Skip to main content
PMC home page
The BMJ logoLink to The BMJ
. 1991 Jul 13;303(6794):81–87. doi: 10.1136/bmj.303.6794.81

Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.

E R Mathiesen 1, E Hommel 1, J Giese 1, H H Parving 1
PMCID: PMC1670656  PMID: 1860008

Abstract

OBJECTIVE--To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN--Open randomised controlled study of four years' duration. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS--The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES--Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS--Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS--The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.

Full text

PDF
81

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson S., Rennke H. G., Brenner B. M. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest. 1986 Jun;77(6):1993–2000. doi: 10.1172/JCI112528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson S., Rennke H. G., Garcia D. L., Brenner B. M. Short and long term effects of antihypertensive therapy in the diabetic rat. Kidney Int. 1989 Oct;36(4):526–536. doi: 10.1038/ki.1989.227. [DOI] [PubMed] [Google Scholar]
  3. Borch-Johnsen K., Andersen P. K., Deckert T. The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1985 Aug;28(8):590–596. doi: 10.1007/BF00281993. [DOI] [PubMed] [Google Scholar]
  4. Chavers B. M., Bilous R. W., Ellis E. N., Steffes M. W., Mauer S. M. Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria. N Engl J Med. 1989 Apr 13;320(15):966–970. doi: 10.1056/NEJM198904133201503. [DOI] [PubMed] [Google Scholar]
  5. Cohen D., Dodds R., Viberti G. Effect of protein restriction in insulin dependent diabetics at risk of nephropathy. Br Med J (Clin Res Ed) 1987 Mar 28;294(6575):795–798. doi: 10.1136/bmj.294.6575.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooper M. E., Allen T. J., Macmillan P. A., Clarke B. E., Jerums G., Doyle A. E. Enalapril retards glomerular basement membrane thickening and albuminuria in the diabetic rat. Diabetologia. 1989 May;32(5):326–328. doi: 10.1007/BF00265552. [DOI] [PubMed] [Google Scholar]
  7. Deckert T., Poulsen J. E., Larsen M. Prognosis of diabetics with diabetes onset before the age of thirty-one. I. Survival, causes of death, and complications. Diabetologia. 1978 Jun;14(6):363–370. doi: 10.1007/BF01228130. [DOI] [PubMed] [Google Scholar]
  8. Feldt-Rasmussen B., Mathiesen E. R., Deckert T. Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet. 1986 Dec 6;2(8519):1300–1304. doi: 10.1016/s0140-6736(86)91433-9. [DOI] [PubMed] [Google Scholar]
  9. Feldt-Rasmussen B., Mathiesen E. R., Jensen T., Lauritzen T., Deckert T. 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 Mar;34(3):164–170. doi: 10.1007/BF00418270. [DOI] [PubMed] [Google Scholar]
  10. Fogo A., Yoshida Y., Glick A. D., Homma T., Ichikawa I. Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis. J Clin Invest. 1988 Jul;82(1):322–330. doi: 10.1172/JCI113590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hommel E., Mathiesen E. R., Giese J., Nielsen M. D., Schütten H. J., Parving H. H. On the pathogenesis of arterial blood pressure elevation early in the course of diabetic nephropathy. Scand J Clin Lab Invest. 1989 Oct;49(6):537–544. doi: 10.3109/00365518909089133. [DOI] [PubMed] [Google Scholar]
  12. Hommel E., Mathiesen E., Edsberg B., Bahnsen M., Parving H. H. Acute reduction of arterial blood pressure reduces urinary albumin excretion in type 1 (insulin-dependent) diabetic patients with incipient nephropathy. Diabetologia. 1986 Apr;29(4):211–215. doi: 10.1007/BF00454877. [DOI] [PubMed] [Google Scholar]
  13. Hostetter T. H., Rennke H. G., Brenner B. M. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982 Mar;72(3):375–380. doi: 10.1016/0002-9343(82)90490-9. [DOI] [PubMed] [Google Scholar]
  14. Kappelgaard A. M., Nielsen M. D., Giese J. Measurement of angiotensin II in human plasma: technical modifications and practical experience. Clin Chim Acta. 1976 Mar 15;67(3):299–306. doi: 10.1016/0009-8981(76)90338-7. [DOI] [PubMed] [Google Scholar]
  15. Ladegaard-Pedersen H. J., Engell H. C. A comparison of the distribution volumes of inulin and ( 51 Cr)EDTA in man and nephrectomized dogs. Scand J Clin Lab Invest. 1972 Nov;30(3):267–270. doi: 10.3109/00365517209084289. [DOI] [PubMed] [Google Scholar]
  16. Maroni B. J., Steinman T. I., Mitch W. E. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985 Jan;27(1):58–65. doi: 10.1038/ki.1985.10. [DOI] [PubMed] [Google Scholar]
  17. Mathiesen E. R., Hommel E., Olsen U. B., Parving H. H. Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient diabetic nephropathy. Diabet Med. 1988 Mar;5(2):145–149. doi: 10.1111/j.1464-5491.1988.tb00961.x. [DOI] [PubMed] [Google Scholar]
  18. Mathiesen E. R., Oxenbøll B., Johansen K., Svendsen P. A., Deckert T. Incipient nephropathy in type 1 (insulin-dependent) diabetes. Diabetologia. 1984 Jun;26(6):406–410. doi: 10.1007/BF00262210. [DOI] [PubMed] [Google Scholar]
  19. Mathiesen E. R., Rønn B., Jensen T., Storm B., Deckert T. Relationship between blood pressure and urinary albumin excretion in development of microalbuminuria. Diabetes. 1990 Feb;39(2):245–249. doi: 10.2337/diab.39.2.245. [DOI] [PubMed] [Google Scholar]
  20. Mathiesen E. R., Saurbrey N., Hommel E., Parving H. H. Prevalence of microalbuminuria in children with type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1986 Sep;29(9):640–643. doi: 10.1007/BF00869263. [DOI] [PubMed] [Google Scholar]
  21. Mauer S. M., Steffes M. W., Ellis E. N., Sutherland D. E., Brown D. M., Goetz F. C. Structural-functional relationships in diabetic nephropathy. J Clin Invest. 1984 Oct;74(4):1143–1155. doi: 10.1172/JCI111523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mogensen C. E., Chachati A., Christensen C. K., Close C. F., Deckert T., Hommel E., Kastrup J., Lefebvre P., Mathiesen E. R., Feldt-Rasmussen B. Microalbuminuria: an early marker of renal involvement in diabetes. Uremia Invest. 1985;9(2):85–95. doi: 10.3109/08860228509088195. [DOI] [PubMed] [Google Scholar]
  23. Mogensen C. E., Christensen C. K. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984 Jul 12;311(2):89–93. doi: 10.1056/NEJM198407123110204. [DOI] [PubMed] [Google Scholar]
  24. Mogensen C. E. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. Br Med J (Clin Res Ed) 1982 Sep 11;285(6343):685–688. doi: 10.1136/bmj.285.6343.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Morelli E., Loon N., Meyer T., Peters W., Myers B. D. Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopathy. Diabetes. 1990 Jan;39(1):76–82. doi: 10.2337/diacare.39.1.76. [DOI] [PubMed] [Google Scholar]
  26. Niazy S., Feldt-Rasmussen B., Deckert T. Microalbuminuria in insulin-dependent diabetes: prevalence and practical consequences. J Diabet Complications. 1987 Jul-Sep;1(3):76–80. doi: 10.1016/s0891-6632(87)80060-0. [DOI] [PubMed] [Google Scholar]
  27. Nørgaard K., Storm B., Graae M., Feldt-Rasmussen B. Elevated albumin excretion and retinal changes in children with type 1 diabetes are related to long-term poor blood glucose control. Diabet Med. 1989 May-Jun;6(4):325–328. doi: 10.1111/j.1464-5491.1989.tb01173.x. [DOI] [PubMed] [Google Scholar]
  28. Osterby R., Parving H. H., Nyberg G., Hommel E., Jørgensen H. E., Løkkegaard H., Svalander C. A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy. Diabetologia. 1988 May;31(5):265–270. doi: 10.1007/BF00277406. [DOI] [PubMed] [Google Scholar]
  29. Parving H. H., Andersen A. R., Smidt U. M., Svendsen P. A. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet. 1983 May 28;1(8335):1175–1179. doi: 10.1016/s0140-6736(83)92462-5. [DOI] [PubMed] [Google Scholar]
  30. Parving H. H., Hommel E., Mathiesen E., Skøtt P., Edsberg B., Bahnsen M., Lauritzen M., Hougaard P., Lauritzen E. Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes. Br Med J (Clin Res Ed) 1988 Jan 16;296(6616):156–160. doi: 10.1136/bmj.296.6616.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Parving H. H., Hommel E., Smidt U. M. Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy. BMJ. 1988 Oct 29;297(6656):1086–1091. doi: 10.1136/bmj.297.6656.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Parving H. H., Oxenbøll B., Svendsen P. A., Christiansen J. S., Andersen A. R. Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endocrinol (Copenh) 1982 Aug;100(4):550–555. doi: 10.1530/acta.0.1000550. [DOI] [PubMed] [Google Scholar]
  33. Parving H. H., Smidt U. M., Friisberg B., Bonnevie-Nielsen V., Andersen A. R. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia. 1981 Apr;20(4):457–461. doi: 10.1007/BF00253407. [DOI] [PubMed] [Google Scholar]
  34. Parving H. H., Viberti G. C., Keen H., Christiansen J. S., Lassen N. A. Hemodynamic factors in the genesis of diabetic microangiopathy. Metabolism. 1983 Sep;32(9):943–949. doi: 10.1016/0026-0495(83)90210-x. [DOI] [PubMed] [Google Scholar]
  35. Rønn B., Mathiesen E. R., Vang L., Lørup B., Deckert T. Evaluation of insulin pump treatment under routine conditions. Diabetes Res Clin Pract. 1987 Jul-Aug;3(4):191–196. doi: 10.1016/s0168-8227(87)80038-4. [DOI] [PubMed] [Google Scholar]
  36. Tochikubo O., Minamisawa K., Miyajima E., Ishii M., Yanaga A., Yukinari Y. A new compact 24-hour indirect blood-pressure recorder and its clinical application. Jpn Heart J. 1988 May;29(3):257–269. doi: 10.1536/ihj.29.257. [DOI] [PubMed] [Google Scholar]
  37. Viberti G. C., Hill R. D., Jarrett R. J., Argyropoulos A., Mahmud U., Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet. 1982 Jun 26;1(8287):1430–1432. doi: 10.1016/s0140-6736(82)92450-3. [DOI] [PubMed] [Google Scholar]
  38. Viberti G. C., Pickup J. C., Jarrett R. J., Keen H. Effect of control of blood glucose on urinary excretion of albumin and beta2 microglobulin in insulin-dependent diabetes. N Engl J Med. 1979 Mar 22;300(12):638–641. doi: 10.1056/NEJM197903223001202. [DOI] [PubMed] [Google Scholar]
  39. Zatz R., Dunn B. R., Meyer T. W., Anderson S., Rennke H. G., Brenner B. M. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986 Jun;77(6):1925–1930. doi: 10.1172/JCI112521. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES