Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury

Abstract

Importance: Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up.

Objective: To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease.

Design, setting, and participants: Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013).

Exposures: Demographic, laboratory, and comorbidity variables measured prior to discharge.

Main outcomes and measures: Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year.

Results: The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%).

Conclusions and relevance: A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research.

Figure 1.. Formation of the Derivation, Internal Validation, and External Validation Cohorts Hospitalized With Acute Kidney Injury

^aPatients without prehospitalization serum creatinine measurements were excluded from the study (49 patients of 2946 [1.6%] had advanced chronic kidney events from the Alberta source population). ^bTo ascertain whether patients had advanced chronic kidney disease, the first estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m² was obtained a median of 75 days (interquartile range [IQR], 40-160 days) after discharge and the last a median of 267 days (IQR, 125-321 days) after discharge in the derivation and internal validation cohorts. There were 29 patients (0.2%) in the derivation and internal validation cohorts with only 1 eGFR less than 30 mL/min/1.73 m² and did not have a subsequent measurement during follow-up. They were not considered to have developed advanced chronic kidney disease. Patients were followed up through March 2015.

Figure 2.. Six-Variable Risk Index for Advanced Chronic Kidney Disease Following Hospitalization With Acute Kidney Injury

Acute kidney injury stage 1 is defined by serum creatinine (SCr) increase of 0.3 mg/dL or more or 1.5 to 1.9 times the baseline within index hospitalization; stage 2, serum creatinine increase of between 2.0 and 2.9 times baseline within index hospitalization; stage 3, serum creatinine increase of 3.0 mg/g or more times baseline or 4.0 mg/dL or more within index hospitalization. Normal albuminuria is indicated by an albumin:creatinine ratio (ACR) of 30 or less or a dipstick negative urinalysis protein; mild, ACR of 30 mg/g to 300 mg/g or dipstick positive urinalysis protein trace or 1+; heavy, ACR of more than 300 mg/g or dipstick positive urinalysis protein of 2+ or more. To convert urine ACR to mg/mmol, multiply by 0.113. Points assigned to values of each variable can be summed to obtain a patient’s total risk score, which can be used to determine his/her corresponding predicted risk of developing advanced chronic kidney disease (Supplement 2). A smartphone app is available on Calculate by QxMD for iOS, Android, and Windows (free install at https://qxmd.com/getcalculate).

Figure 3.. Predicted vs Observed Probability of Advanced Chronic Kidney Disease by the 6-Variable Risk index in the Internal Validation and External Validation Cohorts

Internal validation cohort (n = 4956) and external validation cohort (n = 2761). Error bars indicate 95% confidence intervals. The risk scores observed in both cohorts ranged from a minimum value of 0 to maximum value of 24.