Skip to main content

Advertisement

Log in

Potential risks of calcium channel blockers in chronic kidney disease

  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Antihypertensive therapy remains the most effective strategy for slowing the progression of chronic kidney disease (CKD). However, in proteinuric nephropathies, calcium channel blockers (CCBs) are less effective than other antihypertensives unless normotension is achieved. This is because the glomerular capillaries, rather than larger vessels, are the primary site of hypertensive injury in proteinuric nephropathies. CCBs impair renal autoregulation, which protects glomerular capillaries against the transmission of systemic pressures. CCBs’ renoprotective inferiority in the comparator group likely accounts for the greater renoprotection observed with renin-angiotensin system blockade rather than blood pressure (BP)-independent renoprotective superiority. Nevertheless, CKD patients are at greater absolute risk for cardiovascular events rather than end-stage renal disease. Therefore, if the needed BP reductions cannot be achieved with other agents, it may be appropriate to use CCBs because of their antihypertensive effectiveness, provided care is taken to ensure normotension and to closely monitor proteinuria and renal disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure [no authors listed ]. JAMA 2003, 289:2560–2572.

  2. Turnbull F; Blood Pressure Lowering Treatment Trialists’ Collaboration: Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomized trials. Lancet 2003, 362:1527–1535.

    Article  PubMed  CAS  Google Scholar 

  3. Turnbull F, Neal B, Algert C, et al.: Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med 2005, 165:1410–1419.

    Article  PubMed  Google Scholar 

  4. The ALLHAT Offices and Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic; the antihypertensive and lipid-lowering treatment to prevent heart attack trial. JAMA 2002, 288:2981–2997.

    Article  Google Scholar 

  5. Jafar TH, Stark PC, Schmid CH, et al.: Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition. A patient-level meta-analysis. Ann Intern Med 2003, 139:244–252.

    PubMed  CAS  Google Scholar 

  6. Kidney Disease Outcomes Quality Initiative (K/DOQI): K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Disease 2004, 43(5 Suppl 1):S1–S290.

    Google Scholar 

  7. Casas JP, Chua W, Loukgeorgakis S, et al.: Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 2005, 366:2026–2033.

    Article  PubMed  CAS  Google Scholar 

  8. Griffin KA, Bidani AK: Calcium-channel blockers and the progression of renal disease. Curr Hypertens Rep 1999, 1:436–445.

    Article  PubMed  CAS  Google Scholar 

  9. Bidani AK, Griffin KA: The benefits of renin-angiotensin blockade in hypertension are dependent on blood-pressure lowering. Nat Clin Pract Nephrol 2006, 2:542–543.

    Article  PubMed  Google Scholar 

  10. Griffin KA, Bidani AB: Progression of renal disease: renoprotective specificity of renin-angiotensin system blockade. Clin J Am Soc Nephrol 2006, 1:1054–1065.

    Article  PubMed  Google Scholar 

  11. Bidani AK, Griffin KA: Long-term renal consequences of hypertension for normal and diseased kidneys. Curr Opin Nephrol Hypertens 2002, 11:73–80.

    Article  PubMed  Google Scholar 

  12. Bidani AK, Griffin KA: Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension 2004, 44:595–601.

    Article  PubMed  CAS  Google Scholar 

  13. Bidani AK, Hacioglu R, Abu-Amarah I, et al.: “Step” vs “dynamic” autoregulation: implications for susceptibility to hypertensive injury. Am J Physiol 2003, 285:F113–F120.

    CAS  Google Scholar 

  14. Loutzenhiser R, Griffin KA, Williamson G, Bidani AK: Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol 2005, 290:R1153–R1167.

    Google Scholar 

  15. Olson JL: Renal disease caused by hypertension. In Heptinstall’s Pathology of the Kidney, edn 6. Edited by Jennette JC, Olson JL, Schwartz MM, Silva FG. Philadelphia: Lippincott Williams & Wilkins; 2007: 937–990.

    Google Scholar 

  16. Bidani AK, Griffin KA, Picken M, Lansky DM: Continuous telemetric BP monitoring and glomerular injury in the rat remnant kidney model. Am J Physiol 1993, 265:F391–F398.

    PubMed  CAS  Google Scholar 

  17. Griffin KA, Churchill PC, Picken M, et al.: Differential salt-sensitivity in the pathogenesis of renal damage in SHR and stroke prone SHR. Am J Hypertens 2001, 14:311–320.

    Article  PubMed  CAS  Google Scholar 

  18. Kurtz TW, Griffin KA, Bidani AK, et al.: Recommendation for blood pressure measurements in humans and animals. Part 2: Blood pressure measurements in experimental animals: a statement for professionals from the subcommittee of professional and public education of the American Heart Association council on high blood pressure research. Hypertension 2005, 45:299–310.

    Article  PubMed  CAS  Google Scholar 

  19. Bidani AK, Schwartz MM, Lewis EJ: Renal autoregulation and vulnerability to hypertensive injury in remnant kidney. Am J Physiol 1987, 252:1003–1010.

    Google Scholar 

  20. Pelayo JC, Westcott JY: Impaired autoregulation of glomerular capillary hydrostatic pressure in the rat remnant nephron. J Clin Invest 1991, 88:101–105.

    Article  PubMed  CAS  Google Scholar 

  21. Griffin KA, Picken M, Bidani AK: Method of renal mass reduction is a critical determinant of subsequent hypertension and glomerular injury. J Am Soc Nephrol 1994, 4:2023–2031.

    PubMed  CAS  Google Scholar 

  22. Christensen PK, Hansen HP, Parving HH: Impaired autoregulation of GFR in hypertensive non-insulin dependent diabetic patients. Kidney Int 1997, 52:1369–1374.

    Article  PubMed  CAS  Google Scholar 

  23. Christensen PK, Hommel EE: Impaired autoregulation of the glomerular filtration rate in patients with nondiabetic nephropathy. Kidney Int 1999, 56:1517–1523.

    Article  PubMed  CAS  Google Scholar 

  24. Griffin KA, Abu-Amarah I, Picken M, Bidani AK: Renoprotection by ACE inhibition or aldosterone blockade is blood pressure dependent. Hypertension 2003, 41:201–206.

    Article  PubMed  CAS  Google Scholar 

  25. Griffin KA, Picken M, Litbarg N, Bidani AK: All major antihypertensive classes provide comparable and BP-dependent renoprotection in the model of malignant nephrosclerosis in the stroke prone SHR. J Am Soc Nephrol 2005, 16:186A.

    Google Scholar 

  26. Nakamura Y, Ono H, Frohlich ED.: Differential effects of T- and L-type calcium antagonists on glomerular dynamics in spontaneously hypertensive rats. Hypertension 1999, 34:273–278.

    PubMed  CAS  Google Scholar 

  27. Kloke HJ, Branten AJ, Hyysmans FT, Wetzels JF: Antihypertensive treatment of patients with proteinuric renal diseases: risks or benefits of calcium channel blockers? Kidney Int 1998, 53:1559–1573.

    Article  PubMed  CAS  Google Scholar 

  28. Bidani AK, Picken MM, Bakris G, Griffin KA: Lack of evidence of BP independent protection by renin-angiotensin system blockade after renal ablation. Kidney Int 2000, 57:1651–1661.

    Article  PubMed  CAS  Google Scholar 

  29. Griffin KA, Picken MM, Bidani AK: Deleterious effects of calcium channel blockade on pressure transmission and glomerular injury in rat remnant kidneys. J Clin Invest 1995, 96:793–800.

    Article  PubMed  CAS  Google Scholar 

  30. Griffin KA, Picken MM, Bakris GL, Bidani AK: Class differences in the effects of calcium blockers in the rat remnant kidney model. Kidney Int 1999, 55:1849–1860.

    Article  PubMed  CAS  Google Scholar 

  31. Griffin KA, Picken MM, Bakris GL, Bidani AK: Comparative effects of T- and L-type calcium channel blockade in the remnant kidney model. Hypertension 2001, 37:1268–1272.

    PubMed  CAS  Google Scholar 

  32. Loutzenhiser R, Epstein M: Effects of calcium channel antagonists on renal hemodynamics. Am J Physiol 1985, 249:F619–F629.

    PubMed  CAS  Google Scholar 

  33. Griffin KA, Hacioglu R, Abu-Amarah, I, et al.: Effects of calcium channel blockers on “dynamic” and “steady-state step” renal autoregulation. Am J Physiol 2004, 286:F1136–F1143.

    Article  CAS  Google Scholar 

  34. Griffin KA, Picken M, Bidani AK: Radiotelemetric BP monitoring, antihypertensives and glomeruloprotection in remnant kidney model. Kidney Int 1994, 46:1010–1018.

    Article  PubMed  CAS  Google Scholar 

  35. Griffin KA, Kramer H, Bidani AK: Adverse renal consequences of obesity. Am J Physiol 2008, 294:F685–F696.

    CAS  Google Scholar 

  36. McDonald TF, Pelzer S, Trautwein W, Pelzer DJ: Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol Rev 1994, 74:365–507.

    PubMed  CAS  Google Scholar 

  37. Griffin KA, Picken M, Giobbie-Hurder A, Bidani AK: Low protein diet mediated renoprotection in remnant kidneys: renal autoregulatory vs hypertrophic mechanisms. Kidney Int 2003, 63:607–616.

    Article  PubMed  Google Scholar 

  38. Dworkin LK, Tolbert E, Recht PA, et al.: Effects of amlodipine on glomerular filtration, growth, and injury in experimental hypertension. Hypertension 1996, 27:245–250.

    PubMed  CAS  Google Scholar 

  39. Karam H, Clozel JP, Brumeval P, et al.: Contrasting effects of selective T- and L-type calcium channel blockade on glomerular damage in DOCA hypertensive rats. Hypertension 1999, 34:673–678.

    PubMed  CAS  Google Scholar 

  40. Christensen PK, Akram K, Konig KB, et al.: Autoregulation of glomerular filtration rate in patients with type 2 diabetes during isradipine therapy. Diabetes Care 2003, 26:156–162.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  42. Randomised placebo-controlled trials of effect of ramipril on decline in glomerular filtration rate and risks of terminal renal failure in proteinuric, non-diabetic nephropathy. The Gisen Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) [no authors listed ]. Lancet 1997, 349:1857–1863.

  43. Ruggenenti P, Perna A, Benini R, et al.: Effects of dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibition, and blood pressure control on chronic, nondiabetic nephropathies. J Am Soc Nephrol 1998, 9:2096–2101.

    PubMed  CAS  Google Scholar 

  44. Brenner BM, Cooper ME, de Zeeuw D, et al.: Effect of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001, 345:861–869.

    Article  PubMed  CAS  Google Scholar 

  45. Hou FF, Zhang X, Zhang GH, et al.: Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 2006, 354:131–140.

    Article  PubMed  CAS  Google Scholar 

  46. Lewis EJ, Hunsicker LG, Clarke WR, et al.: Renoprotective effect of the angiotensin receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001, 345:851–860.

    Article  PubMed  CAS  Google Scholar 

  47. Wright JT Jr, Bakris G, Greene T, et al.: Effect of blood pressure and antihypertensive drug class on progression of hypertensive kidney disease. Results from the AASK trial. JAMA 2002, 288:2421–2431.

    Article  PubMed  CAS  Google Scholar 

  48. Rahman M, Pressel S, Davis BR, et al.: Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic. Arch Intern Med 2005, 165:936–946.

    Article  PubMed  CAS  Google Scholar 

  49. Foley RN, Murray AM, Li S, et al.: Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population 1998–1999. J Am Soc Nephrol 2005, 16:489–495.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Karen A. Griffin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Griffin, K.A., Bidani, A.K. Potential risks of calcium channel blockers in chronic kidney disease. Curr Cardiol Rep 10, 448–455 (2008). https://doi.org/10.1007/s11886-008-0071-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-008-0071-8

Keywords

Navigation