Association of oliguria with the development of acute kidney injury in the critically ill
2015; Elsevier BV; Volume: 89; Issue: 1 Linguagem: Inglês
10.1038/ki.2015.269
ISSN1523-1755
AutoresSuvi T. Vaara, Ilkka Parviainen, Ville Pettilä, Sara Nisula, Outi Inkinen, Ari Uusaro, Raili Laru‐Sompa, Anni Pulkkinen, Minna Saarelainen, Mikko Reilama, Sinikka Tolmunen, Ulla Rantalainen, Markku Suvela, Katrine Pesola, Pekka Saastamoinen, Ville Pettilä, Kirsi‐Maija Kaukonen, Anna‐Maija Korhonen, Sara Nisula, Suvi T. Vaara, Raili Suojaranta-Ylinen, Leena Mildh, Mikko Haapio, Laura Nurminen, Sari Sutinen, Leena Pettilä, Helinä Laitinen, Heidi Syrjä, Kirsi Henttonen, Elina Lappi, Tero Varpula, Päivi Porkka, Mirka Sivula, Mira Rahkonen, Anne Tsurkka, Taina T. Nieminen, Ari Alaspää, Ville Salanto, Hanna Juntunen, Ilkka Parviainen, Ari Uusaro, Esko Ruokonen, Stepani Bendel, Niina Rissanen, Maarit Lång, Sari Rahikainen, Saija Rissanen, Merja Ahonen, Elina Halonen, Meri Poukkanen, Esa Lintula, Jorma Heikkinen, Timo Lavander, Kirsi Heinonen, Tadeusz Kamiński, Fiia Gäddnäs, Tuija Kuusela, Sari Karlsson, Matti Reinikainen, Tero Surakka, Helena Jyrkönen, Tanja Eiserbeck, Tero Ala‐Kokko, Jouko Laurila, Vesa Lund, Päivi Tuominen, Pauliina Perkola, Riikka Tuominen, Marika Hietaranta, Seppo Hovilehto, Anne Kirsi, Pekka Tiainen, Tuija Myllärinen, Pirjo Leino, Anne Kuitunen, Jyrki Tenhunen, Ilona Leppänen, Markus Levoranta, Sanna Hoppu, Jukka Sauranen, Atte Kukkurainen, Samuli Kortelainen, Outi Inkinen, Niina Koivuviita, Jutta Kotamäki, Simo-Pekka Koivisto, Raku Hautamäki, Maria Skinnar,
Tópico(s)Chronic Kidney Disease and Diabetes
ResumoUrine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria (<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy (RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%) developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6–12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h. Thus, our findings underlie the importance of hourly UO measurements. Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria (<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy (RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%) developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6–12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h. Thus, our findings underlie the importance of hourly UO measurements. Acute kidney injury (AKI) is a frequently diagnosed syndrome in the intensive care unit (ICU) that associates with increased mortality.1Uchino S. Kellum J.A. Bellomo R. et al.Acute renal failure in critically ill patients: a multinational, multicenter study.JAMA. 2005; 294: 813-818Crossref PubMed Scopus (3154) Google Scholar, 2Chertow G.M. Burdick E. Honour M. et al.Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.J Am Soc Nephrol. 2005; 16: 3365-3370Crossref PubMed Scopus (2502) Google Scholar, 3Joannidis M. Metnitz B. Bauer P. et al.Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database.Intensive Care Med. 2009; 35: 1692-1702Crossref PubMed Scopus (385) Google Scholar The diagnosis of AKI is based on an abrupt increase in plasma creatinine (Cr) and/or a decrease in urine output (UO).4Bellomo R. Ronco C. Kellum J.A. et al.Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care. 2004; 8: R204-R212Crossref PubMed Google Scholar, 5Mehta R.L. Kellum J.A. Shah S.V. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5230) Google Scholar, 6Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group: KDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Abstract Full Text Full Text PDF Scopus (1987) Google Scholar Even small increases in Cr are associated with increased short- and long-term mortality and morbidity.2Chertow G.M. Burdick E. Honour M. et al.Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.J Am Soc Nephrol. 2005; 16: 3365-3370Crossref PubMed Scopus (2502) Google Scholar, 6Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group: KDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Abstract Full Text Full Text PDF Scopus (1987) Google Scholar Cr criteria for AKI have been extensively studied7Ricci Z. Cruz D. Ronco C. The RIFLE criteria and mortality in acute kidney injury: a systematic review.Kidney Int. 2008; 73: 538-546Abstract Full Text Full Text PDF PubMed Scopus (619) Google Scholar and recently updated.6Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group: KDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Abstract Full Text Full Text PDF Scopus (1987) Google Scholar On contrary, the UO criterion has been empirically derived4Bellomo R. Ronco C. Kellum J.A. et al.Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care. 2004; 8: R204-R212Crossref PubMed Google Scholar, 5Mehta R.L. Kellum J.A. Shah S.V. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5230) Google Scholar and its further validation has been suggested.5Mehta R.L. Kellum J.A. Shah S.V. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5230) Google Scholar Few studies, however, have been able to employ it without modifications. Combining UO and Cr criteria increases the sensitivity of the AKI definition.3Joannidis M. Metnitz B. Bauer P. et al.Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database.Intensive Care Med. 2009; 35: 1692-1702Crossref PubMed Scopus (385) Google Scholar, 8Macedo E. Malhotra R. Bouchard J. et al.Oliguria is an early predictor of higher mortality in critically ill patients.Kidney Int. 2011; 80: 760-767Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar, 9McIlroy D.R. Argenziano M. Farkas D. et al.Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes.J Cardiothorac Vasc Anesth. 2013; 27: 1145-1152Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 10Wlodzimirow K.A. Abu-Hanna A. Slabbekoorn M. et al.A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ill patients.Crit Care. 2012; 16: R200Crossref PubMed Scopus (101) Google Scholar A recent database analysis showed that patients with both UO and Cr criteria had highest short- and long-term mortality rates.11Kellum J.A. Sileanu F.E. Murugan R. et al.Classifying AKI by Urine Output versus SerumCreatinine Level.J Am Soc Nephrol. 2015; Google Scholar Isolated oliguria without fulfillment of Cr criterion also associated with long-term mortality11Kellum J.A. Sileanu F.E. Murugan R. et al.Classifying AKI by Urine Output versus SerumCreatinine Level.J Am Soc Nephrol. 2015; Google Scholar and in some studies UO has outperformed Cr in mortality prediction.12Mandelbaum T. Lee J. Scott D.J. et al.Empirical relationships among oliguria, creatinine, mortality, and renal replacement therapy in the critically ill.Intensive Care Med. 2013; 39: 414-419Crossref PubMed Scopus (38) Google Scholar, 13Mandelbaum T. Scott D.J. Lee J. et al.Outcome of critically ill patients with acute kidney injury using the Acute Kidney Injury Network criteria.Crit Care Med. 2011; 39: 2659-2664Crossref PubMed Scopus (124) Google Scholar Oliguria (UO <0.5 ml/kg/h) has been shown to associate with occurrence of AKI by Risk, Injury, Failure, Loss of Function, and End-stage Renal Disease Cr criterion, but to be only a fair predictor of consequent AKI.14Prowle J.R. Liu Y.L. Licari E. et al.Oliguria as predictive biomarker of acute kidney injury in critically ill patients.Crit Care. 2011; 15: R172Crossref PubMed Scopus (165) Google Scholar Among patients with septic shock, consecutive oliguria of 3–5 h has been demonstrated to predict occurrence of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 or 3 AKI by Cr criterion.15Leedahl D.D. Frazee E.N. Schramm G.E. et al.Derivation of urine output thresholds that identify a very high risk of AKI in patients with septic shock.Clin J Am Soc Nephrol. 2014; 9: 1168-1174Crossref PubMed Scopus (40) Google Scholar However, a single center study found that UO <0.3 ml/kg/h for 6 h corresponded to the current Cr-based definition of AKI better than UO <0.5 ml/kg/h for 6 h, and was associated with mortality after adjustments whereas UO <0.5 ml/kg/h was not.16Md Ralib A. Pickering J.W. Shaw G.M. et al.The urine output definition of acute kidney injury is too liberal.Crit Care. 2013; 17: R112Crossref PubMed Scopus (93) Google Scholar Moreover, UO is prone to confounders such as use of diuretics, differences in fluid management and balance, and in administration of renal replacement therapy (RRT). In this large prospective multicenter study we aimed to find out whether the empirically derived threshold for oliguria <0.5 ml/kg/h is independently associated with adverse outcome. We studied the confounder-adjusted association of oliguria of different severity (mild oliguria from 0.3 to <0.5 ml/kg/h, moderate oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria <0.1 ml/kg/h) and their duration (3–6 h, 6–12 h, 12–24 h, and over 24 h) primarily with the development of AKI defined by Cr criterion (Cr-AKI) or administration of RRT. Secondarily, we studied the association of oliguria with 90-day mortality. After exclusions presented in the study flow chart (Figure 1), 2160 patients were included in the analysis. Altogether 924 patients (42.8%) fulfilled the KDIGO criteria (UO, Cr, or RRT) for AKI. Of all, 225 (10.4%) patients received RRT, and 222 patients commenced RRT within the first 24 h in the ICU. The 90-day mortality (95% confidence interval) of all AKI patients was 29.3% (26.4–32.3%). Patients, who fulfilled both Cr and UO criteria, were most severely ill and had the highest rates for administration of RRT and 90-day mortality (Table 1).Table 1Incidence, patient characteristics, and outcomes according to the presence of UO and/or Cr criteria for AKINo AKIUO-AKICr-AKICr and UO AKIP-valueaComparison between UO-AKI, Cr-AKI, and UO and Cr AKI groups.No of patients – number (%; 95% CI)1246 (57.7; 55.6–59.8%)296 (13.7; 12.3–15.2%)306 (14.2; 12.7–15.6%)312 (14.4; 13.0–15.9%)Age63 (52–73)64 (54–73)66 (56–75)68 (57–77)<0.001Male sex795 (63.8)196 (66.2)205 (67.0)207 (66.3)0.63Chronic kidney disease43 (3.5)21 (7.1)33 (10.8)45 (14.4)<0.001Chronic heart failure138 (11.1)35 (11.8)38 (12.4)54 (17.3)0.02Hypertension548 (44.0)146 (49.3)174 (56.9)184 (59.0)<0.001Operative admission495 (39.7)123 (41.6)93 (30.4)117 (37.5)0.01Emergency admission1036 (83.1)247 (83.4)271 (88.6)273 (87.5)0.03SAPS II score34.0 (27.0–44.0)36.5 (29.0–50.0)41.0 (34.0–49.3)51.0 (38.0–64.0)<0.001Non-renal non-age SAPS II score21.0 (14.0–30.0)23.0 (16.0–33.0)21.5 (15.0–29.0)25.0 (17.0–34.0)0.01SOFA score, day 17 (4–8)7 (6–9)8 (6–10)10 (8–13)<0.001Severe sepsis diagnosed by day 5317 (25.4)82 (27.7)150 (49.0)167 (53.5)<0.001Use of vasoactives (admission day)732 (58.7)221 (74.7)222 (72.7)262 (84.0)<0.001Use of diuretics (admission day)357 (28.7)87 (29.4)137 (44.8)141 (45.2)<0.001Cumulative UO within first 24 h in ICU (ml/kg/h)2500 (1859–3546)1720 (1195–2512)2300 (1725–3749)787 (295–1406)<0.001Fluid accumulation % of baseline weight on day 11.4 (−1.1–3.7)2.0 (0.3–5.3)1.9 (−0.4–5.3)5.1 (1.8–9.7)<0.001Highest AKI stagebCr-AKI by Cr criterion, UO-AKI by UO criterion, Cr- or UO-AKI by the 1 with the highest stage. Stage 1—235 (79.4)157 (51.3)43 (13.8) Stage 2—47 (15.9)90 (29.4)72 (23.1) Stage 3—14 (4.7)59 (19.3)197 (63.1)RRT – number (%; 95% CI)10 (0.8; 0.3–1.3%)20 (6.8; 3.9–9.6%)23 (7.5; 4.6–10.5%)172 (55.1; 49.6–60.6%)<0.001Length of stay in the ICU (days)2.7 (1.8–5.2)3.8 (2.2–7.3)3.7 (2.2–5.4)4.5 (2.7–9.0)<0.00190-day mortality – number (%; 95% CI)207 (16.6; 14.5–18.7%)80 (27.0; 22.0–31.1%)60 (19.6; 15.2–24.1%)129 (41.3; 35.9–46.8%)<0.001AKI, acute kidney injury; CI, confidence interval; Cr, creatinine; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment; SAPS, Simplified Acute Physiology Score; UO, urine output.P-values for comparisons of separate groups. Fluid accumulation: no AKI versus Cr-AKI <0.001, no AKI versus UO-AKI <0.001, and UO-AKI versus Cr-AKI 0.85. RRT: no AKI versus Cr-AKI <0.001, no AKI versus UO-AKI <0.001, and UO-AKI versus Cr-AKI 0.75. Ninety-day mortality: no AKI versus Cr-AKI 0.24, no AKI versus UO-AKI <0.001, and UO-AKI versus Cr-AKI 0.03. Data presented as median (interquartile range) or number (%).a Comparison between UO-AKI, Cr-AKI, and UO and Cr AKI groups.b Cr-AKI by Cr criterion, UO-AKI by UO criterion, Cr- or UO-AKI by the 1 with the highest stage. Open table in a new tab AKI, acute kidney injury; CI, confidence interval; Cr, creatinine; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment; SAPS, Simplified Acute Physiology Score; UO, urine output. P-values for comparisons of separate groups. Fluid accumulation: no AKI versus Cr-AKI <0.001, no AKI versus UO-AKI <0.001, and UO-AKI versus Cr-AKI 0.85. RRT: no AKI versus Cr-AKI <0.001, no AKI versus UO-AKI <0.001, and UO-AKI versus Cr-AKI 0.75. Ninety-day mortality: no AKI versus Cr-AKI 0.24, no AKI versus UO-AKI <0.001, and UO-AKI versus Cr-AKI 0.03. Data presented as median (interquartile range) or number (%). At least one episode of oliguria (UO below 0.5 ml/kg/h for a minimum of 0.5 h) occurred in 1990 (92.1%) patients. Episodes longer than 30 min of moderate oliguria (UO <0.3 ml/kg/h) occurred in 1694 (78.4%) of the patients and of severe oliguria (UO <0.1 ml/kg/h) in 900 (41.7%) of the patients. The median (interquartile range) day of the beginning of the longest oliguric episode was day 1 (0–2). Altogether 608 (28.1%) patients had oliguria with UO <0.5 ml/kg/h for ≥6 consecutive hours, and thus, oliguric AKI. Of these, 330 (54.3%) had stage 1 AKI, 132 (21.7%) stage 2 AKI, and 146 (24.0%) stage 3 AKI according to the KDIGO UO criterion. As short episodes of oliguria of all severities were very frequent, categories of UO from 0.3 to <0.5 ml/kg/h and from 0.1 to <0.3 ml/kg/h were formed by excluding patients with more severe oliguria for longer than 3 h. The incidence of oliguric episodes (the longest episode of each patient included) of different degrees of severity is presented in Table 2.Table 2Incidence of separate types of oliguric episodes3–6 h6–12 h12–24 hOver 24 hBefore diagnosis of AKI by Cr/RRT or until day 5 if no AKI (n = 1966)a219 (11.1%) With no oliguria and 705 (35.9%) with oliguria lasting <3 h. 0.3 to <05 ml/kg/h385 (19.6%)113 (5.7%)6 (0.3%)0 0.1 to <03 ml/kg/h320 (16.3%)78 (4.0%)3 (0.2%)0 <0.1 ml/kg/h85 (4.3%)38 (1.9%)14 (0.7%)0During ICU stay until day 5 (n = 2160)b170 (7.9%) With no oliguria and 731 (33.8%) with oliguria lasting <3 h. 0.3 to <0.5 ml/kg/h411 (19.0%)116 (5.4%)5 (0.2%)0 0.1 to <0.3 ml/kg/h342 (15.8%)79 (3.7%)12 (0.6%)0 <0.1 ml/kg/h110 (5.1%)60 (2.8%)58 (2.7%)66 (3.1%)AKI, acute kidney injury; Cr, creatinine criterion; ICU, intensive care unit; RRT, renal replacement therapy.a 219 (11.1%) With no oliguria and 705 (35.9%) with oliguria lasting <3 h.b 170 (7.9%) With no oliguria and 731 (33.8%) with oliguria lasting <3 h. Open table in a new tab AKI, acute kidney injury; Cr, creatinine criterion; ICU, intensive care unit; RRT, renal replacement therapy. We studied the association of oliguria and development of AKI based on Cr criterion and/or initiation of RRT (AKI by Cr/RRT) in 1966 patients. Because 194 patients developed AKI by Cr/RRT within 3 h from ICU admission, they were excluded from the analysis regarding the development of AKI. UO data were screened until the diagnosis of AKI by Cr/RRT and among those who did not develop AKI, until ICU discharge or day 5. Of the 1966 patients, 454 (23.1%) developed AKI by Cr/RRT, 312 (68.7%) of them developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. The median (interquartile range) time to reach AKI diagnosis by Cr/RRT was 16.9 (10.7–34.3) hours. Altogether 1747 (88.9%) patients had at least one oliguric episode lasting over 30 min. Oliguric AKI was diagnosed in 147 (32.4%) patients before the diagnosis of AKI by Cr/RRT and in 276 (18.3%) of those who did not develop AKI by Cr/RRT criteria (P < 0.001). Episodes of UO <0.5 ml/kg/h for more than 12 h occurred in 94 (4.8%) patients, and 52 (55.3%) of them developed AKI by Cr/RRT. None of the patients presented with oliguria lasting over 24 h. Figure 2 presents the proportions of patients who developed AKI by Cr/RRT according to the severity and duration of oliguria. Of the 1042 patients with UO <0.5 ml/kg/h for more than 3 h, only 248 (23.8%) did not receive diuretics in the ICU. We constructed logistic regression models to study the independent association of different types of oliguric episodes with the development of AKI by Cr/RRT. The reference group comprised those with no oliguria or oliguric episodes lasting <3 h. We adjusted for age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II diagnosis group, Simplified Acute Physiology Score (SAPS) II score without age and renal components, use of vasoactives, diuretics, and the cumulative fluid balance (% of baseline weight) on the day of oliguric episode. The results of the regression models are presented in Table 3. UO from 0.3 to <0.5 ml/kg/h for 3–6 h was associated with a decreased risk for the development of AKI by Cr/RRT. UO <0.1 ml/kg/h for 3–6 h, 6–12 h, or 12–24 h were the only oliguric episodes that were associated with an increased risk for the development of AKI by Cr/RRT.Table 3Univariate and multivariateaAdjusted for age, sex, Acute Physiology And Chronic Health Evaluation II diagnosis group, Simplified Acute Physiology Score II score without age and renal components, use of vasoactives, diuretics, and the cumulative fluid balance (% of baseline weight) on the day of oliguric episode. regression models for the development of AKI based on Cr criterion or initiation of RRTNo with endpoint/no with episodeUnivariate odds ratio (95% CI)bResults are relative to those without oliguria or with oliguria lasting <3 h.Univariate P-valueMultivariable odds ratio (95% CI)bResults are relative to those without oliguria or with oliguria lasting <3 h.Multivariable P-valueUO from 0.3 to <0.5 ml/kg/h 3–6 h59/385 (15.3%)0.65 (0.47–0.89)0.010.55 (0.39–0.77)<0.001 Over 6 h27/119 (22.7%)1.05 (0.67–1.66)0.840.38 (0.12–1.27)cIncludes interaction term between oliguria and use of vasoactives.0.12UO from 0.1 to <0.3 ml/kg/h 3–6 h68/320 (21.3%)1.07 (0.79–1.44)0.660.84 (0.61–1.15)0.28 Over 6 h27/81 (33.3%)1.98 (1.23–3.20)0.011.43 (0.85–2.42)0.18UO <0.1 ml/kg/h 3–6 h38/85 (44.7%)3.05 (1.96–4.75)<0.0012.17 (1.35–3.48)<0.001 6–12 h23/38 (60.5%)5.79 (2.99–11.20)<0.0012.95 (1.20–7.25)dIncludes interaction term of presence of oliguria and cumulative fluid balance.0.02 12–24 h10/14 (71.4%)9.44 (2.94–30.26)<0.0015.74 (1.67–19.73)0.01AKI, acute kidney injury; CI, confidence interval; Cr, creatinine; RRT, renal replacement therapy; UO, urine output.a Adjusted for age, sex, Acute Physiology And Chronic Health Evaluation II diagnosis group, Simplified Acute Physiology Score II score without age and renal components, use of vasoactives, diuretics, and the cumulative fluid balance (% of baseline weight) on the day of oliguric episode.b Results are relative to those without oliguria or with oliguria lasting <3 h.c Includes interaction term between oliguria and use of vasoactives.d Includes interaction term of presence of oliguria and cumulative fluid balance. Open table in a new tab AKI, acute kidney injury; CI, confidence interval; Cr, creatinine; RRT, renal replacement therapy; UO, urine output. Of the 2160 studied patients, 476 (22.0%; 95% confidence interval 20.3–23.8%) had died by day 90. Crude 90-day mortality rose along with increasing severity of oliguria (Figure 3). When patients treated with RRT were excluded, the 90-day mortality of patients with oliguric episodes below 12 h was comparable to the main cohort (sensitivity analysis as Supplementary Figure S1 online). In univariate analysis, oliguric episodes from 0.3 to <0.5 ml/kg/h for over 6 h and more severe episodes were associated with 90-day mortality (Table 4).Table 4Univariate and multivariableaAdjusted for: age, sex, Acute Physiology And Chronic Health Evaluation II diagnosis group, Simplified Acute Physiology Score II score without age and renal components, use of vasoactives, diuretics, and RRT, and the cumulative fluid balance (% of baseline weight) on the day of oliguric episode. regression models for 90-day mortalityCrude 90-day mortalitybExpressed as number/total number of patients with episode (%).Univariate odds ratio (95% CI)cResults are relative to those without oliguria or with oliguria lasting <3 h.Univariate P-valueMultivariable odds ratio (95% CI)cResults are relative to those without oliguria or with oliguria lasting <3 h.Multivariable P-valueUO from 0.3 to <0.5 ml/kg/h 3–6 h69/411 (16.8%)1.06 (0.078–1.45)0.710.96 (0.68–1.37)0.83 Over 6 h31/121 (25.6%)1.81 (1.16–2.83)0.011.65 (1.00–2.72)0.05UO from 0.1 to <0.3 ml/kg/h 3–6 h78/342 (22.8%)1.44 (1.08–1.92)0.011.20 (0.87–1.65)0.28 Over 6 h26/91 (28.6%)1.95 (1.21–3.14)0.011.96 (1.13–3.38)0.02UO <0.1 ml/kg/h 3–6 h34/110 (30.9%)1.95 (1.28–2.97)0.012.08 (1.27–3.42)0.01 6–12 h24/60 (40.0%)2.91 (1.71–4.94)<0.0013.04 (1.50–6.15)0.01 12–24 h31/58 (53.4%)5.01 (2.95–8.50)<0.0016.78 (2.79–16.44)<0.001 Over 24 h39/66 (59.1%)6.30 (3.81–10.43)<0.0019.76 (4.07–23.43)<0.001RRT, renal replacement therapy; UO, urine output.a Adjusted for: age, sex, Acute Physiology And Chronic Health Evaluation II diagnosis group, Simplified Acute Physiology Score II score without age and renal components, use of vasoactives, diuretics, and RRT, and the cumulative fluid balance (% of baseline weight) on the day of oliguric episode.b Expressed as number/total number of patients with episode (%).c Results are relative to those without oliguria or with oliguria lasting <3 h. Open table in a new tab RRT, renal replacement therapy; UO, urine output. We adjusted the analyses for age, sex, APACHE II diagnosis group, SAPS II score without age and renal components, use of vasoactives, diuretics, or RRT, and the cumulative fluid balance (% of baseline weight) on the day of oliguric episode. Accordingly, UO from 0.1 to <0.3 ml/kg/h for over 6 h and all episodes of UO <0.1 ml/kg/h for longer than 3 h were independently associated with an increased risk for 90-day mortality (Table 4). In addition, UO 0.3–0.5 ml/kg/h for 6–12 h (n = 116) was associated with an OR of 1.75 (95% confidence interval 1.06–2.90, P = 0.03) with an increased risk for mortality. A total of 795 (36.8%) patients presented with oliguria for over 3 h but did not develop AKI by Cr/RRT. None of them had severe oliguria over 24 h. Figure 4 presents the crude 90-day mortality according to severity of oliguria and presence or absence of AKI by Cr/RRT. After multivariable adjustments among these patients with isolated oliguria compared with those with no oliguria or oliguria for <3 h, only UO from 0.1 to <0.3 ml/kg/h for over 6 h was associated with an increased risk for 90-day mortality with an OR of 2.36 (95% confidence interval 1.19–4.66), P = 0.01. The median (interquartile range) duration of UO <0.3 ml/kg/h among these patients was 7.1 (6.3–8.1) h and fluid accumulation on day 1 was 1.7 (0.2–4.0)% of baseline weight. In this large prospective multicenter study among critically ill patients we analyzed the confounder-adjusted associations of consecutive oliguria of different severity and duration with the development of AKI defined by Cr criterion and/or RRT, and secondarily, with 90-day mortality. We found that episodes of severe oliguria (UO <0.1 ml/kg/h) for more than 3 h were independently associated with the development of AKI by Cr/RRT. The association of severe oliguria with the development of Cr-AKI makes physiological sense. Oliguria is defined as UO <400 ml/d (0.2–0.3 ml/kg/h), which corresponds to the maximally concentrated urine volume needed to excrete the solute load normally ingested.17Klahr S. Miller S.B. Acute oliguria.N Engl J Med. 1998; 338: 671-675Crossref PubMed Scopus (114) Google Scholar Critically ill patients receive large amounts of fluid and electrolytes during the resuscitation phase, which typically leads to fluid accumulation if kidneys are unable to respond. Most patients with AKI in the current study had fluid accumulation already on day 1. Co-existing fluid retention might obscure the detection of changes in serum Cr among oliguric patients.18Liu K.D. Thompson B.T. Ancukiewicz M. et al.Acute kidney injury in patients with acute lung injury: impact of fluid accumulation on classification of acute kidney injury and associated outcomes.Crit Care Med. 2011; 39: 2665-2671Crossref PubMed Scopus (263) Google Scholar Moreover, because ICU patients generally do not receive full nutrition during their first days in the ICU, the amount of Cr to be excreted may be lower. These factors may explain why only severe oliguria as a sign of very low GFR was associated with AKI by Cr/RRT. We found the results regarding isolated oliguria interesting. First, patients with oliguric AKI but no Cr-AKI had higher crude mortality compared with those without any AKI. These results corroborate those of a database analysis reporting isolated stage 2–3 UO AKI to be associated with decreased age-adjusted one-year survival.11Kellum J.A. Sileanu F.E. Murugan R. et al.Classifying AKI by Urine Output versus SerumCreatinine Level.J Am Soc Nephrol. 2015; Google Scholar Second, moderate isolated oliguria for over 6 h was independently associated with 90-day mortality. Notably, the median duration of oliguria among these patients was about 7 h. Patients presenting with severe isolated oliguria were few and the sample size may have been too small to show a significant association among them. Again, fluid accumulation may explain why these patients did not develop Cr-AKI. However, moderate isolated oliguria might be a sign of primarily non-renal derangements (e.g. hemorrhagic shock) that if resolved, may not ever lead to a rise in Cr or prolonged oliguria. The primary cause of these derangements may still expose the patients to adverse outcome. Thus, oliguria is an important warning sign regardless of later development of Cr-AKI. In our analysis, very few patients with severe oliguria did not develop Cr-AKI, but only a third of patients with mild or moderate oliguria developed Cr-AKI or received RRT. Notably, patients were diagnosed with AKI by Cr/RRT very early, after a median of 16 h in the ICU. Previously almost 50% of episodes of UO <0.5 ml/kg/h for over 4 h have been reported not to be followed by Cr-AKI.14Prowle J.R. Liu Y.L. Licari E. et al.Oliguria as predictive biomarker of acute kidney injury in critically ill patients.Crit Care. 2011; 15: R172Crossref PubMed Scopus (165) Google Scholar Although the incidence of Cr-AKI/RRT rose with increasing severity of oliguria, over a third of patients without oliguria developed Cr-AKI. Potentially, the etiology and clinical course for AKI may be different in Cr-AKI only patients compared with those presenting with oliguria also. Surprisingly, patients with Cr-AKI only did not have significantly higher crude 90-day mortality compared with patients without AKI of any type. This is in contrast with the findings by Kellum et al.11Kellum J.A. Sileanu F.E. Murugan R. et al.Classifying AKI by Urine Output versus SerumCreatinine Level.J Am Soc Nephrol. 2015; Google Scholar However, the 90-day mortality of non-AKI patients in our analysis was higher (16.6%) compared with 7.3% reported previously,11Kellum J.A. Sileanu F.E. Murugan R. et al.Classifying AKI by Urine Output versus SerumCreatinine Level.J Am Soc Nephrol. 2015; Google Scholar which is plausibly due to exclusion of patients with scheduled post-surgery admission <24 h from the FINNAKI study. We defined the duration of oliguria as consecutive hours below the studied threshold according to the strictest interpretation of the UO criterion.4Bellomo R. Ronco C. Kellum J.A. et al.Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care. 2004; 8: R204-R212Crossref PubMed Google Scholar, 5Mehta R.L. Kellum J.A. Shah S.V. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5230) Google Scholar The distinct ways of defining oliguria may explain the
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