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Wazir S, Sethi SK, Agarwal G, et al. Neonatal acute kidney injury risk stratification score: STARZ study. Pediatr Res. Published online May 19, 2021. doi:10.1038/s41390-021-01573-9
, 8Sethi SK, Raina R, Rana A, et al. Validation of the STARZ neonatal acute kidney injury risk stratification score. Pediatr Nephrol. Published online January 12, 2022. doi:10.1007/s00467-021-05369-1
). The variables of the STARZ score are shown in Table 1. This research letter reports cut-off scores required for identifying risk of severe AKI and dialysis need in neonates. The methodology and statistical analysis of the study is provided in Supplementary materials.Table 1STARZ scoring model
ˆFirst 12 hours post admission in NICU
dl: decilitre; hr; hour; kg: kilogram; mg: milligram; ml: millilitre; NICU: Neonatal Intensive Care Unit; PPV: Positive pressure ventilation.
• Nephrotoxic drugs included Vancomycin or Colistin or Amphotericin B
• Significant cardiac disease included hemodynamically significant patent ductus arteriosus, persistent pulmonary hypertension of the newborn, cardiogenic shock and other congenital heart disease
• Inotropes included Dopamine or Dobutamine or Epinephrine or Norepinephrine
The current study included 1,005 neonates [without AKI: 646 and with AKI: 359] that met the inclusion criteria. The flow of the study is shown in Supplementary Figure 1. Of these 359 neonates, 16.2% (n=58) had stage 1, 21.4% (n=77) had stage 2 and 62.4% (n=224) had stage 3 AKI. The neonates with gestational age at birth <28 weeks [34 (3.4%)], requirement of positive pressure ventilation in delivery room [189 (18.8%)], age at entry in NICU (<25.5 hours) [580 (57.7%)], sepsis during NICU stay [684 (68.1%)], significant cardiac disease [288 (28.7%)], serum creatinine ≥0.98 mg/dl [314 (31.2%)], urine output <1.32 ml/kg/hr [512 (50.9%)], nephrotoxic drug use [920 (91.5%)], furosemide use [44 (4.4%)] and inotrope use [388 (38.6%)]. A total of 52 (5.2%) neonates died during the NICU stay. The median (IQR) STARZ score was 34 (23 - 57) and length of NICU stay was 10 (5 - 18) days [Supplementary Table 1].
Table 2 shows the comparison of different variables among neonates with severe AKI (AKI-3) versus mild-moderate AKI (AKI 1-2). The proportion of neonates with significant cardiac disease [107 (47.8%) vs. 39 (28.9%); pFigure 1]. The median (IQR) time to AKI was observed to be significantly lower [1 (1Jetton J.G. Boohaker L.J. Sethi S.K. et al.Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study., 2Agrawal G. Wazir S. Sethi S.K. et al.Incidence, Risk Factors, and Outcomes of Neonatal Acute Kidney Injury: Protocol of a Multicentric Prospective Cohort Study [The Indian Iconic Neonatal Kidney Educational Registry]., 3Charlton J.R. Boohaker L. Askenazi D. et al.Incidence and Risk Factors of Early Onset Neonatal AKI.) vs. 3 (1Jetton J.G. Boohaker L.J. Sethi S.K. et al.Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study., 2Agrawal G. Wazir S. Sethi S.K. et al.Incidence, Risk Factors, and Outcomes of Neonatal Acute Kidney Injury: Protocol of a Multicentric Prospective Cohort Study [The Indian Iconic Neonatal Kidney Educational Registry]., 3Charlton J.R. Boohaker L. Askenazi D. et al.Incidence and Risk Factors of Early Onset Neonatal AKI.) days; pTable 2Comparison of different variables among neonates without AKI vs. Stage 1 AKI vs. Stage 2 AKI vs. Stage 3 AKI
#reported as median (IQR); for others as proportion
*First 12 hours post admission in NICU
IQR: Interquartile range; AKI: Acute Kidney Injury; NICU: Neonatal Intensive Care Unit; hr: hour; mg: milligram; dl: decilitre; cm: centimetre; ml: millilitre; L: Liter; Hb: haemoglobin; g: gram; IV: Intravenous; hr: hour; kg: kilogram; d: day; meq: milliequivalent; PPV: Positive pressure ventilation; Y: Yes
• Nephrotoxic drugs included Vancomycin or Colistin or Amphotericin B
• Inotropes included Dopamine or Dobutamine or Epinephrine or Norepinephrine
• Significant cardiac disease included PDA: Patent ductus arteriosus; PPHN: pulmonary hypertension of the newborn; VSD: Ventricular septal defect; shock
• Severe peripartum event included cord prolapsed, precipitate labour, abruption
• Multiple seizures were defined as>1 seizure episode in the first 12 h
• Fluid overload defined as >10% during the first 12 h post admission
• Even a single exposure of the drug has been considered as usage of drug
• Maternal characteristics recorded were- maternal diabetes, maternal pregnancy induced hypertension, maternal bacterial/ viral infections/ IUGR/ oligohydramnios/ polyhydramnios/ use of drugs during pregnancy (ACE-inhibitors, NSAIDs, tobacco, alcohol, anti-depressants, steroids)
Figure 1Area under the ROC for severe neonatal AKI
Supplementary Table 2 shows the comparison of different variables among stage 3 AKI neonates with versus without peritoneal dialysis (PD). The proportion of neonates with gestational age at birth <28 weeks [5 (14.7%) vs. 8 (4.2%); p=0.031], with significant cardiac disease [28 (82.4%) vs. 79 (41.6%); p<0.001], with furosemide usage [6 (17.6%) vs. 10 (5.3%); p=0.02], with inotropes usage [33 (97.1%) vs. 129 (67.9%); p<0.001], and with urine output <1.32 ml/kg/hr [30 (88.2%) vs. 113 (59.5%); p=0.001] were significantly higher among those with severe versus mild-moderate AKI. As expected, the median (IQR) STARZ score was observed to be significantly higher [77 (71 - 84) vs. 64 (50 - 77); p<0.001] among stage 3 AKI neonates with PD vs. without PD. The best cut-off value STARZ Score was found to be 66 with a sensitivity of 97% and specificity of 52% for PD use with an area under the ROC curve of 0.804 (95% CI: 0.738 – 0.870), p<0.001 [Supplementary Figure 2]. The median (IQR) time to AKI was observed to be significantly lower [1 (1 - 2) vs. 1 (1 - 3) days; p=0.017] among stage 3 AKI neonates with versus without PD.
The mortality was observed to be significantly higher among those with severe AKI versus mild-moderate AKI [39 (17.4%) vs. 3 (2.2%); odds ratio (95% CI): 9.28 (2.81-30.65)] and stage 3 AKI with PD vs. without PD [30 (88.2%) vs. 9 (4.7%); 150.83 (43.67-521.0)]. However, the median (IQR) duration of stay in the NICU was significantly lower among those with severe AKI versus mild-moderate AKI [11 (5 - 22) vs. 14 (7 - 25) days; p=0.033] and stage 3 AKI with versus without PD [7 (3 - 11) vs. 12 (6 - 23) days; p=0.001] [Table 2 and Supplementary Table 2].To summarize, we found the following cut-offs for neonatal AKI prediction: STARZ score 9Albert C. Zapf A. Haase M. et al.Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.). To our knowledge, this is the first of its kind study to use a scoring system that can easily be replicated in NICU, however further studies are needed to validate the cut-off scores. These cut-offs can help a clinician to determine the need for dialysis requirement, anticipate severe neonatal AKI and acts as a beneficial and easy clinical adjunct to neonatal intensive care units of all types.Supplementary dataSupplementary MaterialReferencesJetton J.G. Boohaker L.J. Sethi S.K. et al.Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study.
Lancet Child Adolesc Health. 1: 184-194https://doi.org/10.1016/S2352-4642(17)30069-XAgrawal G. Wazir S. Sethi S.K. et al.Incidence, Risk Factors, and Outcomes of Neonatal Acute Kidney Injury: Protocol of a Multicentric Prospective Cohort Study [The Indian Iconic Neonatal Kidney Educational Registry].
Front Pediatr. 9690559https://doi.org/10.3389/fped.2021.690559Charlton J.R. Boohaker L. Askenazi D. et al.Incidence and Risk Factors of Early Onset Neonatal AKI.
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Intensive Care Med. 28: 204-207https://doi.org/10.1007/s00134-001-1185-2Medvedev M.M. Brotherton H. Gai A. et al.Development and validation of a simplified score to predict neonatal mortality risk among neonates weighing 2000 g or less (NMR-2000): an analysis using data from the UK and The Gambia.
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Kidney Int. 85: 659-667https://doi.org/10.1038/ki.2013.349Wazir S, Sethi SK, Agarwal G, et al. Neonatal acute kidney injury risk stratification score: STARZ study. Pediatr Res. Published online May 19, 2021. doi:10.1038/s41390-021-01573-9
Sethi SK, Raina R, Rana A, et al. Validation of the STARZ neonatal acute kidney injury risk stratification score. Pediatr Nephrol. Published online January 12, 2022. doi:10.1007/s00467-021-05369-1
Albert C. Zapf A. Haase M. et al.Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.
Am J Kidney Dis. 76 (): 826-841https://doi.org/10.1053/j.ajkd.2020.05.015Article InfoPublication HistoryAccepted: June 27, 2022
Received in revised form: June 25, 2022
Received: March 28, 2022
Publication stageIn Press Journal Pre-ProofFootnotesAuthor Contributions: All authors made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafting the article or revising it critically for important intellectual content. All authors gave final approval of the version to be published.
Statement of financial support: No financial assistance received
Disclosure: None
Competing interests: All the authors declared no competing interests.
IdentificationDOI: https://doi.org/10.1016/j.ekir.2022.06.020
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