What do we know…
The AKI-EPI study, found an incidence of AKI in 57 % of the 1800 included patients. Severity was associated with adverse patient and kidney outcome at hospital discharge .
Analysis of a large cohort (32,045) confirmed a high prevalence (74.5 %) and further illustrated that both AKI severity, duration and the criteria used to define it (creatinine, urine output, or both) had significant impact on short and long-term outcomes .
Another large cohort study in 580 patients with out-of-hospital cardiac arrest found severe AKI in 43 % of the patients and the association with mortality but not with neurological outcome .
Last, it must be noted that the first validation of the Kidney Disease Improving Global Outcomes (KDIGO) criteria was performed in a large pediatric population .
Attempts to detect and capture A.K.I in evolution…
Studies demonstrate limits of the usual renal dysfunction criteria and of biomarkers in assessing renal function or predicting renal prognosis.
- Short episodes of oliguria in ICU patients are frequent and do not always predict subsequent AKI by creatinine criteria. AKI biomarkers have been extensively looked at and drawn at the point of oliguria. They have been shown to be on a par with serum creatinine as a predictor of AKI. The furosemide stress test may still hold more merit than these.  .
- The gold standard for glomerular filtration rate (GFR) determination is inulin clearance, but this cannot be measured easily. Carlier and co-workers compared inulin clearance with creatinine clearance and several creatinine and/or cystatin C-based GFR equations in 68 critically ill patients with stable kidney function. Measured creatinine clearance resulted in a slight overestimation of GFR while creatinine-based equations had the worst performance with overestimation of the true GFR; the overestimation increased with hospital stay . Reduced creatinine excretion resulting from muscle loss was the main determinant of this difference . Since cystatin is not influenced by muscle mass, the cystatin-based equations did not share the hospital stay-induced bias .
Recovery from AKI
Another relatively new research field is the association between AKI and long-term kidney outcome. A post hoc analysis of the EPaNiC trial showed significant impact of the chosen definitions for renal recovery and of the use of a surrogate to estimate baseline creatinine on the incidence of renal recovery. This analysis confirmed the limitations of serum creatinine when assessing recovery since discharge eGFR overestimated true GFR because of sarcopenia as mentioned above. Indeed, as many as 40 % of the patients with known baseline creatinine had a discharge creatinine lower than their baseline .
One of the big controversies in medicine – which, why, what, outcome, best, worst etc etc!!
Recent large randomized trials have suggested an impact of the choice of fluids for resuscitation on kidney function. A change from saline to buffered crystalloid solutions might decrease the risk of AKI . However, the study in question announcing this also reported large fluctuations in AKI incidence across 6-month study periods suggesting unidentified confounders . The neutral results of the subsequent trial comparing buffered crystalloid solution to saline (SPLIT trial) indicated no harm from saline, but…patients enrolled tended to have low illness severity and were admitted mainly after elective surgery . So…we need to do more trials in more severely ill, those with sepsis, and patients requiring large volumes of fluid .
In a follow-up of the 6S trial, Perner and colleagues followed up patients for an average of 22 months and reported that the long-term mortality rate did not differ in patients with severe sepsis receiving starches when compared to crystalloids. There was a trend toward fewer days alive / out of hospital in the starches group [24 % (0–87) vs. 63 % (0–90); P = 0.07] . Why; amongst other things, starches accumulate in tissues with frequently deleterious effects and these are sustained throughout the accumulation period . Interestingly, dermal deposits and subsequent pruritus were observed with cumulated dose as low as 0.4 mL/kg .
The results of trials comparing colloids, mainly starches, to crystalloids have progressively changed practices of fluid resuscitation. A large study reporting results of six cross-sectional point prevalence studies on the use of resuscitation fluids in Australia and New Zealand ICUs demonstrated a progressively decreased use of colloids over crystalloids and a progressive increase in the use of buffered crystalloid solutions over 0.9 % saline . The FENICE study further confirmed that buffered crystalloid solutions have become the most used fluid by intensivists worldwide [15, 16].
Extracorporeal blood purification
Blood purification techniques to put out the fire of sepsis have been much debated recently. Any efficacy has yet to be supported by evidence however. The IVOIRE trial, demonstrated no benefit of the CASCADE technique, allowing very high volume hemofiltration (up to 12oml/kg/h), in a pilot study of 60 patients. Another study of 224 patients in post cardiac surgery shock found no benefit of high volume hemofiltration . Finally, Payen and colleagues found no benefit of polymyxin (PMX) hemoperfusion in 232 adult postoperative patients with documented peritonitis and septic shock .
Optimal timing of renal replacement therapy (RRT) remains unknown although the START-AKI pilot study provided interesting results. This study randomized 101 patients with AKI stage 2 according to modified criteria to receive either RRT in the 12 h following inclusion or based upon predefined classical criteria for RRT. Even though the design of this feasibility study precludes any conclusions regarding outcome, it must be noted that accelerated RRT initiation resulted in a 50 % increase in need for RRT when compared to standard indications .
References for those that care!
Hoste EAJ, Bagshaw SM, Bellomo R et al (2015) Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 41:1411–1423. doi:10.1007/s00134-015-3934-7
Kellum JA, Sileanu FE, Murugan R et al (2015) Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol 26:2231–2238. doi:10.1681/ASN.2014070724
Geri G, Guillemet L, Dumas F et al (2015) Acute kidney injury after out-of-hospital cardiac arrest: risk factors and prognosis in a large cohort. Intensive Care Med 41:1273–1280. doi:10.1007/s00134-015-3848-4
Selewski DT, Cornell TT, Heung M et al (2014) Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population. Intensive Care Med 40:1481–1488. doi:10.1007/s00134-014-3391-8
Legrand M, Jacquemod A, Gayat E et al (2015) Failure of renal biomarkers to predict worsening renal function in high-risk patients presenting with oliguria. Intensive Care Med 41:68–76. doi:10.1007/s00134-014-3566-3
Koyner JL, Davison DL, Brasha-Mitchell E et al (2015) Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol 26:2023–2031. doi:10.1681/ASN.2014060535
Carlier M, Dumoulin A, Janssen A et al (2015) Comparison of different equations to assess glomerular filtration in critically ill patients. Intensive Care Med 41:427–435. doi:10.1007/s00134-014-3641-9
Schetz M, Gunst J, Van den Berghe G (2014) The impact of using estimated GFR versus creatinine clearance on the evaluation of recovery from acute kidney injury in the ICU. Intensive Care Med 40:1709–1717. doi:10.1007/s00134-014-3487-1
Schetz M, Gunst J, De Vlieger G, Van den Berghe G (2015) Recovery from AKI in the critically ill: potential confounders in the evaluation. Intensive Care Med 41:1648–1657. doi:10.1007/s00134-015-3946-3
Yunos NM, Bellomo R, Glassford N et al (2015) Chloride-liberal vs. chloride-restrictive intravenous fluid administration and acute kidney injury: an extended analysis. Intensive Care Med 41:257–264. doi:10.1007/s00134-014-3593-0
Young P, Bailey M, Beasley R et al (2015) Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial. JAMA 314:1701–1710. doi:10.1001/jama.2015.12334
Shaw AD, Raghunathan K, Peyerl FW et al (2014) Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Med 40:1897–1905. doi:10.1007/s00134-014-3505-3
Perner A, Haase N, Winkel P et al (2014) Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer’s acetate. Intensive Care Med 40:927–934. doi:10.1007/s00134-014-3311-y
Wiedermann CJ, Joannidis M (2014) Accumulation of hydroxyethyl starch in human and animal tissues: a systematic review. Intensive Care Med 40:160–170. doi:10.1007/s00134-013-3156-9
Hammond NE, Taylor C, Saxena M et al (2015) Resuscitation fluid use in Australian and New Zealand intensive care units between 2007 and 2013. Intensive Care Med 41:1611–1619. doi:10.1007/s00134-015-3878-y
Cecconi M, Hofer C, Teboul J-L et al (2015) Fluid challenges in intensive care: the FENICE study: a global inception cohort study. Intensive Care Med 41:1529–1537. doi:10.1007/s00134-015-3850-x
Quenot J-P, Binquet C, Vinsonneau C et al (2015) Very high volume hemofiltration with the Cascade system in septic shock patients. Intensive Care Med 41:2111–2120. doi:10.1007/s00134-015-4056-y
Combes A, Bréchot N, Amour J et al (2015) Early high-volume hemofiltration versus standard care for post-cardiac surgery shock. The HEROICS study. Am J Respir Crit Care Med 192:1179–1190. doi:10.1164/rccm.201503-0516OC
Payen DM, Guilhot-Gaudefroy J, Launey Y et al (2015) Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med 41:975–984
Wald R, Adhikari NKJ, Smith OM et al (2015) Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. Kidney Int 88:897–904. doi:10.1038/ki.2015.184