Early Renal Hyperfunction and Hypertrophy in IDDM Patients Including Comments on Early Intervention

  • Margrethe Mau Pedersen


Since diabetic nephropathy constitutes the principal background for reduced survival in insulin-dependent diabetes, much interest is being paid to early alterations in kidney function and structure, and to the possible relationship between such early abnormalities and later development of diabetic nephropathy. A modest increase in urinary albumin excretion, microalbuminuria, has been identified as an early marker of diabetic nephropathy, and interventions postponing the onset of overt nephropathy has been introduced. In this chapter the earliest renal changes in IDDM, glomerular hyperfunction and renal hypertrophy, will be addressed.


Glomerular Filtration Rate Diabetic Nephropathy Atrial Natriuretic Peptide Urinary Albumin Excretion Renal Plasma Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mogensen CE. Glomerular filtration rate and renal plasma flow in short-term and long-term juvenile diabetes mellitus. Scand J Clin Lab Invest 1971; 28: 91–100.PubMedCrossRefGoogle Scholar
  2. 2.
    Ditzel J, Schwartz M. Abnormally increased glomerular filtration rate in short-term insulin-treated diabetic subjects. Diabetes 1976; 16: 264–267.Google Scholar
  3. 3.
    Chnstensen JS, Gammelgaard J, Frandsen M, Parving H-H. Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics. Diabetologia 1981; 20: 451–456.Google Scholar
  4. 4.
    Brøchner-Mortensen J, Ditzel J. Glomerular filtration rate and extracellular fluid volume in insulin-dependent patients with diabetes mellitus. Kidney Int 1982; 21: 696–698.PubMedCrossRefGoogle Scholar
  5. 5.
    Hansen KW, Mau Pedersen M, Chnstensen CK, Schmitz A, Christiansen JS, Mogensen CE. Normoalbuminuria ensures no reduction of renal function in type 1 (insulin-dependent) diabetic patients. J Intern Med 1992; 232: 161–167.PubMedCrossRefGoogle Scholar
  6. 6.
    Mogensen CE. Kidney function and glomerular permeability to macromolecules in juvenile diabetes. Dan Med Bull 1972; 19: 1–36.PubMedGoogle Scholar
  7. 7.
    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
  8. 8.
    Nyberg G, Granerus G, Aurell M. Renal extraction ratios for 51Cr-EDTA, PAH, and glucose in early insulin-dependent diabetic patients. Kidney Int 1982; 21: 706–708.PubMedCrossRefGoogle Scholar
  9. 9.
    Chnstensen CK, Mogensen CE. The course of incipient diabetic nephropathy: studies of albumin excretion and blood pressure. Diabetic Med 1985; 2: 97–102.CrossRefGoogle Scholar
  10. 10.
    Mogensen CE, Chnstensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 1984; 311: 89–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Ellis EN, Steffes MW, Coetz FC, Sutherland DER, Mauer SM. Glomerular filtration surface in type 1 diabetes mellitus. Kidney Int 1986; 29: 889–894.PubMedCrossRefGoogle Scholar
  12. 12.
    Christiansen JS, Frandsen M, Parving H-H. The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus. Diabetologia 1981; 20: 199–204.PubMedGoogle Scholar
  13. 13.
    Mogensen CE, Andersen MJF. Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 1973; 22: 706–713.PubMedGoogle Scholar
  14. 14.
    Mogensen CE, Andersen MJF. Increased kidney size and glomerular filtration rate in untreated juvenile diabetes: Normalization by insulin-treatment. Diabetologia 1975; 11: 221–224.PubMedCrossRefGoogle Scholar
  15. 15.
    Puig JG, Anton FM, Grande C, Pallardo LF, Arnalich F, Gil A, Vázquez JJ, Garcia AM. Relation on kidney size to kidney function in early insulin-dependent diabetes. Diabetologia 1981; 21: 363–367.CrossRefGoogle Scholar
  16. 16.
    Schwieger J, Fine LG. Renal hypertrophy, growth factors, and nephropathy in diabetes mellitus. Semin Nephrol 1990; 10: 242–253.PubMedGoogle Scholar
  17. 17.
    Feldt-Rasmussen B, Hegedüs L, Mathiesen ER, Deckert T. Kidney volume in type 1 (insulin-dependent) diabetic patients with normal or increased urinary albumin excretion: effect of long-term improved metabolic control. Scand J Lab Invest 1991; 51: 31–36.Google Scholar
  18. 18.
    Østerby R, Gundersen HJG. Glomerular size and structure in diabetes mellitus: I. Early abnormalities. Diabetologia 1975; 11: 225–229.PubMedCrossRefGoogle Scholar
  19. 19.
    Seyer-Hansen K, Hansen J, Gundersen HJG. Renal hypertrophy in experimental diabetes: a morphometric study. Diabetologia 1980; 18: 501–505.PubMedCrossRefGoogle Scholar
  20. 20.
    Tuttle KR, Bruto JL, Perusek MC, Lancaster JL, Kopp DT, DeFronzo RA. Effect of strict glycemic control on renal hemodynamic response to amino acids and renal enlargement in insulin-dependent diabetes mellitus. N Engl J Med 1991; 324: 1626–1532.PubMedCrossRefGoogle Scholar
  21. 21.
    Wisemann MJ, Saunders AJ, Keen H, Viberti GC. Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes. N Engl J Med 1985; 312: 617–621.CrossRefGoogle Scholar
  22. 22.
    Mathiesen ER, Hilsted J, Feldt-Rasmussen B, Bonde-Petersen F, Christensen NJ, Parving H-H. The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients. Diabetes 1985; 34: 1301–1305.PubMedCrossRefGoogle Scholar
  23. 23.
    Wolpert HA, Kinsley BT, Clermont AC, Wald H, Bursell S-E. Hyperglycaemia modulates retinal hemodynamics in IDDM. Diabetes 1993; 42: A489.Google Scholar
  24. 24.
    Gray SD. Effect of hypertonicity on vascular dimensions in skeletal muscle. Microvasc Res 1971; 3: 117–124.PubMedCrossRefGoogle Scholar
  25. 25.
    Bank N. Mechanisms of diabetic hyperfiltration. Kidney Int 1991; 40: 792–807.PubMedCrossRefGoogle Scholar
  26. 26.
    Harvey JN, Edmundson AW, Jaffa AA, Martin LL, Mayfield RK. Renal excretion of kallikrein and eicosanoids in patients with Type 1 (insulin-dependent) diabetes mellitus. Relationship to glomerular and tubular function. Diabetologia 1992; 35: 857–862.PubMedCrossRefGoogle Scholar
  27. 27.
    Perico N, Benigni A, Gabanelli M, Piccinelli A, Rog M, De-Riva C, Remuzzi G. Atrial natriuretide peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats. Diabetes 1992; 41: 533–538.PubMedCrossRefGoogle Scholar
  28. 28.
    Blantz RC, Peterson OW, Gushwa L, Tucker BJ. Effect of modest hyperglycemia on tubuloglomerular feedback activity. Kidney Int 1982; 22: S206–S212.Google Scholar
  29. 29.
    Mogensen CE. Glomerular filtration rate and renal plasma flow in normal and diabetic man during elevation of blood sugar levels. Scand J Clin Lab Invest 1971; 28: 177–182.PubMedCrossRefGoogle Scholar
  30. 30.
    Christiansen JS, Frandsen M, Parving H-H. Effect of intravenous glucose infusion on renal function in normal man and in insulin-dependent diabetics. Diabetologia 1981; 21: 368–373.PubMedCrossRefGoogle Scholar
  31. 31.
    Mathiesen ER, Gall M-A, Hommel E, Skøtt P, Parving H-H. Effects of short-term strict metabolic control on kidney function and extracellular fluid volume in incipient diabetic nephropathy. Diabetic Med 1989; 6: 595–600.PubMedCrossRefGoogle Scholar
  32. 32.
    Mogensen CE, Christensen CK, Mau Pedersen M, Alberti KGMM, Boye N, Christensen T, Christiansen JS, Flyvbjerg A, Ingerslev J, Schmitz A, Ørskov H. Renal and glycemic determinants of glomerular hyperfiltration in normoalbuminuric diabetics. J Diabetic Complications 1990; 4: 159–165.CrossRefGoogle Scholar
  33. 33.
    Mau Pedersen M, Christiansen JS, Pedersen EB, Mogensen CE. Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycemic control. Clin Sci 1992; 83: 445–451.Google Scholar
  34. 34.
    Marre M, Dubin T, Hallab M, Berrut G, Bouhanick B, Lejeune J-J, Fressinaud P. Different renal response to hyperglycemia in insulin-dependent diabetics at risk for, or protected against diabetic nephropathy. Diabetes 1993; 42: A423.Google Scholar
  35. 35.
    Skøtt P, Vaag A, Hother-Nielsen O, Andersen P, Bruun NE, Giese J, Beck-Nielsen H, Parving H-H. Effects of hyperglycaemia on kidney function, atrial natriuretic factor and plasma renin in patients with insulin-dependent diabetes mellitus. Scand J Clin Lab Invest 1991; 51: 715–727.PubMedCrossRefGoogle Scholar
  36. 36.
    Greene DA, Lattimer SA, Sima AAF. Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 1987; 316: 599–606.PubMedCrossRefGoogle Scholar
  37. 37.
    Mau Pedersen M, Christiansen JS, Mogensen CE. Reduction of glomerular hyper-filtration in normoalbuminuric IDDM patients by 6 mo of aldose reductase inhibition. Diabetes 1991; 40: 527–531.CrossRefGoogle Scholar
  38. 38.
    Passariello N, Sepe J, Marrazzo G, De Cicco A, Peluso A, Pisano MCA, Sgambato S, Tesauro P, D’Onofrio F. Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate in IDDM subjects with nephropathy. Diabetes Care 1993; 16: 789–795.PubMedCrossRefGoogle Scholar
  39. 39.
    Trevisan R, Nosadini R, Fioretto P, Avogaro A, Duner E, Iori E, Valerio A, Doria A, Crepaldi G. Ketone bodies increase glomerular filtration rate in normal man and in patients with type 1 (insulin dependent) diabetes. Diabetologia 1987; 30: 214–221.PubMedCrossRefGoogle Scholar
  40. 39.
    Trevisan R, Nosadini R, Fioretto P, Avogaro A, Duner E, Iori E, Valerio A, Doria A, Crepaldi G. Ketone bodies increase glomerular filtration rate in normal man and in patients with type 1 (insulin dependent) diabetes. Diabetologia 1987; 30: 214–221.PubMedCrossRefGoogle Scholar
  41. 41.
    Skøtt P, Hother-Nielsen O, Bruun NE, Giese J, Nielsen MD, Beck-Nielsen H, Parving H-H. Effects of insulin on kidney function and sodium excretion in healthy subjects. Diabetologia 1989; 32: 694–699.PubMedCrossRefGoogle Scholar
  42. 42.
    Ortola FV, Ballermann BJ, Anderson S, Mendez RE, Brenner BM. Elevated plasma atrial natriuretic peptide levels in diabetic rats. Potential mediator of hyperfiltration. J Clin Invest 1987; 80: 670–674.PubMedCrossRefGoogle Scholar
  43. 43.
    Haneda M, Kikkawa R, Sakamoto K, Nakanishi S, Matsuda Y, Shigeta Y. Amelioration of glomerular hyperfiltration and hyperperfusion in diabetic rats by non-peptide antagonist for atrial natriuretic peptide receptors. Diabetes 1993; 42: A284.Google Scholar
  44. 44.
    Christiansen JS, Gammelgaard J, Frandsen M, Ørskov H, Parving H-H. Kidney function and size in normal subjects before and during growth hormone administration for one week. Eur J Clin Invest 1981; 11: 487–490.PubMedCrossRefGoogle Scholar
  45. 45.
    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
  46. 46.
    Hoogenberg K, Dullaart RPF, Freling NJM, Meijer S, Sluiter WJ. Contributory roles of glycated haemoglobin, circulatory glucagon and growth hormone to increased renal haemodynamics in type 1 (insulin-dependent) diabetes mellitus (abstract). Eur J Clin Invest 1993; 23: A42.Google Scholar
  47. 47.
    Flyvbjerg A. The role of insulin-like growth factor I in initial renal hypertrophy in experimental diabetes. In: Flyvbjerg A, Ørskov H, Alberti KGMM (eds). Growth Hormone and Insulin-Like Growth Factor I. John Wiley & Sons Ltd. 1993; pp. 271–306.Google Scholar
  48. 48.
    Castellino P, Hunt W, DeFronzo RA. Regulation of renal hemodynamics by plasma amino acid and hormone concentrations. Kidney Int 1987; 32: S-15–S-20.CrossRefGoogle Scholar
  49. 49.
    Mau Pedersen M, Mogensen CE, Schönau Jørgensen F, Møller B, Lykke G, Pedersen O. Renal effects from limitation of high dietary protein in normoalbuminuric diabetic patients. Kidney Int 1989; 36: S-115–S-121.Google Scholar
  50. 50.
    Jones MG, Lee K, Swaminathan R. The effect of dietary protein on glomerular filtration rate in normal subjects. Clin Nephrol 1987; 27: 71–75.PubMedGoogle Scholar
  51. 51.
    Kraus ES, Cheng L, Sikorski I, Spector DA. Effects of phosphorus restriction on renal response to oral and intravenous protein loads in rats. Am J Physiol 1993; 264: F752–F759.Google Scholar
  52. 52.
    Wang YX, Brooks DP. The role of adenosine in glycine-induced glomerular hyper-filtration in rats. J Pharmacol Exp Ther 1992; 263: 1188–1194.PubMedGoogle Scholar
  53. 53.
    Angielski S, Redlak M, Szczepanska KM. Intrarenal adenosine prevents hyperfiltration induced by atrial natriuretic factor. Miner Electrolyte Metab 1990; 16: 57–60.PubMedGoogle Scholar
  54. 54.
    Wang YX, Gellai M, Brooks DP. Dopamine DAI receptor agonist, fenoldopam, reverses glycine-induced hyperfiltration in rats. Am J Physiol 1992; 262: F1055-F1060.Google Scholar
  55. 55.
    Jaffa AA, Vio CP, Silva RH, Vavrek RJ, Stewart JM, Rust PF, Mayfield RK. Evidence for renal kinins as mediators of amino acid-induced hyperfusion and hyperfiltration in the rat. J Clin Invest 1992; 89: 1460–1468.PubMedCrossRefGoogle Scholar
  56. 56.
    Friedlander G, Blanchet BF, Nitenberg A, Laborie C, Assan R, Amiel C. Glucagon secretion is essential for aminoacid-induced hyperfiltration in man. Nephrol Dial Transplant 1990; 5: 110–117.PubMedCrossRefGoogle Scholar
  57. 57.
    Hostetter TH. Diabetic nephropathy. Metabolic versus hemodynamic considerations. Diabetes Care 1992; 15: 1205–1215.PubMedCrossRefGoogle Scholar
  58. 58.
    Mogensen CE. Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. Scand J Clin Lab Invest 1986; 46: 201–206.PubMedCrossRefGoogle Scholar
  59. 59.
    Rudberg S, Persson B, Dalqvist G. Increased glomerular filtration rate predicts diabetic nephropathy-results form an 8 year prospective study. Kidney Int 1992; 41: 822–828.PubMedCrossRefGoogle Scholar
  60. 60.
    Lervang H-H, Jensen S, Brøchner-Mortensen J, Ditzel J. Does increased glomerular filtration rate or disturbed tubular function early in the course of childhood type 1 diabetes predict the development of nephropathy? Diabetic Med 1992; 9: 635–640.PubMedCrossRefGoogle Scholar
  61. 61.
    Jones SL, Wiseman MJ, Viberti GC. Glomerular hyperfiltration as a risk factor for diabetic nephropathy: five-year report of a prospective study. Diabetologia 1991; 34: 59–60.PubMedCrossRefGoogle Scholar
  62. 62.
    Schmieder RE, Messerli FH, Garavaglia G, Nunez B. Glomerular hyperfiltration indicates early target organ damage in essential hypertension. JAMA 1990; 264: 2775–2780.PubMedCrossRefGoogle Scholar
  63. 63.
    Mau Pedersen M, Christensen SE, Christiansen JS, Pedersen EB, Mogensen CE, Ørskov H. Acute effects of a somatostatin analogue on kidney function in type i diabetic patients. Diabetic Med 1990; 7: 304–309.CrossRefGoogle Scholar
  64. 64.
    Serri O, Beauregard H, Brazeau P, Abribat T, Lamber J, Harris A, Vachon L. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes. JAMA 1991; 265; 888–892.PubMedCrossRefGoogle Scholar
  65. 65.
    Mau Pedersen M, Schmitz A, Pedersen EB, Danielsen H, Christiansen JS. Acute and long-term renal effects of angiotensin converting enzyme inhibition in normotensive, normoalbuminuric insulin-dependent diabetic patients. Diabetic Med 1988; 5: 562–569.CrossRefGoogle Scholar
  66. 66.
    Ichikawa I, Harris RC. Angiotensin actions in the kidney: Renewed insight into the old hormone (Editorial Review). Kidney Int 1991; 40: 583–596.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Margrethe Mau Pedersen

There are no affiliations available

Personalised recommendations