Background. Data on the long-term survival and renal function of patients with acute kidney injury (AKI) treated with continuous renal replacement therapy are scarce. Methods. We investigated the 3-year survival and need for chronic dialysis in critically ill patients, who had survived an episode of AKI requiring continuous renal replacement therapy. Results. A total of 206 ICU patients with AKI were randomized in a trial comparing haemofiltration versus haemodiafiltration. Of these, 95 (46%) survived at 90 days. Post-discharge information relating to 3-year survival and renal function was successfully obtained in 89 (94%) of the patients. Of the 89 patients studied, chronic kidney disease (CKD) was present in 32 subjects from the onset, and CKD developed de novo in 25 patients following AKI. End-stage renal disease (ESRD) developed in 9 patients (of whom 8 had pre-existing CKD) and 29 patients died. Three-year survival was 67% overall; the mortality at 3 years was 50% for those with pre-existing kidney disease, and 71 and 82% for those with de novo and without CKD, respectively. Conclusion. After an episode of AKI necessitating a continuous renal replacement therapy, rapid progression to ESKD is commonly observed in patients with pre-existing chronic renal impairment. Medical care with an emphasis on nephroprotection is necessary in these patient

Martin, Pierre-Yves

Perneger, Thomas

Pugin, Jerome

Romand, Jacques

Saudan, Patrick

Triverio, Pierre-Alain

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2186 P. A. Triverio et al.20. Kumar VA, Yeun JY, Depner TA et al. Extended daily dialysis versuscontinuous hemodialysis for ICU patients with acute renal failure: atwo-year single center report. Int J Artif Organs 2004; 27: 371–37921. Lonnemann G, Floege J, Kliem V et al. Extended daily veno-venoushigh-flux haemodialysis in patients with acute renal failure and mul-tiple organ dysfunction syndrome using a single path batch dialysissystem. Nephrol Dial Transplant 2000; 15: 1189–119322. Marshall MR, Golper TA, Shaver MJ et al. Sustained low-efficiencydialysis for critically ill patients requiring renal replacement therapy.Kidney Int 2001; 60: 777–78523. Marshall MR, Golper TA, Shaver MJ et al. Urea kinetics dur-ing sustained low-efficiency dialysis in critically ill patients requir-ing renal replacement therapy. Am J Kidney Dis 2002; 39: 556–57024. Eloot S, Van Biesen W, Dhondt A et al. Impact of hemodialysisduration on the removal of uremic retention solutes. Kidney Int 2008;73: 765–77025. Vanholder R, De SR, Glorieux G et al. Review on uremic toxins:classification, concentration, and interindividual variability. KidneyInt 2003; 63: 1934–1943Received for publication: 3.6.08; Accepted in revised form: 19.1.09Nephrol Dial Transplant (2009) 24: 2186–2189doi: 10.1093/ndt/gfp072Advance Access publication 19 February 2009Long-term prognosis after acute kidney injury requiring renalreplacement therapyPierre-Alain Triverio1, Pierre-Yves Martin1, Jacques Romand2, Jerome Pugin2, Thomas Perneger3 andPatrick Saudan11Service de Ne´phrologie, 2Services des Soins Intensifs de Chirurgie et de Me´decine and 3Groupe Qualite´, Hoˆpitaux Universitaires deGene`ve, Geneva, SwitzerlandCorrespondence and offprint requests to: Patrick Saudan; E-mail: Patrick.Saudan@hcuge.chAbstractBackground. Data on the long-term survival and renalfunction of patients with acute kidney injury (AKI) treatedwith continuous renal replacement therapy are scarce.Methods. We investigated the 3-year survival and need forchronic dialysis in critically ill patients, who had survivedan episode of AKI requiring continuous renal replacementtherapy.Results. A total of 206 ICU patients with AKI were random-ized in a trial comparing haemofiltration versus haemodi-afiltration. Of these, 95 (46%) survived at 90 days. Post-discharge information relating to 3-year survival and renalfunction was successfully obtained in 89 (94%) of the pa-tients. Of the 89 patients studied, chronic kidney disease(CKD) was present in 32 subjects from the onset, and CKDdeveloped de novo in 25 patients following AKI. End-stagerenal disease (ESRD) developed in 9 patients (of whom8 had pre-existing CKD) and 29 patients died. Three-yearsurvival was 67% overall; the mortality at 3 years was 50%for those with pre-existing kidney disease, and 71 and 82%for those with de novo and without CKD, respectively.Conclusion. After an episode of AKI necessitating a con-tinuous renal replacement therapy, rapid progression toESKD is commonly observed in patients with pre-existingchronic renal impairment. Medical care with an emphasison nephroprotection is necessary in these patients.Keywords: acute kidney injury; continuous renal replacement therapy;long-term survivalIntroductionAcute kidney injury (AKI) affects as many as 30% of pa-tients admitted in intensive care units (ICU) [1]. The aeti-ology in 90% of ICU-related AKI is acute tubular necrosis(ATN), occurring most commonly in the context ofmultiple-organ failure. Due to recent improvements in in-tensive care techniques, the in-hospital mortality rate ofpatients with AKI requiring dialysis has declined over thepast 20 years from 41 to 28% [2]. However, many pa-tients who have an episode of ICU-related AKI nowadaysare elderly and have severe co-morbidities and in this con-text, the incidence of AKI has been increasing over thepast decades [2–4]. Data on their long-term survival arescarce and often conflicting. Before 1980, <10% of patientswith ATN ended in end-stage renal failure [5]. At 1-yearfollow-up, only 1% of the patients surviving an episodeof ICU-related AKI requiring renal replacement therapy(RRT) were found to have an ongoing requirement for RRT[6]. No prognostic factor for end-stage renal failure could beidentified in this study. Longer follow-up of this cohort wasC© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.For Permissions, please e-mail: journals.permissions@oxfordjournals.orgLong-term prognosis in severe acute kidney injury 2187recently published and at 5 years, 5% of the patients stillalive needed maintenance dialysis [7]. The longest follow-up (10 years) of 187 patients with AKI showed that 71%of those with chronic renal dysfunction prior to the episodeof AKI (n = 100) died within the follow-up but only 2 pa-tients needed dialysis in this cohort [8]. Other authors areless optimistic, reporting a chronic dialysis rate up to 20%in survivors of ATN [9]. In this study, we investigated the3-year survival and need for chronic dialysis in critically illpatients who had both taken part in a randomized controlledtrial comparing different doses of RRT, and were still alive90 days after their episode of AKI [10].Patients and methodsBetween October 2000 and December 2003, 206 ICU patients with AKIwere included in a controlled randomized trial comparing haemofiltrationand haemodiafiltration [10]. Details of this study were already published.Data on 3-year survival and level of renal function prior to and after AKIwere obtained in those who survived >90 days by referring to the Genevapopulation registry or their medical records (hospital or private physician).Normal renal function prior to the episode of AKI was determined byan estimated GFR (eGFR) ≥60 ml/min according to the MDRD studyequation [11]. Only serum creatinine values measured 1 month prior toAKI were considered as valid when calculating the eGFR to determine therenal function prior to AKI. Patients without premorbid creatinine but whohad at discharge an eGFR ≥60 ml/min were considered to have no CKDprior to AKI. Non-return to baseline values was diagnosed as incompleterecovery. An eGFR ≤ 60 ml/min prior to AKI was defined as prior CKDand at hospital discharge or at 90 days post-AKI as de novo CKD. End-stage kidney disease (ESKD) was defined as CKD requiring maintenancedialysis.Statistical analysisThe chi-square and t-tests were used to compare demographic and baselinecharacteristics of 3-year survivors and non-survivors. Significant P-valueswere <0.05.A Kaplan–Meyer analysis was used to determine 3-yearsurvival among patients without CKD and those with known or de novoCKD.ResultsOf the 206 patients who took part in the randomized trial,95 were still alive at 90 days after implementation of RRT.Three-year data on survival and level of renal function wereobtained in 89 (94%) patients. Six patients were transferredto other countries and were lost to follow-up. Premorbid cre-atinine values were obtained in 71 patients. Baseline demo-graphic and clinical characteristics of 3-year survivors andnon-survivors are listed in Table 1. At discharge, completerecovery (within ± 10% baseline eGFR or discharge eGFR>60 ml/min) was present in 32 out of 89 patients, dialysisdependence was present in 4 patients and the remainderhad partial recovery. The 32 patients with full recovery atdischarge had a steady renal function during follow-up.Patients with de novo CKD after AKIDuring the 3-year follow-up, of the 25 patients who devel-oped CKD after AKI, 1 became dependent on dialysis, 5improved their eGFR, 13 decreased their eGFR and 6 hada steady eGFR.Table 1. Clinical and laboratory characteristics of patients at 3-yearsurvival (except for serum creatinine)Survivors(n = 60)Non-survivors(n = 29)Age (year) 58 ± 16 68 ± 11†Male gender (%) 50 66Diabetes (%) 18 21Diagnosis of AKI (trauma/surgical/medical)6/9/45 1/12/16†Apache II score 23 ± 8 18 ± 6††Sepsis (%) 60 41.4RRT duration (day) 3 (2–5) 4 (2–5)Serum creatinine prior to AKIMean, median, (range)(µmol/l)118, 98 (40–302) 141,119 (54–350)eGFR prior to AKI(ml/min)52 (14) 47 (14)CKD prior to ARF (%) 27 55††Serum creatinine at discharge or 90 daysMean, median, (range)(µmol/l)144, 100 (52–1060) 161, 135 (39–378)eGFR at discharge or 90days (ml/min)46 (17) 40 (20)CKD at discharge or 90days (%)55 79Last serum creatinine prior to death or at 3 yearsMean, median, (range)(µmol/l)121, 88 (54–535) 196, 154 (53–546)††eGFR prior to death or at 3years (ml/min)47 (17) 30 (19)CKD prior to death or at 3years (%)57 79†Data are given as mean ± SD or median and IQR.†P < 0.05, ††P < 0.01.BUN: blood urea nitrogen.Patients with CKD prior to AKIAmong the 32 patients with CKD prior to AKI, 4 had anincrease in eGFR, 10 had a decrease, 8 ended in ESKDand the remainder had a stable renal function during thefollow-up.At discharge, eight patients were classified with stage V(NKF/DOQI classification), of whom one improved duringfollow-up (stage IV CKD). Fifteen were classified withstage IV CKD of whom 2 improved during follow-up (stageIII CKD), 8 remained stage IV and 5 ended in stage V.Among the 26 classified at discharge with stage III CKD,1 improved his renal function during follow-up (stage IICKD), 9 worsened their renal function (2 stage V CKDand 7 stage IV) and 16 remained stage III. Among the 40classified at discharge with ≤stage II CKD, 28 remainedstable and 12 worsened their renal function during follow-up (2 stage V CKD, 1 stage IV, 9 stage III).SurvivalOverall survival in patients with AKI requiring continuousRRT (CRRT) dropped from 46% (n = 95/206) at 90 daysto 30% (n = 60/201) at 3 years.Overall 3-year survival in the 89 survivors at 90 days was67%. Among those who died within these 3 years, 79% had2188 P. A. Triverio et al.months403020100Cum Survival (%)100806040200No CKDDe novoCKDPrior CKDLR 8.32 p = 0.016Fig. 1. Kaplan–Meyer analysis of 3-year survival rates in patients without(no CKD prior to AKI) and with prior (prior CKD to AKI) or de novoCKD after AKI.CKD either prior to AKI (55%) or de novo developingafter AKI (24%), whereas only 55% of survivors had CKD(27% prior to AKI and 28% de novo developing after AKI).Three-year survival was 50, 71 and 82% in 90-day survivorswith prior, de novo and without CKD (log-rank test = 8.32,P = 0.016), respectively (Figure 1).DiscussionIn our study of critically ill patients with AKI, those whosurvived 90 days had a yearly mortality of almost 6%/yearduring the following 3 years. This rate is more than 10-foldhigher than the annual mortality observed in the generalpopulation of Geneva residents aged 61–70 (0.8% mortalityfor the years 2004–2006; Office Cantonal de la Statistique,Geneva). Overall 3-year mortality in the 206 patients orig-inally enrolled in our trial was 70%. These results arein accordance with those previously published. A recentprospective cohort study with 425 patients treated for ATNwith RRT mentioned 53 and 35% survival at discharge andat 1-year follow-up, respectively [6]. In the studies with along follow-up period, 5-year mortality in Finnish patientsrequiring RRT was reported to be between 50 and 70%[12,13]. A retrospective survey of 301 German ICU pa-tients with severe AKI found a 5-year survival of only 50%amongst discharged patients [14].Mortality increased in our patients with CKD, with thehighest rate observed in those with known CKD prior toAKI, and our results confirm CKD as an important riskfactor for death in the general population [15].It is often accepted that the outcome of AKI is binary:death or survival without the need of RRT, principally be-cause AKI is commonly held to recover in the vast majorityof survivors. In a recently published analysis of an inter-national cohort encompassing 1218 patients treated withCRRT, 14% were still dialysis dependent at hospital dis-charge [16]. Patients who are, however, dialysis free at 90days post-AKI generally remain so at 1 year, as suggestedby the recently reported 1 and 5% incidences of ESKD at 1and 5 years in patients with ATN requiring RRT [5,7]. In thisprospective study, nearly half of the survivors were, how-ever, discharged with moderate-to-severe CKD and noneof these patients were known to have CKD prior to theonset of AKI. More discouraging results have, however,also been reported, with prevalence of ESKD ranging from10 to 16.2% in studies with a long follow-up [9,14,17]. Alarge retrospective cohort study of 2202 patients treated byRRT (86% by CRRT and 15% by intermittent haemodial-ysis), of whom 1102 survived 90 days post-AKI, showeda long-term 11.9% incidence of ESKD [14]. Informationon post-discharge renal function of 301 German ICU long-term survivors was obtained in 130 patients [14]. CKD waspresent in 41% of the patients and 10% required mainte-nance dialysis. The results of our study support these dataas the 3-year incidence of ESKD among our survivors was10%. Notably, our patients with previous CKD had a 25%incidence of ESKD at 3 years. In addition, the prevalenceof CKD was elevated with nearly one in two patients withno known CKD prior to AKI progressing to CKD within3 years.Our study has some limitations. Though prospective, thisobservational study relies on a limited sample of patientsand lacks statistical power to determine which factors arepredictive of long-term survival and the need of RRT.Our population also had a high prevalence of patientswith previous CKD and results may not be extrapolated toother world populations, particularly outside the westernhemisphere.Data were not collected on other co-morbidities such asneoplasia or cardiovascular disorders, nor was the presenceor absence of a nephrological follow-up recorded.Despite its shortcomings, this observational study con-firms that after an episode of AKI necessitating CRRT,rapid progression to ESKD is only exceptionally observedin patients with normal renal function prior to the acuterenal injury, although one in two patients will progress toCKD. These results will, however, need to be confirmed bya larger prospective study analysing long-term outcomes inthese patients. We, however, recommend that patients whodevelop CKD after AKI should be considered at risk ofprogressing to ESKD. In this regard, they should receivemedical care with an emphasis on nephroprotection, forexample detection and treatment of hypertension, coronaryheart disease, calcium and phosphate metabolism distur-bances and anaemia. Also of note, patients with pre-existingCKD prior to the episode of AKI are at high risk of pro-gressing rapidly to ESKD following an episode of AKI;25% of our patients with previous CKD developed end-stage renal disease within 3 years after AKI. Pre-dialysiscare with preparation for RRT is therefore recommendedfor these patients.Acknowledgement. We thank Dr Sebastian Carballo for his linguisticexpertise.Conflict of interest statement. None declared.Long-term prognosis in severe acute kidney injury 2189References1. Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet2005; 365: 417–4302. Waikar SS, Curhan GC, Wald R et al. 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Long-term prognosis after acute kidney injury requiring renal replacement therapy

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