Acute Kidney Injury
Acute kidney injury (AKI) is a clinical syndrome that reflects the clinical manifestation of isolated or multiple insults to the kidney. The degree of renal damage ranges from the trivial, that is, a transient increase in serum creatinine (SCr) or a decrease in urine output, to the profound, that is, established acute renal failure (ARF) requiring renal replacement therapy (RRT). A consensus definition of AKI by a multinational expert panel, the Acute Dialysis Quality Initiative Group (ADQI), attempts to standardize the classification and reporting of AKI ( Table 30-1 ). The classification is based on the degree of elevation of SCr or calculated glomerular filtration rate (GFR), severity and duration of oliguria, and the requirement for RRT. The acronym RIFLE serves to organize a hierarchy of severity of AKI into risk of injury (R), acute injury (I), established failure (F), sustained loss of function (L) and end-stage renal disease (E).
| Class | SCr Increase | GFR Decrease | Oliguria (UO < 0.5 mL/kg/hr) |
|---|---|---|---|
| R isk | ×1.5 | >25% | >6 hr |
| I njury | ×2 | >50% | >12 hr |
| F ailure | ×3 (or >4 mg/dL, with an abrupt increase >0.5 mg/dL) | >75% | >24 hr (or anuria >12 hr) |
| Loss | ARF >4 wk | ||
| E SRD | ARF >3 mo | ||
A consensus definition of ARF in critically ill patients such as RIFLE is long overdue, given that more than 30 different definitions can be found in the literature. However, there are some important caveats. RIFLE does not take into consideration that about three quarters of ARF is nonoliguric in nature, that abrupt changes in GFR may not be reflected by rapid changes in SCr, or that SCr may increase slowly and subtly in patients with depleted muscle mass. It was also not designed to examine the specific AKI associated with surgery and may not be as useful for anesthesiologists as a criterion such as peak percentage change in postoperative SCr. Nonetheless, there have been several investigations of the predictive ability, internal validity, robustness, ease of application, and clinical relevance of RIFLE in a variety of settings. These retrospective and prospective studies do demonstrate a broad correlation between the RIFLE severity and overall mortality from AKI. It does appear that the RIFLE classification is easy to use, identifies patients with early signs of dysfunction that may progress to more severe renal disease, and can identify patients of different mortality risk. However, the RIFLE criteria have yet to be used in large multicenter randomized controlled clinical trials in a wide variety of patient populations.
Perioperative AKI, characterized by postoperative elevation of SCr, is generally uncommon. However, it has a predilection for certain surgical procedures, particularly vascular surgery involving aortic manipulation, in which the incidence is between 10% and 25%. One study demonstrated a relatively static incidence over a 12-year period. The risk of AKI is enhanced by nephrotoxic factors such as obstructive jaundice or exposure to radiocontrast agents ( Box 30-1 ). Regardless of its etiology, pathogenesis, or requirement for RRT, postoperative AKI is associated with increased length of hospital stay, an increased mortality rate, and impaired quality of life.
Cardiac surgery
Pre-existing renal insufficiency
Emergency procedures
Sepsis
Prolonged cardiopulmonary bypass
Postoperative cardiac dysfunction
Vascular surgery
Pre-existing renal insufficiency
Postoperative dye studies
Sepsis
Aortic cross clamp
Direct renal ischemia
Myocardial ischemia, low cardiac output
Declamping hypotension
Renal artery atheromatous embolization
Ruptured aortic aneurysm
Biliary tract and hepatic surgery including liver transplantation
Kidney transplantation
Urogenital surgery
Complicated obstetrics
Major trauma
Direct renal trauma
Hemorrhagic shock
Massive blood transfusion
Elevated intra-abdominal pressure
Rhabdomyolysis
Sepsis and multiorgan dysfunction syndrome
A considerable research effort has been marshaled to evaluate perioperative interventions to protect the kidneys when they are placed at risk by pre-existing impairment, nephrotoxins, renal ischemia, and the inflammatory process. Preventive strategies have focused on preoperative optimization of renal function, judicious perioperative fluid balance, and “renoprotective” pharmacologic agents. However, given the wide variety of renal insults that contribute to perioperative AKI, outcome studies of therapeutic interventions have addressed only a limited territory of perioperative renal protection.
These strategies appear to have had some benefit because, although the incidence of postoperative AKI has been increasing over the last two decades, the mortality rate of ARF requiring RRT is decreasing. For example, a study on coronary artery bypass grafting (CABG) in a sample of 20% of U.S. hospitals revealed an increase in incidence of postoperative ARF from 1% to 4% between 1988 and 2003. However, the proportion of cases requiring RRT declined from about 16% to less than 9%, and the mortality rate declined from nearly 40% to less than 18%. These figures may be influenced by less stringent criteria for the diagnosis of ARF, but the proportion of survivors requiring special care after discharge almost doubled from 35% to 65%, emphasizing the increasing burden of perioperative AKI on our health care system.
Perioperative Risk Factors for Acute Kidney Injury
An isolated risk factor or insult rarely induces AKI. Inevitably, AKI is the consequence of the complex, often sequential interaction of multiple factors. Indeed, AKI may be the final common pathway of a confluence of factors such as pre-existing renal insufficiency or a genetic predisposition, high-risk surgery, compromised hemodynamic function, nephrotoxic insults, and acute inflammation. It is little wonder that no single intervention has been shown to be the magic bullet that prevents AKI.
Patient Factors
Patient factors demonstrated to be associated with an increased risk of the development of postoperative AKI include advanced age, hypertension, diabetes mellitus, ventricular dysfunction, sepsis, hepatic failure, and chronic kidney disease (CKD). Because CKD also has various definitions, the association between preoperative CKD and postoperative AKI is difficult to quantify accurately, but it is strong. Poorly controlled diastolic hypertension is an established risk factor for AKI, but wide pulse pressure hypertension (isolated systolic hypertension) is independently associated with worsened renal function after cardiac surgery.
Genetic polymorphisms may also play a role in the predisposition to AKI. The Duke University group demonstrated a negative association between the possession of the apolipoprotein E4 allele and postoperative increases in SCr levels in a prospective study of 564 patients undergoing CABG. This renal protective effect is interesting because the same polymorphism is associated with atherosclerotic disease and an increased risk of perioperative neurologic impairment.
Intraoperative Factors
Ischemia and Inflammation
Ischemia–Reperfusion Injury.
Ischemia compromises the supply of oxygen to the tissues and can interfere with normal physiologic function. Re-establishment of the oxygen supply, while essential for minimizing ischemia, can also contribute to cell injury and subsequent death. The etiology of the reperfusion injury is multifactorial, including interstitial edema, capillary obstruction, and inflammatory cell infiltration.
Although the renal medulla receives less than 10% of renal blood flow (RBF), the medullary process of urinary concentration has a high metabolic requirement. Any compromise to RBF increases the regional perfusion imbalance and renders the medulla ischemic. Compromise may result from aortic occlusion, atheromatous embolism, hypotension, low blood flow states, and hypovolemia.
Suprarenal aortic cross-clamping creates an ischemia–reperfusion injury and self-limited acute tubular necrosis (ATN) that takes up to 48 hours to recover. Injury is exacerbated by the proinflammatory cytokine liberation that follows reperfusion. Infrarenal aortic cross-clamping also significantly compromises RBF, most likely through reflex renal vasoconstriction.
Atheromatous renal artery embolism is a devastating complication that may be provoked by trauma as trivial as coughing, aortic and renal angiography, manipulation of the renal arteries by the proximate application of the cross-clamp, or by placement of an endovascular graft. Patchy or confluent renal infarction that is usually irreversible can occur.
Cardiorenal Syndrome.
Besides local factors, renal perfusion is manifestly affected by global changes in intravascular volume, renal perfusion pressure, and RBF. Deleterious changes in cardiac function in the perioperative period (such as after cardiopulmonary bypass [CPB]), in addition to any preoperative cardiac impairment, can more than additively affect perfusion variables for the kidney. Cardiorenal syndrome broadly describes the bidirectional negative influences of impairment or failure of either the kidney or the heart on the other.
The Inflammatory Response.
Ischemia–reperfusion injury provokes an inflammatory response that may be more detrimental than the original ischemic insult itself. Major surgery itself provokes inflammation. A cascade of stress responses is elicited, mediated by the release of various cytokines and stress hormones, culminating in the systemic inflammatory response syndrome. The kidneys sequester proinflammatory cytokines and may be damaged by them. Systemic inflammatory response syndrome is activated to a variable degree in all patients who undergo CPB and in many who undergo major operations.
Gut ischemia and portal endotoxemia frequently complicate major aortic surgery. The insult appears to be more frequent in patients who undergo surgery via the intraperitoneal abdominal aorta rather than with the endovascular approach. Endotoxin and other activated cytokines cause afferent arteriolar constriction, mesangial contraction, and direct tubular injury that diminish RBF, GFR, sodium excretion, and urine flow. Compared with open aortic repair, endovascular techniques require shorter aortic occlusion times and are associated with a diminished early-phase response and proinflammatory surge.
Glucose Homeostasis.
Abnormal glucose homeostasis (hyperglycemia) is characteristic of the acute inflammatory response and is exacerbated by the perioperative administration of high-dose steroids (e.g., in patients undergoing transplantation). Strict perioperative glycemic control has been advocated in the intensive care setting on the basis of data indicating improved survival rates with a concomitant decrease in the incidence of ARF. In one study evaluating persistent intraoperative hyperglycemia despite an insulin protocol, hyperglycemia was associated with worsened renal outcomes. However, in another randomized, controlled trial in patients undergoing cardiac surgery, tight glucose control did not reduce the incidence of perioperative ARF. Presently, it is unclear whether intraoperative hyperglycemia is simply a marker of acute illness or whether it is a reversible, treatable, and independent effector of renal outcome.
Nephrotoxins
Renin–Angiotensin System Blocking Drugs.
Drugs that block the renin–angiotensin system include the angiotensin-converting enzyme (ACE) inhibitors and the selective angiotensin II receptor antagonists. These groups of drugs have become well-established in the treatment of hypertension and promote beneficial cardiac remodeling in congestive heart failure (CHF). As such, they may prevent the progression of chronic renal disease.
However, angiotensin release is an important protective mechanism that induces efferent renal arteriolar constriction in states of decreased RBF or perfusion pressure. The presence of ACE inhibitors or angiotensin II receptor antagonists may impair the maintenance of RBF and GFR when renal perfusion is compromised. In one prospective study of 249 patients undergoing aortic surgery, long-term preoperative ACE inhibitor administration was the only factor independently associated with a 20% decline in GFR after surgery.
Aprotinin.
Aprotinin is an inhibitor of endogenous serine proteases such as kallikrein and plasmin. Its effectiveness in decreasing bleeding after CPB—through its antifibrinolytic action and platelet stabilization—was established more than 20 years ago. Numerous observations have suggested that aprotinin administration is associated with elevations in postoperative SCr levels, likely mediated through its effects on kinin pathways and subsequent alteration of intrarenal hemodynamics. Aprotinin may cause vasoconstriction of the afferent arteriole, which reduces glomerular perfusion pressure and renal excretory function. Indeed, there may be a deleterious interaction of ACE inhibitors and aprotinin on renal function when neither drug alone has any effect.
Two retrospective observational reports published in 2006 evoked much debate. They indicated that significant increases in adverse postoperative events, including renal failure, occurred with aprotinin, whereas the reduction in blood loss was no better than simpler, safer antifibrinolytic agents such as epsilon aminocaproic acid or tranexamic acid. In contrast, meta-analyses of 13 randomized controlled trials that reported data on AKI published before these observational studies failed to show an adverse effect of aprotinin on renal or other organ function. A large Canadian randomized controlled trial of antifibrinolytic drugs in high-risk cardiac surgery was halted after a higher mortality rate was seen in patients randomly allocated to receive aprotinin, although there appeared to be no difference in renal outcomes between the different antifibrinolytic agents.
Nonsteroidal Antiinflammatory Drugs.
Nonsteroidal antiinflammatory drugs (NSAIDs) exert multiple renal effects. Their inhibition of cyclooxygenase suppresses the formation of endogenous prostaglandins that induce afferent arteriolar vasodilatation during situations of renal stress. Thus administration of NSAIDs causes little harm when renal circulation is normal but may exacerbate renal injury during low flow states or in conjunction with other nephrotoxic agents. Administration of NSAIDs has also been implicated in interstitial and membranous nephritis and minimal change protein leak disease. NSAIDs may be harmful in conditions such as cirrhosis, CKD, and CHF, in which maintenance of RBF is dependent on precapillary vasodilation.
Calcineurin Inhibitors.
In the early 1980s, the introduction of supplemental immunosuppression by the calcineurin phosphatase inhibitor, cyclosporine A, revolutionized solid organ transplantation. It soon became apparent that its benefit was limited by dose-dependent acute nephrotoxicity, induced by afferent arteriolar vasoconstriction. Subsequently, the importance of chronic nephrotoxicity was also appreciated, but the mechanisms are more complex, involving the renin–angiotensin system, endothelin, nitric oxide, and inflammatory activation. Another widely used calcineurin inhibitor, tacrolimus, shares the propensity for nephrotoxicity, and its actions on growth factor may promote fibrogenesis as a component of chronic renal impairment. Strategies of altering the timing of calcineurin introduction, minimizing calcineurins, or replacing calcineurins with other immunosuppressives have no conclusive evidence of minimizing renal injury and may carry a higher rejection risk.
Myoglobin.
In the presence of acidic urine, myoglobin and uric acid precipitate and form obstructive casts within the tubules. Furthermore, at a urinary pH less than 5.6, myoglobin dissociates into the nephrotoxic ferrihematin with further potentiation of ATN. Myoglobin appears less nephrotoxic in the absence of intravascular hypovolemia and acidic urine.
Radiocontrast Media.
The mechanism of nephrotoxicity of radiocontrast media is multifactorial. They cause direct cytotoxic injury, whereas their hyperosmolality crenates red cells and causes microcirculatory obstruction. They induce an imbalance of renal oxygen supply and demands, by promoting acute vasoconstriction that impairs renal medullary perfusion, whereas the osmotic load they induce increases medullary oxygen consumption. Contrast material filtered through the glomerulus precipitates in the renal tubules and liberates damaging free oxygen radicals. The risk of radiocontrast nephropathy (RCN) is greatly exacerbated by dehydration and hypovolemia and the concomitant administration of other nephrotoxic agents.
Options and Therapies
- •
Optimize renal function preoperatively and minimize nephrotoxic insults.
- •
Minimize hemodynamic insults to the kidney
- •
Avoid prolonged aortic cross-clamping.
- •
Maintain RBF and perfusion pressure.
- •
Avoid pharmacologic agents that may compromise RBF or increase the metabolic demand of the kidney.
- •
- •
Consider pharmacologic renoprotective strategies.
Evidence
Overall, studies on prophylactic and therapeutic interventions in patients at high risk of developing perioperative AKI are limited. The majority of studies have concentrated on RCN, and their findings may not be applicable to perioperative AKI. Tables 30-2, 30-3, and 30-4 summarize and grade the evidence using established criteria.
| Level | Type of Evidence |
|---|---|
| 1a | Systematic review (with homogeneity * ) of RCTs |
| 1b | Individual RCT (with narrow confidence interval) |
| 1c | All or none † |
| 2a | Systematic review (with homogeneity * ) of cohort studies |
| 2b | Individual cohort study (including low-quality RCT) |
| 2c | “Outcomes” research |
| 3a | Systematic review (with homogeneity * ) of case-control studies |
| 3b | Individual case-control studies |
| 4 | Case series (and poor quality cohort and case-control studies) |
| 5 | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” |
* Homogeneity of both direction and degree of results between the individual studies.
† When all patients developed renal failure before the therapy was available, but now some do not; or when some patients developed renal failure before therapy was available, but now none do.
| Grade | Criteria |
|---|---|
| A | Consistent Level 1 studies |
| B | Consistent Level 2 or 3 studies or extrapolations * from Level 1 studies |
| C | Level 4 studies or extrapolations from Level 2 or 3 studies |
| D | Level 5 evidence or troubling inconsistent or inconclusive studies of any level |
* Extrapolations are from data regarding renal failure obtained from studies with a different clinical focus.
| Study | Level of Evidence | Patient Group | Comments |
|---|---|---|---|
| Dopamine, Diuretics, Calcium Channel Blockers, Angiotensin-Converting Enzyme Inhibitors, Hydration Fluids | |||
| Zacharias et al | 1a | Systematic review | Cochrane Database Systematic review of 53 studies indicated that certain interventions showed some benefits, but all the results suffered from significant heterogeneity. There is no reliable evidence from available literature to suggest that interventions during surgery can protect the kidneys from damage. |
| Perioperative Optimization | |||
| Brienza et al | 2a | Systematic review | Twenty studies suggested that perioperative optimization in elective and emergency surgical patients was effective in reducing renal injury. No guidance of methods or goals of therapy could be promoted. |
| Remote Ischemic Conditioning | |||
| Desai et al | 2a | Systematic review | Four vascular surgical studies involving 115 patients (remote ischemic preconditioning) and 117 patients without. Small numbers led to inconclusive results. No difference in mortality or renal failure. |
| Dopamine | |||
| Kellum | 1a | Systematic review | Routine use of diuretics or dopamine for the prevention of acute renal failure cannot be justified on the basis of available evidence. |
| Kellum and Decker | 1a | Systematic review | No justification for the use of low-dose dopamine for the treatment or prevention of acute renal failure. |
| Marik | 1a | Systematic review | Dopamine demonstrates no renoprotective effect in patients at high risk of developing renal failure. |
| Bellomo et al | 1b | Critically ill | Large placebo-controlled RCT ( n = 328) of dopamine in critically ill patients with signs of sepsis. No differences in peak creatinine, need for RRT, or mortality. |
| Fenoldopam | |||
| Halpenny et al | 2b | Cardiac surgery | Small placebo-controlled RCT ( n = 31) of fenoldopam during cardiac surgery with cardiopulmonary bypass. The fenoldopam group was spared decline in postoperative creatinine clearance. |
| Halpenny et al | 2b | Vascular surgery | Small placebo-controlled RCT ( n = 28) of fenoldopam in aortic surgical patients undergoing infrarenal cross-clamping. Fenoldopam was associated with postoperative maintenance of creatinine clearance and prevention of deterioration of serum creatinine. |
| Cogliati et al | 2b | Cardiac surgery | Single center, double-blind RCT ( n = 193). Fenoldopam infusion for 24 hr after cardiac surgery associated with less AKI, decreased need for RRT, and lower postoperative rise in serum creatinine. |
| Landoni et al | 2b | Cardiac surgery | Meta-analysis of 1059 patients in 13 studies was associated with less need for RRT, less in-hospital death, and shorter ICU stay. |
| Dopamine versus Fenoldopam | |||
| Bove et al | 2b | Cardiac surgery | Prospective single-center, randomized, double-blind trial ( n = 80). Fenoldopam or dopamine after the induction of anesthesia for a 24-hr period. No difference in clinical outcome. |
| Oliver et al | 2b | Vascular surgery | Single center, randomized, double-blind trial ( n = 60). Fenoldopam or dopamine with nitroprusside after the induction of anesthesia in patients undergoing aortic cross-clamping. No difference in clinical outcome. |
| Furosemide | |||
| Lassnigg et al | 1b | Cardiac surgery | Prospective ( n = 126) RCT of cardiac surgical patients that received either “renal dose” of dopamine or furosemide or placebo until 48 hr postoperatively. Furosemide administration was associated with greater creatinine deterioration, lower creatinine clearance, and more need for RRT with the conclusion of a possible negative treatment effect. |
| Kellum | 1a | Systematic review | Level 1 evidence exists against the use of diuretics for prevention of perioperative renal failure after vascular surgery. |
| Mannitol | |||
| Tiggeler et al | 2b | Renal transplantation | Prospective ( n = 61) study of cadaveric renal transplant recipients receiving restricted fluids (1.1 L), or restricted fluids (1.5 L) plus mannitol, or moderate fluids (2.5 L) plus mannitol. The incidence of ATN was 43%, 53%, and 4.8%, respectively. |
| Nicholson et al | 2b | Vascular surgery | Prospective ( n = 28) study of mannitol or placebo for aortic surgery with infrarenal aortic cross-clamping. No differences in BUN, SCr, or creatinine clearance. Mannitol group had lower urinary albumin and N -acetyl glucosaminidase. |
| Ip-Yam et al | 2b | Cardiac surgery | Prospective ( n = 23) study of hypothermic CPB, normothermic CPB, or normothermic CPB plus mannitol in bypass prime. No significant differences between groups in markers of renal function. |
| Homsi et al | 4 | Rhabdomyolysis | Retrospective case series ( n = 24) of saline versus saline plus bicarbonate plus mannitol for rhabdomyolysis (CK >500 U/L). No additive benefit with the addition of bicarbonate or mannitol. |
| Gubern et al | 2b | Obstructive jaundice | Prospective RCT ( n = 31) of mannitol in postoperative patients with obstructive jaundice. Mannitol had no beneficial effects on renal function. |
| Urinary Alkalinization | |||
| Haase et al | 2b | Cardiac surgery | Prospective RCT ( n = 100) of NaHCO 3 (4 mmol/kg) versus saline. Bicarbonate group had lower markers of renal dysfunction. |
| Heringlake et al | 2b | Cardiac surgery | Prospective observational cohort study comparing 280 patients (4 mmol NaHCO 3 /kg) versus 304 patients (control). Bicarbonate group had more hypotension and needed more fluids but no improvement in postoperative renal function. |
| Antioxidants | |||
| Haase et al | 1b | Cardiac surgery | Placebo-controlled RCT ( n = 60) of a 24-hr infusion of N -acetylcysteine. No difference in creatinine change, peak creatinine, urine output, or serum cystatin C. |
| Wijnen et al | 2b | Vascular surgery | Small RCT ( n = 44) of standard therapy plus antioxidants (allopurinol, vitamins E and C, acetylcysteine, mannitol) versus standard therapy only. No difference in urine albumin/creatinine ratio but antioxidant group had higher creatinine clearance at postoperative day 2. |
| Burns et al | 1b | Cardiac surgery | CABG patients. Randomized, quadruple-blind, placebo-controlled trial ( n = 295) of intravenous N -acetylcysteine or placebo over 24 hr. No difference in the proportion of patients with postoperative renal dysfunction. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N -acetylcysteine group compared with the placebo group. |
| Calcium Channel Blockers | |||
| Shilliday et al | 1a | Renal transplantation /systematic review | Cochrane Database Systematic Review. Ten trials included. Treatment with calcium channel blockers in the peritransplant period was associated with a significant decrease in the incidence of post-transplant ATN and delayed graft function. There was no difference between control and treatment groups in graft loss, mortality, or requirement for hemodialysis. |
| van Riemsdijk et al | 2b | Renal transplantation | Placebo-controlled RCT ( n = 210) of isradipine after renal transplantation. Isradipine was associated with better renal function at 3 and 12 mo without changes in acute rejection or delayed graft function. |
| Antonucci et al | 2b | Vascular surgery | Small RCT ( n = 16) of nifedipine or dopamine for aortic surgery with infrarenal cross-clamping. Immediate postoperative GFR was maintained in the nifedipine group (but not dopamine group). |
| Young et al | 4 | Cardiac surgery | Case series of perioperative diltiazem infusion ( n = 271) and control ( n = 143). Diltiazem was associated with higher SCr rise and greater need for dialysis (4.4% versus 0.7%). |
| Statins | |||
| Prowle et al | 2b | Cardiac surgery | Prospective, double-blind, randomized, placebo-controlled study ( n = 100). Patients with normal renal function randomly assigned to atorvastatin or placebo. No difference in incidence of postoperative AKI or urinary neutrophil gelatinase–associated lipocalin. |
| Liakopoulos et al | 2a | Cardiac surgery | Meta-analysis of studies of preoperative statins and postoperative complications of cardiac surgery suggested renoprotective benefit. |
| Mithani et al | 1b | Cardiac surgery | Single-center prospective RCT of 2104 patients undergoing CABG or valve surgery. Statins (high or low dose) had no influence on postoperative AKI or need for hemodialysis. |
| Natriuretic Peptides | |||
| Sward et al | 2b | Postcardiac surgery | Prospective, double-blind, randomized, placebo-controlled study ( n = 61). Patients with normal preoperative renal function post cardiac surgery randomly assigned to receive recombinant h-ANP or placebo when serum creatinine increased by >50% from baseline. Significant reduction in the proportion of patients requiring dialysis before or at day 21 and significant reduction in the proportion of patients with the composite endpoint of dialysis or death before or at day 21 compared with placebo. |
| Sward et al | 4 | Postcardiac surgery | Case series ( n = 11) of longer than 48-hr infusion of ANP in postcardiac surgical patients with acute renal impairment needing pharmacologic support. ANP was associated with increased urine flow, GFR, and renal blood flow. |
| Sezai et al | 2b | Cardiac surgery | RCT ( n = 504) of carperitide (0.02 then 0.01 mcg/kg/min) versus placebo in elective CABG with normal renal function. Less increase in creatinine and less need for RRT. |
| Sezai et al | 2b | Cardiac surgery | RCT ( n = 303) of carperitide versus placebo in cardiac surgical patients with chronic kidney disease. Lower postoperative creatinine and need for RRT in carperitide group. No difference in 1-yr mortality. |
| Mitaka et al | 1a | Cardiovascular surgery | Systematic review and meta-analysis of 11 studies of ANP analog (carperitide) and four studies of BNP analog (nesiritide). ANP analog associated with lower peak creatinine, reduced need for RRT, and reduced ICU and hospital stay. BNP analog associated with decreased ICU and hospital stay. |
| Langrehr et al | 2b | Liver transplantation | Placebo-controlled RCT ( n = 70) of ularitide immediately after liver transplantation. No difference in course of urea or creatinine. There was no difference in urine flow or need for dialysis. Less diuretic use in the ularitide group. |
| Weibe et al | 2b | Cardiac surgery | Small placebo-controlled RCT ( n = 14) of 7 days of ularitide in postcardiac surgical patients with anuric acute renal failure. No patients taking ularitide needed hemodialysis (compared with 6 of 7 in control group). |
| Brenner et al | 2b | Cardiac surgery | Small placebo-controlled RCT ( n = 24) of 6 days of ularitide immediately after cardiac transplantation. Equal numbers of each group (50%) required hemodialysis, although the duration and frequency were less in the ularitide group. |
| Prostaglandins | |||
| Manasia et al | 2b | Liver transplantation | Small ( n = 21) placebo-controlled RCT of PGE 1 for 5 days immediately after liver transplantation in patients with an immediate postoperative GFR less than 50 mL/min. No difference in GFR or effective renal plasma flow. |
| Klein et al | 2b | Liver transplantation | Larger ( n = 118) placebo-controlled multicenter RCT of PGE 1 immediately after liver transplantation. PGE 1 associated with lower peak creatinine, “severe renal dysfunction,” need for dialysis, and ICU length of stay. |
| Abe et al | 4 | Cardiac surgery | Small ( n = 10) case-control study of PGE 1 during cardiopulmonary bypass. Rise in N -acetyl-glucosaminidase less, and no change in free water clearance in PGE 1 group. |
| Abe et al | 2b | Cardiac surgery | Small ( n = 20) placebo-controlled RCT of PGE 1 during cardiopulmonary bypass. PGE 1 group had better results for N -acetyl-glucosaminidase, free water clearance, and beta-2 microglobulin. |
| Feddersen et al | 4 | Cardiac surgery | Small ( n = 36) case-control study of prostacyclin during cardiopulmonary bypass. Prostacyclin was associated with a postoperative increase in GFR but more hypotension than control group. |
| Insulin-like Growth Factor-1 | |||
| Franklin et al | 2b | Vascular surgery | Small ( n = 54) placebo-controlled RCT of 72 hr IGF-1 with primary endpoint as change in creatinine clearance within 72 hr after surgery involving suprarenal aorta or renal arteries. Fewer patients with IGF-1 had postoperative decline in creatinine clearance (22% versus 33%). |
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