro LJ. Shear stress-induced release of nitric oxide from endothelial cells grown on beads. Hypertension 1991; 17: 187–193.PubMedCrossRefGoogle Scholar
  57. 57.
    Ohno M, Cooke JC, Dzau VJ, Gibbons GH. Fluid shear stress induces endothelial transforming growth factor beta-1 transcription and production. Modulation by potassium-channel blockade. J Clin Invest 1995; 95: 1363–1369.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Ott MJ, Bailermann BJ. Shear stress augments glomerular endothelial cell PDGF mRNA expression and mitogen production (Abstract). J Am Soc Nephrol 1992; 3: 476.Google Scholar
  59. 59.
    Malek AM, Gibbons GH, Dzau VJ, Izumo S. Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium. J Clin Invest 1993. 92: 2013–2021.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Riser BL, Cortes P, Zhao X, Bernstein J, Dumler F, Narins RG. Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat. J Clin Invest 1992; 90: 1932–1943.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Yasuda T, Becker B, Kondo S, et al. Mechanical stretch/ relaxation increases type 1 angiotensin II receptor expression and angiotensinogen mRNA in cultured rat mesangial cells (Abstract). J Am Soc Nephrol 1994; 4: 554.Google Scholar
  62. 62.
    Harris RC, Haralson MA, Badr KF. Continuous stretch-relaxation in culture alters rat mesangial cell morphology, growth characteristics, and metabolic activity. Lab Invest 1992; 66: 548–554.PubMedGoogle Scholar
  63. 63.
    Homma T, Akai Y, Burns KD, Harris RC. Activation of S6 kinase by repeated cycles of stretching and relaxation in rat glomerular mesangial cells. J Biol Chem 1992; 267: 23129–23135.PubMedGoogle Scholar
  64. 64.
    Yasuda T, Kondo S, Homma T, Harris RC. Mechanisms for accumulation of extracellular matrix in rat mesangial cells in response to stretch/relaxation (Abstract). J Am Soc Nephrol 1994; 4: 824.Google Scholar
  65. 65.
    Harris RC, Akai Y, Yasuda T, Homma T. The role of physical forces in alterations of mesangial cell function. Kidney Int 1995; 45: Suppl. 45: S17–S22.Google Scholar
  66. 66.
    Mattana J, Singhal PC. Applied pressure modulates mesangial cell proliferation and matrix synthesis. Am J Hypertension 1995; 8: 1112–1120.CrossRefGoogle Scholar
  67. 67.
    Anderson S, Rennke HG, Garcia DL, Brenner BM. Short and long term effects of antihypertensive therapy in the diabetic rat. Kidney Int 1989; 36: 526–532.PubMedCrossRefGoogle Scholar
  68. 68.
    Anderson S, Rennke HG, Brenner BM. Nifedipine versus fosinopril in uninephrectomized diabetic rats. Kidney Int 1992; 41: 891–897.PubMedCrossRefGoogle Scholar
  69. 69.
    Cooper ME, Rumble JR, Allen TJ, et al. Antihypertensive therapy and experimental diabetic nephropathy. Kidney Int 1992; 41: 898–903.PubMedCrossRefGoogle Scholar
  70. 70.
    Fujihara C, Padilha RM, Zatz R. Glomerular abnormalities in long-term experimental diabetes. Diabetes 1992;41:286–293.PubMedCrossRefGoogle Scholar
  71. 71.
    Geiger H, Bahner U, Vaaben W, et al. Effects of angiotensin-converting enzyme inhibition in diabetic rats with reduced renal function. J Lab Clin Med 1992; 120: 861–867.PubMedGoogle Scholar
  72. 72.
    O’Brien R, Cooper ME, Jerums G, Doyle AE. The effects of perindopril and triple therapy in a normotensive model of diabetic nephropathy. Diabetes 1993; 42: 604–609.PubMedCrossRefGoogle Scholar
  73. 73.
    Brown SA, Walton CL, Crawford P, Bakris GL. Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria. Kidney Int 1993; 43: 1210–1218.PubMedCrossRefGoogle Scholar
  74. 74.
    Anderson S, Jung FF, Ingelfinger JR. Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biologic correlations. Am J Physiol 1993; 265: F477–F486.PubMedGoogle Scholar
  75. 75.
    Remuzzi A, Perico N, Amuchastegui CS, Malanchini B, Mazerska M, Battaglia C, Bertani C, Remuzzi G. Short-and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes. J Am Soc Nephrol 1993; 4: 40–49.PubMedGoogle Scholar
  76. 76.
    Kasiske BL, Kalil RSN, Ma JZ, Liao M, Keane WF. Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann Intern Med 1993; 118: 129–138.PubMedCrossRefGoogle Scholar
  77. 77.
    Böhlen L, de Courten M, Weidmann P. Comparative study of the effect of ACE-inhibitors and other antihypertensive agents on proteinuria in diabetic patients. Am J Hypertension 1994; 7: 84S–92S.Google Scholar
  78. 78.
    Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456–1462.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Sharon Anderson
    • 1
  1. 1.Division of Nephrology and HypertensionOregon Health Sciences UniversityPortlandUSA

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