Postoperative Acute Kidney Injury Is Associated With Progression of Chronic Kidney Disease Independent of Severity

Jamie R. Privratsky, MD, PhD; Vijay Krishnamoorthy, MD, MPH, PhD; Karthik Raghunathan, MBBS, MPH; Tetsu Ohnuma, MD, MPH; Mohammad R. Rasouli, MD; Thorir E. Long, MD, PhD; Martin I. Sigurdsson, MD, PhD

Disclosures

Anesth Analg. 2022;134(1):49-58. 

In This Article

Abstract and Introduction

Abstract

Background: Both postoperative acute kidney injury (AKI) and preoperative chronic kidney disease (CKD) are associated with significantly worse outcomes following surgery. The relationship of both of these conditions with each other and with CKD progression after surgery remains poorly studied. Our objective was to assess if there was an interaction between preoperative kidney function estimated by preoperative estimated glomerular filtration rate (eGFR)/CKD stage, postoperative AKI, and eGFR/CKD progression within 1 year of surgery. Our hypothesis was that AKI severity would be associated with a faster time to eGFR/CKD stage progression within 1 year of surgery in a graded-fashion, which would be exacerbated by preoperative kidney dysfunction.

Methods: This was a retrospective cohort study at Landspitali University Hospital in Iceland, which serves about 75% of the population. Participants included adults receiving their first major anesthetic between 2005 and 2018. Patients with CKD stage 5, undergoing major urologic procedures, or having missing creatinine values for follow-up of eGFR stage were excluded from analysis. The primary exposure was postoperative AKI stage within 7 days after surgery classified by the kidney disease improving global outcome (KDIGO) criteria. The primary outcome was time to progression of CKD by at least 1 eGFR/CKD stage within 1-year following surgery. Multivariable Cox proportional hazards models were used to estimate hazard of eGFR/CKD stage progression, including an interaction between AKI and preoperative CKD on eGFR/CKD stage progression.

Results: A total of 5548 patients were studied. In the multivariable model adjusting for baseline eGFR/CKD stage, when compared to patients without AKI, postoperative AKI stage 1 (hazard ratio [HR], 5.91; 95% confidence interval [CI], 4.34–8.05), stage 2 (HR, 3.86; 95% CI, 1.82–8.16), and stage 3 (HR, 3.61; 95% CI, 1.49–8.74) were all independently associated with faster time to eGFR/CKD stage progression within 1 year following surgery, though increasing AKI severity did not confer additional risk. The only significant interaction between the degree of AKI and the preexisting renal function was for stage 1 AKI, where the odds of 1-year eGFR/CKD stage progression actually decreased in patients with preoperative CKD categories 3a, 3b, and 4.

Conclusions: KDIGO-AKI was independently associated with eGFR/CKD stage progression within the year following surgery after adjustment for baseline eGFR/CKD stage and without an interaction between worse preoperative kidney function and higher stage AKI. Our observations suggest that further studies are warranted to test whether CKD progression could be prevented by the adoption of perioperative kidney protective practices.

Introduction

Acute kidney injury (AKI) is one of the most common forms of postoperative organ injury, occurring in up to 10% of noncardiac surgical patients,[1–3] 25% to 30% of cardiac surgery patients,[4] and 52% of patients admitted to the intensive care unit (ICU) following surgery.[5] AKI is a significant postsurgical complication as it results in longer ICU and hospital stays and increased long-term morbidity and mortality.[1,6,7] The heightened morbidity and mortality after an episode of AKI are due, at least in part, to the increased risk for progression of chronic kidney disease (CKD) and end-stage renal disease (ESRD).[8,9] Recently, a single-center study reported that postoperative AKI was associated with CKD progression.[10]

CKD is itself a major cause of morbidity and is known to increase future cardiovascular events and mortality.[9] In the surgical setting, CKD is known to increase the risk of postsurgical complications and hospital stay.[11–14] Whether postoperative AKI increases the risk for CKD progression in patients with CKD remains unclear, and it is also not clear if increasing severity of either postoperative AKI or preoperative CKD confers additional risk.

Along these lines, surgery may increase kidney risk due to inflammation, exposure to nephrotoxins,[15] and perioperative physiologic derangements such as hypotension, hypoperfusion, and hypoxemia. However, overt kidney injury does not have to occur for future kidney-associated morbidity as even small subclinical changes in glomerular filtration rate (GFR; where serum creatinine [S-Cr] is minimally changed) are associated with increased perioperative and long-term mortality.[1,6,7] This implies that patients who have minimal kidney reserve or who lose all kidney reserve would be at increased risk of kidney disease progression. Even though independent associations have been demonstrated among AKI, CKD, and worse outcomes following surgery, it is unknown whether postoperative AKI is associated with a faster CKD progression after surgery in patients with preoperative kidney dysfunction. Therefore, the aim of this study was to assess whether severity of postoperative AKI was dose-dependently associated with CKD progression within 1 year of surgery in patients stratified for baseline kidney function. We hypothesized that AKI severity would be associated with a faster time to CKD progression within 1 year of surgery in a graded fashion, which would be exacerbated by preoperative kidney dysfunction. In light of the significant longitudinal burden of CKD, identification of patients at greatest risk for CKD progression following surgery could lead to interventions that limit not only perioperative but also long-term, morbidity and mortality.

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