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  • Review Article
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Managing kidney disease with blood-pressure control

Nature Reviews Nephrology volume 7, pages 434–444 (2011)Cite this article

Subjects

Abstract

The progression of chronic kidney disease (CKD) is largely independent of the underlying kidney disorder once renal function has fallen below a critical level. Hypertension is an independent risk factor for disease progression in both adult and pediatric patients with kidney disorders. Increasing evidence from clinical trials indicates that the rate of CKD progression can be lowered by pharmacological interventions. Nephroprotective strategies currently focus on the blockade of the renin–angiotensin system. Angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers provide efficient control not only of blood pressure, but also of proteinuria, an effect associated with improved long-term nephroprotection compared with other antihypertensive drug classes. In addition, evidence for an additional nephroprotective advantage of tight blood-pressure control towards the low–normal range in young patients and patients with proteinuria is emerging. In this Review, we describe the role of hypertension in CKD and discuss the therapeutic principle of the prevention of CKD progression with antihypertensive agents.

Key Points

  • Hypertension and proteinuria are the most important independent risk factors for disease progression in both adult and pediatric patients with chronic kidney disease (CKD)

  • Pharmacological intervention can slow the rate of renal-disease progression

  • Blockade of the renin–angiotensin system should be the first-line pharmacological intervention in progressive CKD

  • Tight blood-pressure control exerts a beneficial effect on CKD progression in patients with proteinuria

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Figure 1: Effect of residual proteinuria on renal survival in pediatric CKD.
Figure 2: Effect of strict blood-pressure control on renal survival.
Figure 3: Late proteinuria escape despite persistent blood-pressure control owing to partial secondary resistance to ACE inhibition.

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References

  1. Klag, M. J. et al. Blood pressure and end-stage renal disease in men. N. Engl. J. Med. 334, 13–18 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Iseki, K., Ikemiya, Y., Iseki, C. & Takishita, S. Proteinuria and the risk of developing end-stage renal disease. Kidney Int. 63, 1468–1474 (2003).

    Article  PubMed  Google Scholar 

  3. Locatelli, F. et al. Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italien Cooperative Study Group. Nephrol. Dial. Transplant. 11, 461–467 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Remuzzi, G., Benigni, A. & Remuzzi, A. Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J. Clin. Invest. 116, 288–296 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ardissino, G. et al. Epidemiology of chronic renal failure in children: Data from the ItalKid Project. Pediatrics 111, e382–e387 (2003).

    Article  PubMed  Google Scholar 

  6. Celedón, C. G., Bitsor, M. & Tullus, K. Progression of chronic renal failure in children with dysplastic kidneys. Pediatr. Nephrol. 22, 1014–1020 (2007).

    Article  Google Scholar 

  7. Hostetter, T. H., Olson, J. L., Rennke, H. G., Venkatachalam, M. A. & Brenner, B. M. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am. J. Physiol. 241, F85–F93 (1981).

    CAS  PubMed  Google Scholar 

  8. Zandi-Nejad, K., Luyckx, V. A. & Brenner, B. M. Adult hypertension and kidney disease: the role of fetal programming. Hypertension 47, 502–508 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Takano, T. & Brady, H. R. The endothelium in glomerular inflammation. Curr. Opin. Nephrol. Hypertens. 4, 277–286 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Malek, A. M., Greene, A. L. & Izumo, S. Regulation of endothelin 1 gene by fluid shear stress is transcriptionally mediated and independent of protein kinase C and cAMP. Proc. Natl Acad. Sci. USA 90, 5999–6003 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lee, L. K., Meyer, T. W., Pollock, A. S. & Lovett, D. H. Endothelial cell injury initiates glomerular sclerosis in the rat remnant kidney. J. Clin. Invest. 96, 953–964 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Remuzzi, G. & Bertani, T. Pathophysiology of progressive nephropathies. N. Engl. J. Med. 339, 1448–1456 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Olbricht, C. J., Cannon, L. K., Garg, L. C. & Tisher, C. C. Activities of cathepsins B and L in isolated nephron segments from proteinuric and nonproteinuric rats. Am. J. Physiol. 250, F1055–F1062 (1986).

    CAS  PubMed  Google Scholar 

  14. Peterson, J. C. et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann. Intern. Med. 123, 754–762 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Hirschberg, R. & Wang, S. Proteinuria and growth factors in the development of tubulointerstitial injury and scarring in kidney disease. Curr. Opin. Nephrol. Hypertens. 14, 43–52 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Wang, S. N., Lapage, J. & Hirschberg, R. Glomerular ultrafiltration and apical tubular action of IGF-1, TGF-β, and HGF in nephrotic syndrome. Kidney Int. 56, 1247–1251 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. Wang, S. N. & Hirschberg, R. Growth factor ultrafiltration in experimental diabetic nephropathy contributes to interstitial fibrosis. Am. J. Physiol. Renal Physiol. 278, F554–F560 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Donadelli, R. et al. Protein traffic activates NF-κB gene signaling and promotes MCP-1-dependent interstitial inflammation. Am. J. Kidney Dis. 36, 1226–1241 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Morigi, M. et al. Protein overload-induced NF-κB activation in proximal tubular cells requires H2O2 through a PKC-dependent pathway. J. Am. Soc. Nephrol. 13, 1179–1189 (2002).

    CAS  PubMed  Google Scholar 

  20. Zoja, C. et al. Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins. Am. J. Kidney Dis. 26, 934–941 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Kees-Folts, D., Sadow, J. L. & Schreiner, G. F. Catabolism of albumin is associated with the release of an inflammatory lipid. Kidney Int. 45, 1697–1709 (1994).

    Article  CAS  PubMed  Google Scholar 

  22. Zoja, C. et al. Protein overload stimulates RANTES production by proximal tubular cells depending on NF-κB activation. Kidney Int. 53, 1608–1615 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Schalenkamp, M. A. & Danser, A. H. Angiotensin II production and distribution in the kidney: I. A kinetic model. Kidney Int. 69, 1543–1552 (2006).

    Article  CAS  Google Scholar 

  24. Schalenkamp, M. A. & Danser, A. H. Angiotensin II production and distribution in the kidney—II. Model-based analysis of experimental data. Kidney Int. 69, 1553–1557 (2006).

    Article  CAS  Google Scholar 

  25. Navar, L. G. & Nishiyama, A. Why are angiotensin concentrations so high in the kidney? Curr. Opin. Nephrol. Hypertens. 13, 107–115 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Schmitz, D. & Berk, B. C. Angiotensin II signal transduction stimulation of multiple mitogen activated protein kinase pathways. Trends Endocrinol. Metab. 8, 261–266 (1997).

    Article  CAS  PubMed  Google Scholar 

  27. Nitschke, R. et al. Angiotensin II increases the intracellular calcium activity in podocytes of the intact glomerulus. Kidney Int. 57, 41–49 (2000).

    Article  CAS  PubMed  Google Scholar 

  28. Bohrer, M. P., Deen, W. M., Robertson, C. R. & Brenner, B. M. Mechanism of the angiotensin II-induced proteinuria in the rat. Am. J. Physiol. 233, F13–F21 (1977).

    CAS  PubMed  Google Scholar 

  29. Yoshioka, T. et al. Role of antiotensin II in overt functional proteinuria. Kidney Int. 52, 687–693 (1997).

    Article  Google Scholar 

  30. Taal, M. W., Omer, S. A., Nadim, M. K. & Mackenzie, H. S. Cellular and molecular mediators in common pathway mechanisms of chronic renal disease progression. Curr. Opin. Nephrol. Hypertens. 9, 323–331 (2000).

    Article  CAS  PubMed  Google Scholar 

  31. Taal, M. W. et al. Mechanisms underlying renoprotection during renin-angiotensin system blockade. Am. J. Physiol. Renal Physiol. 280, F343–F355 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Converse, R. L. et al. Sympathetic overactivity in patients with chronic renal failure. N. Engl. J. Med. 327, 1912–1918 (1992).

    Article  PubMed  Google Scholar 

  33. Hausberg, M. et al. Sympathetic nerve activity in end-stage renal disease. Circulation 165, 1974–1979 (2002).

    Article  Google Scholar 

  34. Bakris, G. L. et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am. J. Kidney Dis. 36, 646–661 (2000).

    Article  CAS  PubMed  Google Scholar 

  35. Bakris, G. L. et al. Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Arch. Intern. Med. 15, 1555–1565 (2003).

    Article  Google Scholar 

  36. Ohkubo, T. et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J. Hypertens. 20, 2183–2189 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Ligtenberg, G. et al. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N. Engl. J. Med. 340, 1321–1328 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Kimura, G., Dohi, Y. & Fukuda, M. Salt sensitivity and circadian rhythm of blood pressure: the keys to connect CKD with cardiovascular events. Hypertens. Res. 33, 515–520 (2010).

    Article  PubMed  Google Scholar 

  39. Jacob, P., Hartung, R., Bohlender, J. & Stein, G. Utility of 24-h ambulatory blood pressure measurement in a routine clinical setting of patients with chronic renal disease. J. Hum. Hypertens. 18, 745–751 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Timio, M. et al. 'Non-dipper' hypertensive patients and progressive renal insufficiency: a 3-year longitudinal study. Clin. Nephrol. 43, 382–387 (1995).

    CAS  PubMed  Google Scholar 

  41. Agarwal, R., Kariyanna, S. S. & Light, R. P. Prognostic value of circadian blood pressure variation in chronic kidney disease. Am. J. Nephrol. 30, 547–553 (2009).

    Article  PubMed  Google Scholar 

  42. Tarver-Carr, M., Brancati, F., Eberhardt, M. & Powe, N. Proteinuria and the risk of chronic kidney disease (CKD) in the United States. J. Am. Soc. Nephrol. 11, 168A (2000).

    Google Scholar 

  43. Hoy, W. E., Wang, Z., vanBuynder, P., Baker, P. R. & Mathews, J. D. The natural history of renal disease in Autralian Aborigines. Part, I. Changes in albuminuria and glomerular filtration rate over time. Kidney Int. 60, 243–248 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Iseki, K., Kinjo, K., Iseki, C. & Takishita, S. Relationship between predicted creatinine clearance and proteinuria and the risk of devolping ESRD in Okinawa, Japan. Am. J. Kidney Dis. 44, 806–814 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Risdon, R. A., Sloper, J. C. & de Wardener, H. E. Relationship between renal function and histological changes found in renal biopsy specimens from patients with persistant glomerular nephritis. Lancet 2, 363–366 (1968).

    Article  CAS  PubMed  Google Scholar 

  46. Remuzzi, G., Ruggenenti, P. & Perico, N. Chronic renal disease: renoprotective benefits of renin-angiotensin system inhibition. Ann. Intern. Med. 136, 604–615 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Ruggenenti, P. et al. Proteinuria predicts end-stage renal failure in non-diabetic chronic nephropathies. The “Gruppo Italiano di Studi Epidemiologici in Nefrologia” (GISEN). Kidney Int. Suppl. 63, S54–S57 (1997).

    CAS  PubMed  Google Scholar 

  48. Wingen, A. M., Fabian-Bach, C., Schaefer, F. & Mehls, O. Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood. Lancet 349, 1117–1123 (1997).

    Article  CAS  PubMed  Google Scholar 

  49. Ardissino, G. et al. Proteinuria as a predictor of disease progression in children with hypodysplastic nephropathy. Pediatr. Nephrol. 19, 172–177 (2004).

    Article  PubMed  Google Scholar 

  50. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 349, 1857–1863 (1997).

  51. Wright, J. T. Jr et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK trial. JAMA 288, 2421–2431 (2003).

    Article  Google Scholar 

  52. Remuzzi, G., Ruggenenti, P. & Benigni, A. Understanding the nature of renal disease progression. Kidney Int. 51, 2–15 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Ruggenenti, P., Perna, A. & Remuzzi, G. Retarding progression of chronic renal disease: the neglected issue of residual proteinuria. Kidney Int. 63, 2254–2261 (2003).

    Article  CAS  PubMed  Google Scholar 

  54. ESCAPE Trial Group; Wühl, E. et al. Strict blood pressure control and renal failure progression in children. N. Engl. J. Med. 361, 1639–1650 (2009).

    Article  PubMed  Google Scholar 

  55. Jafar, T. H. et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann. Intern. Med. 135, 73–87 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Ruggenenti, P., Schieppati, A. & Remuzzi, G. Progression, remission, regression of chronic renal diseases. Lancet 357, 1601–1608 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Sarnak, M. J. et al. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Ann. Intern. Med. 142, 342–351 (2005).

    Article  PubMed  Google Scholar 

  58. Chobanian, A. V. et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289, 2560–2571 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. European Society of Hypertension–European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J. Hypertens. 21, 1011–1053 (2003).

  60. Klahr, S., Levy, A. D. & Beck, G. J. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. N. Engl. J. Med. 330, 877–884 (1994).

    Article  CAS  PubMed  Google Scholar 

  61. Ruggenenti, P. et al. Blood pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicenter, randomized controlled trial. Lancet 365, 939–946 (2005).

    Article  PubMed  Google Scholar 

  62. Wright, J. T. Jr et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 288, 2421–2431 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. Appel, L. J. et al. Intensified blood-pressure control in hypertensive chronic kidney disease. N. Engl. J. Med. 363, 918–929 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Schrier, R. W., Estacio, R. O., Mehler, P. S. & Hiatt, W. R. Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial. Nat. Clin. Pract. Nephrol. 3, 428–438 (2008).

    Article  Google Scholar 

  65. Gimpel, C. et al. Superior consistency of ambulatory blood pressure monitoring in children: implications for clinical trials. J. Hypertens. 27, 1568–1574 (2009).

    Article  CAS  PubMed  Google Scholar 

  66. Yusuf, S. et al. Renal outcomes with telmisartan, ramipril, or both, in patients at high vascular risk (The ONTARGET Study): a multicenter, randomized, double-blind, controlled trial. N. Engl. J. Med. 358, 1547–1559 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Schrier, R. W., Estacio, R. O., Esler, A. & Mehler, P. Effects of agressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 61, 1086–1097 (2002).

    Article  PubMed  Google Scholar 

  68. Nakao, N. et al. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 361, 117–124 (2003).

    Article  CAS  PubMed  Google Scholar 

  69. Gansevoort, R. T., de Zeeuw, D. & de Jong, P. E. ACE inhibitors and proteinuria. Pharm. World Sci. 18, 204–210 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Brenner, B. M. et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl. J. Med. 345, 861–869 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Lewis, E. J., Hunsicker, L. G., Raymond, P. B. & Rohde, R. D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N. Engl. J. Med. 329, 1456–1462 (1993).

    Article  CAS  PubMed  Google Scholar 

  72. Ross, S. D., Akhras, K. S., Zhang, S., Rozinsky, M. & Nalysnyk, L. Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis. Pharmacotherapy 21, 940–953 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. 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 271, 275–279 (1994).

    Article  CAS  PubMed  Google Scholar 

  74. 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 297, 1086–1091 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Maschio, G. et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N. Engl. J. Med. 334, 939–945 (1996).

    Article  CAS  PubMed  Google Scholar 

  76. 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 1, 1175–1179 (1983).

    Article  CAS  PubMed  Google Scholar 

  77. Zucchelli, P. et al. Long-term comparison between captopril and nifidepin in the progression of renal insufficiency. Kidney Int. 42, 452–458 (1992).

    Article  CAS  PubMed  Google Scholar 

  78. Kamper, A. L., Strandgaard, S. & Leyssac, P. Effect of enalapril on the progression of chronic renal failure: a randomized controlled trial. Am. J. Hypertens. 5, 423–430 (1992).

    Article  CAS  PubMed  Google Scholar 

  79. van Essen, G. G. et al. Are angiotensin converting enzyme inhibitors superior to beta blockers in retarding progressive renal function decline? Kidney Int. Suppl. 63, S58–S62 (1997).

    CAS  PubMed  Google Scholar 

  80. Hannedouche, T. et al. Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure. BMJ 309, 833–837 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bannister, K. M., Weaver, A., Clarkson, A. R. & Woodroffe, A. J. Effect of angiotensin converting enzyme and calcium channel inhibition on progression of IgA nephropathy. Contrib. Nephrol. 111, 184–192 (1995).

    Article  CAS  PubMed  Google Scholar 

  82. Ihle, B. U. et al. Angiotensin-converting-enzyme inhibition in non-diabetic progresive renal insufficiency: a controlled double-blind trial. Am. J. Kidney Dis. 27, 489–495 (1996).

    Article  CAS  PubMed  Google Scholar 

  83. Ruggenenti, P. et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 354, 359–364 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. Casas, J. P. et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 366, 2026–2033 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Mooser, V. et al. Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition. J. Cardiovasc. Pharmacol. 15, 276–282 (1990).

    Article  CAS  PubMed  Google Scholar 

  86. van den Meiracker, A. H. et al. Partial escape of agiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the antihypertensive response? J. Hypertens. 10, 803–812 (1992).

    Article  CAS  PubMed  Google Scholar 

  87. Shiigai, T. & Shichiri, M. Late escape from the antiproteinuric effect of ACE inhibitors in nondiabetic renal disease. Am. J. Kidney Dis. 37, 477–483 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Bomback, A. S. & Klemmer, P. J. The incidence and implications of aldosterone breakthrough. Nat. Clin. Pract. Nephrol. 3, 486–492 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Burgess, E. et al. Supramaximal dose of candesartan in proteinuric kidney disease. J. Am. Soc. Nephrol. 20, 893–900 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bakris, G. L. & Weir, M. R. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch. Int. Med. 160, 685–693 (2000).

    Article  CAS  Google Scholar 

  91. Navaneethan, S. D., Nigwekar, S. U., Sehgal, A. R. & Strippoli, G. F. M. Aldosterone antagonists for preventing the progression of chronic kidney disease: A systematic review and meta-analysis. Clin. J. Am. Soc. Nephrol. 4, 542–551 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Oparil, S. et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomized, double-blind trial. Lancet 370, 221–229 (2007).

    Article  CAS  PubMed  Google Scholar 

  93. Parving, H. H. et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N. Engl. J. Med. 358, 2433–2446 (2008).

    Article  CAS  PubMed  Google Scholar 

  94. Wilmer, W. A. et al. Management of glomerular proteinuria: a commentary. J. Am. Soc. Nephrol. 14, 3217–3232 (2003).

    Article  CAS  PubMed  Google Scholar 

  95. Marchi, F. & Ciriello, G. Efficacy of carvedilol in mild to moderate essential hypertension and effects on microalbuminuria: a multicenter, randomized, open-label, controlled study versus atenolol. Adv. Ther. 12, 212–221 (1995).

    CAS  PubMed  Google Scholar 

  96. Fassbinder, W., Quarder, O. & Waltz, A. Treatment with carvedilol is associated with a significant reduction in microalbuminuria: a multicenter randomized study. Int. J. Clin. Pract. 53, 519–522 (1999).

    CAS  PubMed  Google Scholar 

  97. Dhaun, N. et al. Blood pressure independent reduction in proteinuria and arterial stiffness after acute endothelin-a receptor antagonism in chronic kidney disease. Hypertension 54, 113–119 (2009).

    Article  CAS  PubMed  Google Scholar 

  98. Bakris, G. L. et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomized controlled trial. Lancet 375, 1173–1181 (2010).

    Article  CAS  PubMed  Google Scholar 

  99. Doulton, T. W., He, F. J. & MacGregor, F. A. Systemic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension 45, 880–886 (2005).

    Article  CAS  PubMed  Google Scholar 

  100. Campbell, R. et al. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int. 63, 1094–1103 (2003).

    Article  CAS  PubMed  Google Scholar 

  101. MacKinnon, M. et al. Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data. Am. J. Kidney Dis. 48, 8–20 (2006).

    Article  CAS  PubMed  Google Scholar 

  102. Hermida, R. C., Calvo, C., Ayala, D. E. & Lopez, J. E. Decrease in urinary albumin excretion associated with the normalization of nocturnal blood pressure in hypertensive subjects. Hypertension 46, 960–968 (2005).

    Article  CAS  PubMed  Google Scholar 

  103. Muntner, P., Coresh, J., Clinton Smith, J., Eckfeldt, J. & Klag, M. J. Plasma lipids and risk of developing renal dysfunction: the Atherosclerosis Risk in Communities Study. Kidney Int. 58, 293–301 (2000).

    Article  CAS  PubMed  Google Scholar 

  104. de Brito-Ashurst, I., Varagunam, M., Raftery, M. J. & Yaqoob, M. M. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J. Am. Soc. Nephrol. 20, 2075–2084 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ritz, E., Gross, M. L. & Dikow, R. Role of calcium-phosphorous disorders in the progression of renal failure. Kidney Int. 68 (Suppl. 99), S66–S70 (2005).

    Article  Google Scholar 

  106. Fliser, D., Bahlmann, F. H. & Haller, H. EPO: renoprotection beyond anemia correction. Pediatr. Nephrol. 21, 1785–1789 (2006).

    Article  PubMed  Google Scholar 

  107. Wright, J. T. J. et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease. JAMA 288, 2421–2431 (2002).

    Article  CAS  PubMed  Google Scholar 

  108. Maschio, G. et al. Effect of angiotensin-converting-enzme inhibitor benazepril on the progression of chronic renal insufficiency. N. Engl. J. Med. 334, 939–945 (1996).

    Article  CAS  PubMed  Google Scholar 

  109. Hou, F. F. et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N. Engl. J. Med. 354, 131–140 (2006).

    Article  CAS  PubMed  Google Scholar 

  110. Mann, J. F. et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 372, 547–553 (2008).

    Article  CAS  PubMed  Google Scholar 

  111. Jafar, T. H. et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-meta-analysis. Ann. Intern. Med. 139, 244–252 (2003).

    Article  CAS  PubMed  Google Scholar 

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C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, Heidelberg, 69120, Germany

    Elke Wühl & Franz Schaefer

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  1. Elke Wühl
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  2. Franz Schaefer
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Both authors contributed equally to researching, discussing, writing, editing and reviewing data for this article.

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Correspondence to Franz Schaefer.

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Wühl, E., Schaefer, F. Managing kidney disease with blood-pressure control. Nat Rev Nephrol 7, 434–444 (2011). https://doi.org/10.1038/nrneph.2011.73

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