A Comparison of Progression in Diabetic and Non-Diabetic Renal Disease: Similarity of Progression Promoters

  • Gerjan Navis
  • Paul E. De Jong
  • Dick De Zeeuw


The prevention of progressive renal function loss remains the major challenge for nephrologists today. Traditionally the progressive nature of renal function loss was attributed to the underlying disease, with a major role for hypertension [1]. The hypothesis, however, that common mechanisms account for the progressive renal function loss in many different renal conditions regardless the nature of initial renal damage[2] was fueled by several observations. These include the linear renal function deterioration that occurs in many patients regardless their initial renal disease [3], as well as the similarity in histopathological abnormalities in end-stage kidneys with different underlying diseases. Systemic [4] and glomerular [5] hypertension, proteinuria [6] and lipid abnormalities [7] are assumed to be common mediators in the pathogenesis of focal segmental glomerulosclerosis, the alleged final common pathway of progressive renal disease [8]. Here we will briefly review current knowledge on progressive renal function loss in human diabetic and non-diabetic renal disease and on the response to intervention treatment. As to diabetic patients we will, for the sake of brevity, mainly focus on patients with type I (insulin-dependent) diabetes. We will specifically address the question whether current clinical evidence supports the hypothesis that common mechanisms underlie progressive renal function loss in diabetic and non-diabetic renal disease; this will help to devise future prevention strategies.


Diabetic Nephropathy Polycystic Kidney Disease Nephrol Dial Transplant Progressive Renal Disease Antiproteinuric Effect 
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.
    Ellis A. Natural history of Bright’s disease; clinical, histological and experimental observations. The vicious circle in Bright’s disease. Lancet 1942; i:72–76.CrossRefGoogle Scholar
  2. 2.
    Klahr Sm Schreiner G, Ichikawa I. The progression of renal disease. N Engl Med 1988; 318:1657–1666.CrossRefGoogle Scholar
  3. 3.
    Mich WE, Buffington G, Lemaan J, Walser M Progression of renal failure: a simple method of estimation. Lancet 1976; ii:1326–1331.CrossRefGoogle Scholar
  4. 4.
    Alvestrand A, Gutierrez A, Bucht H, Bergström J. Reduction of blood pressure retards the progression of chronic renal failure in man. Nephrol Dial Transplant 1988; 3: 624–631.Google Scholar
  5. 5.
    Brenner BM, Meyer TW, Hostetter TW. Dietary protein and the progressive nature of kidney disease: role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis of aging, renal ablation and intrinsic renal disease. N Engl J Med 1982; 307: 652–659.PubMedCrossRefGoogle Scholar
  6. 6.
    Williams PS, Fass G, Bone JM. Renal pathology and proteinuria determine progression in untreated mild/moderate chronic renal failure. Quart J Med 1988; 67: 343–354.PubMedGoogle Scholar
  7. 7.
    Keane WF, Kasiske B, O’Donnell MP, Kin Y. The role of altered lipid metabolism in the progression of renal disease. Am J Kidney Dis 1991; 17:S38– S42.PubMedGoogle Scholar
  8. 8.
    Remuzzi G, Bertani T. Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? [editorial]. Kidney Int 1990; 38:384–94.PubMedCrossRefGoogle Scholar
  9. 9.
    Mogensen CE. Natural history and potential prevention of diabetic nephropathy in insulin-dependent and non-insulin-dependent diabetic patients. In: Prevention of progressive chronic renal failure. El Nahas A, Mallick NP, Anderson S, (eds). Oxford 1993; pp 278–279.Google Scholar
  10. 10.
    Levey AS. Measurement of renal function in chronic renal disease. Kidney Int 1990; 38:167–184.PubMedCrossRefGoogle Scholar
  11. 11.
    Apperloo AJ, de Zeeuw D, de Jong PE. Precision of GFR determinants for long term slope calculations is improved by simultaneous infusion of 125I-iothalamate and 131I-Hippuran. JASN 1996; 7: 567–572.PubMedGoogle Scholar
  12. 12.
    Walser M, Drew HH, LaFrance LD. Creatinine measurements often yield false estimates in chronic renal failure. Kidney Int 1988; 34: 412–418.PubMedCrossRefGoogle Scholar
  13. 13.
    Jones RH, Mackay JD, Hayakawa H, Parsons V, Watkins PJ. Progression of diabetic nephropathy. Lancet 1979; i:1105–1106.CrossRefGoogle Scholar
  14. 14.
    Bergström J, Alvestrand A, Bucht H, Gutierrez A, Stenvinkel P. Is renal failure always progressive? Contrib Neprol 1989; 75:60–67.Google Scholar
  15. 15.
    Gall M-A, Nielsen FS, Smidt UM, Parving H-H. The course of kidney function in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy. Diabetologia 1993; 36: 1071–1078.PubMedCrossRefGoogle Scholar
  16. 16.
    Williams PS, Mallick NP. The natural history of chronic renal failure. In: Prevention of progressive chronic renal failure. El Nahas AM, Mallick NP, Anderson S (eds). Oxford 1993, p210–259.Google Scholar
  17. 17.
    Tamow L. Genetic pattern in diabetic nephropathy. Nephrol Dial Transplant 1996; 11:410–412.CrossRefGoogle Scholar
  18. 18.
    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 1985; 82: 5963–5967.PubMedCrossRefGoogle Scholar
  19. 19.
    Parving H-H, Kastrup H, Smidt UM, Andersen AR, Feldt-Rasmussen B, Sandahl Christiansen J. Impaired autoregulation of glomerular filtration rate in type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 1984; 27: 547 – 552.PubMedCrossRefGoogle Scholar
  20. 20.
    Poulsen PL, Hansen KW, Mogensen CE. Ambulatory blood pressure in the transition from normo-to microalbuminuria: a longitudinal study in IDDM. Diabetes 1994; 43: 1248–53.PubMedCrossRefGoogle Scholar
  21. 21.
    Parving H-H, Jensen HE, Mogensen CE. Increased urinary albumin excretion in benign essential hypertension. Lancet 1974; 231–237.Google Scholar
  22. 22.
    du Cailar G, Ribstein J, Mimran A. Glomerular hyperfiltration and left ventricular mass in mild never-treated essential hypertension. J Hypertens 1990; 9 suppl. 6: S158– S159.Google Scholar
  23. 23.
    Brazy PC, Fitzwilliam JF. Progressive renal disease: role of race and antihypertensive medications. Kidney Int 1990; 37:1113–1119.PubMedCrossRefGoogle Scholar
  24. 24.
    Ahlem J. Incidence of human chronic renal insufficiency. A study of the incidence and pattern of renal insufficiency in adults during 166–71 in Gothenburg Acta Med Scand 1975; suppl 582:1–50.Google Scholar
  25. 25.
    Stenvinkel P, Alvestrand A, Bergström J. Factors influencing progression in patients with chronic renal failure. J Int Med 1989; 226: 183–188.CrossRefGoogle Scholar
  26. 26.
    Locatelli F, Marcelli D, Comelli M, Alberti D, Graziani G, Buccianti G, Redaelli B, Giangrande A et al. Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Nephrol Dial Transplant 1996; 11; 461–67.PubMedCrossRefGoogle Scholar
  27. 27.
    Rutherford WE, Blondin J, Miller JP, Greenwak AS, Vavra JD. Chronic progressive renal disease: rate of change of serum creatinine concentration. Kidney Int 1977; 11:62–70.PubMedCrossRefGoogle Scholar
  28. 28.
    Hannedouche T, Chaveau P, Fehrat A, Albouze G, Jungers. Effect of moderate protein restriction on the rate of progression of renal failure. Kidney Int 1989; 36 (suppl 27) S91–95.Google Scholar
  29. 29.
    Rosman JB, Langer K, Brandi M, Piers-Becht TPM, van der Hem GK, ter Wee PM, Donker AJM. Protein-restricted diets in chronic renal failure: a four-year follow-up shows limited indications. Kidney Int. 1989; 36 (suppl 27): S96–102.Google Scholar
  30. 30.
    Wight JP, Salzano S, Brown CB, El Nahas AM. Natural history of chronic renal failure: a reappraisal. Nephrol Dial Transplant 1992; 7: 379–383.PubMedGoogle Scholar
  31. 31.
    Oldrizzi L, Rugiu C, Valvo E, Lupo A, Loschiavo C, Gammaro L, Tessitore N, Fabris A, Panzetta G, Maschio G. Progression of renal failure in patients with renal disease of diverse etiology on protein-restricted diet Kidney Int 1985; 27: 553–557.PubMedCrossRefGoogle Scholar
  32. 32.
    Mallick NP, Short CD, Hunt LP. How far since Ellis? Nephron 1987; 46:113–24.PubMedCrossRefGoogle Scholar
  33. 33.
    Woo DJ. Apoptosis and loss of renal tissue in polycystic kidney diseases. N Engl J Med 1995; 333: 18–25.PubMedCrossRefGoogle Scholar
  34. 34.
    Grantham JJ. Polycystic kidney disease: there goes the neighbourhood. N Engl J Med 1995; 333:56–57.PubMedCrossRefGoogle Scholar
  35. 35.
    Hasslacher C, Ritz E, Terpstra J, Gallasch G, Kunowski G, Rall C. Natural history of nephropathy in type 1 diabetes. Hypertension 1985; 7 (suppl II): II74– II78.Google Scholar
  36. 36.
    Mogensen CE, Christensen CK. Blood pressure changes and renal function in incipient and overt diabetic nephropathy. Hypertension 1985; 7 (suppl II): II64– II73.Google Scholar
  37. 37.
    Rossing P, Hommel E, Smidt U, Parving H-H. Impact of blood pressure and albuminuria on the progression of diabetic nephropathy in IDDM patients. Diabetes 1993; 42:715–719.PubMedCrossRefGoogle Scholar
  38. 38.
    Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE, Shulman NB, Stamler J. Blood pressure and end-stage renal disease in men. N Engl J Med 1996; 334:13–18.PubMedCrossRefGoogle Scholar
  39. 39.
    Apperloo AJ, de Zeeuw D, de Jong PE. Short-term antiproteinuric response to antihypertensive therapy predicts long-term GFR decline in patients with non-diabetic renal disease. Kidney Int 1994; 45 (suppl 45): S174–178.Google Scholar
  40. 40.
    Mulec H, Johnson S-A, Björck S. Relation between serum cholesterol and diabetic nephropathy. Lancet 1990; 335:1536–1538.CrossRefGoogle Scholar
  41. 41.
    van Essen GG, Rensma PL, de Zeeuw D, de Jong PE. Association between angtotensin-converting enzyme gene polymorphism and failure of renoprotective therapy. Lancet 1996; 347:94–95.PubMedCrossRefGoogle Scholar
  42. 42.
    Parving H-H, Jacobsen P, Tamow L, Rossing PP, Lecrof L, Poirier O, Cambien F. Effect of deletion polymorphism of the angiotensin converting enzyme gene on progression of diabetic nephropathy during inhibition of angiotensin converting enzyme: observational follow-up study. BMJ 1996; 313: 591–594.PubMedCrossRefGoogle Scholar
  43. 43.
    Rossing K, Rossing P, Jacobsen P, Tamow L, Cambien F, Parving H-H. (1996) Role of angiotensin-converting enzyme (ACE) gene polymorphism and antiproteinuric effects of ACE inhibition in diabetic nephropathy. J Am Soc Nephrol 7:1364(A).Google Scholar
  44. 44.
    The Euclid Study Group. Differences in albumin excretion rate response to lisinopril by ACE-genotype in insulin-dependent diabetes (IDDM) Diabetologia 1996; 39: suppl 1: A60.Google Scholar
  45. 45.
    van der Kleij FGH, Schmidt A, Navis GJ, Haas M, Yilmaz N, de Jong PE, Mayer G, de Zeeuw D. ACE I/D polymorphism and short term response to ACE inhibition; role of sodium status. Kidney Int 1997; 52; suppl. 63; S23– S26.Google Scholar
  46. 46.
    Yoshida H, Mitarai T, Kawamura T, Kitajima T, Miyazaki Y, Nagasawa R, Kawaguchi Y, Kubo H, Ichikawa I, Sakai O. Role of the deletion polymorphism of the angiotensin-converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. J Clin Invest 1995; 96:2162–2169.PubMedCrossRefGoogle Scholar
  47. 47.
    Hauser AC, Derfler K, Balcke P. Progression of renal insuffiency in analgesic nephropathy: impact of drug abuse. J Clin Epidemiol 1991; 44: 53–56.PubMedCrossRefGoogle Scholar
  48. 48.
    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: 977–86.CrossRefGoogle Scholar
  49. 49.
    Parving H-H, Andersen AR, Smidt UM, Svendsen PA. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983; 1175–1179.Google Scholar
  50. 50.
    Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein restriction on the progression of diabetic and non-diabetic renal disease: a meta-analysis. Ann Int Med 1996; 124:627–632.PubMedCrossRefGoogle Scholar
  51. 51.
    Levey AS, Adler S, Caggiula AW, England BK, Greene T, Hunsicker LG. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease. (MDRD) Study. Am J Kidney Dis 1996; 27: 652–663.PubMedCrossRefGoogle Scholar
  52. 52.
    Apperloo AJ, de Zeeuw D, de Jong PE. A short term antihypertensive treatment induced fall in glomerular filtration rate predicts long term stability of renal function. Kidney Int 1997; 51:793–797.PubMedCrossRefGoogle Scholar
  53. 53.
    El Nahas AM, Masters-Thomas A, Brady AS, Farrington K, Wilkinson V, Hilson AJW, Varghese Z, Moorhead JFI. Selective effect of low protein diets in chronic renal diseases BMJ 1984; 289:1337–1341.PubMedCrossRefGoogle Scholar
  54. 54.
    Rossing P, Hommel E, Smidt UM, Parving H-H. Reduction in albuminuria predicts diminished progression in diabetic nephropathy. Kidney Int. 1994; 45 (suppl 45): S145–149.Google Scholar
  55. 55.
    Gansevoort RT, de Zeeuw D, de Jong PE. Long-term benefits of the antiproteinuric effect of ACE-inhibition in non-diabetic renal disease. Am J Kidney Dis 1993; 2: 202–206.Google Scholar
  56. 56.
    The GISEN Group: Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349:1857–1863.CrossRefGoogle Scholar
  57. 57.
    Praga M, Hernández E, Montoyo C, Andrés A, Ruilope L, Rodicio JL. Long-term beneficial effects of angiotensin-converting enzyme inhibition with nephrotic proteinuria. Am J Kidney Dis 1992; 20: 240–248.PubMedGoogle Scholar
  58. 58.
    Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G, et al. The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease. N Engl Med 1994; 330: 877–884.CrossRefGoogle Scholar
  59. 59.
    Rudberg S, Aperia A, Freyschuss U, Persson B. Enalapril reduces microalbuminuria in young normotensive Type 1 (insulin-dependent) diabetic patients irrespective of its hypotensive effect. Diabetologia 1990; 33:470–476.PubMedCrossRefGoogle Scholar
  60. 60.
    Mathiesen ER, Hommel E, Giese J, Parving H-H. Efficacy of Captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. Br Med J 1991; 303:81–87.CrossRefGoogle Scholar
  61. 61.
    Heeg JE, de Jong PE, van der Hem GK, de Zeeuw D. Efficacy and variability of the antiproteinuric effect of lisinopril. Kidney Int 1989; 36: 272–279.PubMedCrossRefGoogle Scholar
  62. 62.
    Björck S, Nyberg G, Mulec H, Granerus G, Herlitz H, Aurell M. Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy Br Med J 1986; 293:471–474.CrossRefGoogle Scholar
  63. 63.
    Heeg JE, de Jong PE, van der Hem GK, de Zeeuw D. Reduction of proteinuria by angiotensin converting enzyme inhibition. Kidney Int 1987; 32: 78–83.PubMedCrossRefGoogle Scholar
  64. 64.
    Björck S, Mulec H, Johnson SA, Nordén G, Aurell M. Renal protective effect of enalapril in diabetic nephropathy. Br Med J 1992; 304: 339–343.CrossRefGoogle Scholar
  65. 65.
    Lewis EJ, Hunsicker LG, Bain RP, Ronde RD et al. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456–1462.PubMedCrossRefGoogle Scholar
  66. 66.
    Maschio G, Alberti D, Janin G, Locatelli F, Mann JFE, Motolese M, Ponticelli C, Ritz E, Zuchelli P et al. Effect of the angiotensin converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996; 334–945.Google Scholar
  67. 67.
    Kamper A-L, Strandgaard S, Leyssac PP. Late outcome of a controlled trial of enalapril treatment in progressive chronic renal failure. Hard end-points and influence of proteinuria. Nephrol Dial Transplant 1995; 10:1182–1188.PubMedGoogle Scholar
  68. 68.
    Hannedoudie T, Landais P, Goldfarb B, El Esper N, Foumier A, Godin M, Durand D, Chanard J, Mognon F, Sue J-M, Grünfeld J-P. Randomized controlled trial of enalapril and beta-blockers in non-diabetic chronic renal failure. Br J Med 1994; 309 833–837.CrossRefGoogle Scholar
  69. 69.
    Giatras I, Lau J, Levey A. for the angiotensin converting enzyme inhibition and progressive renal disease study group. Effect of angiotensin converting enzyme inhibitors on the progression of non-diabetic renal disease: a meta-analysis of randomized trials. Ann Int Med 1997; 127: 337–345.PubMedCrossRefGoogle Scholar
  70. 70.
    van Essen GG, Apperloo AJ, Rensma PL, Stegeman CA, Sluiter WJ, de Zeeuw D, de Jong PE. Are ACE-inhibitors superior to beta-blockers in retarding progressive renal function decline? Kidney Int 1997; 52; suppl 63; S58– S62.Google Scholar
  71. 71.
    Navis GJ, de Zeeuw D, de Jong PE. ACE-inhibitors: panacea for progressive renal disease? Lancet 1997; 349:1852–1853.PubMedCrossRefGoogle Scholar
  72. 72.
    Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE. Antiproteinuric effect of blood-pressure lowermg agents; a meta-analysis of comparative trials. Nephrol Dial Transplant 1995; 10:1963–1974.PubMedGoogle Scholar
  73. 73.
    Maki DD, Ma JZ, Louis TA, Kasiske BL. Long-term effects of antihypertensive agents on proteinuria and renal function. Arch Int Med 1995; 155:1073–1080.CrossRefGoogle Scholar
  74. 74.
    Weidmann P, Schneider M, Bohlen L. Therapeutic efficacy of different antihypertensive drugs in human diabetic nephropathy.: An updated meta-analysis. Nephrol Dial Transplant 1995; 10 (suppl 9): 39–45.PubMedGoogle Scholar
  75. 75.
    Petersson JC, Adler S, Burkart JM, Greene T, Herbert LA, Hunsicker LG, King AJ, Klahr S, Massry S, Seifter JL, for the MDRD study group. Blood pressure control, proteinuria and the progression of renal disease. Ann Int Med 1995; 123: 754–762.CrossRefGoogle Scholar
  76. 76.
    Mogensen CE, Keane WF, Bennett PH, Jerums G, Parving H-H, Passa P, Steifes MW, Striker GE, Viberti GC. Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995; 346:1080–1084.PubMedCrossRefGoogle Scholar
  77. 77.
    Lazarus JM, Bourgoignie JJ, Buckalew VM, Greene T, Levey AS, Milas NC, Parandi L, Peterson JC, Porush JG, Rauch S, Soucie JM, Stouar C for the Modification of Diet in Renal Disease Study Group. Achievement and safety of a low blood pressure goal in chronic renal disease. Hypertension 1997; 29:641–650.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • Gerjan Navis
    • 1
  • Paul E. De Jong
    • 1
  • Dick De Zeeuw
    • 1
  1. 1.Department of Internal Medicine, Division of Nephrology and Department of Clinical PharmacologyState UniversityGroningenThe Netherlands

Personalised recommendations