Table 1 Trial Summary Table by Study Type (n=36)
Author, Year | Study Design | Country | Duration | Exclusion | Patient Population | Patients (n) | Age (mean) yrs | Illness Severity Score | Early RRT Criteria | Late RRT Criteria | Study Quality | Primary Outcome | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Total | Early RRT | Late RRT | ||||||||||||
Randomized Trials | ||||||||||||||
Bouman, 2002 [12] | RCT, two-center study | Netherlands | May 1998 - Mar 2000 | Pre-existing renal disease | Multisystem | 106 | 70 | 36 | EHV: 68; ELV: 70; LLV: 67 | EHV: SOFA 10.3 - APACHE2=23.5, ELV: SOFA 10.1 - APACHE2=21.7; LLV: SOFA 10.6 - APACHE2=23.6 | TIME: Early < 12 h (200ml); Early Low Vol < 12 h (100-150ml) | TIME: Late > 12h | HIGH | 28 d mortality: EHV: 9/35(26%) died, ELV: 11/35(31%) died, LLV: 9/36(25%) died; p=0.8 |
Durmaz, 2003 [13] | RCT | Turkey | Sept 1999 - Aug 2001 | Age<18, chronic dialysis | Post Cardiac Surgery | 44 | 21 | 23 | Early 58; Late 54 | NR | BIOCHEM: Cr rise >10% from pre-op level within 48hrs of surgery | Cr rise >50% from pre-op level; or Urine output <400ml/24hrs with coexistent K+/H+ unresponsive to med mgmt | LOW | Hospital mortality: Early 1/21 (4.8%) died, Late 7/23 (30.4%) died p=0.048; Favors Early |
Sugahara, 2004 [14] | RCT | Japan | Jan 1995 - Dec 1997 | Pregnancy, Bili > 5mg/dL, Mental disorder, Cancer, Early recovery of urine output >30ml/kg/hr prior to RRT | Post Cardiac Surgery | 28 | 14 | 14 | Early: 65; Late: 64 | Early: APACHE2=19; Late: APACHE2=18 | BIOCHEM: UOP <30ml/hr × 3hrs OR UOP <750ml/day; Mean time to RRT start 18d±0.9 post op | UOP<20ml/hr × 2hrs+ OR UOP <500ml/day; Mean time to RRT start 1.7d±0.8 post op | HIGH | 14 d mortality: Early 2/14 died (14%), Late 12/14 died (86%); p<0.01 Favors Early |
Payen, 2009 [7] | RCT, multicenter | France | Jan 1997 - Jan 2000 | Age<18, chronic dialysis, pregnant, moribund state, prior immunosuppressive therapy | Multisystem | 76 | 37 | 39 | Early 58 Late 59 | Early: SOFA 11.6- SAPS2 54.3; Late: SOFA 10.4- SAPS2 52.4 | TIME: Protocolized RRT × 96hrs w/ diagnosis of ‘sepsis’. Mean time to initiation of RRT not specified | Control = No RRT unless metabolic renal failure & classic indications for RRT present | HIGH | Early 20/37 (54%) died, Late 17/37 (44%) died; p = 0.49 |
Jamale, 2013 [15] | RCT, single center | India | April 2010 - July 2012 | Required urgent dialysis at time of randomization | Multisystem | 208 | 102 | 106 | Early 43 Late 42 | Early: SOFA 7.3; Late: SOFA 8.2 | BIOCHEM: Cr > 618μmol/L | Classic indications for RRT, Symptomatic uremia unresponsive to med mgmt | HIGH | Mortality: Early 21/102 (20.5%) died, Late 13/106 (12%); p=0.2 |
Combes, 2015 [16] | RCT, multicenter | USA | 2009-2012 | <18, Pregnant, Chronic RRT, Weight >120kg, SAPS II>90 (i.e. moribund) | Post Cardiac Surgery | 224 | 112 | 112 | Early 61 Late 58 | Early: SOFA 11.5- SAPS2=54; Late: SOFA 12.0- SAPS2=55.1 | TIME: RRT initiated <24hrs and continued for min of 48hrs; Mean time to randomization 12hrs | Classic indications for RRT, Lifethreatening metabolic derangements unresponsive to med mgmt | HIGH | Mortality: Early 40/112 (36%) died, Late 40/112 (36%) died; p = 1.0 |
Wald, 2015 [17] | RCT, multicenter | Canada | May 2012 - Nov 2013 | Intoxication requiring RRT, Limited resuscitation directives, RRT within the previous 2 months, RPGN, Obstructive uropathy, > 48hrs to doubling time of Cr | Multisystem | 100 | 48 | 52 | Early 62 Late 64 | Early: SOFA 13.3 Late: SOFA 12.8 | TIME: Time from randomization < 12h; Mean time to RRT = 9.7hrs | Intensivist judgement regarding hyperkalemia, volume overload, acidemia refractory to medical therapy, Uremic symptoms Mean time to RRT=32hrs | HIGH | Mortality: Early 16/48 (33%) died, Late 19/52 died; p = 0.74 |
RCT Totals | 786 | 404 | 382 | Pooled mortality: Early 120/404 (29.7%), Late 117/382 (30.6%); n=7 | ||||||||||
Prospective Trials | ||||||||||||||
Liu, 2006 [18] | Prospective Observational Multicentre | Multi countries | Feb 1999 - Aug 2001 | GFR<30ml/min/1.73m2 | Multisystem | 243 | 122 | 121 | Early 54 Late 58 | NR | Azotemia defined by BUN<76mg/dL | Azotemia defined by BUN>76mg/dL | LOW NOQA=6 | 28 d mortality: Early 43/122(35%) died vs Late 50/121(41%) P=0.09 Favors Early |
Iyem, 2009 [19] | Prospective Observational cohort | Turkey | May 2004 - April 2007 | Preexisting renal disease and pre operative high levels of urea and creatinine | Post cardiac surgery | 185 | 95 | 90 | Early: 64; Late: 62 | NR | TIME: Evidence of 50% increase in BUN, low urine output (<0.5mL/kg/h) triggering RRT started < 48hrs | TIME > 48hrs to start of RRT for similar markers of renal failure managed medically for minimum 48hrs | LOW NOQA=7 | In hosp mortality: Early 5/95(5%) died, Late 6/90(7%) died; NS |
Bagshaw, 2009 [20] | Prospective Observational Multicentre (BEST Kidney) | 23 countries | Sept 2000 - Dec 2001 | Pre existing chronic RRT, drug toxicity, age <12 | Multisystem | 1227 | 959 | 268 | Early: 60, Delayed: 63, Late: 64; p=0.003 | Early: SOFA 10.9- SAPS2=53.5 Delayed: SOFA 11.1- SAPS2=46 Late: SOFA 10.7- SAPS2=43.1; p=0.04 | TIME: Early RRT started for azotemia (Urea>30mmol/L or low urine output × 12h) <2d (n=785), Delayed RRT started 2-5d (n=174) from ICU admission | RRT started >5d from ICU admission | LOW NOQA=7 | Hosp mortality: Early 462/785(59%) died, Delayed 108/174(62%) died, Late 195/268(72%) died; P<0.0011 Favors Early |
Shiao, 2009 [21] | Prospective Observational Multicentre | Taiwan | Jan 2002 - Dec2005 | Prior dialysis, without surgery, or surgery did not involve abdominal cavity. History of renal trasplant | Major abdominal surgery | 98 | 51 | 47 | Early: 65; Late: 68 | Early: SOFA 8.3- APACHE2=18.2; Late: SOFA 8.5- APACHE2=18.8 | BIOCHEM: RIFLE criteria: RISK or pre-RISK criteria (Mean Time to RRT from ICU Admit = 7.3d) | RIFLE criteria: INJURY or FAILURE criteria (Mean Time to RRT from ICU Admit=8.4d) | HIGH NOQA=7 | Hosp mortality: Early 22/51(43%), Late35/47(75%); p=0.0028 Favors Early |
Sabater, 2009 [22] | Prospective Observational | Spain | 2 years | NR | Multisystem | 148 | 44 | 104 | All patients mean = 60; NR | Early: APACHE2=26; Late: APACHE2=24 | BIOCHEM: RRT initiated for RIFLE: RISK & INJURY; (Mean RRT start 2.2d post ICU admit) | RRT initiated for RIFLE: FAILURE; (Mean RRT start 6.4d post ICU admit) | LOW NOQA=7 | Mortality: Early 21/44 died, Late 68/104 died. P=0.047 Favors Early |
Elseviers, 2010 [23] | Prospective Observational Multicentre | Belgium | 2001-2005 | Pre existing renal disease (Cr<1.5mg/dl), reduced kidney size on ultrasound | Multisystem | 1303 | 653 | 650 | Early 64; Late 67 | Early: SOFA 9.9- APACHE2=25.2; Late: SOFA 8.5- APACHE2=5.2, p=0.001 | BIOCHEM: Unspecified SHARF scoring criteria w/serum Cr > 2mg/dL | Conservative approach = No RRT | LOW NOQA=5 | Mortality: Early 379/653 (58%) died, Late 280/650 (43%) died; p<0.001 Favors Late |
Vaara, 2012 [24] | Prospective Observational Multicentre (FINNAKI Study) | Finland | Sep 2011 - Feb 2012 | NR | Sepsis, Cardiogenic Shock | 261 | NR | NR | NR | Survivors: SAPS2=47; Non-survivors: SAPS2=66 | TIME: Time<24hrs from ICU admit | Time> 24hrs from ICU admit | LOW NOQA=5 | OR for late 2.69 (1.07-6.73, p=0.035). Favors Early |
Perez, 2012 [25] | Prospective Observational | Spain | NR | Sepsis | 244 | 135 | 109 | Early 62; Late 62 | Early: SOFA 12; Late: SOFA 11 | TIME: Time from ICU admission to RRT < 48h | TIME >48hrs | LOW NOQA=5 | 90 d mortality: Early 71/135(53%) died, Late 78/109(72%) died; p=0.003. Favors Early | |
Lim, 2014 [27] | Single Centre Prospective Cohort | Singapore | Dec 2010 - April 2013 | Chronic dialysis patients, Dialysis initiated prior to ICU admission | Medical & Surgical patients | 140 | 84 | 56 | Early 60; Late 64 | Early: SOFA 7; Late: SOFA 11; p=0.001 | BIOCHEM: AKIN stage 1 or 2 AND compelling indication or AKIN stage 3 (Cr≥354μmol/l or Cr>300% baseline w/urine <0.3cc/kg/h for 24h or anuria >12h) | Traditional indications: K>6mmol/L, Urea ≥30mmol/L, pH<7.25, Bicarb <10mmol/L, Pulm edema, Uremic encephalopathy/pericarditis | LOW NOQA=6 | Hosp mortality: Early 36/84(43%) died, Late 37/56(66%) died; p=0.007 Favors Early |
Jun, 2014 [26] | Nested Observational, Multi-Centre Study ‘RENAL’ Study Group | NZ, Australia | Dec 2005 - Nov 2008 | Age<18, Prior RRTduring admission, Prior RRT for CKD | Sepsis | 439 | 219 | 220 | Early 65; Late 64 | Early: SOFA: 2.0- APACHE3=107, Late: SOFA 2.1- APACHE3=100, P<0.001 | TIME: AKI diagnosis to randomization < 17.6 hrs | Time from AKI diagnosis to randomization >17.6hrs | LOW NOQA=6 | 28 d mortality: Early 82/219(37%) died; Late 84/220(38%) died (p=0.923) NS |
PROSPECTIVE TOTALS | 4288 | 2362 | 1665 | Pooled mortality: Early 1229/2362 (52%), Late 833/1665 (50%); n=10 | ||||||||||
Retrospective Trials | ||||||||||||||
Gettings, 1999 [28] | Retrospective cohort | USA | 1989 - 1997 | CRRT duration <48hrs, Pediatric patients, Incomplete records | Trauma | 100 | 41 | 59 | Early 40; Late 48 | Early ISS = 33.0; Late ISS = 37.2 | BIOCHEM: BUN < 60mg/dL AND Oliguria, Vol overload, Electrolytes, Uremia; Mean RRT start post admission day 10; p<0.0001 | BUN > 60 mg/dL AND Oliguria, Vol overload, Electrolytes, Uremia; Mean RRT start post admission day 19 | LOW NOQA=5 | Hosp mortality: Early 25/41(61%) died, Late 47/59(80%) died; p=0.041 Favors Early |
Elahi, 2004 [29] | Retrospective cohort | UK | Jan 2002 - Jan 2003 | Preexisting renal disease | Post cardiac surgery | 64 | 36 | 28 | Early 69; Late 68 | NR | BIOCHEM: Low urine output = less than 100 ml within 8h after surgery;Mean RRT start 0.78 days | Traditional indications: Urea ≥30mmol/L, Cr Elahi, 2004 [29] ≥250mmol/L, K > 6.0mEq/L; Mean RRT start 2.5 days | LOW NOQA=6 | 28 d mortality: Early-8/36 died (22%), Late-12/28 (43%); p<0.05 Favors Early |
Demirkilic, 2004 [30] | Retrospective cohort | Turkey | Mar 1992 - Sep 2001 | NR | Post Cardiac Surgery | 61 | 34 | 27 | NR p=0.3 | NR | BIOCHEM: Low urine output = less than 100ml within 8hrs post op; Mean RRT start 0.88 days | Cr≥5mg/dL, or K>5.5 mEq/L w/med mgmt; Mar 92-Jun 96; Mean RRT start 2.56 days | LOW NOQA=6 | Hosp mortality: Early 8/34(23%), Late 15/27(56%); P=0.016 Favors Early |
Wu, 2007 [32] | Retrospective cohort | Taiwan | July 2002- Jan2005 | Hepatorenal syndrome from cirrhosis, liver trasplant, cardiopolmunary resuccitation | Acute liver failure | 80 | 54 | 26 | Early 55; Late 63; p=0.03 | Early: SOFA 12.4- APACHE2=18.2; Late: SOFA 13.2- APACHE2=20.5 | BIOCHEM: BUN < 80 mg/dL AND traditional indications present | Traditional indications present with BUN > 80mg/dL | LOW NOQA=6 | 30 d mortality: Early 34/54(63%) died vs Late 22/26(85%) died; P=0.04 Favors Early |
Andrade, 2007 [31] | Retrospective cohort | Brazil | 2002-2005 | Patients who did not have both AKI and respiratory failure believed secondary to leptospirosis | Leptospirosis | 33 | 18 | 15 | Early 42; Late 44 | Early: APACHE2=24.5; Late: APACHE2=26 | TIME: Mean time to RRT = 265 min | Mean time to RRT = 1638 min | LOW NOQA=5 | Hosp mortality: Early 3/18(17%) died, Late 10/15(67%) died; P=0.01 Favors Early |
Manche, 2008 [33] | Retrospective cohort | Malta | 1995-2006 | NR | Post Cardiac Surgery | 71 | 56 | 15 | Early 66; Late 63 | NR | BIOCHEM: Urine output<0.5ml/kg/hr unresponsive to med mgmt; Mean RRT start 8.6hrs post-op | Oliguria (output < 0.5ml/Kg/hr) refractory to med mgmt; Mean RRT start 41.2hrs post-op | LOW NOQA=6 | Mortality: Early 14/56(25%) died, Late 13/15(87%) died; P=0.0000125 Favors Early |
Lundy, 2009 [34] | Retrospective cohort | US | Nov 2005 - Aug 2007 | Preexisting renal disease, burn size of less than 40% Non-thermal injury, lithium toxicity | Severe Burned patients | 57 | 29 | 28 | Early 27; Late 38 P=0.06 | Early: SOFA 13- APACHE2=35; Late: SOFA 13- APACHE2=36 | BIOCHEM: AKIN stage 2(+shock)/3; Mean time from admit to RRT = 17 days | Mean time from admit to AKIN stage 2(+shock)/3 but not dialyzed = 23 days | LOW NOQA=6 | 28 d mortality: Early 9/29(31%) died, Late 24/28(85%) died; P<0.002; Favors Early |
Carl, 2010 [35] | Retrospective cohort | US | 2000-2004 | Baseline eGF0R <30ml/min, Age <18 & prisoners | Sepsis | 147 | 85 | 62 | Early 52; Late 56 | Early: APACHE2=24.8; Late: APACHE2=24.7 | BIOCHEM: BUN <100mg/dL + AKIN stage >2; Mean ICU stay prior to RRT =6.3days | BUN > 100mg/dL + AKIN stage >2; Mean ICU stay prior to RRT=12.3days | HIGH NOQA=7 | 28 d mortality: Early 44/85(52%) died, Late 42/62(68%); P<0.05 Favors Early |
Chou, 2011 [37] | Retrospective cohort ‘NSARF’ database | Taiwan | Jan 2002 - Oct 2009 | Age< 18, ICU stay <2days, RRT < 2days | Sepsis + AKI | 370 | 192 | 178 | Early 64; Late 66 | Early: SOFA 10.8- APACHE2=12.3; Late: SOFA 11.6- APACHE2=14.0 | BIOCHEM: RIFLE criteria: RISK or pre-RISK criteria | RIFLE criteria: INJURY or FAILURE criteria | LOW NOQA=6 | Hosp mortality: Early 135/192(71%) died, Late 124/178 (70%) died (P=0.98) |
Vats, 2011 [38] | Retrospective cohort | USA | Jan1999 - Feb 2006 | Renal transplant, Pre-morbid ESRD on dialysis, RRT<24h, insufficient data | Multisystem | 230 | NR | NR | All patients mean = 66 NR | NR | TIME: Time from AKI to RRT < 6 days | Time from AKI to RRT≥6d | LOW NOQA=5 | OR for Late Mortality (>6d) 11.66 (1.26-107.9) P=0.0305, Favors Early |
Ji, 2011 [36] | Retrospective cohort | China | Ap 2004 - Mar 2009 | Patients readmitted post discharge, Discharged against medical advice, Death <24hrs | Post cardiac surgery | 58 | 34 | 24 | Early 64; Late 62 | Early: APACHE3=69.3; Late: APACHE3=88.2 p<0.001 | TIME: Time from urine output <0.5ml/kg/h to RRT<12h; Mean oliguria to start of RRT 8.4hrs | Urine output <0.5ml/kg/h & Time to RRT>12h post oliguria; Mean oliguria to start of RRT 21.5hrs | LOW NOQA=6 | Hosp mortality: Early 3/34 (9%) died, Late 9/24 (37%); p=0.02 Favors Early |
Shiao, 2012 [41] | Retrospective cohort ‘NSARF’ database | Taiwan | Jan 2002 - Apr 2009 | Dialysis before surgery, ESRD | Surgical | 648 | 436 | 212 | Early 62; Late 66; P=0.009 | Early: SOFA 11.4- APACHE2=12.7; Late: SOFA 11.3- APACHE2=12.8 | TIME: Time to development of tradtional RRT indications < 3d; Mean time to start of RRT 1.4days | Traditional RRT indications AND start of RRT > 3 days; Mean time to start of RRT 18days | LOW NOQA=6 | Hosp mortality: Early 236/436 (54%) died, Late 143/212 (67%) died; P=0.001 Favors Early |
Chon, 2012 [40] | Retrospective cohort | South Korea | Apr 2009 - Oct 2010 | Liver cirrhosis, Pre existing chronic | Sepsis | 55 | 36 | 19 | Early 63; Late 62 | Early: SOFA 13.5- APACHE2= 28.7; Late: SOFA 12- APACHE2=28.3 | TIME: Time to RIFLE ‘Injury’/‘Failure’ < 24hrs; Mean time to RRT=12.5hrs | Time to RIFLE ‘Injury’/‘Failure’ > 24hrs; Mean time to RRT= 42.2hrs | HIGH NOQA=7 | 28 d mortality: Early 7/36(38%), Late 9/19(47%); P=0.03 Favors Early |
Boussekey, 2012 [39] | Retrospective cohort | France | Jan 2008 - Dec 2010 | Early trasfer to another unit | Multisystem | 110 | 67 | 43 | Early 62; Late 66 | Early: SOFA: 11.1- SAPS2=70; Late: SOFA 8.8- SAPS2=57; p=0.002 | TIME: Time from RIFLE- ‘Injury’ to RRT < 16hrs; Mean time to RRT=6hrs | Time from RIFLE-‘Injury’ to RRT > 16hrs; Mean time to RRT=64hrs | LOW NOQA=7 | 28 d mortality: Early-28/67 (41%), Late- 28/43 (65%); P = 0.0425 Favors Early |
Suzuki, 2013 [43] | Retrospective cohort | Japan | Jan 2009 - Feb 2013 | <18, RRT for ESRD | Sepsis, Cardiogenic Shock | 189 | 52 | 137 | All patients mean = 72 NR | All patients SAPS II Mean= 57 | BIOCHEM: RIFLE ‘Risk’ | RIFLE ‘Injury’ or ‘Failure’ | LOW NOQA=6 | Early: OR 0.361 (95 % CI 0.17–0.78); P = 0.009, Favors Early |
Shum, 2013 [43] | Retrospective cohort | China | Jan 2008 - Jun 2011 | Age<18, Chronic dialysis, RRT prior to ICU | Sepsis | 120 | 31 | 89 | qEarly 74; Late 73 | Early: SOFA 12- APACHE4=119; Late: SOFA 13- APACHE4=133; P=0.011 | BIOCHEM: sRIFLE-‘pre- Risk’ or ‘Risk’ criteria; Mean time from ICU admit to RRT =20.7hrs, P=0.056 | sRIFLE ‘Injury’ or ‘Failure’ criteria; Mean time from ICU admit to RRT=10.8hrs | LOW NOQA=6 | 28 d mortality: Early-15/31 died (48.4%), Late- 43/89 died (48.3%); P=0.994 |
Tian, 2014 [46] | Retrospective cohort | China | Nov 2009 - Dec 2011 | Age < 12, Chronic renal disease, Terminal illness,0 Pre-admit CRRT, ICU stay < 72hrs | Sepsis - AKIN 1 | 49 | 23 | 26 | Early 48; Control 54 | Early: SOFA 7.6- APACHE2=12.9; Control: SOFA 8.4- APACHE2=15.3 | BIOCHEM: AKIN 1 (Cr≥26.4μmol/L or >150- 200% baseline & urine <0.5cc/kg/h for >6h) | No RRT (Control): Patients refused CRRT for “personal reasons” | LOW NOQA=6 | 28 d mortality: Early 5/23(22%) died, Control 11/26 (42%) died (NS) |
Sepsis - AKIN 2 | 52 | 31 | 21 | Early 54; Control 61 | Early: SOFA 9.3- APACHE2=19; Control SOFA 9.6- APACHE2=18.3 | AKIN 2 (Cr>200-300% baseline & urine <0.5cc/kg/h for >12h) | No RRT (Control): Patients refused CRRT for “personal reasons” | 28 d mortality: Early 12/31 (39%) died, Control 14/21 (67%) died; P<0.05 Favors Early | ||||||
Sepsis - AKIN 3 | 59 | 46 | 13 | Early 50; Control 55 | Early SOFA 10- APACHE2=21.8; Control SOFA 11.2- APACHE2=20.5 | AKIN 3 (Cr≥354μmol/L or Cr>300% baseline w/urine <0.3cc/kg/h for 24h or anuria >12h) | No RRT (Control): Patients refused CRRT for “personal reasons” | 28 d mortality: Early 31/46(67%) died, Control 11/13(85%) died; NS | ||||||
Serpytis, 2014 [45] | Retrospective cohort | Lithuania | 2007-2011 | NR | Sepsis | 85 | 42 | 43 | All patients mean = 72 NR | NR | TIME: Time from anuria to RRT < 12hrs | Time from anuria to RRT > 12hrs | LOW NOQA=5 | Mortality: Early 30/42 (71%) died, Late 39/43(91%) died; p=0.028; Favors Early |
Gaudry, 2014 [44] | Retrospective cohort | France | Jan 2004 - Nov 2011 | Age<18, limitation in medical therapy, death<24hrs, chronic renal insufficiency, RRT prior to ICU, kidney transplant, lithium toxicity, multiple myeloma | Sepsis | 203 | 91 | 112 | Early 65; Late 65 | Early: SOFA 9- SAPS2=60; Control SOFA 8- SAPS2=55, P<0.01 | BIOCHEM: RRT criteria: Cr≥300μmol/L, Urea>25mmol/L, K>6.5mmol/L, pH<7.2, Oliguria, Vol overload, | No RRT initiated/Criteria not met for RRT | LOW NOQA=5 | Hosp Mortality: Early 44/91(48%) died, Control (No RRT) 29/112 (26%) died; P<0.001 Favors no RRT |
Retrospective TOTALS | 2841 | 1434 | 1177 | Pooled mortality: Early 714/1434 (50%), Late 732/1177 (62.2%); n=19 | ||||||||||