Subclinical cardiopulmonary dysfunction in stage 3 chronic kidney disease

Alexander Nelson, James Otto, John Whittle, Robert C M Stephens, Daniel S Martin, John R Prowle, Gareth L Ackland, Alexander Nelson, James Otto, John Whittle, Robert C M Stephens, Daniel S Martin, John R Prowle, Gareth L Ackland

Abstract

Objective: Reduced exercise capacity is well documented in end-stage chronic kidney disease (CKD), preceded by changes in cardiac morphology in CKD stage 3. However, it is unknown whether subclinical cardiopulmonary dysfunction occurs in CKD stage 3 independently of heart failure.

Methods: Prospective observational cross-sectional study of exercise capacity assessed by cardiopulmonary exercise testing in 993 preoperative patients. Primary outcome was peak oxygen consumption (VO2peak). Anaerobic threshold (AT), oxygen pulse and exercise-evoked measures of autonomic function were analysed, controlling for CKD stage 3, age, gender, diabetes mellitus and hypertension.

Results: CKD stage 3 was present in 93/993 (9.97%) patients. Diabetes mellitus (RR 2.49 (95% CI 1.59 to 3.89); p<0.001), and hypertension (RR 3.20 (95% CI 2.04 to 5.03); p<0.001)) were more common in CKD stage 3. Cardiac failure (RR 0.83 (95% CI 0.30 to 2.24); p=0.70) and ischaemic heart disease (RR 1.40 (95% CI 0.97 to 2.02); p=0.09) were not more common in CKD stage 3. Patients with CKD stage 3 had lower predicted VO2peak (mean difference: 6% (95% CI 1% to 11%); p=0.02), lower peak heart rate (mean difference:9 bpm (95% CI 3 to 14); p=0.03)), lower AT (mean difference: 1.1 mL/min/kg (95% CI 0.4 to 1.7); p<0.001) and impaired heart rate recovery (mean difference: 4 bpm (95% CI 1 to 7); p<0.001)).

Conclusions: Subclinical cardiopulmonary dysfunction in CKD stage 3 is common. This study suggests that maladaptive cardiovascular/autonomic dysfunction may be established in CKD stage 3, preceding pathophysiology reported in end-stage CKD.

Keywords: AUTONOMIC NERVOUS SYSTEM; CARDIAC FUNCTION; RENAL DISEASE.

Figures

Figure 1
Figure 1
Study analysis plan. CKD, chronic kidney disease; CPET, cardiopulmonary exercise testing; eGFR, estimated glomerular filtration rate; ITT, intention to treat.

References

    1. Hallan SI. Kidney function for the non-nephrologist: an emerging tool for predicting mortality risk. Kidney Int 2011;79:8–10. 10.1038/ki.2010.362
    1. de Jager DJ, Vervloet MG, Dekker FW. Noncardiovascular mortality in CKD: an epidemiological perspective. Nat Rev Nephrol 2014;10:208–14. 10.1038/nrneph.2014.8
    1. Muntner P, Judd SE, Gao L et al. . Cardiovascular risk factors in CKD associate with both ESRD and mortality. J Am Soc Nephrol 2013;24:1159–65. 10.1681/ASN.2012070642
    1. Bello AK, Hemmelgarn B, Lloyd A et al. . Associations among estimated glomerular filtration rate, proteinuria, and adverse cardiovascular outcomes. Clin J Am Soc Nephrol 2011;6:1418–26. 10.2215/CJN.09741110
    1. Herzog CA, Asinger RW, Berger AK et al. . Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011;80:572–86. 10.1038/ki.2011.223
    1. Ting SM, Hamborg T, McGregor G et al. . Reduced Cardiovascular Reserve in Chronic Kidney Failure: A Matched Cohort Study. Am J Kidney Dis 2015;66:274–84. 10.1053/j.ajkd.2015.02.335
    1. Sietsema KE, Amato A, Adler SG et al. . Exercise capacity as a predictor of survival among ambulatory patients with end-stage renal disease. Kidney Int 2004;65:719–24. 10.1111/j.1523-1755.2004.00411.x
    1. Sezer S, Elsurer R, Ulubay G et al. . Factors associated with peak oxygen uptake in hemodialysis patients awaiting renal transplantation. Transplant Proc 2007;39:879–82. 10.1016/j.transproceed.2007.02.013
    1. Ting SM, Iqbal H, Kanji H et al. . Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation. J Am Soc Nephrol 2014;25:187–95. 10.1681/ASN.2013040348
    1. McCullough PA, Franklin BA, Leifer E et al. . Impact of reduced kidney function on cardiopulmonary fitness in patients with systolic heart failure. Am J Nephrol 2010;32:226–33. 10.1159/000317544
    1. Poulikakos D, Banerjee D, Malik M. Repolarisation descriptors and heart rate variability in hemodialysed patients. Physiol Res 2015;64:487–93.
    1. Poulikakos D, Banerjee D, Malik M. Risk of sudden cardiac death in chronic kidney disease. J Cardiovasc Electrophysiol 2014;25:222–31. 10.1111/jce.12328
    1. Park M, Hsu CY, Li Y et al. . Associations between kidney function and subclinical cardiac abnormalities in CKD. J Am Soc Nephrol 2012;23:1725–34. 10.1681/ASN.2012020145
    1. American Thoracic Society; American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167:211–77. 10.1164/rccm.167.2.211
    1. Levey AS, Bosch JP, Lewis JB et al. . A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. AnnInternMed 1999;130:461–70.
    1. Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol 1986;60:2020–7.
    1. Pina IL, Balady GJ, Hanson P et al. . Guidelines for clinical exercise testing laboratories. A statement for healthcare professionals from the Committee on Exercise and Cardiac Rehabilitation, American Heart Association. Circulation 1995;91:912–21. 10.1161/01.CIR.91.3.912
    1. Reindl I, Wernecke KD, Opitz C et al. . Impaired ventilatory efficiency in chronic heart failure: possible role of pulmonary vasoconstriction. Am Heart J 1998;136:778–85. 10.1016/S0002-8703(98)70121-8
    1. Chua TP, Ponikowski P, Harrington D et al. . Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol 1997;29:1585–90. 10.1016/S0735-1097(97)00078-8
    1. Hansen JE, Sue DY, Wasserman K. Predicted values for clinical exercise testing. Am Rev Respir Dis 1984;129:S49–55. 10.1164/arrd.1984.129.2P2.S49
    1. Uth N, Sørensen H, Overgaard K et al. . Estimation of VO2max from the ratio between HRmax and HRrest–the Heart Rate Ratio Method. Eur J Appl Physiol 2004;91:111–15. 10.1007/s00421-003-0988-y
    1. Whipp BJ, Higgenbotham MB, Cobb FC. Estimating exercise stroke volume from asymptotic oxygen pulse in humans. J Appl Physiol 1996;81:2674–9.
    1. Oelberg DA, Kacmarek RM, Pappagianopoulos PP et al. . Ventilatory and cardiovascular responses to inspired He-O2 during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;158:1876–82. 10.1164/ajrccm.158.6.9802015
    1. Arena R, Myers J, Abella J et al. . Determining the preferred percent-predicted equation for peak oxygen consumption in patients with heart failure. Circ Heart Fail 2009;2:113–20. 10.1161/CIRCHEARTFAILURE.108.834168
    1. London MJ, Hollenberg M, Wong MG et al. . Intraoperative myocardial ischemia: localization by continuous 12-lead electrocardiography. Anesthesiology 1988;69:232–41. 10.1097/00000542-198808000-00013
    1. Fihn SD, Gardin JM, Abrams J et al. . 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012;60:e44–e164. 10.1016/j.jacc.2012.07.013
    1. Rywik TM, O'Connor FC, Gittings NS et al. . Role of nondiagnostic exercise-induced ST-segment abnormalities in predicting future coronary events in asymptomatic volunteers. Circulation 2002;106:2787–92. 10.1161/01.CIR.0000039329.47437.3B
    1. Cole CR, Blackstone EH, Pashkow FJ et al. . Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999;341:1351–7. 10.1056/NEJM199910283411804
    1. Jouven X, Empana JP, Schwartz PJ et al. . Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 2005;352:1951–8. 10.1056/NEJMoa043012
    1. Joshi S, Viljoen A. Renal biomarkers for the prediction of cardiovascular disease. Curr Opin Cardiol 2015;30:454–60. 10.1097/HCO.0000000000000177
    1. Whittle J, Nelson A, Otto JM et al. . Sympathetic autonomic dysfunction and impaired cardiovascular performance in higher risk surgical patients: implications for perioperative sympatholysis. Open Heart 2015;2:e000268 10.1136/openhrt-2015-000268
    1. Bibbins-Domingo K, Lin F, Vittinghoff E et al. . Predictors of heart failure among women with coronary disease. Circulation 2004;110:1424–30. 10.1161/01.CIR.0000141726.01302.83
    1. Chae CU, Albert CM, Glynn RJ et al. . Mild renal insufficiency and risk of congestive heart failure in men and women > or=70 years of age. Am J Cardiol 2003;92:682–6. 10.1016/S0002-9149(03)00822-1
    1. Bongartz LG, Cramer MJ, Doevendans PA et al. . The severe cardiorenal syndrome: ‘Guyton revisited’. Eur Heart J 2005;26: 11–7. 10.1093/eurheartj/ehi020
    1. Paoletti E, Bellino D, Cassottana P et al. . Left ventricular hypertrophy in nondiabetic predialysis CKD. Am J Kidney Dis 2005;46:320–7. 10.1053/j.ajkd.2005.04.031
    1. Levin A, Thompson CR, Ethier J et al. . Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis 1999;34:125–34. 10.1053/AJKD03400125
    1. Bibbins-Domingo K, Lin F, Vittinghoff E et al. . Renal insufficiency as an independent predictor of mortality among women with heart failure. J Am Coll Cardiol 2004;44:1593–600. 10.1016/j.jacc.2004.07.040
    1. Tonelli M, Muntner P, Lloyd A et al. . Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 2012;380: 807–14. 10.1016/S0140-6736(12)60572-8
    1. Mastitskaya S, Marina N, Gourine A et al. . Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones. Cardiovasc Res 2012;95:487–94. 10.1093/cvr/cvs212
    1. Andersson U, Tracey KJ. Reflex principles of immunological homeostasis. Annu Rev Immunol 2012;30:313–35. 10.1146/annurev-immunol-020711-075015
    1. Brotman DJ, Bash LD, Qayyum R et al. . Heart rate variability predicts ESRD and CKD-related hospitalization. J Am Soc Nephrol 2010;21:1560–70. 10.1681/ASN.2009111112
    1. Yeboah MM, Xue X, Duan B et al. . Cholinergic agonists attenuate renal ischemia-reperfusion injury in rats. Kidney Int 2008;74:62–9. 10.1038/ki.2008.94
    1. Ackland GL, Moran N, Cone S et al. . Chronic kidney disease and postoperative morbidity after elective orthopedic surgery. Anesth Analg 2011;112:1375–81. 10.1213/ANE.0b013e3181ee8456
    1. Asfar P, Meziani F, Hamel JF et al. . High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014;370:1583–93. 10.1056/NEJMoa1312173

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