Recent aspects of antihypertensive treatment in patients with diabetic nephropathy

Authors: Silvester Krčméry 1;  Ľubomír Polaščín 2;  Rastislav Tahotný 1;  Zuzana Gábrišová 1;  Klára Soláriková 1
Authors‘ workplace: II. klinika geriatrie LFUK UNsP Milosrdní bratia a LF UK v Bratislave 1;  FMC – dialyzačné služby, s. r. o., UN Bratislava – Nemocnica Ružinov 2
Published in: Forum Diab 2012; 1(1): 24-31


The occurrence and progression of diabetic nephropathy (DN) is a result of interaction of different metabolic and haemodynamic factors, abnormal stimulation of rennin-angiotensin system (RAS), with the contribution of endothelium dysfunction and reactive oxygen radicals. The increase in intraglomerular pressure is the key haemodynamic abnormality and all therapeutic interventions to decrease intraglomerular hypertension, e.g. RAS inhibitors or low-protein diet, form part of the basic nephroprotective treatment strategy. Microalbuminuria (MAU) is one of the most important parameters in monitoring diabetic patients and is of critical diagnostic, therapeutic and prognostic importance, not only from the nephrological point of view. The main therapeutic interventions include consistent metabolic control of DM and the control of blood pressure. The objective of treatment of manifest diabetic nephropathy is to prevent the progression of diabetic nephropathy to renal failure. Aggressive antihypertensive treatment based on RAS inhibition is the principal objective at this phase.

Kidney Disease Outcome Quality Initiative (K/DOQI) prefers some classes of antihypertensives to prevent the progression of DN. These are primarily ACE-inhibitors (ACEI), angiontensin II AT1-receptor antagonists (sartans; ARB), aliskiren and non-dihydropyridine calcium channel blockers. There are a number of clinical studies which prove the increased benefit of the above groups of antihypertensives for the reduction of proteinuria and slowing down the progression of nephropathy. Also important from the adverse effect point of view is the fact that the above-mentioned antihypertensives have less adverse metabolic effects than diuretics and betablockers. A number of clinical studies suggest that combined ACEI – sartan therapy can be more effective than monotherapy in the reduction of proteinuria and in slowing down the progression to renal insufficiency. Recent findings suggest that only certain groups of patients with diabetic nephropathy (i.e. those with proteinuria > 1g/24 h, with rapidly progressing decrease of glomerular filtration) are eligible for the treatment using such combination. Among potential risks of the ACEI – sartan combination are primarily the worsening of renal anaemia and hyperkaliemia. Aliskiren is the first representative of the new class of antihypertensives with a unique mechanism of action – direct rennin inhibition. Its antihypertensive effect has been proven in both monotherapy and combined treatment of hypertension in nephropathy patients.

Key words:
diabetic nephropathy – ACE-inhibitors – sartans – aliskiren


1. Krčméry S, Tahotný R, Soláriková K, Gábrišová Z, Palfy E. Čo hovoria nové odporúčania o liečbe hypertenzie u pacientov s nefropatiou? Súč klin prax 2011; 9(1): 22–26.

2. Rosolová H. Studie STAR. Lékařské listy 2008, 4: 7–8.

3. Krčméry S, Tahotný R, Soláriková K. Využitie nefroprotektívnych účinkov ACE inhibítorov a sartanov – kedy ich indikovať ? Interná medicína 2006; 6(10): 525–530.

4. Krčméry S, Dukát A, Murín J. Aktuálne problémy internej medicíny – nefrológie. Via Practica 2007; 4(11): 540–542.

5. Ďuriš I, Hulín I, Bernadič M. Princípy internej medicíny. Bratislava, SAP 2001: 588–596, 1253–1257.

6. The BENEDICT Group (Ruggenenti P et al). The BErgamo Nephrologic DIabetes Complications Trial. N Engl J Med 2004; 351(19): 1934–1936.

7. Gajdoš M. Miesto inhibítorov angiotenzín konvertujúceho enzýmu v klinickej praxi. Edukafarm medinews 2005; 2: 122–125.

8. Vítovec J, Špinar J a kolektív. Farmakoterapie kardiovaskulárních onemocnění 2. vydání. Praha: Grada Publishing 2004.

9. Databáza AISLP. Dostupné z

10. Guidelines Committee: 2003 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension 2003; 21(5): 1011–1053.

11. Phillips PA, Hodsman GP, Johnston CI. Neuroendocrine mechanisms and cardiovascular homeostasis in the elderly. Cardiovasc Drugs Ther 199; 4(Suppl 6): 1209–1213.

12. Voors AA, Ruilope LM. Angiotensin receptor blockers in 2005. An expanding area in cardiovascular and renal disease. Academic Pharmaceuticals Productions, Utrecht 2005.

13. Momga S, Kaplan NM. Hypertension and renin angiotensin system. New York: Pergamon Press 1998.

14. Wolf G, Ritz E. Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int 2005; 67(3): 799–812.

15. Nakao N, Yoshimura A, Morita H et al. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting enzyme inhibitor in non-diabetic renal disease (COOPERATE): A randomized controlled trial. Lancet 2003; 361(9364): 117–124.

16. Iodice C, Balletta MM, Minutolo R et al: Maximal suppression of renin – angiotensin system in nonproliferative glomerulonephritis. Kidney Int 2003; 63(6): 2214–2221.

17. National kidney foundation k/doqi guidelines 2010. Dostupné z:

18. Prehodnotenie Európskych odporúčaní manažmentu hypertenzie: Dokument Pracovnej skupiny Európskej hypertenziologickej spoločnosti. Kardiológia 2010; 19(2): 147–153.

19. National kidney foundation k/doqi guidelines 2010. Dostupné z:

20. Zoccali V, Valvo E, Russo D et al. Antiproteinuric effect of losartan in patients with renal diseases. Nephrol Dial Transplant 1997; 12(1): 234–235.

21. Russo D, Pisani A, Balletta MM et al. Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis 1999; 33(5): 851–856.

22. Mogensen CE, Neldam S, Tikkanen I et al. Randomized 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 2000; 321(7274): 1440–1444.

23. Russo D, Minutolo R, Pisani A et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effects in IgA nephropathy. Am J Kidney Dis 2001; 38(1): 18–25.

24. Luno J, Barrio V, Goicoechea A et al. Effects of dual blockade of the rein-angiotensin system in primary proteinuric nephropathiens. Kidney Int 2002; 62(Suppl 82): S47–S52.

25. Rossing K, Christensen PK, Jensen BR, Parving HH. Dual blockade of the renin – angiotensin system in diabetic nephropathy. Diabetes Care 2002; 25(1):95–100.

26. Berger ED, Bader BD, Ebert C et al. Reduction of proteinuria; combined effects of receptor blockade and low dose angiotensin converting enzyme inhibition. J Hypertens 2002; 20(4):739–743.

27. Laverman GD, Navis G. Henning RH et al. Dual renin angiotensin system blockade at a optimal doses for proteinuria. Kidney Int 2002; 62(3): 1020–1025.

28. Jacobsen P, Andersen S, Rossing K et al. Dual blockade of the renin – angiotensin system in type 1 patients with diabetic nephropathy. Nephrol Dial Transplant 2002; 17(6): 1019–1024.

29. Kincaid–Smith P, Fairley K, Packham D. Randomized controlled crossover study of the effect on proteinuria and blood pressure of adding an angiotensin II receptor antagonist to an angiotensin converting enzyme inhibitor in normotensive patients with chronic renal disease and proterinuria. Nephrol Dial Transplant 2002; 17(4): 597–601.

30. Ferrari P, Marti HP, Pfister M, Frey FJ. Additive antiproteinuric affect of combined ACE inhibition and angiotensin II receptor blockade. J Hypertens 2002; 20(1): 125–130.

31. Renke M, Tylicki L, Rutkowski P et al. Low-dose angiotensin II receptor antagonists and angiotensin II-converting enzyme inhibitors alone or in combination for treatment of primary glomerulonephritis. Scand J Urol Nephrol 2004; 38(5): 427– 433.

32. Seung HH, Sang-Jin L, Byung Chun O et al. The additive beneficial effects of ramipril combined with candesartan in hypertensive patients on insulin resistance, Plasma Adiponectin. Korean Circ J 2007; 37(4): 173–179.

33. Yusuf S, Koon KT, Pogue J et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358(15): 1547–1559.

34. Mancia G et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009, 27(11): 2121–2158.

35. Rouleau JL, Packer M, Moyé L et al. Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of captopril. J Am Coll Cardiol 1994; 24(3): 583–591.

36. Latini R, Masson S, Anand I et al. For the Val-HeFT Investigators. The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT. Eur Heart J 2004; 25(4): 292–299.

37. Vergaro G, Fontana M, Poletti R et al. Plasma renin activity is an independent prognostic factor in chronic heart failure. Eur Heart J 2008; 29(Suppl): 393 [Abstract].

38. Bair TL, May HT, Prescott MF et al. Association between baseline levels of plasma renin activity and risk of cardiovascular events. J Am Coll Cardiol 2009; 53(10 Suppl A): 383 [Abstract].

39. Parving HH, Persson F, Lewis JB et al. Aliskiren combined with losartan in Type 2 diabetes and nephropathy. N Engl J Med 2008; 358(23): 2433–2446.

40. Price DA et al. The state and responsiveness of the renin-angiotensin-aldosterone system in patients with type II diabetes mellitus. Am J Hypertens 1999; 12(4): 348–355.

41. Gordon et al. Blunted suppression of plasma renin activity in diabetes J Renin Angiotensin Aldosterone Syst 2000; 1(3): 252–256.

42. Parving HH et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrol Dial Transplant 2009; 24(5): 1663–1671.

43. Parving HH et al. Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Published online 14 February 2012 Journal of Renin-Angiotensin-Aldosterone System DOI: 10.1177/1470320311434818.

44. Komers R, Kvapil M. Diabetická nefropatie. In: Teplan V (ed). Praktická nefrologie. Praha: Grada Publishing 2006: 269–294.

Diabetology Endocrinology Internal medicine
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account