Skip to main content
SpringerLink
Log in

Clinical effects of calcium channel blockers and renin-angiotensin-aldosterone system inhibitors on changes in the estimated glomerular filtration rate in patients with polycystic kidney disease

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

In the tubular cells of patients with polycystic kidney disease (PKD), a reduced intracellular Ca2+ level accelerates cell proliferation, resulting in cyst formation. Thus, whether calcium channel blockers (CCB) are useful for the treatment of hypertension in patients with PKD is questionable.

Methods

Thirty-two outpatients with autosomal dominant PKD (ADPKD) were treated at Tokyo Women's Medical University between 2003 and 2008; these patients were studied retrospectively. Periods during which the antihypertensive drug prescriptions for CCB and/or renin-angiotensin-aldosterone system inhibitors (RAAS-I; including angiotensin converting enzyme inhibitor and angiotensin II receptor blocker) had not been changed for at least 1 year and during which time a diuretic agent had not been prescribed were selected from among the clinical histories of the 32 outpatients. Consequently, 31 periods of 31 patients were analyzed, and mean treatment duration was 2.4 years in this study. The estimated glomerular filtration rate (eGFR) was used to evaluate renal function. To evaluate the influence of CCB and RAAS-I with respect to the decrease of the eGFR, analysis of covariance (ANCOVA), including confounding factors [baseline eGFR, mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP)], was used. Only CCB significantly contributed to a reduction in ∆eGFR in both a univariable ANCOVA and a multivariable ANCOVA. None of the confounding factors, RAAS-I, the baseline eGFR, or blood pressure, contributed to reductions in ∆eGFR.

Conclusion

These results suggest that from a renoprotective perspective, CCB should possibly be avoided in patients with PKD unless treatment for resistant hypertension is necessary.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Wang D, Strandgaard S. The pathogenesis of hypertension in autosomal dominant polycystic kidney disease. J Hypertens. 1997;15:925–33.

    Article  CAS  PubMed  Google Scholar 

  2. Yoder BK, Mulroy S, Eustace H, Boucher C, Sandford R. Molecular pathogenesis of autosomal dominant polycystic kidney disease. Expert Rev Mol Med. 2006;8:1–22.

    Article  PubMed  Google Scholar 

  3. Hanaoka K, Qian F, Boletta A, Bhunia AK, Piontek K, Tsiokas L, et al. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature. 2000;408:990–4.

    Article  CAS  PubMed  Google Scholar 

  4. Vandorpe DH, Chernova MN, Jiang L, Sellin LK, Wilhelm S, Stuart-Tilley AK, et al. The cytoplasmic C-terminal fragment of polycystin-1 regulates a Ca2+-permeable cation channel. J Biol Chem. 2001;276:4093–101.

    Article  CAS  PubMed  Google Scholar 

  5. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003;33:129–37.

    Article  CAS  PubMed  Google Scholar 

  6. Yoder BK, Hou X, Guay-Woodford LM. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol. 2002;13:2508–16.

    Article  CAS  PubMed  Google Scholar 

  7. Nauli SM, Rossetti S, Kolb RJ, Alenghat FJ, Consugar MB, Harris PC, et al. Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J Am Soc Nephrol. 2006;17:1015–25.

    Article  CAS  PubMed  Google Scholar 

  8. Yamaguchi T, Hempson SJ, Reif GA, Hedge AM, Wallace DP. Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells. J Am Soc Nephrol. 2006;17:178–87.

    Article  CAS  PubMed  Google Scholar 

  9. Nagao S, Nishii K, Yoshihara D, Kurahashi H, Nagaoka K, Yamashita T, et al. Calcium channel inhibition accelerates polycystic kidney disease progression in the Cy/+ rat. Kidney Int. 2008;73:269–77.

    Article  CAS  PubMed  Google Scholar 

  10. Kanno Y, Okada H, Moriwaki K, Nagao S, Takahashi H, Suzuki H. The effects of antihypertensive agents on the survival rate of polycystic kidney disease in Han:SPRD rats. Hypertens Res. 2002;25:939–43.

    Article  CAS  PubMed  Google Scholar 

  11. Higashikuni Y, Ishizaka N, Ishizaka Y, Toda E, Nagai R, Yamakado M. Relationship between blood pressure and chronic kidney disease in the Japanese population: the lower the better even in individuals without hypertension? Hypertens Res. 2008;31:213–9.

    Article  CAS  PubMed  Google Scholar 

  12. Nutahara K, Higashihara E, Horie S, Kamura K, Tsuchiya K, Mochizuki T, et al. Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease. Nephron Clin Pract. 2005;99:c18–23.

    Article  CAS  PubMed  Google Scholar 

  13. Ecder T, Chapman AB, Brosnahan GM, Edelstein CL, Johnson AM, Schrier RW. Effect of antihypertensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2000;35:427–32.

    Article  CAS  PubMed  Google Scholar 

  14. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y, et al. Modification of the modification of diet in renal disease (MDRD) study equation for Japan. Am J Kidney Dis. 2007;50:927–37.

    Article  PubMed  Google Scholar 

  15. Matsunaga H, Stanton BA, Gesek FA, Friedman PA. Epithelial Ca2+ channels sensitive to dihydropyridines and activated by hyperpolarizing voltages. Am J Physiol. 1994;267:C157–65.

    CAS  PubMed  Google Scholar 

  16. Zhang MI, O’Neil RG. Regulated calcium channel in apical membranes renal proximal tubule cells. Am J Physiol. 1996;271:C1757–64.

    CAS  PubMed  Google Scholar 

  17. Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, et al. Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol. 2002;4:191–7.

    Article  CAS  PubMed  Google Scholar 

  18. Yamaguchi T, Wallace DP, Magenheimer BS, Hempson SJ, Grantham JJ, Calvet JP. Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J Biol Chem. 2004;279:40419–30.

    Article  CAS  PubMed  Google Scholar 

  19. Fujita T, Ando K, Nishimura H, Ideura T, Yasuda G, Isshiki M, et al. Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin–angiotensin inhibition in hypertensive patients with chronic renal disease. Kidney Int. 2007;72:1543–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Japan Research Promotion Society for Cardiovascular Diseases. We especially wish to thank Ai Munekawa, Mayuko Tsuboi and Atsuko Teraoka for their assistance.

Author information

Authors and Affiliations

  1. Department of Medicine IV, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Michihiro Mitobe, Takumi Yoshida, Hidekazu Sugiura, Shunji Shiohira, Kosaku Nitta & Ken Tsuchiya

  2. STATZ Institute Inc., Matsunaga Bldg. 3Fl., 1-18 Haramachi, Shinjuku-ku, Tokyo, 162-0053, Japan

    Katsunori Shimada

Authors
  1. Michihiro Mitobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takumi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hidekazu Sugiura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shunji Shiohira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katsunori Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kosaku Nitta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ken Tsuchiya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ken Tsuchiya.

About this article

Cite this article

Mitobe, M., Yoshida, T., Sugiura, H. et al. Clinical effects of calcium channel blockers and renin-angiotensin-aldosterone system inhibitors on changes in the estimated glomerular filtration rate in patients with polycystic kidney disease. Clin Exp Nephrol 14, 573–577 (2010). https://doi.org/10.1007/s10157-010-0329-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-010-0329-5

Keywords

Search

Navigation