Blog entry by Meguid El Nahas

Anyone in the world

Dr Shanmuga KUMAR (Sheffield Kidney Institute) wrote: 

A recent paper[1] assessing exercise capacity of patients with chronic kidney disease (CKD) has rekindled some interest in the application of cardiopulmonary exercise testing (CPX) in CKD. The last such work was published a decade ago[2] which showed that exercise capacity, as measured by peak oxygen consumption (peak VO2), is a good predictor of survival in dialysis patients. The recent paper has shown similar results albeit utilising a different CPX parameter, anaerobic threshold (AT) presented as a percentage of peak VO2. However the question remains: What do we measure when we measure exercise capacity in CKD patients? The claim that measures of exercise capacity could serve as a surrogate of cardiac reserve function in CKD needs verification. The claim is based on the premise that VO2 is a product of cardiac output (CO) and arterio-venous difference in oxygen concentration [VO2= CO x C(a-v)O2] and hence VO2 could serve as a surrogate of cardiac output. There are several physiological considerations, commonly described in text books of exercise physiology,[3] which would render this simplified model less applicable in CKD.

Anaemia: Oxygen is primarily transported as oxyhaemoglobin (and a small fraction dissolved in plasma) and it has been estimated that the O2 carrying capacity of the blood falls from 22.5ml/dL to 14.1ml/dL as the haemoglobin concentration drops from 16gm/dL to 10gm/dL.3 Hence, for a given cardiac output, the impaired O2 delivery to exercising skeletal muscles results in reduced peak VO2 and anaerobic threshold (AT).

Chronic metabolic acidosis: Exercising skeletal muscles generate acidic end products and the ventilation must keep in pace with the acid load to maintain normal pH. The presence of metabolic acidosis in CKD would add to the acid load and limit exercise capacity because of higher ventilatory requirements.

Peripheral vascular disease: PVD is a common co-morbidity of CKD. The diseased vasculature with reduced internal diameter impairs blood flow to the exercising skeletal muscles. The relative ischaemia leads to early onset of lactic acid production and reduced AT irrespective of normal cardiac performance.3

Skeletal myopathy: Muscle wasting is not an uncommon finding in ESRD. Reduced skeletal muscle mass limits the utilisation of delivered O2. This coupled with the less studied phenomenon of skeletal myopathy secondary to uraemia would limit exercise capacity in spite of a normal cardiac output.

It has indeed been shown that haemoglobin, serum albumin, co-morbid diabetes mellitus and cardiovascular disease are significant determinants of exercise capacity in dialysis patients.[4] Therefore one wonders whether exercise capacity in CKD is just a composite marker of co-morbidities rather than a true representation of cardiac performance. Better interpretation of conventional CPX parameters in CKD can be achieved by employing techniques that simultaneously measure direct indicators of cardiac performance as well as exercise capacity.[5]


[1] Ting S.M. et al. Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation. J Am Soc Nephrol 25, 187-95 (2014).

[2] Sietsema K.E. et al. Exercise capacity as a predictor of survival among ambulatory patients with end-stage renal disease. Kidney Int 65, 719-24 (2004).

[3] Wasserman K. et al. Principles of exercise testing and Interpretation. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2005.

[4] Sietsema K.E. et al. Clinical and demographic predictors of exercise capacity in end-stage renal disease. Am J Kidney Dis 39, 76-85 (2002).

[5]Cooke G.A. et al. Physiological cardiac reserve: development of a non-invasive method and first estimates in man. Heart 79, 289-94 (1998). 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]