Creatinine Increases Have Consistent and Differential Prognostic Impact Across Kidney Function

Abstract Background Within the current criteria for acute kidney injury (AKI), it remains debated whether small absolute creatinine increases are associated with higher mortality in patients with low baseline estimated glomerular filtration rates (eGFRs), and whether these changes carry prognostic value comparable to relative increases. We therefore examined the prognostic impact of rapid creatinine increases across baseline eGFRs in patients undergoing major elective surgery. Methods We pooled data on patients undergoing major elective surgery from Canada, Denmark, Scotland, and Wales. This clinical setting was chosen because creatinine levels in this group are routinely monitored both before and after an acute stress event, regardless of clinical status. We ascertained the highest relative creatinine increase within 7 days and the highest absolute creatinine increase within 2 days during the first 7 days after surgery. We used logistic regressions with splines and interaction terms to construct heatmaps depicting age-, sex-, year-, and surgery type-standardized 90-day mortality according to creatinine increases across baseline eGFRs. Results There were 311,975 surgical procedures performed in 279,554 patients, with 11,568 deaths. Compared to no change in creatinine, a 0.3 mg/dL (26.5 µmol/l) absolute increase was associated with a consistent 2.2-3.3 percentage point increase in mortality for eGFR between 15 and 90 mL/min/1.73 m2. However, while the excess mortality associated with a 0.3 mg/dL and a 50% creatinine increase was similar at baseline eGFR of 90 mL/min/1.73 m2, the excess mortality of a 50% creatinine increase was substantially greater among those with baseline eGFRs < 30 mL/min/1.73 m2. Conclusions A small absolute creatinine increase of 0.3 mg/dL is associated with a consistent increase in mortality across baseline eGFRs, indicating its relevance as a component of the AKI criteria. However, the higher excess mortality associated with a 50% increase at low eGFRs should be emphasized in future guidelines to improve clinical discussions.