Acute Kidney Injury: Call It By Its Name

Shina Menon, MD
Department of Pediatrics, University of Washington
Division of Nephrology, Seattle Children’s Hospital
Twitter: @menonshina

“Morning labs show a bump in creatinine’’

How often have you heard this on rounds? Sometimes it might just be a small increase in creatinine to the magnitude of 0.1-0.2 mg/dL. However, there are times when more significant rises get dismissed as a bump in creatinine. I often joke with my colleagues and residents that acute kidney injury (AKI) is like Lord Voldemort, He Who Must Not Be Named. And similar to Lord Voldemort, perhaps there is a fear associated with invoking the term AKI- the fear of not knowing how to diagnose AKI and of not knowing what to do once diagnosed.

What is AKI? In the past, the term acute kidney failure was used to describe an abrupt decline in kidney function. In 2004, the Acute Dialysis Quality Initiative (ADQI) used the term Acute Kidney Injury and gave the first consensus using the Risk, Injury, Failure, Loss, End Stage (RIFLE) criteria, which was subsequently adapted for pediatrics as the pRIFLE criteria. The definition has evolved since then resulting in the development of the Kidney Disease Improving Global Outcomes (KDIGO) classification system, which provided a standard that was applicable to both adults and children. AKI is defined as an increase in serum creatinine (SCr) by 0.3 mg/dL within 48 h, or an increase in SCr by 1.5 times baseline within 7 days, or urine output (UOP) < 0.5 mL/kg/h for 6 hours. It is further staged according to the severity of rise in SCr or drop in UOP (Table 1). In situations where the urine output and Scr do not correspond to the same stage, it has been recommended that the highest stage should be considered.

Table 1: 

AKI stageSerum Creatinine (SCr) criteriaUrine output (UOP) criteria
Stage 1Increase in SCr 1.5- 1.9 times baseline, OrAbsolute increase > 0.3 mg/dLUOP < 0.5 mL/kg/h for 6-12 h
Stage 2Increase in SCr 2.0-2.9 times baselineUOP < 0.5 mL/kg/h for 12-24 h
Stage 3Increase in SCr > 3.0 times baselineOrSCr > 4 mg/dLOreGFR < 35 mL/min/1.73 m2 OrReceipt of kidney replacement therapyUOP < 0.3 mL/kg/h for 24 hOrAnuria for 12 h

Neither creatinine nor urine output are perfect markers of kidney injury. Creatinine is a good marker of kidney function in steady state, but not when the kidney function is actively changing. Moreover, a rise in SCr may be seen only after the loss of at least 50% of function and may be delayed 24-48 hours after the injury has occurred. Thus the current AKI stage may not reflect current kidney function accurately. It is also dependent on muscle mass, and reduction in creatinine production during acute illness and sarcopenia secondary to prolonged illness can complicate assessment of kidney function. Creatinine is also diluted in the setting of volume overload, which is often seen in AKI. The dilution of creatinine can lead to underestimation of AKI. Cystatin C has been used as an alternative, especially in those with reduced muscle mass. However, cystatin C also has similar limitations regarding steady-state kinetics as SCr. In addition, it may be affected by high dose corticosteroid therapy and presence of systemic inflammation.

Recently, the concept of kinetic estimated glomerular filtration rate (KeGFR) has also been proposed to estimate the kidney function when the creatinine is not yet in a steady state. The KeGFR method relies on a combination of various factors including initial creatinine content, rate of creatinine production, volume of distribution, and the change in SCr over time. It allows one to estimate the kidney function when the creatinine is changing acutely. However this has not yet been validated in large clinical studies. 

How common is AKI? Prior to the use of consensus definition for AKI, epidemiologic studies of AKI used a variety of definitions resulting in inconsistent descriptions. In recent years, the AWARE study provides one of the largest assessments of pediatric AKI epidemiology. In this study looking at 4683 children and young adults (3 month-25 years age) admitted to 32 Intensive Care Units (ICU), the overall incidence of AKI during the first 7 days of hospitalization was 27%. Severe AKI, defined as stage 2/3, was seen in 12% patients. The data outside the ICU is not as clearly defined as discussed in the next section.

How often does AKI go unrecognized? To answer this question, one needs to think about 2 underlying issues: was a diagnosis of AKI made, and was this AKI documented

Outside the ICU setting, AKI is usually diagnosed by a rise in SCr level because urine output is not reliably documented. While SCr is inexpensive and commonly available, one study showed that only 17% of non-ICU admissions had two or more SCr levels allowing for AKI evaluation. Even in a cohort of children at higher risk of AKI due to treatment with aminoglycosides for >5 days, SCr was measured infrequently (at least every 4 days only 50% of the time). The lack of regular SCr checks, particularly in a higher risk population can result in the underdiagnosis of AKI.

Even in patients where SCr is checked, small changes are not easily recognized by the care team, especially in younger children where the baseline SCr may be low to begin with. Similar situation is seen in patients with a low muscle mass, secondary to chronic malnutrition or liver disease or prolonged illness (sarcopenia). 

Another reason for the lack of recognition of AKI is the absence of a known baseline creatinine because the definition of AKI is highly dependent on this baseline. This is a problem for both children and adults. Studies have used different methods to ascertain the baseline serum creatinine (SCr),  including using the admission SCr, a preadmission outpatient creatinine or nadir inpatient SCr. In the absence of a known preadmission value, SCr has been estimated using various methods in both children and adults (Table 2). The diagnosis of AKI can change depending on the approach used to determine baseline SCr. For example, if a patient has community acquired AKI, the admission SCr is likely to be higher than the patient’s true baseline resulting in underdiagnosis of AKI.

Table 2: Methods to estimate baseline creatinine 

MethodFormula used
Back calculated from Bedside Schwartz formula assuming a normal eGFR of 120 mL/min per 1.73m2eGFR = (0.413*height)/SCr
Back-calculated using the Pottel age-based equation assuming a normal eGFR of 120 mL/min per 1.73m2eGFR = 107.3/(SCr/Q)Q = 0.0270*age + 0.2329
Back calculated from Bedside Schwartz formula assuming a normal eGFR of 137 mL/min per 1.73m2 (population mean for healthy children)eGFR = (0.413*height)/SCr 
Estimate bSCr using published upper limits of normal by age categorySee Table 2
Estimate using midpoint normative creatinine values for age and sexSee Table 2

Table 3. Normative Serum Creatinine values for age and gender 

Age (yrs)   GenderLower (mg/dL)   Upper (mg/dL)   Midpoint (mg/dL)
0-1   M/F0.17   0.420.38
1-4   M/F0.19   0.490.44
5-9    M/F0.26   0.610.57
10-14   M/F0.35   0.860.78
15-17   0.44   1.100.99
15-17   F0.44   1.040.96

Even when AKI is recognized by the team, it may go undocumented. There is often a significant discrepancy in the incidence of pediatric AKI when one looks at studies that have used chart review or automated alerts for AKI vs those that have used hospitalization databases with diagnostic codes. The difference in estimates between such studies suggest significant under-reporting of AKI. We saw the same in a pilot study we did on electronic alerts in AKI. Despite alerting the primary physician about the diagnosis of AKI via a text page, AKI was documented in the chart only 75% of the time. The reasons for the lower rates of documentation are not clear.

Why is this important? We know that AKI carries a high burden of morbidity and mortality. In the short term recognition of AKI is important for appropriate management. This is not to say that one has to do something for every episode of AKI. A reflexive action like giving a fluid bolus for every AKI or stopping an essential medication may cause more harm. Sometimes awareness, close monitoring and watchful waiting are the appropriate interventions. Early nephrology involvement may also help guide more appropriate volume management. Care bundles incorporating common sense guidelines have been suggested for management of AKI. While the jury is still out on whether they have any impact on the outcomes of patients with AKI, such guidelines may streamline the management. Recognition of AKI can prompt the team to monitor intake and output more closely, assess the medications being given- if any can be substituted or require dose adjustment, and plan for additional diagnostic work up. Table 4 shows a care bundle we have used in our practice.

Table 4. AKI Care Bundle

When you see AKI, think “AEIOU”
Assess cause of AKI: prerenal, renal or post renal
Evaluate drug doses: adjust medications; hold nephrotoxic drugs if not essential
Intake and output charting
Optimize volume status: ensure euvolemia; restrict fluids if oliguric
Urine dipstick

Some patients who have had an episode of AKI may also be at increased risk of additional episodes of AKI. This could be secondary to medications or complications associated with their underlying disease (like bone marrow transplant or other solid organ transplant), or reduced renal reserve due to Chronic Kidney Disease (CKD). Flagging their medical record for the history of AKI can lead to heightened awareness and reduce exposure to nephrotoxins during future episodes of illness.

Whether it is underlying CKD, or recurrent episodes of injury, or a single prolonged episode of Stage 3 AKI, some patients are also at a higher risk of long term complications like hypertension and proteinuria. Both of these are modifiable cardiovascular risk factors, which, if present in childhood, may lead to long-term increased morbidity. Thus, post hospital discharge, these patients need to be monitored for hypertension and CKD. Documenting the episode of AKI in the discharge summary and medical records can improve follow care post discharge. 

Follow up post-AKI

KDIGO recommends evaluation of patients 3 months after AKI for resolution, new onset, or worsening of pre-existing CKD. Those with more severe episodes of AKI, with incomplete recovery of kidney function, or with risk factors for repeat episodes may benefit from a sooner follow up.  While specifics of ideal post AKI follow up have not been studied in detail, simple interventions like monitoring for recovery of kidney function along with assessment of blood pressure and proteinuria can be impactful. 

It is also important to include patient and caregiver education as part of the post-AKI care. Often the patients referred to my AKI follow up clinic have limited awareness of their episode of AKI or that they may be at an increased risk of long-term adverse outcomes. Educating and empowering the patients and caregivers allows them to participate actively in healthy lifestyle modification, and may improve follow up. 

In conclusion, a small increase in SCr should not be dismissed. If the patient meets criteria for AKI, it is important to diagnose and document it. Most patients may only have stage 1 AKI secondary to a pre-renal etiology, but they should be evaluated and monitored during their hospital stay for progression. Patients who survive severe AKI are at high risk for long term complications, and need appropriate follow up post discharge.

Reviewed by Matthew A. Sparks, Amy Yau, Anju Yadav, and S. Sudha Mannemuddhu

1 comment

  1. Excellent post. I think we should change the nomenclature (a favorite of Dr Sparks) from “prerenal” to “hemodynamic” AKI. Hemodynamic AKI is the most common and diverse form of AKI; it can be caused by sepsis, volume depletion, volume overload, drugs including contrast, toxins, intraabdominal hypertension, and thrombosis, among others. I found “prerenal” most of the time is used as surrogate for mild and easily fixed with fluids, but this is far from the truth.

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