Utilization India Correspondence Address: Dr Gurdeep Singh Dhooria

Utilization of Renal
Angina Index for prediction of subsequent severe acute kidney injury in PICU
of  a developing country


Raina Kaur, Gurdeep Singh Dhooria, Puneet A.
Pooni, Deepak Bhat, Sidharth Bhargava, Shruti Kakkar, 

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Department of
Pediatrics, Dayanand Medical College and Hospital, Ludhiana, Punjab, India


Dr Gurdeep Singh

Department of
Pediatrics, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

[email protected]



Acute kidney injury (AKI) is independently associated with worsened
morbidity and increased mortality in PICU. AKI risk stratification, termed
renal angina index (RAI) has been used in the west  to predict persistent severe AKI. Very few
studies have been done on application of renal angina index in PICU of a
developing country. Aim: To predict
severe subsequent AKI in children admitted in PICU using Renal Angina Index. Design: Prospective observational
study.  Methods: Children admitted
over one year in PICU between one month to 18 years of age with no previous
kidney disease were included. RAI assessment was done from 8-12 hours of
admission to PICU. RAI was calculated from product of Renal Risk  and Renal Injury score. Renal angina
positivity was defined as RAI  ? 8. On
day 4, serum creatinine is noted and GFR is calculated. RAI was correlated with
presence/absence of subsequent severe AKI. RAI positivity was also correlated
with duration of PICU stay, need for dialysis, mechanical ventilation and mortality.
Results: RAI positivity was seen in
16.7 % cases. Of the RAI positive cases, 36.2 % cases developed AKI at 4 days
compared to 2.3% in the RAI negative cases (p value 8) predicted Day-3 AKI with an
AUC of 0.883 95% confidence interval (CI) = 0.823-0.943. RAI > 8
positivity had a
high negative predictive value (NPV)
of 97.67% % (95% CI = 95.84-98.7
%), with sensitivity and specificity of  75% and 88.42 % , respectively, and positive
predictive value (PPV) of 35.29% (95% CI = 27.92-43.44 %).

prediction by GFR criteria and Fluid overload (FO %) criteria

predictive value of  RAI was broken down by composite factors
of kidney injury. The predictive value for Day-3 AKI by GFR score alone by AUC values was consistently
superior when compared to
fluid overload score (FO %) AUC 0.877 (95% CI = 0.817-0.936) vs
0.774 (95% CI = 0.685- 0.864).
The AUC for
RAI for Day-3 AKI improved when
RAI incorporated worse of the two scores (GFR score/FO score). (AUC
0.883(95% CI= 0.823-0.943). 

versus KDIGO stage and PRISM score

Prediction of RA for Day-3 AKI was superior to KDIGO
stage 1 injury at admission;
fulfillment of renal angina demonstrated higher sensitivity (27.27%), PPV of 25%, NPV of 93.63%
and a higher
Youden’s index ( ____________) than KDIGO stage 1,
although specificity was found to be higher with KDIGO stage 1 (92.89%). Similar results were seen when RA was compared to KDIGO stages 2–3 (Youden’s index=_____). When compared directly, RAI outperformed PRISM-II for the
prediction of day 3 AKI. (AUC=0.764)
(95% confidence interval (CI) = 0.672-0.856).

Discussion:  Renal angina index was developed by Goldstein to identify critically
ill patients at greatest risk of AKI.10  In the current study, we operationalize renal
angina index in a tertiary care hospital of a developing country and show that
renal angina index improves prediction of subsequent severe AKI and also
outperforms currently used clinical thresholds for early signs of kidney
injury, or severity of illness scores.

RAI was derived as a composite of risk factors and clinical
signs of AKI. The logic behind the equation dictates that as a patient achieves
higher risk they require less “clinical sign of AKI” early on to fulfill renal
angina. Similarly, if a patient has less risk but shows more overt signs of clinical
AKI signs, renal angina would also be fulfilled.15 RAI derivation was based on available AKI epidemiology
reported in select pediatric populations: children admitted to the ICU carry
increased risk over the general population (4.5–10%),16,17 children receiving bone marrow
transplantation have ~3× risk (11–21%)18, and those who are intubated and on vasopressor support
carry nearly 5× risk versus the general ICU population (51%). 3 The ‘signs of injury’ (i.e.,
kidney pain) in the RAI include GFR and fluid overload.

Troponin measured in patients
who exhibit cardiac angina, a combination of clinical signs and known coronary
disease risk factors, allows practitioners to rule in myocardial infarction. In
this select, risk-stratified population, troponin has great specificity and
PPV. When measured in patients without cardiac angina, troponin loses
performance. Unfortunately, unlike a heart attack, AKI does not carry an easily
identifiable physical prodrome such as cardiac angina. Simply put, a kidney
attack does not ‘hurt’. So clinicians tried to find a novel renal equivalent of
“cardiac angina” so that a suitable biomarker can be applied to select patients
having high risk of AKI.

Renal angina fulfillment identifies children at the highest
risk of suffering subsequent severe AKI. For a clinician, the ability to
predict the presence of severe AKI 3 days in advance carries obvious benefit.

Fluids are the second most
common intervention in acutely ill patients (after oxygen). The benefits of
early fluid resuscitation in patients with shock and acute kidney injury (AKI)
are already accepted. There is evidence that fluid administration beyond the
correction of hypovolaemia is associated with increased morbidity, a longer
hospital stay and mortality. In a recent article in Critical Care, Wang et al.
analysed the data of 2526 patients admitted to 30 intensive care units (ICUs)
in China and showed that even relatively small degrees of fluid overload were
independently associated with an increased risk of AKI and mortality 19.

In the Rajit
Basu etal study,
based on the most optimal Youden’s index (0.49) and highest negative predictive
value (to safely rule out development of subsequent AKI), an RAI > 8 was
taken as cutoff to label Renal Angina positivity.15 Only day 3 AKI was chosen to define outcome as most PICU
patients develop AKI within this time frame and it surpasses the time frame of
functional AKI (prerenal AKI). Also, time frame of 8 h was kept to assess fluid
overload as it was beyond the generally accepted window of ‘early goal-directed
therapy’ (EGDT) of resuscitation. 20

    In our study a
total of 413 patients were included. Day 0 Renal Angina positive was seen in
16.7% patients. Of  renal angina positive
patients 36.2 %  developed subsequent
severe AKI compared to 2.3 % of the other group, which was highly significant


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