Perioperative Renoprotection: Clinical Implications

Khaschayar Saadat-Gilani, MD; Alexander Zarbock, MD; Melanie Meersch, MD


Anesth Analg. 2020;131(6):1667-1678. 

In This Article

Preventive Options: Bundles

Different pharmacological options have been evaluated for the prevention of AKI without success.[69–72] However, most of these options were applied in patients with an already reduced renal function.

The KDIGO guidelines recommend the implementation of supportive measures in patients at high risk for AKI.[13] These include the optimization of hemodynamics and perfusion pressure including the consideration of a functional hemodynamic monitoring to achieve this, the avoidance of hyperglycemia and nephrotoxic agents, consideration of alternatives to radio contrast agents, and close monitoring of renal function. How patients at high risk for AKI should be determined is not specified in the guidelines. In view of the new advances in renal biomarker research, biomarker-based strategies were evaluated for detecting patients at high risk to early implement these recommendations.

The first study using such a biomarker-based approach for implementation of the KDIGO bundle was the Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high-risk patients identified by biomarkers (PrevAKI) randomized controlled, single-center trial (Table 2).[73] Following on-pump cardiac surgery, patients were evaluated for risk of AKI by measuring [TIMP-2] × [IGFBP7] 4 hours after cardiopulmonary bypass. This strategy resulted from a previous trial, where [TIMP-2] × [IGFBP7] levels 4 hours after cardiopulmonary bypass showed best predictive performance for the occurrence of AKI thereby demonstrating patients at high risk especially those exceeding a cutoff of 0.3 (ng/mL)2/1000.[63] Those patients exceeding this prespecified cutoff—and therefore at risk for AKI—were randomized to receive either a strict implementation of the KDIGO bundle (including a functional hemodynamic monitoring, optimization of volume status and perfusion pressure according to a prespecified algorithm, avoidance of nephrotoxic agents and hyperglycemia, consideration of alternatives to radiocontrast agents, close monitoring of serum creatinine and urine output, and the discontinuation of angiotensin receptor inhibitors or angiotensin receptor blockers) or standard of care. The results not only showed that [TIMP-2] × [IGFBP7] helped to identify patients at high risk but also demonstrated that the strict implementation of a bundled strategy significantly reduced the occurrence of AKI by 16.6% (95% confidence interval [CI], 5.5–27.9; P = .004) and the severity of AKI by 15.2% (95% CI, 4.0–26.5; P = .009).

Thereafter, the Biomarker-guided intervention to prevent AKI after major surgery (BigPAK) randomized controlled, single-center trial evaluated a biomarker-based bundled approach in high-risk patients undergoing major abdominal surgeries. The same biomarkers were used for identifying patients at high risk. The bundled strategy included early optimization of volume status guided by central venous pressure according to a prespecified algorithm, the discontinuation of nephrotoxic agents, and nephrology consultation if deemed necessary. The results demonstrated similar findings as in the PrevAKI cohort: a significant reduction in the incidence of all stages of AKI (27% [13/48] intervention vs 48% [24/50] control group; P = .03), moderate and severe AKI (6.7% [4/60] intervention vs 19.7% [12/60] standard care group; P = .04), and a significant shorter ICU and hospital stay.[74] However, these differences were only detectable within a specific biomarker range from 0.3 to 2.0 (ng/mL)2/1000, assuming that in patients with high biomarker levels of higher than 2.0 (ng/mL)2/1000, damage may be extended and AKI not preventable.

To facilitate the necessary interventions as early as possible, Ronco et al[76] proposed a dedicated rapid response team which was assigned to treating at-risk patients identified by [TIMP-2] × [IGFBP7]. In these patients, the supportive measures suggested by the KDIGO guidelines were implemented. This approach significantly reduced the incidence and severity of AKI.[76,77] These promising findings were further consolidated by a study by Engelman et al.[75] Following the routine measurement of [TIMP-2] × [IGFBP7] after cardiac surgery, a dedicated response team was activated to initiate a bundle of interventions (including targeted fluid protocol, liberalized transfusion threshold, avoidance of nephrotoxins, continuation of invasive monitoring and its optimization in ICU) in patients within a specific biomarker range (0.3–2.0 (ng/mL)2/1000). The implementation of this urinary biomarkers-triggered bundle resulted in an 89% relative risk reduction of postoperative AKI stage 2/3 in cardiac surgery patients without increases in cost or length of hospital stay.

The use of a protocolized "bundled therapy" itself has already been advocated in different clinical settings to ensure comprehensive and evidence-based intervention in a timely manner. It has shown beneficial effects in treatment of sepsis[78] and in reduction of intravascular catheter-related infections and now for prevention of AKI.[79] Nonetheless, the adherence to bundles has been shown to be generally poor in different clinical settings and similar findings could recently be established for AKI.[80]