Perioperative Renoprotection: General Mechanisms and Treatment Approaches

Abstract

In the perioperative setting, acute kidney injury (AKI) is a frequent complication, and AKI itself is associated with adverse outcomes such as higher risk of chronic kidney disease and mortality. Various risk factors are associated with perioperative AKI, and identifying them is crucial to early interventions addressing modifiable risk and increasing monitoring for nonmodifiable risk. Different mechanisms are involved in the development of postoperative AKI, frequently picturing a multifactorial etiology. For these reasons, no single renoprotective strategy will be effective for all surgical patients, and efforts have been attempted to prevent kidney injury in different ways. Some renoprotective strategies and treatments have proven to be useful, some are no longer recommended because they are ineffective or even harmful, and some strategies are still under investigation to identify the best timing, setting, and patients for whom they could be beneficial. With this review, we aim to provide an overview of recent findings from studies examining epidemiology, risk factors, and mechanisms of perioperative AKI, as well as different renoprotective strategies and treatments presented in the literature.

Figure 1.

The potential shift in the diagnostic approach to AKI. Currently, the diagnosis of AKI is based only on serum creatinine and urinary output, but this has several pitfalls and limitations. In the last years, more researchers are suggesting the implementation of biomarkers of kidney stress and damage as a tool to allow an early identification of AKI (“subclinical AKI”) and also a better risk stratification of patients who already have developed AKI. Subclinical AKI is a condition in which serum creatinine and urinary output criteria for AKI are still not fulfilled, but the kidney may have already suffered from a reversible/irreversible stress or even damage. During this condition, biomarkers may have already been released and be detectable. AKI indicates acute kidney injury; IGFBP7, insulin-like growth factor–binding protein 7; KIM-1, kidney injury molecule-1; L-FABP, liver-type fatty acid–binding protein; NGAL, neutrophil gelatinase-associated lipocalin; TIMP-2, tissue inhibitor of metalloproteinases-2.

Figure 2.

The principal mechanisms underlying the development of perioperative AKI. Each box represents a different mechanism and the possible causes leading to the above general mechanism. Hypoperfusion can be caused by reduced preload (eg, hypovolemia, bleeding, positive pressure ventilation), systemic vasodilatation (eg, anesthetic drugs, sepsis), increased peripheral resistances, low cardiac output, intra-abdominal hypertension, loss of RAAS compensation (eg, use of ACEi/ARBs, CKD). Venous congestion can be caused by right heart failure (eg, cardioplegia) and intra-abdominal hypertension. Inflammation can be caused by surgery, ischemia, trauma, and sepsis, and it leads to the production of DAMPs, PAMPs, and cytokines, which are ultimately responsible for endothelial damage, microcirculation alteration, microthrombi formation, and oxidative stress. Urinary tract obstruction can be caused by different intrarenal (eg, casts formed following hemolysis, hemoglobinuria, myoglobinuria, dehydration, hypovolemia, tubular cells injury) and extrarenal conditions (eg, abdominal and pelvic cancer, prostate hypertrophy, retroperitoneal fibrosis, surgery complications, nephrolithiasis, Foley catheter misplacement or malfunction). Nephrotoxic drugs and agents have different ways to lead to perioperative AKI and the most involved in the perioperative setting are NSAIDs, ACEi/ARBs, antibiotics (eg, aminoglycosides, vancomycin, piperacillin/tazobactam, ciprofloxacin), antiviral (eg, acyclovir), and contrast agents. ACEi indicates angiotensin-converting enzyme inhibitors; AKI, acute kidney injury; ARBs, angiotensin receptor blockers; CKD, chronic kidney disease; DAMPS, damage-associated molecular patterns; NSAIDs, nonsteroidal anti-inflammatory drugs; PAMPs, pathogen-associated molecular patterns; RAAS, renin-angiotensin-aldosterone system.