Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Morphological evaluation of sympathetic renal innervation in patients with autosomal dominant polycystic kidney disease

  • 88 Accesses

  • 1 Citations

Abstract

Several evidences support the hypothesis that patients affected by autosomal dominant polycystic kidney disease (ASPKD) show a sympathetic renal hyperactivity. Nevertheless, no morphological evidences are available yet. Therefore, the aim of the study was to demonstrate that an increase in sympathetic renal artery innervation was present in the ADPKD patients by using histological methods. In addition, here we correlated the sympathetic renal artery innervation with the evolutionary state of ADPKD (increase in volume of kidney, onset of chronic renal failure and hypertension). To this end, peri-adventitial innervation of renal arteries was studied using morphological methods from 49 patients in total: 29 underwent surgical nephrectomies for ADPKD and 20 non-dialysis patients (CTRL group) undergoing nephrectomy for other diseases. Nerve density (number of nerves per mm2) was evaluated in the peri-adventitial tissue in a concentric ring that was located within 2 mm from the beginning of the adventitia by using immunohistochemistry. The total nerve density was significantly increased in the ADPKD group (1.26 ± 0.82 × mm2) as compared to controls (0.78 ± 0.40 × mm2) (p = 0.02). Hypertensive patients with ADPKD showed a greater nerve density than control hypertensives. However, the increase in renal sympathetic innervation in the ADPKD patients was found to be independent of hypertension, resistance to antihypertensive therapy, age, sex and kidney volume, as demonstrated by the uni and multivariate analysis. In conclusion, our study better clarifies the effect of sympathetic hyperactivity in the progression of polycystic disease.

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

Fig. 1

References

  1. 1.

    Ong AC, Devuyst O, Knebelmann B, Walz G (2015) Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet 385:1993–2002

  2. 2.

    Chapman AB, Devuyst O, Eckardt KU et al (2015) Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 88:17–27

  3. 3.

    Schrier RW, McFann KK, Johnson AM (2003) Epidemiological study of kidney survival in autosomal dominant polycystic kidney disease. Kidney Int 63:678–685

  4. 4.

    Torres VE, Abebe KZ, Chapman AB et al (2014) Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med 371:2267–2276

  5. 5.

    Klein IH, Ligtenberg G, Oey PL, Koomans HA, Blankestijn PJ (2001) Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J Am Soc Nephrol 12:2427–2433

  6. 6.

    Kocyigit I, Eroglu E, Kaynar AS et al (2019) The association of endothelin-1 levels with renal survival in polycystic kidney disease patients. J Nephrol 32:83–91

  7. 7.

    Mauriello A, Rovella V, Anemona L et al (2015) Increased sympathetic renal innervation in hemodialysis patients is the anatomical substrate of sympathetic hyperactivity in end-stage renal disease. J Am Heart Assoc 4:e002426

  8. 8.

    Shetty SV, Roberts TJ, Schlaich MP (2013) Percutaneous transluminal renal denervation: a potential treatment option for polycystic kidney disease-related pain? Int J Cardiol 162:e58–e59

  9. 9.

    Casteleijn NF, de Jager RL, Neeleman MP, Blankestijn PJ, Gansevoort RT (2014) Chronic kidney pain in autosomal dominant polycystic kidney disease: a case report of successful treatment by catheter-based renal denervation. Am J Kidney Dis 63:1019–1021

  10. 10.

    Prejbisz A, Kadziela J, Lewandowski J et al (2014) Effect of percutaneous renal denervation on blood pressure level and sympathetic activity in a patient with polycystic kidney disease. Clin Res Cardiol 103:251–253

  11. 11.

    Sakakura K, Ladich E, Edelman ER et al (2014) Methodological standardization for the pre-clinical evaluation of renal sympathetic denervation. JACC Cardiovasc Interv 7:1184–1193

  12. 12.

    Burke AP, Kolodgie FD, Farb A, Weber D, Virmani R (2002) Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 105:297–303

  13. 13.

    Mauriello A, Rovella V, Borri F et al (2017) Hypertension in kidney transplantation is associated with an early renal nerve sprouting. Nephrol Dial Transplant 32:1053–1060

  14. 14.

    Converse RL Jr, Jacobsen TN, Toto RD et al (1992) Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 327:1912–1918

  15. 15.

    Schlaich MP (2011) Sympathetic activation in chronic kidney disease: out of the shadow. Hypertension 57:683–685

  16. 16.

    Grassi G, Quarti-Trevano F, Seravalle G et al (2011) Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension 57:846–851

  17. 17.

    Rubinger D, Backenroth R, Sapoznikov D (2013) Sympathetic nervous system function and dysfunction in chronic hemodialysis patients. Semin Dial 26:333–343

  18. 18.

    Grassi G, Bertoli S, Seravalle G (2012) Sympathetic nervous system: role in hypertension and in chronic kidney disease. Curr Opin Nephrol Hypertens 21:46–51

  19. 19.

    Kopp UC, Farley DM, Cicha MZ, Smith LA (2000) Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE(2), and substance P. Am J Physiol Regul Integr Comp Physiol 278:R937–R946

  20. 20.

    Xie C, Sachs JR, Wang DH (2008) Interdependent regulation of afferent renal nerve activity and renal function: role of transient receptor potential vanilloid type 1, neurokinin 1, and calcitonin gene-related peptide receptors. J Pharmacol Exp Ther 325:751–757

  21. 21.

    Schrier RW (2009) Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 20:1888–1893

  22. 22.

    Walsh N, Sarria JE (2012) Management of chronic pain in a patient with autosomal dominant polycystic kidney disease by sequential celiac plexus blockade, radiofrequency ablation, and spinal cord stimulation. Am J Kidney Dis 59:858–861

  23. 23.

    Gattone VH 2nd, Wang X, Harris PC, Torres VE (2003) Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 9:1323–1326

  24. 24.

    Rangan GK, Tchan MC, Tong A, Wong AT, Nankivell BJ (2016) Recent advances in autosomal-dominant polycystic kidney disease. Intern Med J 46:883–892

  25. 25.

    Grantham JJ, Mangoo-Karim R, Uchic ME et al (1989) Net fluid secretion by mammalian renal epithelial cells: stimulation by cAMP in polarized cultures derived from established renal cells and from normal and polycystic kidneys. Trans Assoc Am Physicians 102:158–162

  26. 26.

    Torres VE, Chapman AB, Devuyst O et al (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367:2407–2418

Download references

Acknowledgements

Manuel Scimeca is recipient of a fellowship from the “Fondazione Umberto Veronesi” (FUV).

Author information

Correspondence to Alessandro Mauriello.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The study was approved by Institutional Ethical Committee of the “Policlinico Tor Vergata.”Experimental procedures here reported were performed in agreement with the The Code (n°54/14) of Ethics of the World Medical Association (Declaration of Helsinki).

Research involving human participants and/or animals

This study was approved and conducted in accordance with the guidelines of the Human Research Committee of "Fondazione Policlinico Tor Vergata" (n°54/14).

Informed consent

Each subject signed an informed consent before surgery.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rovella, V., Scimeca, M., Giannini, E. et al. Morphological evaluation of sympathetic renal innervation in patients with autosomal dominant polycystic kidney disease. J Nephrol 33, 83–89 (2020). https://doi.org/10.1007/s40620-019-00612-3

Download citation

Keywords

  • ADPKD
  • Histology
  • Sympathetic renal hyperactivity
  • Renal denervation