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When to initiate ACEI/ARB therapy in patients with type 1 and 2 diabetes

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Abstract

Angiotensin converting enzyme inhibitors (ACEI) and angiotensin 2 receptor blockers (ARB) have become a mainstay of adjunctive therapy for the prevention and amelioration of diabetic nephropathy. Although ACEI were shown over 20 years ago to slow the rate of loss of renal function in diabetic subjects with decreased renal function, the question of how early in the course of diabetes to introduce them remains unresolved. Recent studies suggest that very early initiation of ACEI/ARB therapy may not have demonstrable beneficial effects even over a period of years.

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References

  1. Friedman EA (1982) Diabetic nephropathy: Strategies in prevention and management. Kidney Int 21:780–791

    PubMed  CAS  Google Scholar 

  2. Anderson S, Meyer TW, Rennke HG, Brenner BM (1985) Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 76:612–619

    PubMed  CAS  Google Scholar 

  3. Zatz R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM (1986) Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 77:1925–1930

    PubMed  CAS  Google Scholar 

  4. Björck S, Nyberg G, Mulec H, Granerus G, Herlitz H, Aurell M (1986) Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. Br Med J 293:471–474

    Google Scholar 

  5. Anderson S, Rennke HG, Brenner BM (1986) Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest 77:1993–2000

    PubMed  CAS  Google Scholar 

  6. Hommel E, Parving HH, Mathiesen E, Edsberg B, Nielsen MD, Giese J (1986) Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. Br Med J 293:467–470

    CAS  Google Scholar 

  7. Marre M, Chatellier G, Leblanc H, Guyene TT, Menard J, Passa P (1988) Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria. Br Med J 297:1092–1095

    CAS  Google Scholar 

  8. Parving HH, Hommel E, Smidt UM (1988) Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy. Br Med J 297:1086–1091

    CAS  Google Scholar 

  9. Cook J, Daneman D, Spino M, Sochett E, Perlman K, Balfe JW (1990) Angiotensin converting enzyme inhibitor therapy to decrease microalbuminuria in normotensive children with insulin-depedent diabetes mellitus. J Pediatr 117:39–45

    PubMed  CAS  Google Scholar 

  10. Mathiesen ER, Hommel E, Giese J, Parving HH (1991) Efficacy of captopril in postponing nephropathy in normotensive insulin dependent patients with microalbuminuria. Br Med J 303:81–87

    CAS  Google Scholar 

  11. Björck S, Mulec H, Johnsen SA, Nordén G, Aurell M (1992) Renal protective effect of enalapril in diabetic nephropathy. Br Med J 304:339–343

    Google Scholar 

  12. The Melbourne Diabetic Nephropathy Study Group (1991) Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Br Med J 302:210–216

    Google Scholar 

  13. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (for the Collaborative Study Group) (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 329:1456–1462

    Google Scholar 

  14. The EUCLID Study Group (1997) Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet 349:1787–1792

    Google Scholar 

  15. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) (1997) 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 349:1857–1863

    Google Scholar 

  16. Mathiesen ER, Hommel E, Hansen HP, Smidt UM, Parving HH (1999) Randomised controlled trial of long term efficacy of captopril on preservation of kidney function in normotensive patients with insulin dependent diabetes and microalbuminuria. Br Med J 319:24–25

    CAS  Google Scholar 

  17. Ahmad J, Shafique S, Abbas Abidi SM, Parwez I (2003) Effect of 5-year enalapril therapy on progression of microalbuminuria and glomerular structural changes in type 1 diabetic subjects. Diab Res Clin Pract 60:131–138

    CAS  Google Scholar 

  18. The ACE Inhibitors in Diabetic Nephropathy Trialist Group (2001) Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? Ann Intern Med 134:370–379

    Google Scholar 

  19. Ravid R, Savin H, Jutrin I, Bental T, Katz B, Lishner M (1993) Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 118:577–581

    PubMed  CAS  Google Scholar 

  20. The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators (2000) Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 355:253–259

    Google Scholar 

  21. Mann JFE, Gerstein HC, Yi Q-L, Franke J, Lonn EM, Hoogwerf BJ, Rashkow A, Yusuf S (2003) Progression of renal insufficiency in type 2 diabetes with and without microalbuminuria: results of the Heart Outcomes and Prevention Evaluation (HOPE) randomized study. Am J Kidney Dis 42:936–942

    PubMed  Google Scholar 

  22. Brenner BM, Cooper ME, DeZeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869

    PubMed  CAS  Google Scholar 

  23. Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P (2001) The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345:870–878

    PubMed  CAS  Google Scholar 

  24. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I (2001) Renoprotector effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860

    PubMed  CAS  Google Scholar 

  25. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK (2008) Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 358:2433–2446

    PubMed  CAS  Google Scholar 

  26. Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V, Rubis N, Gherardi G, Arnoldi F, Ganeva M, Ene-Iordache B, Gaspari F, Perna A, Bossi A, Trevisan R, Dodesini AR, Remuzzi G (2004) Preventing microalbuminuria in type 2 diabetes. N Engl J Med 351:1941–1951

    PubMed  CAS  Google Scholar 

  27. Marre M, Lievre M, Chatellier G, Mann JFE, Passa P, Ménard J (2004) Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). Br Med J 328:495–500

    CAS  Google Scholar 

  28. ADVANCE Collaborative Group (2007) Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 370:829–840

    Google Scholar 

  29. Bilous R, Chaturvedi N, Sjølie AK, Fuller J, Klein R, Orchard T, Porta M, Parving HH (2009) Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes. Ann Intern Med 151:11–20

    PubMed  Google Scholar 

  30. Mann JFE, Schmieder RE, Dyal L, McQueen M, Schumacher H, Pogue J, Wang X, Probstfield JL, Cardona-Munoz E, Avezum A, Dagenais GR, Diaz R, Fodor G, Maillon JM, Rydén L, Yu CM, Teo KK, Yusuf S, for the TRANSCEND Investigators (2009) Effect of telmisartan on renal outcomes. Ann Intern Med 151:1–10

    PubMed  Google Scholar 

  31. Fioretto P, Steffes MW, Sutherland DER, Mauer M (1995) Sequential renal biopsies in insulin-dependent diabetic patients: Structural factors associated with clinical progression. Kidney Int 48:1929–1935

    PubMed  CAS  Google Scholar 

  32. Drummond K, Mauer M (2002) The early natural history of nephropathy in type 1 diabetes. II. Early renal structural changes in type 1diabetes. Diabetes 51:1580–1587

    PubMed  CAS  Google Scholar 

  33. Rudberg S, Osterby R (1997) Decreasing glomerular filtration rate-an indicator of more advanced diabetic glomerulopathy in the early course of microalbuminuria in IDDM adolescents. Nephrol Dial Transplant 12:1149–1154

    PubMed  CAS  Google Scholar 

  34. Perrin NESS, Torbjörnsdotter TB, Jaremko GA, Berg UB (2006) The course of diabetic glomerulopathy in patients with type 1 diabetes: a 6-year follow-up with serial biopsies. Kidney Int 69:699–705

    PubMed  CAS  Google Scholar 

  35. Pagtalunan ME, Miller PL, Jumping-Eagle S, Nelson RG, Myers BD, Rennke HG, Coplon NS, Sun L, Meyer TW (1997) Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest 99:342–348

    PubMed  CAS  Google Scholar 

  36. Steinke JM, Sinaiko AR, Kramer MS, Suissa S, Chavers BM, Mauer M (2005) The early natural history of nephropathy in type 1 diabetes. III. Predictors of 5-year urinary albumin excretion rate patterns in initially normoalbuminuric patients. Diabetes 54:2164–2171

    PubMed  CAS  Google Scholar 

  37. The European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT) Study Group (2001) Effect of 3 years of antihypertensive therapy on renal structure in type 1 diabetic patients with albuminuria. Diabetes 50:843–850

    Google Scholar 

  38. Cordonnier DJ, Pinel N, Barro C, Maynard C, Zaoui P, Halimi S, De Ligny BH, Reznic Y, Simon D, Bilous RW (1999) Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. J Am Soc Nephrol 10:1253–1263

    PubMed  CAS  Google Scholar 

  39. White KE, Pinel N, Cordonnier DJ, Bilous RW (2001) Does ACE inhibition slow progress of glomerulopathy in patients with type 2 diabetes mellitus? Diabet Med 18:933–936

    PubMed  CAS  Google Scholar 

  40. Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, Drummond K, Donnelly S, Goodyer P, Gubler MC, Klein R (2009) Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med 361:40–51

    PubMed  CAS  Google Scholar 

  41. The DREAM Trial Investigators (2008) Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose. Diabetes Care 31:1007–1014

    Google Scholar 

  42. Drummond K, Levy-Marchal C, Laborde K, Kindermans C, Wright C, Dechaux M, Czernichow P (1989) Enalapril does not alter renal function in normotensive, normoalbuminuric, hyperfiltering Type 1 (insulin-dependent) diabetic children. Diabetologia 32:255–260

    PubMed  CAS  Google Scholar 

  43. Rudberg S, Østerby R, Bangstad HJ, Dahlquist G, Persson B (1999) Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus. Diabetologia 42:589–595

    PubMed  CAS  Google Scholar 

  44. Casas JP, Chua W, Loukogeorgakis S, Vallance P, Hingorani AD, MacAllister RJ, Smeeth L (2005) Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 366:2026–2033

    PubMed  CAS  Google Scholar 

  45. Poulsen PL, Ebbehøj E, Nosadini R, Fioretto P, Deferrari G, Crepaldi G, Mogensen CE (2001) Early ACE-I intervention in microalbuminuric patients with type 1 diabetes: effects on albumin excretion, 24 h ambulatory blood pressure, and renal function. Diabetes Metab 27:123–128

    PubMed  CAS  Google Scholar 

  46. American Diabetes Association (2002) Diabetic nephropathy. Position statement. Diabetes Care 25[Suppl 1]:S85–S89

    Google Scholar 

  47. KDOQI Diabetes and Chronic Kidney Disease Work Group (2007) KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis 49[Suppl 2]:S109–S115

    Google Scholar 

  48. Silverstein J, Klingensmith G, Copeland PL, Kaufman F, Laffel L, Deeb L, Grey M, Anderson B, Holzmeister LA, Clark N (2005) Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care 28:186–212

    PubMed  Google Scholar 

  49. Donaghue KC, Chiarelli F, Trotta D, Allgrove J, Dahl-Jorgensen K (2009) Microvascular and macrovascular complications associated with diabetes in children and adolescents. Pediatr Diab 10[Suppl 12]:195–203

    Google Scholar 

  50. Fioretto P, Steffes MW, Sutherland DER, Goetz FC, Mauer M (1998) Reversal of lesion of diabetic nephropathy after pancreas transplantation. N Engl J Med 339:69–75

    PubMed  CAS  Google Scholar 

  51. Anderson S, Komers R (2009) Inhibition of the renin-angiotensin system: is more better? Kidney Int 75:12–14

    PubMed  CAS  Google Scholar 

  52. Bojestig M, Arnqvist HJ, Hermansson G, Karlberg BE, Ludvigsson J (1994) Declining incidence of nephropathy in insulin-dependent diabetes mellitus. N Engl J Med 330:15–18

    PubMed  CAS  Google Scholar 

  53. Pambianco G, Costacou T, Ellis D, Becker DJ, Klein R, Orchard TJ (2006) The 3-year natural history of type 1 diabetes complications. The Pittsburgh Epidemiology of Diabetes Complications Study Experience. Diabetes 55:1463–1469

    PubMed  CAS  Google Scholar 

  54. Nordwall M, Bojestig M, Arnqvist HJ, Ludvigsson J (2004) Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of type 1 diabetes-the Linköping Diabetes Complications Study. Diabetologia 47:1266–1272

    PubMed  CAS  Google Scholar 

  55. Amin R, Widmer B, Dalton RN, Dunger DB (2009) Unchanged incidence of microalbuminuria in children with type 1 diabetes since 1986: a UK based inception cohort. Arch Dis Child 94:258–262

    PubMed  CAS  Google Scholar 

  56. Mauer M, Zinman B, Klein R (2009) Author reply: Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med 361:1411

    CAS  Google Scholar 

  57. Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1:1430–1432

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  59. Dunger DB, Schwarze CP, Coooper JD, Widmer B, Neil HAW, Shield J, Edge JA, Jones TW, Daneman D, Dalton RN (2007) Can we identify adolescents at high risk for nephropathy before the development of microalbuminuria? Diabetic Med 24:131–136

    PubMed  CAS  Google Scholar 

  60. Rachmani R, Levi Z, Lidar M, Slavachevski I, Half-Onn E, Ravid M (2000) Considerations about the threshold value for microalbuminuria in patients with diabetes mellitus: lessons from an 8-year follow-up study of 599 patients. Diab Res Clin Pract 49:187–194

    CAS  Google Scholar 

  61. Marcovecchio ML, Dalton RN, Schwarze CP, Prevost AT, Neil HAW, Acerini CL, Barrett T, Cooper JD, Edge J, Shield J, Widmer B, Todd JA, Dunger DB (2009) Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes. Diabetologia 52:1173–1181

    PubMed  CAS  Google Scholar 

  62. Myers BD, Boothroyd D, Olshen RA (1998) Angiotensin-converting enzyme inhibitor for slowing progression of diabetic and nondiabetic kidney disease. J Am Soc Nephrol 9:S66–S70

    PubMed  CAS  Google Scholar 

  63. Atkins RC, Briganti EM, Lewis JB, Hunsicker LG, Braden G, Champion de Crespigny PJ, DeFerrari G, Drury P, Locatelli F, Wiegmann TB, Lewis EJ (2005) Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis 45:281–287

    PubMed  Google Scholar 

  64. Lemley KV (2007) An introduction to biomarkers: applications to chronic kidney disease. Pediatr Nephrol 22:1849–1859

    PubMed  Google Scholar 

  65. Andersen S, Bröchner-Mortensen PHH (2003) Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria. Diabetes Care 26:3296–3302

    PubMed  Google Scholar 

  66. The Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2003) Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy. The Epidemiology of Diabetes Interventions and Complications (EDIC) Study. JAMA 290:2159–2167

    Google Scholar 

  67. Levey AS, Cattran D, Friedman A, Miller WG, Sedor J, Tuttle K, Kasiske B, Hostetter T (2009) Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 54:205–226

    PubMed  Google Scholar 

  68. Hunsicker LG, Atkins RC, Lewis JB, Braden G, Champion de Crespigny PJ, DeFerrari G, Drury P, Locatelli F, Wiegmann TB, Lewis EJ (2004) Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes in the Irbesartan Diabetic Nephropathy Trial. Kidney Int 66[Suppl 92]:S99–S101

    Google Scholar 

  69. Eijkelkamp WBA, Zhang Z, Remuzzi G, Parving HH, Cooper ME, Keane WF, Shahinfar S, Gleim GW, Weir MR, Brenner BM, De Zeeuw D (2007) Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: Post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Trial. J Am Soc Nephrol 18:1540–1546

    PubMed  CAS  Google Scholar 

  70. Jerums G, Panagiotopoulos S, Premaratne E, Power DA, MacIsaac RJ (2008) Lowering of proteinuria in response to antihypertensive therapy predicts improved renal function in late but not in early diabetic nephropathy: A pooled analysis. Am J Nephrol 28:614–627

    PubMed  CAS  Google Scholar 

  71. Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH (2004) Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. Br Med J 328:1105–1109

    Google Scholar 

  72. Chobanion AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. JAMA 289:2560–2571

    Google Scholar 

  73. Lemley KV, Abdullah I, Myers BD, Meyer TW, Blouch K, Smith WE, Bennett PH, Nelson RG (2000) Evolution of incipient nephropathy in type 2 diabetes mellitus. Kidney Int 58:1228–1237

    PubMed  CAS  Google Scholar 

  74. Dalla Vestra M, Masiero A, Roiter AM, Saller A, Crepaldi G, Fioretto P (2003) Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes 52:1031–1035

    PubMed  CAS  Google Scholar 

  75. Meyer TW, Bennett PH, Nelson RG (1999) Podocyte number predicts long-term urinary albumin excretion in Pima Indians with type II diabetes and microalbuminuria. Diabetologia 42:1341–1344

    PubMed  CAS  Google Scholar 

  76. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Ebihara I, Koide H (2000) Urinary excretion of podocyte in patients with diabetic nephropathy. Nephrol Dial Transplant 15:1379–1383

    PubMed  CAS  Google Scholar 

  77. Kriz W, Gretz N, Lemley KV (1998) Progression of glomerular diseases: Is the podocyte the culprit? Kidney Int 54:687–697

    PubMed  CAS  Google Scholar 

  78. White KE, Bilous RW (2004) Estimation of podocyte number: A comparison of methods. Kidney Int 66:663–667

    PubMed  Google Scholar 

  79. Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M (2007) Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy. Diabetes 56:2155–2160

    PubMed  CAS  Google Scholar 

  80. Macconi D, Sangalli F, Bonomelli M, Conti S, Condorelli L, Gagliardini E, Remuzzi G, Remuzzi A (2009) Podocyte repopulation contributes to regression of glomerular injury induced by ACE inhibition. Am J Pathol 174:797–807

    PubMed  CAS  Google Scholar 

  81. Macconi D, Abbate M, Morigi M, Angioletti S, Mister M, Buelli S, Bonomelli M, Mundel P, Endlich K, Remuzzi A, Remuzzi G (2006) Permselective dysfunction of podocyte—podocyte contact upon angiotensin II unravels the molecular target for renoprotective intervention. Am J Pathol 168:1073–1085

    PubMed  CAS  Google Scholar 

  82. Langham RG, Kelly DJ, Gow RM, Zhang Y, Cordonnier DJ, Pinel N, Zaouli P, Gilbert RE (2006) Transforming growth factor-β in human diabetic nephropathy. Diabetes Care 29:2670–2675

    PubMed  CAS  Google Scholar 

  83. Rupérez M, Ruiz-Ortega M, Esteban V, Lorenzo Ó, Mezzano S, Plaza JJ, Egido J (2003) Angiotensin II increases connective tissue growth factor in the kidney. Am J Pathol 163:1937–1947

    PubMed  Google Scholar 

  84. Katz A, Caramori MLA, Sisson-Ross S, Groppoli T, Basgen JM, Mauer M (2002) An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients. Kidney Int 61:2058–2066

    PubMed  Google Scholar 

  85. Benigni A, Remuzzi G (2001) How renal cytokines and growth factors contribute to renal disease progression. Am J Kidney Dis 37(Suppl 2):S21–S24

    PubMed  CAS  Google Scholar 

  86. Lemley KV, Blouch KB, Abdullah I, Boothroyd DB, Bennett PH, Myers BD, Nelson RG (2000) Glomerular permselectivity at the onset of nephropathy in type 2 diabetes mellitus. J Am Soc Nephrol 11:2095–2105

    PubMed  CAS  Google Scholar 

  87. Fioretto P, Stehouwer CDA, Mauer M, Chiesura-Corona M, Brocco E, Carraro A, Bortoloso E, van Hinsbergh VWM, Crepaldi G, Nosadini R (1998) Heterogenous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. Diabetologia 41:233–236

    PubMed  CAS  Google Scholar 

  88. Hosojima M, Sato H, Yamamoto K, Kaseda R, Soma T, Kobayashi A, Suzuki A, Kabasawa H, Takeyama A, Ikuyama K, Iino N, Nishiyama A, Thekkumkara TJ, Takeda T, Suzuki Y, Gejyo F, Saito A (2009) Regulation of megalin expression in cultured proximal tubule cells by angiotensin II type 1A receptor-and insulin-mediated signaling cross talk. Endocrinology 150:871–878

    PubMed  CAS  Google Scholar 

  89. The Heart Outcomes Prevention Evaluation Study Investigators (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 342:145–153

    Google Scholar 

  90. Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Loumanmäki K, Dahlöf B, de Faire U, Mörlin C, Karlberg BE, Wester PO, Björck J-E (1999) Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 353:611–616

    PubMed  CAS  Google Scholar 

  91. Lindholm LJ, Ibsen H, Borch-Johnsen K, Olsen MH, Wachtell K, Dahlöf B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Kristianson K, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman JM, Snapinn S (2002) Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens 20:1879–1886

    PubMed  CAS  Google Scholar 

  92. Perkins BA, Aiello LP, Krolewski AS (2009) Diabetes complications and the renin-angiotensin system. N Engl J Med 361:83–85

    PubMed  CAS  Google Scholar 

  93. Nordwall M, Arnqvist HJ, Bojestig M, Ludvigsson J (2009) Good glycemic control remains crucial in prevention of late diabetic complications-the Linköping Diabetes Complications Study. Pediatr Diabetes 10:169–176

    Google Scholar 

  94. de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM (2009) Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 20:2075–2084

    PubMed  Google Scholar 

  95. Gæde P, Lund-Andersen H, Parving HH, Pedersen O (2008) Effect of a multifactorial intervention on mortality in type 2 diabetes. N Eng J Med 358:580–591

    Google Scholar 

  96. Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Geng RW (2006) Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 354:131–140

    PubMed  CAS  Google Scholar 

  97. Gavin L, MacKay AP, Brown K, Harrier S, Ventura SJ, Kann L, Rangel M, Berman S, Dittus P, Liddon N, Markowitz L, Sternberg M, Weinstock H, David-Ferdon C, Ryan G, Centers for Disease Control and Prevention (CDC) (2009) Sexual and reproductive health of persons aged 10–24 years-United States, 2002–2207. MMWR Surveill Summ 58:1–58

    PubMed  Google Scholar 

  98. Strippoli GFM, Bonifati C, Craig ME, Navaneethan SD, Craig JC (2006) Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev (4):CD006257

  99. Mann JFE, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, Wang X, Maggioni A, Budaj A, Chaithiraphan S, Dickstein K, Keltai M, Metsärinne K, Oto A, Parkhomenko A, Piegas LS, Svendsen TI, Teo KK, Yusuf S (2008) Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 372:547–553

    PubMed  CAS  Google Scholar 

  100. Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, Cooper ME (2000) 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. Br Med J 321:1440–1444

    CAS  Google Scholar 

  101. Rossing K, Schjoedt KJ, Jensen BR, Boomsa F, Parving HH (2005) Enhanced renoprotective effects of ultrahigh doses of irbesartan in patient with type 2 diabetes and microalbuminuria. Kidney Int 68:1190–1198

    PubMed  CAS  Google Scholar 

  102. Burgess E, Muirhead N, de Cotret PR, Chiu A, Pichette V, Tobe S (2009) Supramaximal dose of candesartan in proteinuric renal disease. J Am Soc Nephrol 20:893–900

    PubMed  CAS  Google Scholar 

  103. Hou FF, Xie D, Zhang X, Chen PY, Zhang WR, Liang M, Guo ZJ, Jiang JP (2007) Renoprotection of optimal antiproteinuric doses (ROAD) study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency. J Am Soc Nephrol 18:1889–1898

    PubMed  CAS  Google Scholar 

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Acknowledgments

The author would like to express his gratitude to Dr. Robert G. Nelson for very helpful comments on this manuscript.

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  1. Division of Nephrology, MS#40, Childrens Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA, 90027, USA

    Kevin V. Lemley

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  1. Kevin V. Lemley
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Lemley, K.V. When to initiate ACEI/ARB therapy in patients with type 1 and 2 diabetes. Pediatr Nephrol 25, 2021–2034 (2010). https://doi.org/10.1007/s00467-010-1498-x

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  • DOI: https://doi.org/10.1007/s00467-010-1498-x

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