Current Hypertension Reports

, Volume 1, Issue 5, pp 423–430

Importance of blood pressure reduction for prevention of progression of renal disease

  • Stephen C. Textor
  • Vincent J. Canzanello
Article

Abstract

Despite reduction of stroke and coronary mortality rates, progression of renal disease to end stage continues to occur with increasing frequency. Recent studies emphasize common pathways of elevated arterial pressures that produce increased glomerular capillary pressures and increase filtered proteins in the urinary space. Such proteinuria, along with activation of the intrarenal renin-angiotensin system, endothelin, and inflammatory cytokines, magnifies progressive renal injury and fibrosis. Malignant forms of hypertension with severe arteriolar injury and proteinuria can be treated effectively with current antihypertensive regimens with improved patient survival. Several recent studies indicate improved renal outcomes in proteinuric diseases, generally regardless of the specific antihypertensive agent. Recent trials of hypertensive subjects with minimal proteinuria demonstrate slower rates of disease progression than that seen in subjects with proteinuria above 1 gram per day. Reduction of arterial pressures, particularly when it leads to reduced proteinuria, can slow the progression of many renal diseases.

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References and Recommended Reading

  1. 1.
    JNC Committee: Sixth Report of the Joint National Committee on Prevention, detection, evaluation and treatment of high blood pressure. Bethesda, MD: NIH Publication, 1997.Google Scholar
  2. 2.
    Buckalew VM, Berg RL, Wang SR, et al.: Prevalence of hypertension in 1795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Am J Kidney Dis 1996, 28:811–821.PubMedGoogle Scholar
  3. 3.
    Cowley Aw, Roman RJ: The role of the kidney in hypertension. JAMA 1996, 275:1581–1589.PubMedCrossRefGoogle Scholar
  4. 4.
    Converse RL, Jacobsen TN, Toto RD, et al.: Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 1992, 327:1912–1918.PubMedCrossRefGoogle Scholar
  5. 5.
    DiBona G: Central sympathoexcitatory actions of angiotensin II: role of type 1 angiotensin II receptors. J Am Soc Nephrol 1999, 10:S90-S94.PubMedGoogle Scholar
  6. 6.
    Johnston CI, Risvanis J, Naitoh M, Tikkanen I: Mechanism of progression of renal disease: current hemodynamic concepts. J Hypertens 1998, 16(suppl 4):S3-S7. Brief but good review of current concepts related to end-stage renal disease progression. The hemodynamic argument is that elevated glomerular capillar pressures produce injury. This review argues that endothelial cell stretch in glomerulus, capable of releasing angiotensin II, vasopressin, endothelin, and catecholamines. Reviews data that these substances may activate cytokines and modulate TI fibrosis and extracellular matrix formation.Google Scholar
  7. 7.
    Arendhorst WJ, Brannstrom K, Ruan X: Actions of angiotensin II on the renal microvasculature. J Am Soc Nephrol 1999, 10:S149-S161.Google Scholar
  8. 8.
    Ligtenberg G, Blankestijn PJ, Oey PL, et al.: Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med 1999, 340:1321–1328. Remarkable clinical investigation in patients with chronic renal failure. Elevated sympathetic nerve activity (confirmed by measurement of nerve traffic) could be diminished by enalapril therapy. A shift in the baroreflex curve to near normal occurred during ACE inhibition, but not during administration of calcium-channel blocker (amlodipine). Provides convincing data regarding interaction between renal disease and sympathetic nervous system.PubMedCrossRefGoogle Scholar
  9. 9.
    Weinrauch LA, Kennedy FP, Gleason RE, et al.: Relationship between autonomic function and progression of renal disease in diabetic proteinuria: clinical correlations and implications for blood pressure control. Am J Hypertens 1998, 11:302–308.PubMedCrossRefGoogle Scholar
  10. 10.
    Remuzzi G: Sympathetic overactivity in hypertensive patients with chronic renal disease. N Engl J Med 1999, 340:1360–1361.PubMedCrossRefGoogle Scholar
  11. 11.
    Fortepiani LA, Rodrigo E, Cachofeiro MCOV, et al.: Pressure natriuresis in nitric oxide-deficient hypertensive rats: effect of antihypertensive treatments. J Am Soc Nephrol 1999, 10:21–27.PubMedCrossRefGoogle Scholar
  12. 12.
    Mountokalakis TD: The renal consequences of arterial hypertension. Kidney Int 1997, 51:1639–1653. Nice review of issues related to progressive renal injury attributed to hypertension. Makes case that early untreated trials establish risks of renal failure in patients with hypertension. Recent treated groups with mild hypertension have low, but definite, incidence of renal disease (tends to accept the concept of renal injury from mildhypertension).PubMedCrossRefGoogle Scholar
  13. 13.
    Whelton PK, He J, Perneger TV, Klag MJ: Kidney damage in "benign" essential hypertension. Curr Opin Nephrol Hypertens 1997, 6:177–183.PubMedCrossRefGoogle Scholar
  14. 14.
    Hunsicker LG, Adler S, Caggiula A, et al.: Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. Kidney Int 1997, 51:1908–1919. Reanalysis of (n=840) patients in MDRD. Multivarate analysis of disease progression argues that urine protein, polycystic kidney disease lower serum transferrin, mean arterial pressure, African American race, and lower high-density lipoproteins independently predicted decline in glomerular filtration rate. Urine protein predicted benefit of blood pressure reduction.PubMedCrossRefGoogle Scholar
  15. 15.
    Clark WF, Moist LM: Management of chronic renal insufficiency in lupus nephritis: role of proteinuria, hypertension and dyslipidemia in the progression of renal disease [abstract]. Lupus 1998, 7:649–653.PubMedCrossRefGoogle Scholar
  16. 16.
    Lip GYH, Beevers M, Beevers G: The failure of malignant hypertension to decline: a survey of 24 years experience in a multiracial population in England. J Hypertens 1994, 12:1297–1305.PubMedCrossRefGoogle Scholar
  17. 17.
    Scarpelli PT, Livi R, Maselli G, et al.: Accelerated (malignant) hypertension: a study of 121 cases between 1974 and 1996. J Nephrol 1997, 9:207–215. Series of 121 cases, n = 47 with essential hypertension, the rest with secondary forms, including chonic renal disease. Demonstrated relationship between successful blood pressure reduction and preserved renal function if initial creatinine was < 2.0 mg/dL. Improved 6-year survival was noted in patients treated after the introduction of newer antihypertensive agents (after 1980: 100% survival) as compared to 77% in earlier eras.Google Scholar
  18. 18.
    Madhavan S, Stockwell D, Cohen H, Alderman MH: Renal function during antihypertensive treatment. Lancet 1995, 345:749–751.PubMedCrossRefGoogle Scholar
  19. 19.
    Weisstuch JM, Dworkin LD: Does essential hypertension cause end-stage renal disease? Kidney Int 1992, 41:S38-S42.Google Scholar
  20. 20.
    Flizer D, Ritz E: Does essential hypertension cause progressive renal disease? J Hypertens 1998, 16(suppl 4):S13-S15.Google Scholar
  21. 21.
    Sorof JM, Sullivan EK, Tejani A, Portman RJ: Antihypertensive medication and renal allograft failure: a North American Pediatric Renal Transplant Cooperative Study Report. J Am Soc Nephrol 1999, 10:1324–1330.PubMedGoogle Scholar
  22. 22.
    Bauer JH: Modern antihypertensive treatment and the progression of renal disease [abstract]. J Hypertens 1998, 16(suppl 5):S17-S24.Google Scholar
  23. 23.
    Remuzzi G, Bertani T: Pathophysiology of progressive nephropathies. N Engl J Med 1998, 339:1448–1456. Excellent review of interaction between forms of reduced renal mass and activation of cytokine pathways, including upregulation of transforming growth factor-βΧ, increased fibrogenesis, and other mechanisms in progressive renal disease. Strong case for role of proteinuria in accelerating interstitial inflammation. Paradigm of injury magnified by lipoproteins, which induce tubulointerstitial inflammatory response, potentially via ischemic obliteration of post-glomerular capillaries.PubMedCrossRefGoogle Scholar
  24. 24.
    Verhagen AMG, Rabelink TJ, Braam B, et al.: Endothelin A receptor blockade alleviates hypertension and renal lesions associated with chronic nitric oxide synthase inhibition. J Am Soc Nephrol 1998, 9:755–762.PubMedGoogle Scholar
  25. 25.
    Border WA, Noble NA: Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension 1998, 31[part 2]:181–188. Excellent review of interactions between angiotensin II and transforming growth factor-βЗ (TGF-βЗ). The authors argue that failure to terminate TGF-βΧ is a hallmark distinguishing healing from fibrogenic disease, and postulate that most cytokine effects attributed to angiotensin II are probably mediated by TGF-βΧ. Numerous studies argue for interaction between angiotensin II and TGF-βΧ, primarily by results of angiotensin II blockade.PubMedGoogle Scholar
  26. 26.
    Suzuki D, Miyata T, Saotome N, et al.: Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. J Am Soc Nephrol 1999, 10:822–832.PubMedGoogle Scholar
  27. 27.
    Giatras I, Lau J, Levey AS: Effect of angiotensin-converting enzyme inhibitors on the progression of non-diabetic renal disease: a meta-analysis of randomized trials. Ann Intern Med 1997, 127:337–345.PubMedGoogle Scholar
  28. 28.
    Ots M, Mackenzie HS, Troy JL, et al.: Effects of combination therapy with enalapril and losartan on the rate of progression of renal injury in rats with 5/6 renal mass ablation. J Am Soc Nephrol 1998, 9:224–230.PubMedGoogle Scholar
  29. 29.
    Ruggenenti P, Perna A, Mosconi M, et al.: The angiotensin converting enzyme inhibitor ramipril slows the rate of GFR decline and the progression to end-stage renal failure in proteinuric, non-diabetic chronic renal diseases [abstract]. J Am Soc Nephrol 1997, 8:147A.Google Scholar
  30. 30.
    Ruggenenti P, Perna A, Benini R, et al.: In chronic nephropathies prolonged ACE inhibition can induce remission: dynamics of time-dependent changes in GFR. J Am Soc Nephrol 1999, 10:997–1006.PubMedGoogle Scholar
  31. 31.
    Wilmer WA, Hebert LA, Lewis EJ, et al.: Long-term follow-up of eight patients with diabetic nephropathy who experienced remission of nephrotic syndrome during the captopril study [abstract]. J Am Soc Nephrol 1997, 8:120A-121A.Google Scholar
  32. 32.
    Bakris GL: The role of combination antihypertensive therapy and the progression of renal disease. Am J Hypertens 1998, 11:158S-162S.PubMedCrossRefGoogle Scholar
  33. 33.
    Nosadini R, Brocco E, Saller A, et al.: Renal function in noninsulin-dependent diabetes mellitus patients treated with angiotensin-converting eznyme inhibitors and calcium channel blockers. J Hypertens 1998, 16(suppl 4):S27-S32.Google Scholar
  34. 34.
    UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998, 317:703–713. Risk reductions in patients with type II diabetes with improved blood pressure were 24% in diabetes-related end points, 32% reduction in death from diabetes mellitus, 44% in cerebrovascular accident, 37% fewer microvascular end points, including reduced need for photocoagulation. Importantly, 29% of subjects required three or more drugs for "tight" control (11% for "less tight" control); note that risk reduction was greater for blood pressure control than tight blood glucose control. Relatively few cases of progressive renal failure were seen, although progression of microalbuminuria was delayed by effective blood pressure reduction.Google Scholar
  35. 35.
    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, 317:713–720.Google Scholar
  36. 36.
    Susic D, Frohlich ED: Nephroprotective effect of antihypertensive drugs in essential hypertension. J Hypertens 1998, 16:555–567. Excellent general review of the renal effects of antihypertensive agents and their putative effects in experimental, and where available, clinical hypertension. Emphasizes that all studies require reduction of pressure for optimal effects, and that specific nephroprotective effects in clinical trials have been indistinguishable from improved blood pressure control.PubMedCrossRefGoogle Scholar
  37. 37.
    Estacio R, Jeffers BW, Hiatt WR, et al.: The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin dependent diabetes and hypertension. N Engl J Med 1998, 338:645–652.PubMedCrossRefGoogle Scholar
  38. 38.
    Tatti P, Pahor M, Byington RP, et al.: Outcome results of the Fosinopril versus Amlodipine Cardiovascular Events randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care 1998, 21:597–603.PubMedCrossRefGoogle Scholar
  39. 39.
    Hansson L, Zanchetti A, Carruthers SG, et al.: Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results in the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998, 351:1755–1762.PubMedCrossRefGoogle Scholar
  40. 40.
    Haley WE, Harris TM, Tucker CT, Zachariah PK: Defining the relationship between blood pressure and target organ damage: the HOT target organ substudy [abstract]. Am J Hypertens 1999, 12:81A.CrossRefGoogle Scholar
  41. 41.
    Klahr S: Prevention of progression in nephropathy. Nephrol Dial Transplant 1997, 12(suppl 2):63–66.PubMedGoogle Scholar
  42. 42.
    Hebert LA, Kusek JW, Greene T, et al.: Effects of blood pressure control on progressive renal disease in blacks and whites. Hypertension 1997, 30(part 1):428–435. Subset analysis of MDRD trial comparing black patients with whites patients: 53 black versus 495 white patients with a glomerular filtration rate (GFR) between 25 and 55 mL/min; 28% of black patients had hypertension as the primary renal diagnosis (vs 16% of white patients). The authors claim that in black patients only, an overall lower rate of GFR decline was noted with low blood pressure (65%), although this was blunted by reduced GFR in first months of trial. Despite limited numbers, overall conclusion is supportive of vigorous antihypertensive therapy in black patients to retard disease progression, at least until results of AASKD are available. Most striking effects were observed in those with high urine protein, consistent with overall trial results.PubMedGoogle Scholar
  43. 43.
    Toto RD, Mitchell HC, Smith RD, et al.: "Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis. Kidney Int 1995, 48:851–859.PubMedCrossRefGoogle Scholar
  44. 44.
    Staessen JA, Fagard R, Thijs L, et al.: Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997, 350:757–764.PubMedCrossRefGoogle Scholar
  45. 45.
    Tuomilehto J, Rastenyte D, Birkenhager WH, et al.: Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. N Engl J Med 1999, 340:677–684.PubMedCrossRefGoogle Scholar
  46. 46.
    Berlowitz DR, ASh AS, Hickey EC, et al.: Inadequate management of blood pressure in a hypertensive population. N Engl J Med 1998, 339:1957–1963. Evaluation of 800 veterans over 2 years: mean age, 65.5years; 40% had blood pressure > 160/90 mm Hg, despite more than six blood presure-related visits. Only 6.7% had increased therapy during this period; these patients had a blood pressure reduction by 6.3 mm Hg, whereas less intensive Rx was associated with a 4.8 mm Hg rise in blood pressure. The authors argue that these data reflected a failure on the part of physicians to aggressively treat hypertension. Note: 59% were on two or more drugs.PubMedCrossRefGoogle Scholar
  47. 47.
    Textor SC: Revascularization in atherosclerotic renal artery disease. Kidney Int 1998, 53:799–811.PubMedGoogle Scholar
  48. 48.
    Chen R, Novick AC, Pohl M: Reversible renin mediated massive proteinuria successfully treated by nephrectomy. J Urol 1995, 153:133–134.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science, Inc 1999

Authors and Affiliations

  • Stephen C. Textor
    • 1
  • Vincent J. Canzanello
    • 1
  1. 1.Division of HypertensionMayo ClinicRochesterUSA

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