Advertisement

Central European Journal of Medicine

, Volume 8, Issue 3, pp 302–309 | Cite as

Intensive treatment of persistent microalbuminuria: determinants of treatment resistance

  • Nicolas Roberto Robles
  • Joaquin Velasco
  • Candido Mena
  • Enrique Angulo
  • the MICREX Group Investigators
Research Article
  • 47 Downloads

Abstract

Aims

Persistent microalbuminuria after treatment is a common finding. This study tried to evaluate the causes of treatment resistance.

Patients and methods

Sample: 204 patients treated with renina-angiotensin-axis (RAA) blocking drugs that showed positive microalbuminuria. Treatment was increased during three months to reach a BP < 130/80 mmHg and to obtain maximal RAA blockade. Then patient were classified as normoalbuminuric after treatment (N group) and microalbuminuric in spite of treatment (M).

Results

Mean microalbuminuria at recruitment was 48.5±25.6 mg/24h in N group and 90.0±140.3 mg/24h in M group. It was reduced to 16.1±10.0 mg/day in N group and to 83.5±138.2 mg/day in M group. At start, mean SBP and mean DBP were not different between groups. After treatment SBP and DBP pressure were reduced in both groups (differences between groups were not significant). Combined control of BP showed a slight increase in the two groups but it have only statistical significance in the N group (p = 0.031, McNemar test).

Conclusions

Persistent microalbuminuria seems to be associated to poor blood pressure control. Effective blood pressure reduction was followed by urinary albumin excretion decrease. Baseline severity of microalbuminuria was the only clear predictor of remission after treatment.

Keywords

Microalbuminuria Hypertension Remission Response to treatment 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Dinneen SF, Gerstein HC: The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med 1997; 157:1413–1418.PubMedCrossRefGoogle Scholar
  2. [2]
    Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR, UKPDS Group: Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003; 63:225–232PubMedCrossRefGoogle Scholar
  3. [3]
    Mogensen CE: Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes. J Intern Med 2003; 254:45–66PubMedCrossRefGoogle Scholar
  4. [4]
    Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286:421–426PubMedCrossRefGoogle Scholar
  5. [5]
    Jensen JS, Feldt-Rasmussen B, Strandgaard S, Schroll M, Borch-Johnsen K. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension 2000; 35:898–903PubMedCrossRefGoogle Scholar
  6. [6]
    Bigazzi R, Bianchi S, Baldari D, Campese VM. Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension. J Hypertens 1998; 16:1325–1333PubMedCrossRefGoogle Scholar
  7. [7]
    Hillege HL, Fidler V, Diercks GFH, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, et al. for the Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002; 106:1777–1782PubMedCrossRefGoogle Scholar
  8. [8]
    Robles NR, Mena C, Velasco J, Angulo E, Garrote T, Garcia Gallego F, en representación de los investigadores del estudio MICREX Riesgo cardiovascular asociado a microalbuminuria en pacientes diabéticos y en pacientes con hipertensión arterial. Med. Clin. (Barc.). 2008;130: 206–209CrossRefGoogle Scholar
  9. [9]
    The Seventh Report of Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003; 289:2560–2572Google Scholar
  10. [10]
    Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007; 25: 1105–1187PubMedCrossRefGoogle Scholar
  11. [11]
    Chan JC, Ko GT, Leung DH, Cheung RC, Cheung MY, So WY, Swaminathan R, Nicholls MG, Critchley JA, Cockram CS: Long-term effects of angiotensinconverting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. Kidney Int 2000; 57:590–600PubMedCrossRefGoogle Scholar
  12. [12]
    Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P, Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345:870–878PubMedCrossRefGoogle Scholar
  13. [13]
    Viberti G, Wheeldon NM, MicroAlbuminuria Reduction with VALsartan (MARVAL) Study Investigators: Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002; 106:672–678PubMedCrossRefGoogle Scholar
  14. [14]
    Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS: Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003; 348:2285–2293PubMedCrossRefGoogle Scholar
  15. [15]
    Robles NR, Velasco J, Mena C, Angulo E, Garrote T, en representación de los investigadores del estudio MICREX Microalbuminuria en pacientes diabéticos y en pacientes con hipertensión arterial: estudio de una cohorte de 979 pacientes. Med. ClÍn. (Barc). 2006; 127: 761–764CrossRefGoogle Scholar
  16. [16]
    Robles NR, Velasco J, Espinosa J, Mena C, Angulo E, on behalf of the MICREX Group Investigators. Persistent microalbuminuria after treatment with renin-angiotensin axis blockers; causes and results of treatment intensification. J. Renin Angiotensin System. 2011; 12: 333–339CrossRefGoogle Scholar
  17. [17]
    Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).J Hypertens. 2007; 25: 1105–1187PubMedCrossRefGoogle Scholar
  18. [18]
    American Diabetes Association. Standards of Medical Care in Diabetes-2007. Diabetes Care. 2007; 30(Suppl. 1); S4–S41CrossRefGoogle Scholar
  19. [19]
    The Seventh Report of Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289:2560–2572Google Scholar
  20. [20]
    Pontremoli R, Sofia A, Tirotta A, Ravera M, Nicotella C, Viazzi F et al. The deletion polymorphism of the angiotensin-1 converting enzyme gene is associated with target organ damage in essential hypertension. J Am Soc Nephrol 1996; 7:2250–2258Google Scholar
  21. [21]
    Deckert T, Kofoed-Enevoldsen A, Videl P, Norgaard K, Andreasen HB, Feldt-Rasmussen B. Size and charge selection in glomerular ®ltration in Type 1 diabetic patients with and without albuminuria. Diabetologia 1993; 36: 244–251PubMedCrossRefGoogle Scholar
  22. [22]
    Bianchi S, Bigazzi R, Campese VM, Microalbuminuria in Essential Hypertension: Significance, Pathophysiology, and Therapeutic Implications. Am J Kidney Dis. 1999; 34: 973–995PubMedCrossRefGoogle Scholar
  23. [23]
    Gosling P, Beevers DG. Urinary albumin excretion in the general population. Clin Sci 1989; 76: 39–42PubMedGoogle Scholar
  24. [24]
    West JN, Gosling P, Dimmit SB, Littler WA. Nondiabetic microalbuminuria in clinical practice and its relationship to posture, exercise and blood pressure. Clin Sci 1991; 81: 373–377PubMedGoogle Scholar
  25. [25]
    Rogus JJ, Warram JH, Krolewski AS. Genetic studies of late diabetic complications. The overlooked importance of diabetes duration before complication onset. Diabetes 2002; 51: 1655–1662Google Scholar
  26. [26]
    Tarnow L. Diabetic nephropathy. Pathogenetic aspects and cardiovascular risk factors. Danish Med Bull 2002; 49: 19–42Google Scholar
  27. [27]
    Mogensen CE. Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes. J Intern Med 2003; 254: 45–66PubMedCrossRefGoogle Scholar
  28. [28]
    Guidelines Committee of the 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 21:1011–1053, 2003Google Scholar
  29. [29]
    Böhm M, Reil JC, Danchin N, Thoenes M, Bramlage P, Volpe M. Association of heart rate with microalbuminuria in cardiovascular risk patients: data from I-SEARCH. J Hypertens. 2008; 26: 18–25PubMedCrossRefGoogle Scholar
  30. [30]
    Erley CM, Haefele U, Heyne N, Braun N, Risler T. Microalbuminuria in essential hypertension. Reduction by different antihypertensive drugs. Hypertension 1993; 21:810±815CrossRefGoogle Scholar
  31. [31]
    Anderson S, Diamond JR, Karnovsky MJ, Brenner BM. Mechanisms underlying transition from acute glomerular injury to late glomerular sclerosis in a rat model of nephrotic sÍndrome. J. Clin. Invest. 1988; 82: 1757–1768PubMedCrossRefGoogle Scholar
  32. [32]
    Anderson S, Brenner BM. Therapeutic benefit of converting-enzyme inhibition in progressive renal disease. Am J Hypertens. 1988; 1(4 Pt 2):380S–383SPubMedGoogle Scholar
  33. [33]
    Fogo A, Yoshida Y, Glick AD, Homma T, Ichikawa I. Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis. J Clin Invest. 1988; 82:322–330PubMedCrossRefGoogle Scholar
  34. [34]
    Lax DS, Benstein JA, Tolbert E, Dworkin LD. Effects of salt restriction on renal growth and glomerular injury in rats with remnant kidneys. Kidney Int. 1992; 41: 1527–1534PubMedCrossRefGoogle Scholar
  35. [35]
    Hsueh WA, Do YS, Anderson PW, Law RE. Angiotensin II in cell growth and matrix production. Adv Exp Med Biol. 1995; 377: 217–223PubMedCrossRefGoogle Scholar
  36. [36]
    Ritz E, Viberti GC, Ruilope LM, Rabelink AJ, Izzo JL Jr, Katayama S, et al. Determinants of urinary albumin excretion within the normal range in patients with type 2 diabetes: the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. Diabetologia. 2010; 53: 49–57PubMedCrossRefGoogle Scholar
  37. [37]
    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
  38. [38]
    Afsar B, Sezer S, Elsurer R, Ozdemir FN. Is HOMA index a predictor of nocturnal nondipping in hypertensives with newly diagnosed type 2 diabetes mellitus? Blood Press Monit. 2007; 12: 133–139PubMedCrossRefGoogle Scholar
  39. [39]
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing. Am J Hypertens. 2008; 21: 948–954PubMedCrossRefGoogle Scholar
  40. [40]
    Hermida RC, Calvo C, Ayala DE, Fernández JR, Covelo M, Mojón A, López JE. Treatment of nondipper hypertension with bedtime administration of valsartan. J Hypertens. 2005; 23: 1913–1922PubMedCrossRefGoogle Scholar
  41. [41]
    Kawai T, Ohishi M, Kamide K, Nakama C, Onishi M, Ito N,et al. Differences between daytime and nighttime blood pressure variability regarding systemic atherosclerotic change and renal function. Hypertens Res. 2012 Oct 18. doi: 10.1038/hr.2012.162. [Epub ahead of print]Google Scholar
  42. [42]
    Ulusoy S, Ozkan G, Konca C, Kaynar K. A comparison of the effects of fixed dose vs. single-agent combinations on 24-h blood pressure variability. Hypertens Res. 2012; 35: 1111–1117PubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Nicolas Roberto Robles
    • 1
  • Joaquin Velasco
    • 2
  • Candido Mena
    • 3
  • Enrique Angulo
    • 4
  • the MICREX Group Investigators
  1. 1.Cátedra de Riesgo CardiovascularFacultad de Medicina Universidad de SalamancaSalamancaSpain
  2. 2.Centro de Salud Mérida NorteMéridaSpain
  3. 3.Centro de Salud Jose Maria AlvarezDon BenitoSpain
  4. 4.Centro de Salud Ciudad JardinBadajozSpain

Personalised recommendations