Choice of Reference Serum Creatinine in Defining Acute Kidney Injury

Abstract

Background/aims: The study of acute kidney injury (AKI) has expanded with the increasing availability of electronic health records and the use of standardized definitions. Understanding the impact of AKI between settings is limited by heterogeneity in the selection of reference creatinine to anchor the definition of AKI. In this mini-review, we discuss different approaches used to select reference creatinine and their relative merits and limitations.

Methods: We reviewed the literature to obtain representative examples of published baseline creatinine definitions when pre-hospital data were not available, as well as literature evaluating the estimation of baseline renal function, using PubMed and reference back-tracing within known works.

Results: (1) Pre-hospital creatinine values are useful in determining reference creatinine, and in high-risk populations, the mean outpatient serum creatinine value 7-365 days before hospitalization closely approximates nephrology adjudication, (2) in patients without pre-hospital data, the eGFR 75 approach does not reliably estimate true AKI incidence in most at-risk populations, (3) using the lowest inpatient serum creatinine may be reasonable, especially in those with preserved kidney function, but may generously estimate AKI incidence and severity and miss community-acquired AKI that does not fully resolve, (4) using more specific definitions of AKI (e.g., KIDGO stages 2 and 3) may help to reduce the effects of misclassification when using surrogate values and (5) leveraging available clinical data may help refine the estimate of reference creatinine.

Conclusions: Choosing reference creatinine for AKI calculation is important for AKI classification and study interpretation. We recommend obtaining data on pre-hospital kidney function, wherever possible. In studies where surrogate estimates are used, transparency in how they are applied and discussion that informs the reader of potential biases should be provided. Further work to refine the estimation of reference creatinine is needed.

Figure 1. Potential Direction of Bias Associated with Surrogate Estimates of Reference Serum Creatinine

The actual burden of AKI reflected by a mountain analogy (incidence 25.5%). Using admission creatinine (a) will be sensitive to AKI that either only worsens after admission or occurs following hospitalization. As a result, it may only see the ‘tip’ of the mountain (observed incidence 13.7%), tend to underestimate severity, and prognosis will seem worse for a given stage than is actually the case. Using the lowest inpatinet creatinine (b) may overestimate AKI to some degree (gray zone up to 35.9%) depending on whether the lowering of creatinine is counfounded by factors such as fluid overload or reflects true lowering due to reduced generation. Severity may also tend to be inflated and the associated prognosis per given stage may seem lower than actually observed. Not observable is community acquired AKI that does not begin to resolve. The eGFR 75 approach (c) will mistakenly assign patients with stable CKD as having AKI, overestimate AKI incidence (38.3%), and underestimate prognosis.