Skip to main content
Log in

Cost-effective strategies in the prevention of diabetic nephropathy

  • Review Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

A significant subgroup of patients with diabetes mellitus are predisposed to developing diabetic nephropathy and it is in this subgroup that other diabetesrelated complications, and in particular greatly increased cardiovascular disease risk, are concentrated. The high personal, social and financial costs of managing end-stage renal failure and the other complications associated with diabetic nephropathy make a powerful case for screening and effective intervention programmes to prevent the condition or retard its progression.

As major breakthroughs in finding genetic susceptibility factors remain elusive, screening efforts continue to be based on microalbuminuria testing, despite increasing recognition of its limitations as a positive predictor of nephropathy.

Interventions have been extensively studied, but results remain conflicting. Economic evaluations of such screening and intervention programmes are essential for health planners, yet models of the cost/benefit ratio of such interventions often rely on a rather slim evidence base. Where economic models are developed, they are frequently based on those papers that propound the greatest clinical benefits of a given intervention, leading to a possible over-estimation of the advantages of the chosen approach. Furthermore, the benefits of even such generally accepted interventions as ACE inhibitor treatment are less firmly established than generally appreciated. Lifestyle interventions are instinctively attractive, but are by no means a low-cost option (as is often assumed by both medical professionals and politicians).

This review critically assesses the evidence for clinical efficacy and economic benefit of microalbuminuria screening and interventions such as intensive glycaemic control, antihypertensive treatment, ACE inhibition and angiotensin receptor blockade, dietary protein restriction and lipid-modifying therapy. The various costs associated with diabetic nephropathy are so great that even expensive interventions may have a favourable cost/benefit ratio, provided they are truly effective.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Notes

  1. The St Vincent declaration is a European consensus framework document published in 1989 with the goal of reducing morbidity and mortality from diabetes mellitus and its complications; one of the targets was to reduce the number of people entering end-stage renal failure by one-third.

References

  1. Andersen AR, Christiansen IS, Andersen JK, et al. Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: an epide-miological study. Diabetologia 1983; 25: 496–501

    CAS  PubMed  Google Scholar 

  2. Borch-Johnsen K, Andersen PK, Deckert T. The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1985; 28: 590–6

    CAS  PubMed  Google Scholar 

  3. Kofoed-Enevoldsen A, Borch-Johnsen K, Kreiner S, et al. Declining incidence of persistent proteinuria in type I (insulindependent) diabetic patients in Denmark. Diabetes 1987; 36: 205–9

    CAS  PubMed  Google Scholar 

  4. Ballard DJ, Humphrey LL, Melton III LJ, et al. Epidemiology of persistent proteinuria in type II diabetes mellitus. Population-based study in Rochester, Minnesota. Diabetes 1988; 37: 405–12

    CAS  PubMed  Google Scholar 

  5. Torffvit O, Agardh CD. The impact of metabolic and blood pressure control on incidence and progression of nephropathy. A 10-year study of 385 type 2 diabetic patients. J Diabetes Complications 2001; 15: 307–13

    CAS  PubMed  Google Scholar 

  6. Krolewski AS, Warram JH, Christlieb AR, et al. The changing natural history of nephropathy in type I diabetes. Am J Med 1985; 78: 785–94

    CAS  PubMed  Google Scholar 

  7. Borch-Johnsen K, Kreiner S. Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus. Br Med J (Clin Res Ed) 1987; 294: 1651–4

    CAS  Google Scholar 

  8. Jensen T, Borch-Johnsen K, Kofoed-Enevoldsen A, et al. Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors. Diabetologia 1987; 30: 144–8

    CAS  PubMed  Google Scholar 

  9. Kofoed-Enevoldsen A, Jensen T, Borch-Johnsen K, et al. Incidence of retinopathy in type I (insulin-dependent) diabetes: association with clinical nephropathy. J Diabet Complications 1987; 1: 96–9

    CAS  PubMed  Google Scholar 

  10. Parving HH, Hommel E, Mathiesen E, et al. Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes. Br Med J (Clip Res Ed) 1988; 296: 156–60

    CAS  Google Scholar 

  11. Seaquist ER, Goetz FC, Rich S, et al. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 1989; 320: 1161–5

    CAS  PubMed  Google Scholar 

  12. Quinn M, Angelico MC, Warram JH, et al. Familial factors determine the development of diabetic nephropathy in patients with IDDM. Diabetologia 1996; 39: 940–5

    CAS  PubMed  Google Scholar 

  13. Parving HH. Benefits and cost of antihypertensive treatment in incipient and overt diabetic nephropathy. J Hypertens Suppl 1998; 16: S99–101

    CAS  PubMed  Google Scholar 

  14. Meinders AE, Hes R, de Leeuw PW. Effects of ACE inhibition on the course of nephropathy in type I diabetes mellitus [editorial]. Neth J Med 1992; 40: 217–20

    CAS  PubMed  Google Scholar 

  15. Krans H, Porta M, Keen H. Diabetes care and research in Europe: The St Vincent Declaration action programme: implementation document. Giomale Italiano di Diabetologia 1992; 12 Suppl. 2: 1–56

    Google Scholar 

  16. Messent JW, Elliott TG, Hill RD, et al. Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. Kidney Int 1992; 41: 836–9

    CAS  PubMed  Google Scholar 

  17. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310: 356–60

    CAS  PubMed  Google Scholar 

  18. Jarrett RJ, Viberti GC, Argyropoulos A, et al. Microalbuminuria predicts mortality in non-insulin-dependent diabetics. Diabet Med 1984; 1: 17–9

    CAS  PubMed  Google Scholar 

  19. Schmitz A, Vaeth M. Microalbuminuria: a major risk factor in non-insulin-dependent diabetes. A 10-year follow-up study of 503 patients. Diabet Med 1988; 5: 126–34

    CAS  PubMed  Google Scholar 

  20. Damsgaard EM, Froland A, Jorgensen OD, et al. Eight to nine year mortality in known non-insulin dependent diabetics and controls. Kidney Int 1992; 41: 731–5

    CAS  PubMed  Google Scholar 

  21. Allawi J, Jarrett RJ. Microalbuminuria and cardiovascular risk factors in type 2 diabetes mellitus. Diabet Med 1990; 7: 115–8

    CAS  PubMed  Google Scholar 

  22. Gerstein HC, Mann IF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–6

    CAS  PubMed  Google Scholar 

  23. Mattock MB, Keen H, Viberti GC, et al. Coronary heart disease and urinary albumin excretion rate in type 2 (non-insulindependent) diabetic patients. Diabetologia 1988; 31: 82–7

    CAS  PubMed  Google Scholar 

  24. Watschinger B, Brunner C, Wagner A, et al. Left ventricular diastolic impairment in type 1 diabetic patients with microal-buminuria. Nephron 1993; 63: 145–51

    CAS  PubMed  Google Scholar 

  25. Earle KA, Mishm M, Morocutti A, et al. Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients. Diabetologia 1996; 39: 854–6

    CAS  PubMed  Google Scholar 

  26. Viberti GC, Hill RD, Jarrett RJ, et al. Microalbuminuria as a predictor of clinical nephropathy in insulin- dependent diabe-tes mellitus. Lancet 1982; 1: 1430–2

    CAS  PubMed  Google Scholar 

  27. Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 1984; 311: 89–93

    CAS  PubMed  Google Scholar 

  28. Mathiesen ER, Oxenboll B, Johansen K, et al. Incipient ne-phropathy in type 1 (insulin-dependent) diabetes. Diabetologia 1984; 26: 406–10

    CAS  PubMed  Google Scholar 

  29. Feldt-Rasmussen B, Mathiesen ER. Variability of Urinary Al-bumin Excretion in Incipient Diabetic Nephropathy. Diabetic Nephropathy 1984; 3: 101–3

    Google Scholar 

  30. Feldt-Rasmussen B, Dinesen B, Deckert M. Enzyme immunoassay: an improved determination of urinary albumin in diabetics with incipient nephropathy. Scand J Clin Lab Invest 1985; 45: 539–44

    CAS  PubMed  Google Scholar 

  31. Gilbert RE, Tsalamandris C, Bach LA, et al. Long-term glycemic control and the rate of progression of early diabetic kidney disease. Kidney Int 1993; 44: 855–9

    CAS  PubMed  Google Scholar 

  32. Mathiesen ER, Ronn B, Jensen T, et al. Relationship between blood pressure and urinary albumin excretion in development of microalbuminuria. Diabetes 1990; 39: 245–9

    CAS  PubMed  Google Scholar 

  33. Gilbert RE, Cooper ME, McNally PG, et al. Microalbuminuria: prognostic and therapeutic implications in diabetes mellitus. Diabet Med 1994; 11: 636–45

    CAS  PubMed  Google Scholar 

  34. Forsblom CM, Groop PH, Ekstrand A, et al. Predictive value of microalbuminuria in patients with insulin-dependent diabetes of long duration. BMJ 1992; 305: 1051–3

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Fioretto P, Mauer M, Brocco E, et al. Patterns of renal injury in NIDDM patients with microalbuminuria. Diabetologia 1996; 39: 1569–76

    CAS  PubMed  Google Scholar 

  36. Nosadini R, Velussi M, Brocco E, et al. Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes 2000; 49: 476–84

    CAS  PubMed  Google Scholar 

  37. Kraft SK, Lazaridis EN, Qiu C, et al. Screening and treatment of diabetic nephropathy by primary care physicians. J Gen Intern Med 1999; 14: 88–97

    CAS  PubMed  Google Scholar 

  38. Connell SJ, Hollis S, Tieszen KL, et al. Gender and the clinical usefulness of the albumin: creatinine ratio. Diabet Med 1994; 11: 32–6

    CAS  PubMed  Google Scholar 

  39. Mogensen CE, Viberti GC, Peheim E, et al. Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria. Diabetes Care 1997; 20: 1642–6

    CAS  PubMed  Google Scholar 

  40. Le Floch JP, Charles MA, Philippon C, et al. Cost-effectiveness of screening for microalbuminuria using immunochemical dipstick tests or laboratory assays in diabetic patients. Diabet Med 1994; 11: 349–56

    PubMed  Google Scholar 

  41. McKenna K, Thompson C. Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. Scott Med J 1997; 42: 99–104

    CAS  PubMed  Google Scholar 

  42. Kiberd BA, Jindal KK. Screening to prevent renal failure in insulin dependent diabetic patients: an economic evaluation [see comments]. BMJ 1995; 311: 1595–9

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Wiseman M, Viberti G, Mackintosh D, et al. Glycaemia, arterial pressure and micro-albuminuria in type 1 (insulindependent) diabetes mellitus. Diabetologia 1984; 26: 401–5

    CAS  PubMed  Google Scholar 

  44. Chase HP, Jackson WE, Hoops SL, et al. Glucose control and the renal and retinal complications of insulin-dependent diabetes. JAMA 1989; 261: 1155–60

    CAS  PubMed  Google Scholar 

  45. Alaveras AE, Thomas SM, Sagriotis A, et al. Promoters of progression of diabetic nephropathy: the relative roles of blood glucose and blood pressure control. Nephrol Dial Transplant 1997; 12: 71–4

    PubMed  Google Scholar 

  46. Norgaard K, Storm B, Graae M, et al. Elevated albumin excretion and retinal changes in children with type 1 diabetes are related to long-term poor blood glucose control. Diabet Med 1989; 6: 325–8

    CAS  PubMed  Google Scholar 

  47. Mulec H, Blohme G, Grande B, et al. The effect of metabolic control on rate of decline in renal function in insulin-dependent diabetes mellitus with overt diabetic nephropathy. Nephrol Dial Transplant 1998; 13: 651–5

    CAS  PubMed  Google Scholar 

  48. Nyberg G, Blohme G, Norden G. Impact of metabolic control in progression of clinical diabetic nephropathy. Diabetologia 1987; 30: 82–6

    CAS  PubMed  Google Scholar 

  49. Hasslacher C, Stech W, Wahl P, et al. Blood pressure and metabolic control as risk factors for nephropathy in type 1 (insulin-dependent) diabetes. Diabetologia 1985; 28: 6–11

    CAS  PubMed  Google Scholar 

  50. Berglund J, Lins LE, Lins PE. Metabolic and blood pressure monitoring in diabetic renal failure. Acta Med Scand 1985; 218: 401–8

    CAS  PubMed  Google Scholar 

  51. Viberti GC, Bilous RW, Mackintosh D, et al. Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes. BMJ (Clinical Research Ed) 1983; 286: 598–602

    CAS  Google Scholar 

  52. Feldt-Rasmussen B, Mathiesen ER, Hegedus L, et al. Kidney function during 12 months of strict metabolic control in insulin- dependent diabetic patients with incipient nephropathy. N Engl J Med 1986; 314: 665–70

    CAS  PubMed  Google Scholar 

  53. Beck-Nielsen H, Richelsen B, Mogensen CE, et al. Effect of insulin pump treatment for one year on renal function and retinal morphology in patients with IDDM. Diabetes Care 1985; 8: 585–9

    CAS  PubMed  Google Scholar 

  54. Feldt-Rasmussen B, Mathiesen ER, Deckert T. Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet 1986; 2: 1300–4

    CAS  PubMed  Google Scholar 

  55. Feldt-Rasmussen B, Mathiesen ER, Jensen T, et al. Effect of improved metabolic control on loss of kidney function in type 1 (insulin-dependent) diabetic patients: an update of the Steno studies. Diabetologia 1991; 34: 164–70

    CAS  PubMed  Google Scholar 

  56. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group [see comments]. N Engl J Med 1993; 329: 977–86

  57. Ronn B, Mathiesen ER, Vang L, et al. Evaluation of insulin pump treatment under routine conditions. Diabetes Res Clin Pract 1987; 3: 191–6

    CAS  PubMed  Google Scholar 

  58. Gray A, Raikou M, McGuire A, et al. Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group. BMJ 2000; 320: 1373–8

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Pro spective Diabetes Study (UKPDS) Group [published erratum appears in Lancet 1999 Aug 14; 354 (9178): 602] [see comments]. Lancet 1998; 352: 837–53

  60. Mogensen CE. How to protect the kidney in diabetic patients: with special reference to IDDM. Diabetes 1997; 46 Suppl. 2: S104–11

    CAS  PubMed  Google Scholar 

  61. Chiarelli F, Verrotti A, Basciani F, et al. Controversies on the prevention of diabetic nephropathy. J Pediatr Endocrinol Metab 1998; 11 Suppl. 2: 365–9

    PubMed  Google Scholar 

  62. TDCaCTR. Resource utilization and costs of care in the diabetes control and complications trial. Diabetes Care 1995; 18: 1468–78

    Google Scholar 

  63. Diabetes Control and Complications Trial Research Group. Lifetime benefits and costs of intensive therapy as practiced in the diabetes control and complcations trial. The Diabetes Con trol and Complications Trial Research Group [see comments] [published erratum appears in JAMA 1997; 278 (1): 25]. JAMA 1996; 276: 1409–15

    Google Scholar 

  64. Szucs TD, Smala AM, Fischer T. Costs of intensive insulin therapy in type 1 diabetes mellitus. Experiences from the DCCT study. Fortschr Med 1998; 116: 34–8

    CAS  PubMed  Google Scholar 

  65. Eastman RC, Javitt JC, Herman WH, et al. Model of complica-tions of NIDDM. II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia [see comments]. Diabetes Care 1997; 20: 735–44

    CAS  PubMed  Google Scholar 

  66. Herman WH, Eastman RC. The effects of treatment on the direct costs of diabetes. Diabetes Care 1998; 21 Suppl. 3: C19–24

    Google Scholar 

  67. Palmer AJ, Weiss C, Sendi PP, et al. The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective. Diabetologia 2000; 43: 13–26

    CAS  PubMed  Google Scholar 

  68. Wake N, Hisashige A, Katayama T, et al. Cost-effectiveness of intensive insulin therapy for type 2 diabetes: a 10-year followup of the Kumamoto study. Diabetes Res Clin Pract 2000; 48: 201–10

    CAS  PubMed  Google Scholar 

  69. Feldt-Rasmussen B, Borch-Johnsen K, Mathiesen ER. Hypertension in diabetes as related to nephropathy. Early blood pressure changes. Hypertension 1985; 7: II18–20

    CAS  PubMed  Google Scholar 

  70. Christensen CK, Mogensen CE. The course of incipient diabetic nephropathy: studies of albumin excretion and blood pressure. Diabet Med 1985; 2: 97–102

    CAS  PubMed  Google Scholar 

  71. Microalbuminuria in type I diabetic patients. Prevalence and clinical characteristics. Microalbuminuria Collaborative Study Group. Diabetes Care 1992; 15: 495–501

    Google Scholar 

  72. Hansen KW, Christensen CK, Andersen PH, et al. Ambulatory blood pressure in microalbuminuric type 1 diabetic patients. Kidney Int 1992; 41: 847–54

    CAS  PubMed  Google Scholar 

  73. Viberti GC, Keen H, Wiseman MJ. Raised arterial pressure in parents of proteinuric insulin dependent diabetics. Br Med J (Clip Res Ed) 1987; 295: 515–7

    CAS  Google Scholar 

  74. United Kingdom Prospective Diabetes Study. III. Prevalence of hypertension and hypotensive therapy in patients with newly diagnosed diabetes. A multicenter study. Hypertension 1985; 7:118–13

    Google Scholar 

  75. Muggeo M. Accelerated complications in type 2 diabetes mellitus: the need for greater awareness and earlier detection. Diabet Med 1998; 15: S60–2

    PubMed  Google Scholar 

  76. Allawi J, Rao PV, Gilbert R, et al. Microalbuminuria in non-insulin-dependent diabetes: its prevalence in Indian compared with Europid patients. Br Med J (Clin Res Ed) 1988; 296: 462–4

    CAS  Google Scholar 

  77. Berkman J, Rifkin H. Unilateral nodular diabetic glomerulosclerosis (Kimmelstiel-Wilson): report of a case. Metabolism 1973; 22: 715–22

    CAS  PubMed  Google Scholar 

  78. Mogensen CE. Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment. Scand J Clin Lab Invest 1976; 36: 383–8

    CAS  PubMed  Google Scholar 

  79. Mogensen CE. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. Br Med J (Clin Res Ed) 1982; 285: 685–8

    CAS  Google Scholar 

  80. Parving HH, Andersen AR, Smidt UM, et al. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983; 1: 1175–9

    CAS  PubMed  Google Scholar 

  81. Parving HH, Andersen AR, Smidt UM, et al. Effect of antihypertensive treatment on kidney function in diabetic nephropathy. Br Med J (Clin Res Ed) 1987; 294: 1443–7

    CAS  Google Scholar 

  82. Mathiesen ER, Borch-Johnsen K, Jensen DV, et al. Improved survival in patients with diabetic nephropathy. Diabetologia 1989; 32: 884–6

    CAS  PubMed  Google Scholar 

  83. Parving HH, Hommel E. Prognosis in diabetic nephropathy [see comments]. BMJ 1989; 299: 230–3

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Borch-Johnsen K, Wenzel H, Viberti GC, et al. Is screening and intervention for microalbuminuria worthwhile in patients with insulin dependent diabetes? [published erratum appears in BMJ 1993 Aug 28; 307 (6903): 543] [see comments]. BMJ 1993; 306: 1722–5

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Parving HH, Andersen AR, Smidt UM, et al. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983; 1: 1175–9

    CAS  PubMed  Google Scholar 

  86. Mogensen CE. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. Br Med J (Clin Res Ed) 1982; 285: 685–8

    CAS  Google Scholar 

  87. Parving HH. Benefits and cost of antihypertensive treatment in incipient and overt diabetic nephropathy. J Hypertens Suppl 1998; 16: S99–101

    CAS  PubMed  Google Scholar 

  88. Parving HH. Is antihypertesive treatment the same for NIDDM and IDDM patients? Diabetes Res Clin Pract 1998; 39 Suppl.: S43–7

    CAS  PubMed  Google Scholar 

  89. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. UK Prospective Diabetes Study Group [see comments]. BMJ 1998; 317: 720–6

    PubMed Central  Google Scholar 

  90. Parving HH. Is antihypertensive treatment the same for NIDDM and IDDM patients? Diabetes Res Clin Pract 1998; 39 Suppl.: S43–7

    CAS  PubMed  Google Scholar 

  91. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hyperten sion Optimal Treatment (HOT) randomised trial. HOT Study Group [see comments]. Lancet 1998; 351: 1755–62

    CAS  PubMed  Google Scholar 

  92. Marre M, Chatellier G, Leblanc H, et al. Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria. BMJ 1988; 297: 1092–5

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Mathiesen ER, Hommel E, Giese J, et al. Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria [see comments]. BMJ 1991; 303: 81–7

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 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 [see comments]. Ann Intern Med 1993; 118: 577–81

    CAS  PubMed  Google Scholar 

  95. Viberti G, Mogensen CE, Groop LC, et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group [see comments]. JAMA 1994; 271: 275–9

    CAS  PubMed  Google Scholar 

  96. Laffel LM, McGill JB, Gans DJ. The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbu minuria. North American Microalbuminuria Study Group. Am J Med 1995; 99: 497–504

    CAS  PubMed  Google Scholar 

  97. Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. The Microalbuminuria Captopril Study Group. Diabetologia 1996; 39: 587–93

    Google Scholar 

  98. Parving HH, Hommel E, Smidt UM. Protection of kidney func-tion and decrease in albuminuria by captopril in insulin depen-dent diabetics with nephropathy. BMJ 1988; 297: 1086–91

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angioten-sin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group [see comments] [published erratum appears in N Engl J Med 1993 Jan 13; 330 (2):152]. N Engl J Med 1993; 329: 1456–62

    CAS  PubMed  Google Scholar 

  100. Ravid M, Brosh D, Levi Z, et al. Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med 1998; 128: 982–8

    CAS  PubMed  Google Scholar 

  101. Kshirsagar AV, Joy MS, Hogan SL, et al. Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: a systematic overview of randomized placebo-controlled trials. Am J Kidney Dis 2000; 35: 695–707

    CAS  PubMed  Google Scholar 

  102. Sandeman DD, Shore AC, Tooke JE. Relation of skin capillary pressure in patients with insulin-dependent diabetes mellitus to complications and metabolic control. N Engl J Med 1992; 327: 760–4

    CAS  PubMed  Google Scholar 

  103. Parving HH, Kastrup H, Smidt UM, et al. Impaired autoregulation of glomerular filtration rate in type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 1984; 27: 547–52

    CAS  PubMed  Google Scholar 

  104. Christensen PK, Hansen HP, Parving HH. Impaired autoregulation of GFR in hypertensive non-insulin dependent diabetic patients. Kidney Int 1997; 52: 1369–74

    CAS  PubMed  Google Scholar 

  105. Effects of ramipril on cardiovascular and microvascular out-comes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Preven tion Evaluation Study Investigators [see comments]. Lancet 2000; 355: 253–9

  106. Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Melbourne Diabetic Nephropathy Study Group [see comments]. BMJ 1991; 302: 210–6

  107. Slataper R, Vicknair N, Sadler R, et al. Comparative effects of different antihypertensive treatments on progression of diabetic renal disease. Arch Intern Med 1993; 153: 973–80

    CAS  PubMed  Google Scholar 

  108. Schnack C, Capek M, Banyai M, et al. Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria. Acta Diabetol 1994; 31: 14–8

    CAS  PubMed  Google Scholar 

  109. Agardh CD, Garcia-Puig J, Charbonnel B, et al. Greater reduction of urinary albumin excretion in hypertensive type II diabetic patients with incipient nephropathy by lisinopril than by nifedipine. J Hum Hypertens 1996; 10: 185–92

    CAS  PubMed  Google Scholar 

  110. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID Study Group [see comments]. Lancet 1997; 349: 1787–92

  111. Singh NK. Nephroprotection in diabetes mellitus. Clin Exp Hypertens 1999; 21: 85–94

    CAS  PubMed  Google Scholar 

  112. Borch-Johnsen K. ACE inhibitors in patients with diabetes mellitus. Clinical and economic considerations. Pharmacoeconomics 1996; 9: 392–8

    CAS  PubMed  Google Scholar 

  113. Tatti P, Pahor M, Byington RP, et al. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM [see comments]. Diabetes Care 1998; 21: 597–603

    CAS  PubMed  Google Scholar 

  114. Califf RM, Granger CB. Hypertension and diabetes and the Fosinopril versus Amlodipine Cardiovascular Events Trial (FACET). More ammunition against surrogate end points [comment]. Diabetes Care 1998; 21: 655–7

    CAS  PubMed  Google Scholar 

  115. Estacio RO, Jeffers BW, Hiatt WR, et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension [see comments]. N Engl J Med 1998; 338: 645–52

    CAS  PubMed  Google Scholar 

  116. Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial [see comments]. Lancet 1999; 353: 611–6

    CAS  PubMed  Google Scholar 

  117. Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999; 354: 1751–6

    CAS  PubMed  Google Scholar 

  118. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group [see comments]. BMJ 1998; 317: 713–20

    PubMed Central  Google Scholar 

  119. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Opti mal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351: 1755–62

    CAS  PubMed  Google Scholar 

  120. Gerbrandt KR, Yedinak KC. Formulary management of ACE inhibitors. Pharmacoeconomics 1996; 10: 594–613

    CAS  PubMed  Google Scholar 

  121. Kiberd BA, Jindal KK. Routine treatment of insulin-dependent diabetic patients with ACE inhibitors to prevent renal failure: an economic evaluation. Am J Kidney Dis 1998; 31: 49–54

    CAS  PubMed  Google Scholar 

  122. Golan L, Birkmeyer JD, Welch HG. The cost-effectiveness of treating all patients with type 2 diabetes with angiotensinconverting enzyme inhibitors [see comments]. Ann Intern Med 1999; 131: 660–7

    CAS  PubMed  Google Scholar 

  123. Siegel JE, Krolewski AS, Warram JH, et al. Cost-effectiveness of screening and early treatment of nephropathy in patients with insulin-dependent diabetes mellitus. J Am Soc Nephrol 1992; 3: Sl11–9

    Google Scholar 

  124. Le Pen C, Petitjean P, Levy P, et al. Economic evaluation of the contribution of captopril in the treatment of diabetic nephropathy: a cost-benefit approach. Nephrologie 1996; 17: 321–6

    PubMed  Google Scholar 

  125. Rodby RA, Firth LM, Lewis EJ. An economic analysis of captopril in the treatment of diabetic nephropathy. The Collaborative Study Group. Diabetes Care 1996; 19: 1051–61

    CAS  PubMed  Google Scholar 

  126. Garattini L, Brunetti M, Salvioni F, et al. Economic evaluation of ACE inhibitor treatment of nephropathy in patients with insulin-dependent diabetes mellitus in Italy. Pharmacoeconomics 1997; 12: 67–75

    CAS  PubMed  Google Scholar 

  127. Hendry BM, Viberti GC, Hummel S, et al. Modelling and costing the consequences of using an ACE inhibitor to slow the progression of renal failure in type I diabetic patients. QJM 1997; 90: 277–82

    CAS  PubMed  Google Scholar 

  128. Clark WF, Churchill DN, Forwell L, et al. To pay or not to pay? A decision and cost-utility analysis of angiotensin-convertingenzyme inhibitor therapy for diabetic nephropathy [published erratum appears in CMAJ 2000 Apr 4; 162 (7): 973] [see comments]. CMAJ 2000; 162: 195–8

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Herings RM, de Boer A, Stricker BH, et al. Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme [see comments]. Lancet 1995; 345: 1195–8

    CAS  PubMed  Google Scholar 

  130. Morris AD, Boyle DI, McMahon AD, et al. ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabe tes Audit and Research in Tayside, Scotland. Medicines Moni-toring Unit. Diabetes Care 1997; 20: 1363–7

    CAS  PubMed  Google Scholar 

  131. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145–53

    CAS  PubMed  Google Scholar 

  132. Thamer M, Ray NF, Taylor T. Association between antihyper-tensive drug use and hypoglycemia: a case-control study of diabetic users of insulin or sulfonylureas. Clin Ther 1999; 21: 1387–400

    CAS  PubMed  Google Scholar 

  133. Hollenberg NK. What does the future hold? ACE inhibition, angiotensin II receptor blockade, and diabetic nephropathy. Blood Press Monit 2000; 5: S3–6

    PubMed  Google Scholar 

  134. Kurokawa K. Effects of candesartan on the proteinuria of chronic glomerulonephritis. J Hum Hypertens 1999; 13: S57–60; discussion S1

    CAS  PubMed  Google Scholar 

  135. Osei SY, Price DA, Laffel LM, et al. Effect of angiotensin II antagonist eprosartan on hyperglycemia-induced activation of intrarenal renin-angiotensin system in healthy humans. Hypertension 2000; 36: 122–6

    CAS  PubMed  Google Scholar 

  136. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–9

    CAS  PubMed  Google Scholar 

  137. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60

    CAS  PubMed  Google Scholar 

  138. Parving HH, Lehnert H, Brochner-Mogensen 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: 870–8

    CAS  PubMed  Google Scholar 

  139. Rippin JD, Bain SC, Barnett AH. Rationale and Design of Diabetics Exposed to Telmisartan and Enalapril (DETAIL) Study. American Journal of Hypertension 2000; 13 (4) pt 2: 287A

    Google Scholar 

  140. Hebert LA, Falkenhain ME, Nahman NS, et al. Combination ACE inhibitor and angiotensin II receptor antagonist therapy in diabetic nephropathy. Am J Nephrol 1999; 19: 1–6

    CAS  PubMed  Google Scholar 

  141. Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000; 321: 1440–4

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Gerth WC, Remuzzi G, Viberti G, et al. Losartan reduces the burden and cost of ESRD: Public health implications from the RENAAL study for the European Union. Kidney Int 2002 Dec; 62 Suppl. 82: 68–72

    Google Scholar 

  143. Souchet T, Durand Zaleski I, Hannedouche T, et al. An economic evaluation of Losartan therapy in type 2 diabetic patients with nephropathy: an analysis of the RENAAL study adapted to France. Diabetes Metab 2003 Feb; 29 (1): 29–35

    CAS  PubMed  Google Scholar 

  144. Herman WH, Shahinfar S, Carides GW. Losartan reduces the costs associated with diabetic end-stage renal disease: the RENAAL study economic evaluation. Diabetes Care 2003 Mar; 26 (3): 683–7

    PubMed  Google Scholar 

  145. Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogen esis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 1982; 307: 652–9

    CAS  PubMed  Google Scholar 

  146. Fouque D, Wang P, Laville M, et al. Low protein diets delay end-stage renal disease in non diabetic adults with chronic renal failure. Cochrane Database Syst Rev 2000, 2

    Google Scholar 

  147. Walker JD, Bending JJ, Dodds RA, et al. Restriction of dietary protein and progression of renal failure in diabetic nephropathy [published erratum appears in Lancet 1989 Dec 23-30; 2 (8678-8679): 1540] [see comments]. Lancet 1989; 2: 1411–5

    CAS  PubMed  Google Scholar 

  148. Kopple JD, Levey AS, Greene T, et al. Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study. Kidney Int 1997; 52: 778–91

    CAS  PubMed  Google Scholar 

  149. Cohen D, Dodds R, Viberti G. Effect of protein restriction in insulin dependent diabetics at risk of nephropathy. Br Med J (Clip Res Ed) 1987; 294: 795–8

    CAS  Google Scholar 

  150. Bending JJ, Dodds RA, Keen H, et al. Renal response to restricted protein intake in diabetic nephropathy. Diabetes 1988; 37: 1641–6

    CAS  PubMed  Google Scholar 

  151. Davis JH. Proteins and pathogenesis of renal disease progression. Lancet 1998; 352: 1315

    CAS  PubMed  Google Scholar 

  152. Nyberg G, Norden G, Altman PO, et al. Diabetic nephropathy: is dietary protein harmful? J Diabet Complications 1987; 1: 37–40

    CAS  PubMed  Google Scholar 

  153. Zeller K, Whittaker E, Sullivan L, et al. Effect of restricting dietary protein on the progression of renal failure in patients with insulin-dependent diabetes mellitus. N Engl J Med 1991; 324: 78–84

    CAS  PubMed  Google Scholar 

  154. Pedrini MT, Levey AS, Lau J, et al. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis [see comments]. Ann Intern Med 1996; 124: 627–32

    CAS  PubMed  Google Scholar 

  155. Kasiske BL, Lakatua JD. The effects of dietary protein restriction on chronic progressive renal disease. Miner Electrolyte Metab 1997; 23: 296–300

    CAS  PubMed  Google Scholar 

  156. Kasiske BL, Lakatua JD, Ma JZ, et al. A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function [see comments]. Am J Kidney Dis 1998; 31: 954–61

    CAS  PubMed  Google Scholar 

  157. Klahr S, Levey AS, Beck GJ, et al. The Effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease. New Engl J Med 1994; 330: 877–84

    CAS  PubMed  Google Scholar 

  158. Effects of dietary protein restriction on the progression of moderate renal disease in the Modification of Diet in Renal Disease Study [published erratum appears in J Am Soc Nephrol 1997 Mar; 8 (3): 493]. J Am Soc Nephrol 1996; 7: 2616–26

  159. Hansen HP, Christensen PK, Tauber-Lassen E, et al. Lowprotein diet and kidney function in insulin-dependent diabetic patients with diabetic nephropathy. Kidney Int 1999; 55: 621–8

    CAS  PubMed  Google Scholar 

  160. Short-term effects of protein intake, blood pressure, and antihypertensive therapy on glomerular filtration rate in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol 1996; 7: 2097-109

  161. Levey AS, Greene T, Beck GJ, et al. Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study group. J Am Soc Nephrol 1999; 10: 2426–39

    CAS  PubMed  Google Scholar 

  162. Levey AS, Adler S, Caggiula AW, et al. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis 1996; 27: 652–63

    CAS  PubMed  Google Scholar 

  163. Mitch WE. Dietary therapy in uremia: the impact on nutrition and progressive renal failure. Kidney Int 2000; 57 Suppl. 75: S38–43

    Google Scholar 

  164. Milas NC, Nowalk MP, Akpele L, et al. Factors associated with adherence to the dietary protein intervention in the Modification of Diet in Renal Disease Study. J Am Diet Assoc 1995; 95: 1295–300

    CAS  PubMed  Google Scholar 

  165. Pijls LT, de Vries H, Donker AJ, et al. The effect of protein restriction on albuminuria in patients with type 2 diabetes mellitus: a randomized trial. Nephrol Dial Transplant 1999; 14:1445–53

    CAS  PubMed  Google Scholar 

  166. Castellino P, Giordano M, de Pascale E, et al. Derangements in protein metabolism induced by type I diabetes mellitus. Miner Electrolyte Metab 1998; 24: 41–6

    CAS  PubMed  Google Scholar 

  167. Lahdenpera S, Groop PH, Tilly-Kiesi M, et al. LDL subclasses in IDDM patients: relation to diabetic nephropathy. Diabetologia 1994; 37: 681–8

    CAS  PubMed  Google Scholar 

  168. Groop PH, Elliott T, Ekstrand A, et al. Multiple lipoprotein abnormalities in type I diabetic patients with renal disease. Diabetes 1996; 45: 974–9

    PubMed  Google Scholar 

  169. Bonnet F, Cooper ME. Potential influence of lipids in diabetic nephropathy: insights from experimental data and clinical studies [in process citation]. Diabetes Metab 2000; 26: 254–64

    CAS  PubMed  Google Scholar 

  170. Moorhead IF, Chan MK, El-Nahas M, et al. Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 1982; 2: 1309–11

    CAS  PubMed  Google Scholar 

  171. Kasiske BL, O’Donnell MP, Cleary MP, et al. Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats [published erratum appears in Kidney Int 1988 Jun; 33 (6): 1216]. Kidney Int 1988 Mar; 33 (3): 667–72

    CAS  PubMed  Google Scholar 

  172. Yokota T, Utsunomiya K, Murakawa Y, et al. Mechanism of preventive effect of HMG-CoA reductase inhibitor on diabetic nephropathy. Kidney Int Suppl 1999; 71: S178–81

    CAS  PubMed  Google Scholar 

  173. Jandeleit-Dahm K, Cao Z, Cox AJ, et al. Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. Kidney Int Suppl 1999; 71: S31–6

    CAS  PubMed  Google Scholar 

  174. Keane WF. Lipids and progressive renal failure. Wien Klin Wochenschr 1996; 108: 420–4

    CAS  PubMed  Google Scholar 

  175. Ikeda U, Shimpo M, Ohki R, et al. Fluvastatin inhibits matrix metalloproteinase-1 expression in human vascular endothelial cells. Hypertension 2000; 36: 325–9

    CAS  PubMed  Google Scholar 

  176. Chowdhury TA, Dyer PH, Kumar S, et al. Association of apolipoprotein epsilon2 allele with diabetic nephropathy in Caucasian subjects with IDDM. Diabetes 1998; 47: 278–80

    CAS  PubMed  Google Scholar 

  177. Lam KS, Cheng IK, Janus ED, et al. Cholesterol-lowering therapy may retard the progression of diabetic nephropathy. Diabetologia 1995; 38: 604–9

    CAS  PubMed  Google Scholar 

  178. Sasaki T, Kurata H, Nomura K, et al. Amelioration of proteinuria with pravastatin in hypercholesterolemic patients with diabetes mellitus. Jpn J Med 1990; 29: 156–63

    CAS  PubMed  Google Scholar 

  179. Nielsen S, Schmitz O, Moller N, et al. Renal function and insulin sensitivity during simvastatin treatment in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 1993; 36: 1079–86

    CAS  PubMed  Google Scholar 

  180. Gin H, Rigalleau V, Aparicio M. Lipids, protein intake, and diabetic nephropathy. Diabetes Metab 2000; 26 Suppl. 4: 45–53

    CAS  PubMed  Google Scholar 

  181. Steiner G. Lipid intervention trials in diabetes. Diabetes Care 2000; 23: B49–53

    PubMed  Google Scholar 

  182. Bain SC, Chowdhury TA. Genetics of diabetic nephropathy and microalbuminuria. J R Soc Med 2000; 93: 62–6

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen C. Bain.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rippin, J.D., Barnett, A.H. & Bain, S.C. Cost-effective strategies in the prevention of diabetic nephropathy. Pharmacoeconomic 22, 9–28 (2004). https://doi.org/10.2165/00019053-200422010-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200422010-00002

Keywords

Navigation