Friday, September 9, 2011

Topic Discussion: Recent Advances in Acute Kidney Injury

Our understanding of the pathophysiology of acute kidney injury (AKI) has advanced substantially and we envision that in the not too distant future we may be able to identify AKI much earlier than we are able to do so today and that we will be able to institute therapies that can either limit renal damage or facilitate recovery, potentially through measures such as the administration of growth factors, mesenchymal stem cells and others.  However, our current therapies still consist largely of supportive interventions alone such as attempts to manage fluid and electrolyte balance and dialysis. 

Despite many years of caring for patients with AKI it has been difficult to obtain answers to some relatively simple questions and sometimes what may sound like a logical approach may prove not to be the case.  One such question has been regarding the use of fluids and diuretics.  Administering fluids to help support blood pressure and hopefully cardiac output and renal perfusion might appear to be a sound approach yet there has been concern that the development of fluid overload might counter any such potential benefit by leading to pulmonary edema and other adverse events.  Diuretics might seem to be beneficial as well.  They can decrease the work of the kidney, hence potentially limiting oxygen consumption, and in some patients they may increase urine output (thereby “converting” the patient from oliguric to nonoliguric AKI).  However, to date diuretics do not appear to improve outcomes in patients with AKI and may actually predispose to its development (radiocontrast nephropathy being one such example).  Hence despite decades of experience with fluid and diuretic therapy in patients with AKI this has been an area of uncertainty.  

Recent work by Grams et al in CJASN (1) has provided some insights.  Using data from the Fluid and Catheter Treatment Trial, which was a multicenter, randomized controlled trial evaluating a conservative versus a liberal fluid management strategy in patients with acute lung injury, these authors investigated the impact of fluid balance post-AKI and diuretic use on mortality.  The authors found that having a higher post-AKI fluid balance was associated with a higher mortality rate and that the use of furosemide did not impact on mortality after taking into account the patients’ fluid balance post AKI.  The authors did not find any dose of furosemide above which there was an increase in mortality.   

It is not uncommon that it may take many years to obtain data for what seem to be straightforward clinical questions.  Another example of this is the recent New England Journal of Medicine study comparing diuretic strategies in just 308 patients with decompensated heart failure (2).  While one might have assumed that there was an abundance of prospective data in the literature on this issue, there was not.  These findings highlight the critical importance of well designed clinical research studies to help advance patient care and the need for more trainees and junior faculty to involve themselves in high quality clinical research.        

  1. Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network.  Clin J Am Soc Nephrol 2011; 6:966-73
  2. Felker GM, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 2011; 364:797-805.
Post written by :
Joseph Mattana, M.D.

Dr Mattana is the Chief of Nephrology at the Hofstra NSLIJ School of Medicine, NY

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