Renal Disease


Chronic kidney disease (CKD) is associated with a very high risk of cardiovascular events and the mortality rate from cardiovascular disease is more than double in people with CKD compared to the general population.[38] The ability to identify patients at risk of cardiovascular disease and subsequently monitor the effects of treatment, from the early stages of CKD through to dialysis or transplantation, could lead to improved outcomes for kidney disease patients.

Arterial stiffness and measures of wave reflection have been shown to be powerful predictors of major cardiovascular events in CKD and can provide guidance in therapy selection. [39-44] Arterial stiffness and central arterial pressure waveform analysis with the SphygmoCor® System provide valuable insights into the treatment of chronic kidney disease patients. Measures of arterial stiffness and central hemodynamics have become important tools for providing a better understanding of outcomes with various therapeutic approaches for CKD and ESRD patients.

Arterial stiffness and measures of wave reflection are well established in the field of chronic kidney disease (CKD) and have been shown to be strong independent risk factors for morbidity and mortality in all stages of chronic kidney disease, including end-stage renal disease (ESRD) with dialysis and kidney transplantation.[40-48] Furthermore, these measures also provide prognostic ability for identifying patients at risk of chronic kidney disease progression.[49]

CKD has a number of significant co-morbidities that present additional cardiovascular risk, such as diabetes and hypertension. [38,50] Each of these brings additional treatment considerations.

Antihypertensive therapy is important in CKD patients, as well as dialysis timing and composition and immunosuppressant agents for kidney transplant recipients. [50-52] There is a growing body of research highlighting the effects each of these has on arterial stiffness and measures of wave reflection. [53-55,21]

Arterial stiffness and measures of wave reflection have been well established as a factor in ESRD, but more recently the degree of arterial stiffness has also been shown to be important in CKD patients who are pre-dialysis group.[5] In addition, increases in aortic pulse wave velocity (PWV) and aortic augmentation index (AIx) are commonly associated with other conditions highly prevalent in CKD patients, such as hypertension and diabetes.[6,7]

The most recent European guidelines for the management of arterial hypertension recommend evaluation of aortic PWV for asymptomatic organ damage in hypertensive patients.[8] Furthermore, two key position papers have also recommended the clinical use of aortic PWV for primary and secondary disease prevention[9] and to provide additional information beyond traditional risk factors for prediction of cardiovascular events.[10]

Effect of calcium/phosphate management

Investigation of new and existing approaches to manage calcium/phosphate metabolism, vascular calcification and CKD-related mineral and bone disorders have also been examined in relation to the effects on arterial stiffness.[27,28] Aortic PWV has been shown to increase in hemodialysis patients when a standard calcium-containing phosphate buffer was used, but then decreased significantly following a subsequent six-month period after changing to sevelamar, a phosphate binder that does not contain calcium.[27]

Vitamin D therapy is commonly used for treating bone and mineral disorders in CKD and ESRD, and a recent study highlighted that the pharmacological use of one of the forms of active Vitamin D, α-calcidol, in hemodialysis patients was associated with accelerated progression of aortic PWV and a higher progression of AIx, suggesting that vascular health may need to be further addressed with Vitamin D therapy.[28]

Effect of additional medications

There were similar findings in a study of hemodialysis patients on Warfarin. The use of Warfarin was associated with an accelerated increase in aortic PWV and AIx and the patient group had twice the risk of all-cause mortality, compared to a group with no Warfarin use.[29]

Effect of immunosuppressant therapy

Recent studies have examined the effects of newer classes of immunosuppressant drugs on central blood pressure as measured by central arterial pressure waveform analysis and arterial stiffness after transplantation.[33,34] Betalacept was shown to be associated with lower central augmentation pressure [33] compared to CsA, and drugs in the Proliferative Signal Inhibitors class appear to be associated with an improvement in AIx.[34]

Cyclosporin A (CsA), but not Tacrolimus, has been shown to be associated with higher AIx after kidney transplantation. While both drugs come from the same class of immunosuppressants, CsA has been associated with increased arteriosclerosis, left ventricular hypertrophy, and hypertension in kidney transplant recipients.[30] Maintenance treatment with Tacrolimus has also been associated with a reduction in AIx [31] and no deterioration in aortic PWV 12 months post-transplant.[32]

Effect of hypertension medication

Blood pressure control is an important consideration in all stages of chronic kidney disease. Blood pressure-lowering drugs are prescribed in 70-90% of kidney transplant recipients.[35]

There is a large body of evidence showing the effects of antihypertensive drugs on arterial stiffness, the central arterial pressure waveform, and wave reflections.[36] Furthermore, the value of central arterial pressure waveform analysis to guide hypertensive management has been demonstrated[37] and may result in changes of the medication class selection to better manage arterial stiffness.

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Citations and References

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1. Mills et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010 Kidney Int 2015;88(5):950-957.
2. Mozaffarian et al Heart disease and stroke statistics–2015 update: a report from the American Heart Association Circulation 2015;131(4):e29-322.
3. National Institutes of Health United States Renal Data System. 2015 USRDS annual data report: Epidemiology of kidney disease in the United States. 2015.
4. Khoshdel, Carney SL. Arterial stiffness in kidney transplant recipients: an overview of methodology and applications Urol J 2008;5(1):3-14.
5. Taal. Arterial stiffness in chronic kidney disease: an update Curr Opin Nephrol Hypertens 2014;23(2):169-173.
6. Mariella Catalano Arterial Stiffness: A Review in Type 2 Diabetes 2013(6)
7. Kaess et al. Aortic stiffness, blood pressure progression, and incident hypertension JAMA 2012;308(9):875-881.
8. Mancia et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur Heart J 2013;34(28):2159-2219.
9. Vlachopoulos et al. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society Atherosclerosis 2015;241(2):507-532.
10. Townsend et al. Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association Hypertension 2015;66(3):698-722.
11. Vlachopoulos et al. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis Eur Heart J 2010;31(15):1865-1871.
12. Blacher et al. Impact of aortic stiffness on survival in end-stage renal disease Circulation 1999;99(18):2434-2439.
13. Verbeke et al. Prognostic value of aortic stiffness and calcification for cardiovascular events and mortality in dialysis patients: outcome of the calcification outcome in renal disease (CORD) study Clin J Am Soc Nephrol 2011;6(1):153-159.
14. London et al. Arterial wave reflections and survival in end-stage renal failure Hypertension 2001;38(3):434-438.
15. Verbeke et al Aortic stiffness and central wave reflections predict outcome in renal transplant recipients Hypertension 2011;58(5):833-838. 16. Claes et al. Aortic calcifications and arterial stiffness as predictors of cardiovascular events in incident renal transplant recipients Transpl Int 2013;26(10):973-981.
17. Dahle et al. Aortic Stiffness in a Mortality Risk Calculator for Kidney Transplant Recipients Transplantation 2015;99(8):1730-1737.
18. Karras et al. Large artery stiffening and remodeling are independently associated with all-cause mortality and cardiovascular events in chronic kidney disease Hypertension 2012;60(6):1451-1457.
19. Chirinos et al. Arterial stiffness, central pressures, and incident hospitalized heart failure in the chronic renal insufficiency cohort study Circ Heart Fail 2014;7(5):709-716.
20. Townsend et al. Aortic PWV in chronic kidney disease: a CRIC ancillary study Am J Hypertens 2010;23(3):282-289.
21. Taal et al. Markers of arterial stiffness are risk factors for progression to end-stage renal disease among patients with chronic kidney disease stages 4 and 5 Nephron Clin Pract 2007;107(4):c177-c181.
22. Cohen, Townsend RR. Central blood pressure and chronic kidney disease progression Int J Nephrol 2011;2011:407801.
23. Roman et al. High central pulse pressure is independently associated with adverse cardiovascular outcome the strong heart study J Am Coll Cardiol 2009;54(18):1730-1734.
24. Townsend. Arterial stiffness and chronic kidney disease: lessons from the Chronic Renal Insufficiency Cohort study Curr Opin Nephrol Hypertens 2015;24(1):47-53.
25. Covic et al. Analysis of the effect of hemodialysis on peripheral and central arterial pressure waveforms Kidney Int 2000;57(6):2634-2643.
26. Georgianos et al. Diverse effects of interdialytic intervals on central wave augmentation in haemodialysis patients Nephrol Dial Transplant 2013;28(8):2160-2169.
27. Takenaka et al. Arterial wave reflection is elevated in evening hemodialysis patients Clin Exp Hypertens 2008;30(3):173-181.
28. Fortier et al. Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study Am J Hypertens 2014;27(11):1346-1354.
29. Mac-Way et al. The impact of warfarin on the rate of progression of aortic stiffness in hemodialysis patients: a longitudinal study Nephrol Dial Transplant 2014;29(11):2113-2120.
30. Ferro et al. Central aortic pressure augmentation in stable renal transplant recipients Kidney Int 2002;62(1):166-171.
31. Verbeke et al. Aortic stiffness and central wave reflections predict outcome in renal transplant recipients Hypertension 2011;58(5):833-838. 32. Birdwell et al. Assessment of arterial stiffness using pulse wave velocity in tacrolimus users the first year post kidney transplantation: a prospective cohort study BMC Nephrol 2015;16:93.
33. Seibert et al. Differential impact of belatacept and cyclosporine A on central aortic blood pressure and arterial stiffness after renal transplantation Clin Transplant 2014;28(9):1004-1009.
34. Yong et al. Association of a change in immunosuppressive regimen with hemodynamic and inflammatory markers of cardiovascular disease after kidney transplantation Am J Hypertens 2013;26(7):843-849.
35. Kidney Disease: Improving Global Outcome (KDIGO) Blood Pressure Work Group KDIGO Clinical Practice Guideline in the Management of Blood Pressure in Chronic Kidney Disease. Kidney International 2012;Suppl 2(5).
36. Manisty, Hughes AD. Meta-analysis of the comparative effects of different classes of antihypertensive agents on brachial and central systolic blood pressure, and augmentation index Br J Clin Pharmacol 2013;75(1):79-92.
37. Sharman et al. Randomized trial of guiding hypertension management using central aortic blood pressure compared with best-practice care: principal findings of the BP GUIDE study Hypertension 2013;62(6):1138-1145.
38. Norris KC and Nicholas SB. Ethn Dis. 2015;25(4)515-20.
39. Schiffrin E et al. Circulation. 2007;116 (1), 85-97.
40. Weber T et al. Am J Hypertens. 2011;Jul;24(7):762-9.
41. Cohen DL. Townsend RR. Int J Nephrol. 2011:407801.
42. Mitchell et al. Circulation. 2010; 121 505–11.
43. London GM. Hypertension 2001; 38:434-8.
44. Safar ME. Hypertension 2002; 39:735-8.
45. London GM et al. J Am Soc Nephrol. 2015.
46. Fesler et al. J of H 2007;25:1915-1920;
47. Gosse et al. J of H 2009;27:1303-1308;
48. Ben-Shlomo et al. JACC 2014;63:636–46;
49. Georgianos PI et al. Curr Vasc Pharmacol 2015;13(2):229-38
50. Townsend RR and Taler SJ. Nat Rev Nephrol 2015;11(9):555-63.
51. Slinin Y et al. Am J Kideny Dis 2015;66(5):823-36.
52. Bamoulid J et al. Expert Opin Pharmacother. 2015:16(11):1627-48.
53. Briet M et al. Kidney Int. 2012; 82(4):388-400.
54. Ghiadoni L et al. Curr Hypertens Rep. 2009;11(3):190-6;
55. Mardare. Hemodial Int 2005; 9:376-82.