As I was acutely reminded at the recent 2nd Leeds Critical Care Nephrology Course by Dr Neil Soni, (Intensivist from Chelsea and Westminster Hospital), Acute Kidney Injury (AKI) must not suffer the same fate as sepsis, whereby we lump all types of AKI together and forget to identify the underlying cause. AKI is a syndrome which is most commonly caused by sepsis and hypotension but has a number of other rarer causes which, if overlooked, will have devastating consequences for the patient. Mervyn Singer once told me not to make the same mistake with AKI as has been done with sepsis in terms of not addressing the different types of sepsis and the pathophysiology which will be dependent upon the organism and the patient response which, in turn, will be dependent upon the genotype. Similarly we cannot expect to make progress in the treatment of AKI unless we stratify it to the different types and characterise the underlying genotype and the pathophysiology of the disease process.
The literature is littered with many examples of treatments for AKI that were very effective in scientific models but when applied to the heterogeneous model of human AKI failed to work. This subsequently pushed back progress in terms of development of new therapies for a number of years. However over the last few years it has been pleasing to see a reinvigoration of the interest of Pharma in this area. This is been bolstered by the ability to describe the epidemiology of AKI and identify its association with worse outcomes across many different settings. Biomarkers hold the potential to help us characterise when AKI is occurring and discriminate between pre-renal (functional) AKI and intrinsic (damage) AKI as well as the type of injury. None of these biomarkers have so far made it into routine practice due to a lack of convincing evidence that they will benefit patients or be of economic value to the NHS.
Over the last year there has been the emergence of a new candidate biomarker which is a combination of TIMP 2 and IGF BP 7 known as Nephrocheck which identifies patients on the intensive care unit who are at risk of progressing to severe AKI. Further papers have demonstrated its ability to predict outcomes for patients in terms of mortality and need for long-term dialysis. Alongside this there have been trials of new therapies for AKI. Disappointingly a large study looking at a molecule known as Melanocortin failed to demonstrate efficacy in reducing the incidence of AKI post cardiac surgery. Currently there is a multicentre study identifying the optimal dose of recombinant alkaline phosphatase (anti-inflammatory action) in treating sepsis associated AKI.
There continues to be interest in identifying new therapeutic targets for treating AKI as evidenced by the recent Acute Dialysis Quality Initiative conference that was held in the USA. Kidney disease has suffered over the years from being a rare disease and has had only moderate funding to progress our understanding. It is hoped that with the continued development of new bio markers including improved imaging of the kidneys we may get closer to identifying new therapies for this potentially devastating condition.
Andrew Lewington
Consultant Renal Physician/Honorary Clinical Associate Professor,
Director of Undergraduate Medical Education
Leeds Teaching Hospitals Trust
Andrew studied renal medicine in Leicester and at Washington University USA, where he investigated the molecular mechanisms underlying acute kidney injury.
Andrew provides a specialist renal opinion for critically ill patients on the intensive care units across Leeds. He was an expert adviser on the National Clinical Enquiry into Patient Outcomes and Death (NCEPOD) ‘Adding Insult to Injury’, acute kidney injury report in 2009. He was appointed to the Department of Health Acute Kidney Injury Delivery Board to address the recommendations proposed in the NCEPOD report.
In 2011 Andrew was appointed Chair of the NICE accredited Renal Association Clinical Practice Guidelines Committee. He was a member of the NICE AKI and IV Fluid Therapy Clinical Practice Guideline Committee and is currently on the NICE AKI and RRT Quality Standards Group. Andrew is Co-Chair of the UK Kidney Research Consortium AKI Study Group and his research is focused on biomarker discovery and development. He is a member of the ISN AKI committee and Co-Chair of the Education workstream of the ISN ‘0 by 25’ initiative. Andrew is Chief Investigator for the NIHR Kidney transplant biomarker study and Epidemiology of AKI in Critically Ill Patients on ICU. He is a co-applicant on a £1.2M grant from the NIHR for the Diagnostic Evaluation Cooperative to investigate the clinical and cost effectiveness of biomarkers in the NHS. Most recently he has secured NIHR funding to evaluate ways of preventing acute kidney injury in the community and HTA funding to analyse the economic impact of acute kidney injury on the ICU.
Chair of the NHS England AKI Risk workstream