Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial)

Nuttha Lumlertgul, Sadudee Peerapornratana, Thananda Trakarnvanich, Wanjak Pongsittisak, Kajbundit Surasit, Anan Chuasuwan, Pleumjit Tankee, Khajohn Tiranathanagul, Kearkiat Praditpornsilpa, Kriang Tungsanga, Somchai Eiam-Ong, John A Kellum, Nattachai Srisawat, FST Study Group, Nuttha Lumlertgul, Sadudee Peerapornratana, Thananda Trakarnvanich, Wanjak Pongsittisak, Kajbundit Surasit, Anan Chuasuwan, Pleumjit Tankee, Khajohn Tiranathanagul, Kearkiat Praditpornsilpa, Kriang Tungsanga, Somchai Eiam-Ong, John A Kellum, Nattachai Srisawat, FST Study Group

Abstract

Background: The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT.

Methods: FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT.

Results: FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P < 0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002).

Conclusion: The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation.

Trial registration: clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.

Keywords: Acute kidney injury; Furosemide stress test; Renal replacement therapy.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Institutional Review Board of every participating center.

Consent for publication

The manuscript has been read and its submission approved by all co-authors. Patients were prospectively included with informed consent.

Competing interests

JAK reports grant support and consulting fees from Baxter and NxStage, unrelated to this study. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of patient allocation. AKI, acute kidney injury; CKD, chronic kidney disease; FST, furosemide stress test; ICU, intensive care unit; RRT renal replacement therapy
Fig. 2
Fig. 2
Survival curves of patients receiving early and standard renal replacement therapy (RRT) (straight line, early RRT group; dashed line, standard RRT group). The figure shows the Kaplan-Meier curve of the probability of survival from randomization to day 28. CI, confidence interval; HR, hazard ratio

References

    1. Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, Kellum JA. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10(3):R73. doi: 10.1186/cc4915.
    1. Bagshaw SM, Laupland KB, Doig CJ, Mortis G, Fick GH, Mucenski M, Godinez-Luna T, Svenson LW, Rosenal T. Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study. Crit Care. 2005;9(6):R700–R709. doi: 10.1186/cc3879.
    1. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813–818. doi: 10.1001/jama.294.7.813.
    1. Bagshaw SM, Wald R. Strategies for the optimal timing to start renal replacement therapy in critically ill patients with acute kidney injury. Kidney Int. 2017;91(5):1022–1032. doi: 10.1016/j.kint.2016.09.053.
    1. Shiao CC, Huang TM, Spapen HD, Honore PM, Wu VC. Optimal timing of renal replacement therapy initiation in acute kidney injury: the elephant felt by the blindmen? Crit Care. 2017;21(1):146. doi: 10.1186/s13054-017-1713-2.
    1. Macedo E, Mehta RL. Timing of dialysis initiation in acute kidney injury and acute-on-chronic renal failure. Semin Dial. 2013;26(6):675–681. doi: 10.1111/sdi.12128.
    1. Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstadt H, Boanta A, Gerss J, Meersch M. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA. 2016;315(20):2190–2199. doi: 10.1001/jama.2016.5828.
    1. Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, Boyer A, Chevrel G, Lerolle N, Carpentier D, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122–133. doi: 10.1056/NEJMoa1603017.
    1. Chawla LS, Davison DL, Brasha-Mitchell E, Koyner JL, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Kimmel PL, Seneff MG. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17(5):R207. doi: 10.1186/cc13015.
    1. Koyner JL, Davison DL, Brasha-Mitchell E, Chalikonda DM, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Bennett MR, Kimmel PL, et al. Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol. 2015;26(8):2023–2031. doi: 10.1681/ASN.2014060535.
    1. Group KDIGOKAKIW KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012;2(1):6. doi: 10.1038/kisup.2012.6.
    1. Network TVNARFT. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7–20. doi: 10.1056/NEJMoa0802639.
    1. Chen H, Wu B, Gong D, Liu Z. Fluid overload at start of continuous renal replacement therapy is associated with poorer clinical condition and outcome: a prospective observational study on the combined use of bioimpedance vector analysis and serum N-terminal pro-B-type natriuretic peptide measurement. Crit Care. 2015;19:135. doi: 10.1186/s13054-015-0871-3.
    1. Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Piccinni P, Ronco C. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med. 2010;36(3):444–451. doi: 10.1007/s00134-009-1711-1.
    1. Kumpers P, Hafer C, David S, Hecker H, Lukasz A, Fliser D, Haller H, Kielstein JT, Faulhaber-Walter R. Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome. Intensive Care Med. 2010;36(3):462–470. doi: 10.1007/s00134-009-1726-7.
    1. Besen BAMP, Romano TG, Mendes PV, Gallo CA, Zampieri FG, Nassar AP Jr, Park M. Early Versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients: Systematic Review and Meta-Analysis. J Intensive Care Med. 2017. 10.1177/0885066617710914. [Epub ahead of print].
    1. Bhatt GC, Das RR. Early versus late initiation of renal replacement therapy in patients with acute kidney injury—a systematic review and meta-analysis of randomized controlled trials. BMC Nephrol. 2017;18(1):78. doi: 10.1186/s12882-017-0486-9.
    1. Boussekey N, Capron B, Delannoy PY, Devos P, Alfandari S, Chiche A, Meybeck A, Georges H, Leroy O. Survival in critically ill patients with acute kidney injury treated with early hemodiafiltration. Int J Artif Organs. 2012;35(12):1039–1046. doi: 10.1177/039139881203501202.
    1. Feng YM, Yang Y, Han XL, Zhang F, Wan D, Guo R. The effect of early versus late initiation of renal replacement therapy in patients with acute kidney injury: a meta-analysis with trial sequential analysis of randomized controlled trials. PLoS One. 2017;12(3):e0174158. doi: 10.1371/journal.pone.0174158.
    1. Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, Bagshaw SM. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care. 2011;15(1):R72. doi: 10.1186/cc10061.
    1. Leite TT, Macedo E, Pereira SM, Bandeira SR, Pontes PH, Garcia AS, Militao FR, Sobrinho IM, Assuncao LM, Liborio AB. Timing of renal replacement therapy initiation by AKIN classification system. Crit Care. 2013;17(2):R62. doi: 10.1186/cc12593.
    1. Shiao CC, Wu VC, Li WY, Lin YF, Hu FC, Young GH, Kuo CC, Kao TW, Huang DM, Chen YM, et al. Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery. Crit Care. 2009;13(5):R171. doi: 10.1186/cc8147.
    1. Shum HP, Chan KC, Kwan MC, Yeung AW, Cheung EW, Yan WW. Timing for initiation of continuous renal replacement therapy in patients with septic shock and acute kidney injury. Ther Apher Dial. 2013;17(3):305–310. doi: 10.1111/j.1744-9987.2012.01147.x.
    1. Wald R, Adhikari NKJ, Smith OM. Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. Kidney Int. 2015;88(4):897–904. doi: 10.1038/ki.2015.184.
    1. Wu SC, Fu CY, Lin HH, Chen RJ, Hsieh CH, Wang YC, Yeh CC, Huang HC, Huang JC, Chang YJ. Late initiation of continuous veno-venous hemofiltration therapy is associated with a lower survival rate in surgical critically ill patients with postoperative acute kidney injury. Am Surg. 2012;78(2):235–242.
    1. Smith OM, Wald R, Adhikari NK, Pope K, Weir MA, Bagshaw SM. Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial. Trials. 2013;14:320. doi: 10.1186/1745-6215-14-320.
    1. Alsumrain MH, Jawad SA, Imran NB, Riar S, DeBari VA, Adelman M. Association of hypophosphatemia with failure-to-wean from mechanical ventilation. Ann Clin Lab Sci. 2010;40(2):144–148.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner