Drugs & Aging

, Volume 20, Issue 6, pp 419–435 | Cite as

Prevention and Treatment of Diabetic Nephropathy in Older Patients

  • Eckart Jungmann
Therapy in Practice

Abstract

Renal disease in older diabetic patients is costly in terms of morbidity, mortality and expenditure. Therefore, prevention and treatment of diabetic nephropathy has become a prominent goal in the treatment of patients with diabetes mellitus. Preventive treatment should begin no later than at the stage of microalbuminuria, and regular screening for microalbuminuria is recommended for all patients with diabetes, irrespective of age.

Improved metabolic control has been demonstrated to lower urinary albumin excretion. Target glycosylated haemoglobin levels should be below 7%, or 1% above the upper limit of normal of non-diabetic subjects. The use of an intensified treatment regimen is recommended. Insulin therapy has no adverse effects on renal indexes.

To preserve renal function in older diabetic patients, blood pressure should be kept at or below 130/80mm Hg. Treatment with ACE inhibitors or angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) is superior to other pharmacological therapy, and should be initiated as first-line treatment. Most of the calcium channel antagonists have been found to increase or to have no effect on microalbuminuria despite blood pressure reduction. Moreover, there is substantial controversy as to whether they may be associated with increased cardiovascular morbidity. Non-dihydropyridine derivatives and calcium channel antagonists, such as nitrendipine, may be nephroprotective and have favourable effects on patients outcomes.

A renoprotective action of diuretics may be confined to indapamide. Although β-adrenoreceptor blockers are effective antihypertensive agents, they may not adequately preserve kidney function in older diabetic patients. However, as add-on treatment to ACE inhibitors or ARBs, they are particularly beneficial in nephropathic patients at risk of cardiovascular disease or with arrhythmias, in whom they may prove life-saving.

Keywords

Diabetic Nephropathy Losartan Glycaemic Control Candesartan Mean Arterial Blood Pressure 

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The author has no conflicts of interest that are directly relevant to the content of this manuscript.

References

  1. 1.
    American Diabetes Association. Screening for diabetes. Diabetes Care 2002; 25Suppl. 1: S21–4Google Scholar
  2. 2.
    Singh I, Marshall MC. Diabetes mellitus in the elderly. Endocrinol Metab Clin North Am 1995; 24: 255–72PubMedGoogle Scholar
  3. 3.
    Jungmann E. Chemoprophylaxis of diabetic nephropathy in the elderly. Drugs Aging 1996; 9: 449–56PubMedCrossRefGoogle Scholar
  4. 4.
    Remuzzi G, Schieppati A, Ruggenenti P. Nephropathy in patients with type 2 diabetes. N Engl J Med 2002; 346: 1145–51PubMedCrossRefGoogle Scholar
  5. 5.
    Ritz E, Rychlik I, Locatelli F, et al. End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimension. Am J Kidney Dis 1999; 34: 795–808PubMedCrossRefGoogle Scholar
  6. 6.
    American Diabetes Association. Diabetic nephropathy. Diabetes Care 2002; 25Suppl. 1: S85–93Google Scholar
  7. 7.
    American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 2002; 25Suppl. 1: S33–49Google Scholar
  8. 8.
    Ibrahim HAA, Vora JP. Diabetic nephropathy. Baillieres Clin Endocrin Metab 1999; 13: 239–64CrossRefGoogle Scholar
  9. 9.
    Skyler JS. Microvascular complications. Endocrinol Metab Clin North Am 2001; 30: 833–56PubMedCrossRefGoogle Scholar
  10. 10.
    Thomas SM. What should we do about microalbuminuria? In: Gill GV, Pickup JC, Williams G, editors. Difficult diabetes. Oxford: Blackwell Science, 2001: 53–70CrossRefGoogle Scholar
  11. 11.
    Valmadrid CT, Klein R, Moss SC, et al. The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. Arch Intern Med 2000; 160: 1093–100PubMedCrossRefGoogle Scholar
  12. 12.
    Jungmann E, Graeber S, Scherberich J, et al. The role of rising blood pressure and of human atrial natriuretic peptide in the pathogenesis of diabetic nephropathy in patients with type 1 diabetes mellitus [in German]. Nieren- und Hochdruckkrh 1993; 22: 301–4Google Scholar
  13. 13.
    Jungmann E, Carlberg C, Schallmayer M, et al. Albuminuria in patients with type 2 diabetes mellitus: impact of blood pressure and metabolic control [in German]. Med Klin 1995; 90: 383–9Google Scholar
  14. 14.
    Zelmanovitz T, Paggi A, Gross JL, et al. The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy. Diabetes Care 1997; 20: 516–9PubMedCrossRefGoogle Scholar
  15. 15.
    Adler SG, Kang SW, Feld S, et al. Glomerular mRNAs in human type 1 diabetes: biochemical evidence for microalbuminuria as a manifestation of diabetic nephropathy. Kidney Int 2001; 60: 2330–6PubMedCrossRefGoogle Scholar
  16. 16.
    Forsblom CM, Groop PH, Ekstrand A, et al. Predictive value of microalbuminuria in patients with insulin-dependent diabetes of long duration. BMJ 1992; 305: 1051–3PubMedCrossRefGoogle Scholar
  17. 17.
    Allen KV, Walker JD. The prognostic significance of abnormal urinary albumin excretion in long-duration type 1 diabetes [abstract]. Diabetes 2002; 51Suppl. 2: A37Google Scholar
  18. 18.
    Lurbe E, Redon J, Kesani A, et al. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med 2002; 347: 797–805PubMedCrossRefGoogle Scholar
  19. 19.
    Jungmann E. Excretion of tubular markers in diabetic nephropathy: impact of conversion-enzyme inhibition [in German]. Dtsch Med Wochenschr 1995; 120: 82–3PubMedGoogle Scholar
  20. 20.
    Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 2000; 49: 1399–408PubMedCrossRefGoogle Scholar
  21. 21.
    Gerstein HC, Mann FE, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–6PubMedCrossRefGoogle Scholar
  22. 22.
    Gall MA, Borch-Johnsen K, Hougaard P, et al. Albuminuria and poor glycemic control predict mortality in NIDDM. Diabetes 1995; 44: 1303–9PubMedCrossRefGoogle Scholar
  23. 23.
    The Diabetes Control and Complications Trial (DCCT) Research Group. Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. Kidney Int 1995; 47: 1703–20CrossRefGoogle Scholar
  24. 24.
    Stratton IM, Adler AI, Neil HAW, et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321: 405–12PubMedCrossRefGoogle Scholar
  25. 25.
    Holman RR, Turner RC, Cull CA, et al. A randomised double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UKPDS 44). Diabetes Care 1999; 22: 960–4PubMedCrossRefGoogle Scholar
  26. 26.
    American Diabetes Association. Implications of the UKPDS. Diabetes Care 2002; 25Suppl. 1: S28–32Google Scholar
  27. 27.
    Nakamura T, Ushiyama C, Shimada N, et al. Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-I and albumin excretion in diabetes patients. J Diabetes Complications 2000; 14: 250–4PubMedCrossRefGoogle Scholar
  28. 28.
    Shichiri M, Ohkubo Y, Kishikawa H, et al. Long-term results of the Kumamoto study on optimal diabetes control in type 2 diabetic patients. Diabetes Care 2000; 23Suppl. 2: B21–9PubMedGoogle Scholar
  29. 29.
    Jungmann E, Helling T, Jungmann G. Persistent improvement of metabolic control in type 2 diabetes mellitus enabled by intensive insulin treatment using insulin lispro [abstract]. Diabetologia 2000; 43Suppl. 1: A199Google Scholar
  30. 30.
    Lalau JD, Guerin C, Lacroix C, et al. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995; 18: 779–84PubMedCrossRefGoogle Scholar
  31. 31.
    Ruggenenti P, Dodesini AR, Flores C, et al. Insulin lispro is better than regular insulin in limiting post-prandial hyperglycaemia and fully prevents meal-induced hyperfiltration in type 2 diabetics with overt nephropathy [abstract]. Diabetes 2002; 51Suppl. 2: A191Google Scholar
  32. 32.
    Cooper MA. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet 1998; 325: 213–9CrossRefGoogle Scholar
  33. 33.
    Ribstein J, du Cailar G, Mimran A. Combined renal effects of overweight and hypertension. Hypertension 1995; 26: 610–5PubMedCrossRefGoogle Scholar
  34. 34.
    Jungmann E, Jungmann G. Hypertension, obesity and metabolic control, and microalbuminuria [in German]. J Hyperten 1999; 3: 21–6Google Scholar
  35. 35.
    Dodson PM, Beevers M, Hallworth R, et al. Sodium restriction and blood pressure in hypertensive type 2 diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation. BMJ 1989; 298: 227–30PubMedCrossRefGoogle Scholar
  36. 36.
    Jungmann E. Diabetic sodium retention [in German]. Nieren- und Hochdruckkrh 1992; 21: 709–15Google Scholar
  37. 37.
    Scott LJ, Warram JH, Hanna LS, et al. A nonlinear effect of hyperglycaemia and current cigarette smoking are major determinants of the onset of microalbuminuria in type 1 diabetes. Diabetes 2001; 50: 2842–9PubMedCrossRefGoogle Scholar
  38. 38.
    Nelson RG, Pettitt DJ, Baird HR, et al. Pre-diabetic blood pressure predicts urinary albumin excretion after the onset of type 2 diabetes mellitus in Pima Indians. Diabetologia 1993; 36: 998–1001PubMedCrossRefGoogle Scholar
  39. 39.
    Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis 2000; 36: 646–61PubMedCrossRefGoogle Scholar
  40. 40.
    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 Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: 1755–62PubMedCrossRefGoogle Scholar
  41. 41.
    Adler AI, Stratton IM, Neil AW, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000; 321: 412–9PubMedCrossRefGoogle Scholar
  42. 42.
    Orchard TJ, Kuller LH, Forrest KYZ, et al. Lipid and blood pressure treatment goals for type 1 diabetes. Diabetes Care 2001; 24: 1053–9PubMedCrossRefGoogle Scholar
  43. 43.
    Schrier RW, Estacio RO, Esler A, et al. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int 2002; 61: 1086–97PubMedCrossRefGoogle Scholar
  44. 44.
    Lewis JB, Berl T, Bain RP, et al. Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Am J Kidney Dis 1999; 34: 809–17PubMedCrossRefGoogle Scholar
  45. 45.
    Ravid M, Savin H, Jutrin I, et al. Long-term stabilising effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type 2 diabetic patients. Ann Intern Med 1993; 118: 577–81PubMedGoogle Scholar
  46. 46.
    Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000; 355: 253–9CrossRefGoogle Scholar
  47. 47.
    Jungmann E, Krüger K, Semler B, et al. The renoprotective effect of the converting-enzyme inhibitor ramipril in hypertensive patients with insulin-treated type 2 diabetes mellitus: dependence upon blood pressure and glycemic control [in German]. Nieren- und Hochdruckkrh 1995; 24: 248–50Google Scholar
  48. 48.
    Cordonnier DJ, Zaoui P, Halimi S. Role of ACE inhibitors in patients with diabetes mellitus. Drugs 2001; 61: 1883–92PubMedCrossRefGoogle Scholar
  49. 49.
    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: 851–60PubMedCrossRefGoogle Scholar
  50. 50.
    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: 861–9PubMedCrossRefGoogle Scholar
  51. 51.
    Parving HH, Lehnert J, Bröchner-Mortensen 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: 870–8PubMedCrossRefGoogle Scholar
  52. 52.
    Lindhorm LH, Ibsen H, Dahlöf, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 1004–10CrossRefGoogle Scholar
  53. 53.
    Lacourciere Y, Belanger A, Godin C, et al. Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy. Kidney Int 2000; 58: 762–9PubMedCrossRefGoogle Scholar
  54. 54.
    Mogensen CE, Neldam S, Tikkanen, 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: 1440–4PubMedCrossRefGoogle Scholar
  55. 55.
    Houlihan CA, Casley DJ, Allen TJ, et al. A low-sodium diet potentiates the effects of losartan in type 2 diabetes. Diabetes Care 2002; 25: 663–71PubMedCrossRefGoogle Scholar
  56. 56.
    Rossing K, Jensen BR, Christensen PK, et al. Dual blockade of the renin-angiotensin system in diabetic nephropathy. Diabetes Care 2002; 25: 95–100PubMedCrossRefGoogle Scholar
  57. 57.
    Jungmann E, Schumm-Draeger PM, Scheuermann EH, et al. Long-term antihypertensive treatment with felodipine in diabetic patients: effects on blood pressure and renal function parameters [in German]. Fortschr Med 1992; 110: 224–6PubMedGoogle Scholar
  58. 58.
    Bretzel RG, Bollen CC, Maeser E, et al. Nephroprotective effects of nitrendipine in hypertensive type 1 and type 2 diabetic patients. Am J Kidney Dis 1993; 21Suppl. 3: 53–64PubMedGoogle Scholar
  59. 59.
    Mosconi L, Ruggenenti P, Perna A, et al. Nitrendipine and enalapril improve albuminuria and glomerular filtration rate in non-insulin dependent diabetes. Kidney Int 1996; 49Suppl. 55: 91–3Google Scholar
  60. 60.
    Fogari R, Zoppi A, Corradi L, et al. Long-term effects of ramipril and nitrendipine on albuminuria in hypertensive patients with type 2 diabetes and impaired renal function. J Hum Hypertens 1999; 13: 47–53PubMedCrossRefGoogle Scholar
  61. 61.
    Jungmann E, Haak T, Schumm-Draeger PM, et al. Effect of 2-year treatment with nitrendipine vs. enalapril on urinary albumin excretion in microalbuminuric patients with type 1 diabetes mellitus [in German]. Nieren- und Hochdruckkrh 1994; 23: 38–43Google Scholar
  62. 62.
    Tuomiletho J, Rastenyte D, Birkenhäger WH, et al. Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. N Engl J Med 1999; 340: 677–84CrossRefGoogle Scholar
  63. 63.
    Pahor M, Psaty BM, Furberg CD. Treatment of hypertensive patients with diabetes. Lancet 1998; 351: 689–90PubMedCrossRefGoogle Scholar
  64. 64.
    Stornello M, Valvo EV, Scapellato L. Comparative effects of enalapril, atenolol and chlorthalidone on blood pressure and kidney function of diabetic patients affected by arterial hypertension and persistent proteinuria. Nephron 1991; 58: 52–7PubMedCrossRefGoogle Scholar
  65. 65.
    SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated hypertension. JAMA 1991; 265: 3255–64CrossRefGoogle Scholar
  66. 66.
    Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003PubMedCrossRefGoogle Scholar
  67. 67.
    Yusuf S, Gerstein H, Hoogwerf B, et al. Ramipril and the development of diabetes. JAMA 2001; 286: 1882–5PubMedCrossRefGoogle Scholar
  68. 68.
    UK Prospective Diabetes Study Group. Efficacy of atenolol and Captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998; 317: 713–20CrossRefGoogle Scholar
  69. 69.
    Ebbehoj E, Poulsen PL, Hansen KW, et al. Effects on heart rate variability of metoprolol supplementary to ongoing ACE inhibitor treatment in type 1 diabetic patients with abnormal albuminuria. Diabetologia 2002; 45: 965–75PubMedCrossRefGoogle Scholar
  70. 70.
    Cohn JN, Tognoni G. A randomised trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667–75PubMedCrossRefGoogle Scholar
  71. 71.
    Gaede P, Vedel P, Parving HH, et al. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the steno type 2 randomised study. Lancet 1999; 353: 617–22PubMedCrossRefGoogle Scholar
  72. 72.
    Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002; 324: 1–5Google Scholar
  73. 73.
    American Diabetes Association. Aspirin therapy in diabetes. Diabetes Care 2002; 25Suppl. 1: S78–9Google Scholar
  74. 74.
    Durrington PN. Diabetic dyslipidaemia. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13: 265–78PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Eckart Jungmann
    • 1
  1. 1.St. Vincent’s Hospital WiedenbrückRheda-WiedenbrückGermany

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