Arterial Stiffness and AKI Post-CABG

Acute kidney injury (AKI) affects around 20% of all hospitalised patient. Previously it was believed that recovery from an episode of AKI resulted in full renal recovery and return to normal function in the long term. However this assumption may reflect the fact that many of these patients did not receive long term follow-up and a failure to return to their baseline renal function was not identified. It is now recognised that AKI has both major long-term health and socioeconomic impacts. Studies have demonstrated that an episode of AKI can significantly increase both risk of development of chronic kidney disease and early mortality.

Episodes of dialysis-requiring AKI in patients with previously normal renal function who were not dialysis-dependent on discharge resulted in a 28-fold increase in risk of developing severe chronic kidney disease (CKD) stage 4 or 5 and a 2-fold increase in the risk of death at one year when compared to non-AKI controls. This was also observed over a 5-year follow-up period, during which patients who had suffered an episode of AKI were at a 6-fold increased risk of developing both CKD stage 4 or end stage renal failure (ESRF).

There is also an increased risk of death in patients who have experienced an episode of non-dialysis requiring AKI, which remains apparent even with mild AKI stage 1. AKI has a long-term impact on patient morbidity and mortality, an effect that appears to persist despite 'biochemical resolution'. The size of this impact is dependent upon the degree of severity and duration of AKI experienced. However, there is some controversy regarding the link of AKI to CKD. At the present time there is no specific therapy for AKI and the management of patients is completely supportive. Furthermore, in the absence of more sensitive biomarkers, it would appear that even a non-severe episode of AKI already confers a worse prognosis with regards to the risk of development of CKD and long term survival in patients. Thus perhaps focus should be on prevention of AKI as opposed to cure. This is even more pertinent when one considers that the National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) report in 2009 identified 30% of cases as being 'preventable' and a deficiency of care in 50% of cases. The median length of stay for patients diagnosed with AKI was 17.8 days, which was 4.7 days longer than for those without AKI. Marion Kerr, a health economist, reported that by avoiding 'preventable' cases a potential saving of £130-186 million per year could be made.

The difficulty lies in identification of patients that are at risk of AKI. Although factors such as diabetes, older age and low estimated glomerular filtration rate (eGFR) are all associated with increased risk, there is no standardized scoring method for risk. In addition, it is not fully clear why some patients suffer AKI while others, with similar co-morbidities, do not.

Arterial stiffness (AS) is defined as 'the unit of pressure required to generate a change in volume of one unit' within a specified arterial segment. Clinically it can be assessed non-invasively by measurement of pulse wave velocity (PWV. AS varies significantly with age, gender and race, and it is only in the last few years that studies have been undertaken to attempt to quantify a 'normal' or reference value within various populations. Arterial stiffness is also increased in numerous clinical conditions such as diabetes and hypertension and there is now increasing evidence that AS may be an important predictor of disease progression and potential recovery in a wide spectrum of conditions including cardiovascular risk, development of dementia, functional recovery from strokes and in renal disease. Increased AS has been shown to be associated with decreased kidney function and to be an independent risk factor for cardiovascular events in ESRF and in renal transplant recipients.

The mechanism of injury in CKD from increased AS is thought to be related to barotrauma inflicted on glomeruli in a "stiff" vascular system. However, there is little data with regards to the effects of AS in AKI.

For this initial pilot study, we have selected the cohort of patients who are undergoing elective coronary artery bypass graft surgery (CABG) to see if this type of event is associated with increased risk of AKI. On average 450 patients per year undergo CABG surgery at King's College Hospital (KCH) and of these over 200 are elective operations. All elective patients will attend a pre-assessment clinic, which is run weekly with about 20 patients per clinic. Many of these patients will have co-morbidities associated with both an increased risk of AKI and of AS. We have performed a retrospective analysis of incidence of AKI in patients undergoing elective, isolated CABG surgery at KCH from January to December 2012. Of a total of 219 patients, 42 patients were classified as having post-operative AKI according to serum AKI criteria.