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. 1996 Sep 7;313(7057):591–594. doi: 10.1136/bmj.313.7057.591

Effect of deletion polymorphism of angiotensin converting enzyme gene on progression of diabetic nephropathy during inhibition of angiotensin converting enzyme: observational follow up study.

H H Parving 1, P Jacobsen 1, L Tarnow 1, P Rossing 1, L Lecerf 1, O Poirier 1, F Cambien 1
PMCID: PMC2352037  PMID: 8806248

Abstract

OBJECTIVE: To evaluate the concept that an insertion/deletion polymorphism of the angiotensin converting enzyme gene predicts the therapeutic efficacy of inhibition of angiotensin converting enzyme on progression of diabetic nephropathy. DESIGN: Observational follow up study of patients with insulin dependent diabetes and nephropathy who had been treated with captopril for a median of 7 years (range 3-9 years). SETTING: Outpatient diabetic clinic in a tertiary referral centre. PATIENTS: 35 patients with insulin dependent diabetes and nephropathy were investigated during captopril treatment (median 75 mg/day (range 12.5 to 150 mg/day)) that was in many cases combined with a loop diuretic, 11 patients were homozygous for the deletion allele and 24 were heterozygous or homozygous for the insertion allele of the angiotensin converting enzyme gene. MAIN OUTCOME MEASURES: Albuminuria, arterial blood pressure, and glomerular filtration rate according to insertion/deletion polymorphism. RESULTS: The two groups had comparable glomerular filtration rate, albuminuria, blood pressure, and haemoglobin A1c concentration at baseline. Captopril induced nearly the same reduction in mean blood pressure in the two groups-to 103 (SD 5) mm Hg in the group with the deletion and 102 (8) mm Hg in the group with the insertion-and in geometric mean albumin excretion-573 (antilog SE 1.3) micrograms/min and 470 (1.2) micrograms/min, respectively. The rate of decline in glomerular filtration rate (linear regression of all glomerular filtration rate measurements during antihypertensive treatment) was significantly steeper in the group homozygous for the double deletion allele than in the other group (mean 5.7 (3.7) ml/min/year and 2.6 (2.8) ml/min/year, respectively; P = 0.01). Multiple linear regression analysis showed that haemoglobin A1c concentration, albuminuria, and the double deletion genotype independently influenced the sustained rate of decline in glomerular filtration rate (R1 (adjusted) = 0.51). CONCLUSION: The deletion polymorphism in the angiotensin converting enzyme gene reduces the long term beneficial effect of angiotensin converting enzyme inhibition on the progression of diabetic nephropathy in patients with insulin dependent diabetes.

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Selected References

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  1. Björck S., Mulec H., Johnsen S. A., Nordén G., Aurell M. Renal protective effect of enalapril in diabetic nephropathy. BMJ. 1992 Feb 8;304(6823):339–343. doi: 10.1136/bmj.304.6823.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bröchner-Mortensen J., Rödbro P. Selection of routine method for determination of glomerular filtration rate in adult patients. Scand J Clin Lab Invest. 1976 Jan;36(1):35–43. doi: 10.1080/00365517609068016. [DOI] [PubMed] [Google Scholar]
  3. Brøchner-Mortensen J. Current status on assessment and measurement of glomerular filtration rate. Clin Physiol. 1985 Feb;5(1):1–17. doi: 10.1111/j.1475-097x.1985.tb00742.x. [DOI] [PubMed] [Google Scholar]
  4. Erdös E. G. Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture. Hypertension. 1990 Oct;16(4):363–370. doi: 10.1161/01.hyp.16.4.363. [DOI] [PubMed] [Google Scholar]
  5. Harden P. N., Geddes C., Rowe P. A., McIlroy J. H., Boulton-Jones M., Rodger R. S., Junor B. J., Briggs J. D., Connell J. M., Jardine A. G. Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy. Lancet. 1995 Jun 17;345(8964):1540–1542. doi: 10.1016/s0140-6736(95)91088-3. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Levey A. S., Gassman J. J., Hall P. M., Walker W. G. Assessing the progression of renal disease in clinical studies: effects of duration of follow-up and regression to the mean. Modification of Diet in Renal Disease (MDRD) Study Group. J Am Soc Nephrol. 1991 Mar;1(9):1087–1094. doi: 10.1681/ASN.V191087. [DOI] [PubMed] [Google Scholar]
  8. Marre M., Chatellier G., Leblanc H., Guyene T. T., Menard J., Passa P. Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria. BMJ. 1988 Oct 29;297(6656):1092–1095. doi: 10.1136/bmj.297.6656.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mathiesen E. R., Hommel E., Giese J., Parving H. H. Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. BMJ. 1991 Jul 13;303(6794):81–87. doi: 10.1136/bmj.303.6794.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miles D. W., Mogensen C. E., Gundersen H. J. Radioimmunoassay for urinary albumin using a single antibody. Scand J Clin Lab Invest. 1970 Aug;26(1):5–11. doi: 10.3109/00365517009049206. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Puska P., Iacono J. M., Nissinen A., Korhonen H. J., Vartianinen E., Pietinen P., Dougherty R., Leino U., Mutanen M., Moisio S. Controlled, randomised trial of the effect of dietary fat on blood pressure. Lancet. 1983 Jan 1;1(8314-5):1–5. doi: 10.1016/s0140-6736(83)91556-8. [DOI] [PubMed] [Google Scholar]
  14. Rossing P., Hommel E., Smidt U. M., Parving H. H. Impact of arterial blood pressure and albuminuria on the progression of diabetic nephropathy in IDDM patients. Diabetes. 1993 May;42(5):715–719. doi: 10.2337/diab.42.5.715. [DOI] [PubMed] [Google Scholar]
  15. Tarnow L., Cambien F., Rossing P., Nielsen F. S., Hansen B. V., Lecerf L., Poirier O., Danilov S., Parving H. H. Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients. Diabetes. 1995 May;44(5):489–494. doi: 10.2337/diab.44.5.489. [DOI] [PubMed] [Google Scholar]
  16. Ueda S., Elliott H. L., Morton J. J., Connell J. M. Enhanced pressor response to angiotensin I in normotensive men with the deletion genotype (DD) for angiotensin-converting enzyme. Hypertension. 1995 Jun;25(6):1266–1269. doi: 10.1161/01.hyp.25.6.1266. [DOI] [PubMed] [Google Scholar]
  17. Viberti G., Mogensen C. E., Groop L. C., Pauls J. F. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group. JAMA. 1994 Jan 26;271(4):275–279. [PubMed] [Google Scholar]
  18. Yoshida H., Mitarai T., Kawamura T., Kitajima T., Miyazaki Y., Nagasawa R., Kawaguchi Y., Kubo H., Ichikawa I., Sakai O. Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. J Clin Invest. 1995 Nov;96(5):2162–2169. doi: 10.1172/JCI118270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. van Essen G. G., Rensma P. L., de Zeeuw D., Sluiter W. J., Scheffer H., Apperloo A. J., de Jong P. E. Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy. Lancet. 1996 Jan 13;347(8994):94–95. doi: 10.1016/s0140-6736(96)90213-5. [DOI] [PubMed] [Google Scholar]

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