Cardiopulmonary Bypass-Associated Acute Kidney Injury: A Pigment Nephropathy?

Abstract

Acute kidney injury (AKI) is a common and serious postoperative complication following exposure to cardiopulmonary bypass (CPB). Several mechanisms have been proposed by which the kidney can be damaged and interventional studies addressing known targets of renal injury have been undertaken in an attempt to prevent or attenuate CPB-associated AKI. However, no definitive strategy appears to protect a broad heterogeneous population of cardiac surgery patients from CPB-associated AKI. Although the association between hemoglobinuria and the development of AKI was recognized many years ago, this idea has not been sufficiently acknowledged in past and current clinical research in the context of cardiac surgery-related AKI. Hemoglobin-induced renal injury may be a major contributor to CPB-associated AKI. Accordingly, we now describe in detail the mechanisms by which hemoglobinuria may induce renal injury and raise the question as to whether CPB-associated AKI may actually be, in a significant part, a form of pigment nephropathy where hemoglobin is the pigment responsible for renal injury. If CPB-associated AKI is a pigment nephropathy, alkalinization of urine with sodium bicarbonate might protect from: (1) tubular cast formation from met-hemoglobin; (2) proximal tubular cell necrosis by reduced endocytotic hemoglobin uptake, and (3) free iron-mediated radical oxygen species production and related injury. Sodium bicarbonate is safe, simple to administer and inexpensive. If part of AKI after CPB is truly secondary to hemoglobin-induced pigment nephropathy, prophylactic sodium bicarbonate infusion might help attenuate it. A trial of such treatment might be a reasonable future investigation in higher risk patients receiving CPB.

Serum creatinine role in predicting outcome after cardiac surgery beyond acute kidney injury

“…Angiotensin-converting enzyme inhibitors and ARB are potential nephrotoxic medications commonly used in cardiac patients. Avoiding them has not been shown to change the incidence of CSA-AKI and the subject is still controversial [160,161] .…”

Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery

“…Acute kidney injury (AKI), previously referred to as acute renal failure, is a frequent and serious complication encountered in 30% to 50% of subjects after CPB (2,3). AKI requiring dialysis occurs in up to 5% of these cases, in whom the mortality rate approaches 80%, and is the strongest independent risk factor for death after CPB, with an odds ratio of 7.9 (4).…”

“…Concomitant advances in the basic sciences have illuminated the pathogenesis of AKI and have paved the way for successful therapeutic approaches in animal models (14). However, translational research efforts for the identification of effective therapeutic strategies in humans with AKI have yielded disappointing results (2,15). A major reason for the failure to find an effective treatment in patients is the paucity of early biomarkers for AKI, akin to troponins in acute myocardial disease (16).…”

Reoperation after mitral valve repair in viewpoints of kidney injury as well as hemolytic anemia

“…Hemolysis and subsequent hemoglobinuria involves kidney injury that results from the following three mechanisms [11]: (a) reabsorption and deposition of iron into proximal tubular cell, which leads to generation of reactive oxygen species; (b) obstruction of tubules due to intratubular casts that form by the interaction between hemoglobin and Met-hemoglobin; and (c) a decrease in renal perfusion due to depletion of serum nitric oxide by interaction with plasma-free hemoglobin. In addition, tubular obstruction promotes reabsorption of free hemoglobin into proximal tubular cell, which results in proximal tubular cell injury furthermore.…”

“…However, it is difficult to determine the appropriate time for reoperation. In addition, although hemolysis and subsequent hemoglobinuria are thought to result in kidney injury [11], kidney injury is not considered an indication for surgery, and there have been no reports on kidney injury as an indication for reoperation.…”