Acute Kidney Injury (AKI) PDF

AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 1 ACUTE KIDNEY INJURY (AKI)  High doses of calcineurin inhibitors cyclosporine and...

AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 1 ACUTE KIDNEY INJURY (AKI)  High doses of calcineurin inhibitors cyclosporine and tacrolimus DEFINITION o These drugs can reduce intraglomerular pressure in at-  Acute kidney injury (AKI) is a clinical syndrome generally risk patients, with a resultant decrease in GFR defined by an abrupt reduction in kidney function as  Prompt discontinuation of the offending drug can often evidenced by changes in serum creatinine (Scr), blood urea return kidney function to normal. nitrogen (BUN), and urine output. INTRINSIC ACUTE KIDNEY INJURY  Intrinsic Acute Kidney Injury (AKI) is a condition where kidney damage occurs due to direct injury to the kidney structures. o Depends on the location or part of the kidney/renal system that has the damage  Intrinsic AKI can affect different parts of the kidney, including the: PATHOPHYSIOLOGY o Vasculature o Glomeruli  The pathophysiologic processes involved in the development o Tubules of the three traditional categories of AKI: o Interstitium o Prerenal AKI o Intrinsic AKI RENAL VASCULATURE DAMAGE o Postrenal AKI Renal vasculature damage is a less common cause of AKI, but it can occur when large renal vessels are obstructed. This typically happens through the occlusion of PRERENAL ACUTE KIDNEY INJURY the renal arteries by atheroemboli or thromboemboli.  Prerenal AKI or Prerenal Azotemia results from hypoperfusion of the renal parenchyma, with or without CAUSES OF OCCLUSION systemic arterial hypotension.  Atheroemboli: Often from vascular procedures (e.g.,  Renal hypoperfusion associated with systemic arterial angioplasty, aortic manipulations). o Most often develop during vascular procedures, such as angioplasty or hypotension may be caused by a decline in either the aortic surgery, where plaques in the arteries get dislodged and travel intravascular volume or the effective circulating blood to the kidneys. volume.  Thromboemboli: Can arise from mural thrombus (e.g., heart o Intravascular volume depletion may result from several failure, atrial fibrillation). conditions, including hemorrhage, excessive o Can form in patients with heart failure or atrial fibrillation, whereblood gastrointestinal (GI) losses (severe vomiting or clots from the heart travel to the kidneys. diarrhea), dehydration, extensive burns, and diuretic SMALLER VESSELS therapy.  Can be affected by inflammation leading to microvascular o Effective circulating blood volume may be reduced in damage. conditions associated with a decreased cardiac output o While smaller vessels can also be obstructed, the damage they cause is and systemic vasodilation. usually limited and less likely to result in significant AKI. However, when  Renal hypoperfusion without systemic hypotension is most the renal capillaries are affected, inflammation can cause microvascular damage, leading to ischemia and further complications such as ischemic commonly associated with bilateral renal artery occlusion or acute tubular necrosis (ATN). unilateral occlusion in a patient with a single functioning kidney. NEUTROPHIL INVASION  Mild reduction in effective circulating blood volume or  Promotes thrombus formation, tissue infarction, and collagen volume depletion deposition. o Able to maintain a normal GFR by activating several HYPERTENSION compensatory mechanisms.  Can damage renal microvasculature and cause capillary  If hypotension is present dysfunction. o initial physiologic responses by the body stimulate the o In addition, untreated hypertension can also contribute to renal sympathetic nervous and the renin–angiotensin– vasculature damage, impairing blood flow to the kidneys. aldosterone system and release antidiuretic hormone GLOMERULAR DAMAGE  directly maintain blood pressure via vasoconstriction and stimulation of thirst resulting to RARE CAUSE OF AKI increase fluid intake, as well as sodium and water  Injury occurs when immune complexes deposit in glomeruli.  Drugs may cause a functional AKI when they interfere with o Glomerular damage, which is a less frequent but still important cause autoregulatory mechanisms in the glomerulus. of intrinsic AKI. The glomerulus is responsible for filtering fluid and o This often occurs when the offending drugs are administered to patient’s solutes into the tubules, while preventing the loss of proteins and blood dependent on autoregulation to maximize intraglomerular pressure cells. Glomerular injury often occurs when immune complexes deposit in  Dilation of afferent arterioles (arteries supplying blood to the the glomeruli, triggering an inflammatory response. glomerulus) or constriction of efferent arterioles (arteries removing blood from the glomerulus). EXAMPLES  Nonsteroidal anti-inflammatory drugs (NSAIDs) interfere  Lupus nephritis o A complication of systemic lupus erythematosus. with prostaglandin-mediated dilation of afferent arterioles.  IgA nephropathy  Angiotensin-converting enzyme (ACE) inhibitors and o A condition where IgA antibodies deposit in the kidneys. angiotensin II receptor blockers (ARBs) inhibit angiotensin II– mediated efferent arteriole vasoconstriction.  AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 2 IMPACT PROGRESSION  Causes inflammation in the glomerulus, impairing filtration.  Can lead to fibrosis and irreversible damage if untreated. o These conditions lead to inflammation, impairing the kidney’s ability to o If not addressed promptly, AIN can progress rapidly to fibrosis, which filter blood properly. The treatment for glomerular damage often can lead to long-term kidney damage. depends on the underlying disease. NOTE: Glomerular damage and interstitial nephritis are less common but PROGNOSIS still significant causes of AKI.  Varies by cause, but around 25% of patients may not TUBULAR DAMAGE (ACUTE TUBULAR NECROSIS – ATN) recover baseline kidney function. o The prognosis of AIN depends on the cause and how quickly treatment Tubular damage, which is the most common cause of intrinsic AKI and is typically is initiated, but studies suggest that up to 25% of patients may not due to acute tubular necrosis, or ATN. This condition results from two main factors recover their baseline kidney function. such as renal ischemia and nephrotoxins. POSTRENAL AKI MOST COMMON CAUSE OF INTRINSIC AKI INCIDENCE  Ischemia: Damage due to low blood supply, particularly in  Accounts for less than 5% of all AKI cases. medullary tubules. o Postrenal AKI, which accounts for less than 5% of all AKI cases. This o Which occurs when blood flow to the kidneys is reduced, often due to type of AKI occurs due to obstruction at any level of the urinary tract. hypotension or shock.  Nephrotoxins: Drugs like aminoglycosides and contrast CAUSES dyes.  Obstruction in the urinary collection system. o Including drugs like aminoglycosides and contrast dyes, which can o Bladder Outlet Obstruction: Commonly due to prostatic directly damage the renal tubules. issues (e.g., hypertrophy, cancer). MEDULLA  Is the most common cause, often caused by prostatic conditions o ATN primarily affects the medulla, the inner part of the kidney, which like benign prostatic hyperplasia or prostate cancer. This obstructs urine flow, leading to aki. has a high metabolic demand but receives relatively less oxygen compared to the outer cortex. This makes the tubules in the medulla o Ureteral Obstruction: Caused by nephrolithiasis, blood especially vulnerable to injury during ischemic events. clots, or abdominal pressure.  Can also occur due to nephrolithiasis (kidney stones), blood clots, PHASES OF ATN or external compression from abdominal masses.  Initiation: Vasoconstriction and ischemia reduce GFR. o Crystal Deposition: Can occur from oxalate or o The damage begins with ischemia and vasoconstriction, reducing medication-induced blockages. glomerular filtration rate (GFR).  Crystal deposition in the tubules can occur in some cases,  Extension: Continued hypoxia and inflammation. especially when patients are severely dehydrated or receiving o As hypoxia continues, inflammation worsens, and GFR drops further. drugs that cause low solubility in urine.  Maintenance: GFR reaches a nadir, and cellular repair IMPACT begins.  Obstruction causes urine accumulation, increasing pressure o GFR reaches its lowest point, but repair mechanisms begin. in renal structures and reducing GFR.  Recovery: Tubular cells regenerate, and function is restored. COMPLICATIONS o Tubular cells regenerate, and kidney function starts to improve.  Renal vasoconstriction may further reduce GFR. PATHOPHYSIOLOGY NOTE: Postrenal AKI is less frequent but can result from urinary  Cellular Injury: Tubular epithelial damage due to ischemia obstructions. or toxins. The key point with postrenal AKI is that both kidneys must be obstructed (or one in a patient with a single kidney) for it to cause clinically significant AKI. The  Tubular Obstruction: Cellular debris, casts, and sloughed obstruction leads to increased pressure upstream in the kidney, resulting in a decline cells obstruct urine flow. in GFR. If left untreated, this can lead to irreversible kidney damage. o Interestingly, ATN isn't just about cell death; it involves a range of cellular injuries, from sublethal damage to complete cell loss. The extent CLINICAL MANIFESTATIONS of injury depends on factors like the severity and duration of ischemia, and the specific location and oxygenation status of the kidney cells. PHASES OF ACUTE KIDNEY INJURY NOTE: Tubular damage (ATN) is the most common cause and occurs due Acute Renal Failure, now commonly referred to as Acute Kidney Injury (AKI), to ischemia or nephrotoxins. progresses through distinct phases, each with characteristic clinical manifestations. INTERSTITIAL DAMAGE (ACUTE INTERSTITIAL NEPHRITIS – INITIATION PHASE AIN)  Begins with initial insult and ends when oliguria develops CAUSE OLIGURIC PHASE/ANURIC PHASE  Primarily drug-induced (also infections, autoimmune  Accompanied by rise in serum concentrations of substance s diseases). usually secreted by the kidneys such as urea, creatinine, o Interstitial damage, which is primarily caused by acute interstitial organic acids etc. nephritis (AIN). AIN is an immune-mediated reaction, most commonly triggered by drugs, though it can also be caused by infections or  Usually appears 1-7 days of initiating event autoimmune diseases. o Signs to look out for during initiation phase are oliguria (low urine output) and anuria (absence of urine function) MECHANISM DIURETIC PHASE  Immune Reaction: Activation of T lymphocytes and inflammation in the interstitium.  Kidneys start to recover o The immune response in AIN results in inflammation of the tubules and  Usually appears within 10-12 days of onset oliguric phase interstitial tissues, often with the presence of mononuclear cells, such as o During the diuretic phase, most patients would think that they are okay T lymphocytes and macrophages. since their fluid excretion went back to normal, however, during this o Drug-induced AIN is particularly notable because the immune system phase, there is only an increase in diuresis, but technically their kidney identifies the offending agent as harmful, which activates T lymphocytes function is not yet normal. Only during the recovery phase would their that release proinflammatory molecules. kidney begin to function normally  AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 3 RECOVERY PHASE o Glomerular damage  Tubular function restored o Acute tubular necrosis  Diuresis subsides and kidney begin to function normally o Acute interstitial nephritis  Usually within a month up to 12 months for a full recovery  Postrenal AKI: This occurs when something blocks the flow of urine out of the kidneys, causing pressure and damage. SYMPTOMS OF ACUTE KIDNEY INJURY Causes include:  The initiating signs and symptoms of AKI can differ o Bladder outlet obstruction depending on many factors like the cause, severity, and o Ureteral obstruction other health conditions of the patient. It may be a change in o Renal pelvis/tubular obstruction urinary character (eg, decreased urine output or urine discoloration), edema, electrolyte disturbances, or sudden weight gain. Early recognition and cause identification are critical, as they directly affect the outcome of AKI.  If symptoms do happen, they may include one or more of the following: REDUCED URINE OUTPUT  Oliguria: < 400 mL of urine per day  Anuria: < 100 mL of urine per day o Difference between oliguria and anuria: volume of the urine o More severe & damage: Anuria FLUID OVERLOAD  Edema o Most common manifestation  Pulmonary Edema  Hypertension METABOLIC ACIDOSIS  Deep, rapid breathing as the body tries to compensate ELECTROLYTE IMBALANCES  Hyperkalemia  Hyponatremia  Hyperphosphatemia  Hypocalcemia o Potassium, sodium, phosphate and calcium are the electrolytes that is affected during AKI o Sodium and potassium should not be the same. Hyperkalemia = Hyponatremia. Same with phosphate and calcium, if there is an increase in phosphate there would be a decrease in calcium RISK FACTORS UREMIC SYMPTOMS  Chronic Kidney Disease (CKD)  Fatigue and Weakness  Diabetes  Nausea and Vomiting  Heart and Liver Disease  Confusion or altered mental status  Albuminuria  Metallic taste in mouth or ammonia smelling breath (Uremic  Major Surgery (especially cardiac surgery) Fetor)  Acute Decompensated Heart Failure  Pruritus o High toxins in blood  Sepsis  Hypotension & Volume Depletion (e.g., dehydration, ETIOLOGY diarrhea, vomiting) The etiology of acute kidney injury (AKI) refers to the underlying  Medications (e.g., ACE inhibitors, ARBs, aminoglycosides) causes that lead to this sudden loss of kidney function. It can be  Advanced Age classified based on the anatomic location of the injury  Male Gender associated with the precipitating factor(s).  African American Race  Prerenal AKI: This type occurs when there is a problem with blood flow to the kidneys, which can lead to kidney IMPACT OF RISK FACTORS ON AKI DEVELOPMENT damage if not corrected. Causes include:  CKD: Existing kidney dysfunction increases the likelihood of o Volume depletion developing AKI. o Decreased effective circulatory blood volume  Diabetes & Heart Failure: Both conditions increase o Functional: Medications like NSAIDs (painkillers), ACE vulnerability to kidney injury. inhibitors, or ARBs that affect how the kidneys handle  Sepsis & Hypotension: These conditions reduce renal blood flow. perfusion, making kidneys more susceptible to injury.  Intrinsic AKI: This happens when there is direct damage to  Medications: Certain drugs, such as ACE inhibitors and the kidneys themselves, which can be from: aminoglycosides, can directly harm kidney function. o Vascular damage  AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 4  Age & Gender: Older age and male gender are associated BIOMARKERS with a higher incidence of AKI. CONVENTIONAL BIOMARKERS  Race: African Americans are at increased risk, likely due to genetic and environmental factors.  Traditional or widely used biological indicators used to assess the state or function of organs or to detect disease AKI RISK PREDICTION MODEL conditions. The examples are: o Serum Creatinine o Blood Urea Nitrogen o Urine Output  These are valuable for diagnosing and staging AKI but have limitations, such as a delayed response to kidney injury and variability influenced by factors like hydration status, muscle mass, and diet. SERUM CREATININE  Byproduct of muscle metabolism used to estimate kidney function. An increase in serum creatinine indicates impaired kidney function  Men: 0.7 to 1.3 mg/dL (62 to 115 μmol/L)  Women: 0.6 to 1.1 mg/dL (53 to 97 μmol/L)  These values can vary based on age, muscle mass and overall health. All or nothing for example, if there is no liver disease the score will be zero and in o Can also use to check the progression and recovery of AKI, determine case for hypertension, no matter what the stage it will automatically score as 2 if the treatment is effective. o After determining the basal and medication is given, serum creatinine  A validated scoring system helps identify patients at high is checked again after 1 month. As it recover, patagal ng patagal yung risk for AKI pagcheck ng Scr.  The scoring system is based on 10 risk factors BLOOD UREA NITROGEN (BUN)  Risk Score Interpretation  Measure of urea levels in the blood, which can indicate o 0 to 4 points: Low risk of AKI. kidney dysfunction o 5 or more points: High risk of AKI.  Normal range: 7 to 20 mg/dL (2.5 to 7.1 mmol/L)  Positive Predictive Value: 32%  BUN levels can be affected by factors such as protein  Negative Predictive Value: 95% (patients with a score 7 g/dL.  Monitoring Targets:  Severe Hypoalbuminemia: Albumin infusion o Circuit Calcium: 0.8–1.6 mg/dL (0.2–0.4 mmol/L) o If AKI leads to blood loss or is complicated by symptomatic anemia, o Systemic Calcium: 4.4–5.2 mg/dL (1.1–1.3 mmol/L) red blood cell transfusion to a hemoglobin >7g/dL (70 g/L; 4.34 mmol/L) is the treatment of choice. Albumin is typically preferred in NOTE: Severe hypocalcemia can lead to arrhythmias or death; monitor individuals with severe hypoalbuminemia secondary to cirrhosis or unbound serum calcium frequently. nephrotic syndrome. NUTRITIONAL CONSIDERATIONS IN AKI VASOPRESSORS FOR HEMODYNAMIC SUPPORT  Indications: Use in cases of vasodilatory shock in critically ill CALORIC AND PROTEIN INTAKE GOALS (KDIGO patients. GUIDELINES)  Common Vasopressors: Norepinephrine, vasopressin, or  Caloric Intake: 20–30 kcal/kg/day o Irrespective of the stage of kidney impairment and preferentialy dopamine. through the enteral route. o In critically ill patients with vasodilatory shock, vasopressors such as norepinephrine, vasopressin, or dopamine may be used in conjunction o Where do we get the kcal? Carbohydrates, Protein, Fats with fluids in order to maintain adequate hemodynamics and renal PROTEIN REQUIREMENTS: perfusion.  Proteins are often assessed and adjusted in dialysis patients since it has high ELECTROLYTE MANAGEMENT molecular weight which is not good for the kidneys. Proteins are It is important to monitor electrolytes every now and then recommended in patient in dialysis, but should not exceed the requirement. o Non-Catabolic AKI (No Dialysis): 0.8–1 g/kg/day. SODIUM MANAGEMENT IN AKI o RRT: 1–1.5 g/kg/day.  Hypernatremia & Fluid Retention: Common in AKI patients. o CRRT with Hypercatabolism: Up to 1.7 g/kg/day due  Total Sodium Intake: Monitor closely due to sodium content to nutrient losses in IV drugs and certain foods. o Sodium and fluid goes together, when you change one most probably RENAL REPLACEMENT THERAPY / DIALYSIS the other one will also have a change.  Often utilized to treat the following:  High sodium intake can impair effectiveness o Diuretic-resistant fluid overload o Hypernatremia and fluid retention are frequent complications of AKI. o Electrolyte disturbances Total daily sodium intake should be monitored as unintended sodium  Hyperkalemia (K >6.5 mEq/L) intake from intravenous drugs (ie, antibiotics) or foods can contribute to diuretic therapy failure. o Acid-base imbalances  Hypernatremia = fluid overload  Metabolic acidosis with a pH 90% of potassium is excreted renally). DIALYZABLE AND NON-DIALYZABLE DRUGS o Management is monitoring and avoid increasing potassium level. DIALYZABLE NON-DIALYZABLE  Risk of Arrhythmias: Life-threatening if potassium >6 mEq/L Capable of diffusing through a dialyzing Not removed by dialysis  Avoid foods and medications that increase potassium membrane  Avoid potassium supplement Not given during dialysis o Life-threatening cardiac arrhythmias may occur with serum potassium Isoniazid, Salicylates, Theophyline, concentrations greater than 6 mEq/L, so frequent monitoring of Uremia, Methanol, Metformin, potassium is essential. Avoid foods and medications that increase Barbiturates, Lithium, Ethylene glycol, potassium. In general, exogenous potassium supplementation should be Depakote, Dabigatran avoided in patients with AKI unless warranted by the presence of hypokalemia. CRITERIA  Molecular size PHOSPHORUS AND MAGNESIUM IN AKI o Smaller molecular weight, easier to pass through PHOSPHORUS  Protein binding o Unbound drugs: easier to pass through and more likely to be dialyzable  High levels are common initially, especially in tissue damage o Bound drugs: Less amount of drug available to be dialyzable cases. Restrict dietary intake in advanced AKI.  Volume of distribution  Water solubility  Plasma clearance  AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 8 COMMON INDICATIONS o Usually lasts for 3 days, then assess  The most common indications for initiation of RRT are summarized below:  It can achieve a greater amount of solute removal and remember “AEIOU” higher mean arterial pressures compared with IHD in INDICATION FOR RRT CLINICAL SETTING critically ill patients with AKI. A: Acid-base abnormalities Metabolic acidosis (especially if pH 0.5ml/kg/h  Considered safe and effective GENERAL SUPPORTIVE MANAGEMENT OF AKI & o Recommendation: Taken 30 minutes prior to COMPLICATIONS intravenous loop diuretics to achieve peak effects at the same time to potentially enhance diuresis.  Assessment of the circulating volume and fluid administration CLINICAL PRACTICE GUIDELINES: PREVENTION &  Prevention and/or treatment of hyperkalemia and TREATMENT OF AKI metabolic acidosis HEMODYNAMIC MONITORING & SUPPORT  Monitor pharmacokinetics of potentially nephrotoxic drugs during discontinuation FLUIDS  Dose adaptation of drugs excreted by the kidneys to the  Patients with or at risk of AKI require careful monitoring of patient’s renal function hemodynamic status because: o Hypotension results in decreased renal perfusion and if severe or sustained can lead to AKI o The injured kidney loses autoregulation of blood flow  AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 12 GLYCEMIC CONTROL & NUTRITIONAL SUPPORT FENOLDOPAM GLYCEMIC CONTROL IN CRITICAL ILLNESS: RENAL EFFECTS  Not recommended using fenoldopam to prevent or treat AND OUTCOMES AKI  Recommendation: Initiate Insulin therapy in critically ill  MOA: Fenoldopam mesylate is a pure dopamine type -1 patients. receptor agonist that has similar hemodynamic renal effects o Target Plasma Glucose: 110–149 mg/dL (6.1–8.3 as low-dose dopamine without systemic a- or b-adrenergic mmol/L) stimulation.  Used to address stress hyperglycemia in critical illness and  The pharmacologic strategy of renal vasodilation has not can be normalized by exogenous insulin administration been successful to date, and different approaches are likely needed. NUTRITIONAL ASPECTS IN THE PREVENTION & TREATMENT o While randomized trials of fenoldopam to treat AKI in a variety of OF CRITICALLY ILL PATIENTS WITH AKI settings (critical illness, high-risk surgery— particularly cardiac, sepsis) may be considered. The pharmacologic strategy of renal vasodilatation  Recommendation: has not been successful to date, and different approaches are likely o Total Energy Intake in any stage of AKI: 20– 30 needed. kcal/kg/day (100-130% Resting Energy Expenditure) NATRIURETIC PEPTIDES o Protein administration; avoid protein restriction to  Not recommended using atrial natriuretic peptide (ANP) to prevent/delay the initiation of RRT prevent or treat AKI  Non catabolic AKI patients without need for o ANP has promising effects in some contexts, but its efficacy in dialysis: 0.8–1.0 g/kg/d preventing and treating AKI remains uncertain due to inconsistent  Patients with AKI on RRT: 1.0–1.5 g/kg/d clinical results.  Patients on CRRT or hypercatabolic patients: 1.7  MOA: Produced in atrial myocytes, with increased release g/kg/d due to atrial stretch  Enteral nutrition is recommended in AKI o Increases glomerular filtration rate (GFR) and promotes diuresis by: PEDIATRIC CONSIDERATIONS  Decreasing preglomerular vascular resistance.  Critically ill children should receive 100–130% of the basal  Increasing postglomerular vascular resistance. energy expenditure using the Caldwell-Kennedy equation  Inhibiting renal tubular sodium reabsorption. o [kcal/kg/d] = 22 + 31.05 x weight(kg) + 1.16 GROWTH FACTOR INTERVENTION age(yrs) INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) USE OF DIURETICS IN AKI  Not recommended in preventing AKI or treatment of AKI  Not recommended using insulin-like growth factor-1 (IGF- unless in the management of volume overload. 1) to prevent or treat AKI. o Furosemide does not reduce the severity of AKI, or  Recovery from Acute Kidney Injury (AKI) involves the improves its outcomes increased expression of growth factors through autocrine, paracrine, and endocrine mechanisms. MANNITOL o Research into recombinant growth factors has shown promise in experimental studies, particularly with factors like insulin-like growth  Frequently use in the past in the prevention of AKI but with factor-1 (IGF-1), hepatic growth factor, and erythropoietin. insufficient evidence of its use  Current evidence does not support the use of rhIGF-1 for o Highly probable that it does not convey additional AKI treatment due to concerns over efficacy, safety, and beneficial effects beyond adequate hydration on the cost incidence of AKI o Three RCTs on recombinant human IGF-1 (rhIGF-1) had negative or mixed results. VASODILATOR THERAPY DOPAMINE FOR THE PREVENTION & TREATMENT OF AKI ERYTHROPOIETIN  Not recommended using dopamine for prevention or  Two trials were conducted: treatment of AKI o Pilot Trial on Coronary Artery Bypass Graft (CABG) o Low doses of dopamine can trigger the following adverse effects: Patients  Tachyarrhythmia, myocardial ischemia, decrease intestinal blood o Prospective RCT in ICU Patients at Risk for AKI flow, hypopituitarism, and suppress T-cell function  While a small trial showed promising results in reducing AKI  Was once commonly used as renal protection for the incidence with erythropoietin after CABG, a larger trial in critically ill, and has since been abandoned ICU patients did not show a significant benefit.  MOA: seen to show renal vasodilation, natriuresis, and o This suggests the need for further research to clarify erythropoietin's role in AKI prevention, especially regarding patient selection and timing increased GFR of administration. o can trigger tachyarrhythmias and myocardial ischemia, decrease intestinal blood flow, cause hypopituitarism, ADENOSINE RECEPTOR ANTAGONISTS and suppress T-cell function  Recommendation: single dose of theophylline is o no evidence that dopamine therapy is effective in the recommended for neonates with severe perinatal asphyxia prevention or treatment of AKI who are at high risk of developing AKI o The potential benefits of using adenosine receptor antagonists, like theophylline, to decrease tubuloglomerular feedback-mediated vasoconstriction and improve renal blood flow and GFR in AKI may be limited to very specific populations, such as asphyctic neonates.  AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 13  Tubuloglomerular Feedback plays a crucial role in the early  Due to the altered pharmacokinetics in these patients, the stages of ischemic Acute Kidney Injury (AKI) recommendation leans towards avoiding single-daily o Elevated luminal chloride in the distal renal tubules triggers dosing and increasing the frequency of TDM tubuloglomerular feedback. o This leads to the release of adenosine, which binds to adenosine A1  Recommendation: Monitoring aminoglycoside drug levels receptors in the glomerulus. when treatment with single-daily dosing is used for more  Effects include: than 48 hours. o While single-daily dosing of aminoglycosides has theoretical benefits, o Vasoconstriction of the afferent arteriole. the lack of standardization for monitoring and the variability in patient o Decreased renal blood flow and GFR. response necessitate careful consideration, especially in critically ill or o Sodium and water retention renal-impaired populations PREVENTION OF AMINOGLYCOSIDE AND AMPHOTERICIN CONCENTRATED ANTIMICROBIAL ACTIVITY RELATED AKI  Local administration allows aminoglycosides to achieve high AMINOGLYCOSIDE NEPHROTOXICITY tissue concentrations without significant systemic absorption, thereby minimizing systemic side effects, especially BENEFITS CONCERNS nephrotoxicity. Broad spectrum of activity. Nephrotoxicity is the primary dose-  This strategy is effective in scenarios requiring targete d limiting side effect. Stability and predictable Secondary concerns include antimicrobial activity, such as bone and joint infections, pharmacokinetics. ototoxicity and neuromuscular where aminoglycoside-loaded beads provide sustained blockade. localized drug delivery. Low risk of immunologic side Careful dosing and therapeutic drug  Recommendation: Use topical or local applications of effects. monitoring can reduce the risk of AKI. The high risk of drug-induced AKI associated with aminoglycosides warrants their aminoglycosides (e.g., respiratory aerosols, instilled use only when no safer alternatives exist. The recommendation emphasizes short- antibiotic beads), rather than i.v. application, when feasible term use and careful monitoring in high-risk populations to minimize adverse and suitable. outcomes. o Topical and local administration of aminoglycosides can concentrate o the antibiotic at the infection site with minimal systemic impact, making USAGE CONSIDERATIONS: it a valuable alternative to i.v. routes, especially for minimizing  Restrict use to severe infections where aminoglycosides are nephrotoxicity. Careful monitoring is still essential, particularly when using inhaled formulations. the best or only effective option.  Use should be limited in duration to minimize the risk of AMPHOTERICIN B NEPHROTOXICITY nephrotoxicity.  Acute Kidney Injury (AKI) is a common and significant  Repeated administration increases the risk of nephrotoxicity adverse effect of amphotericin B, occurring in a high due to accumulation in the renal interstitium and tubular percentage of patients. It is associated with higher mortality cells. rates, longer hospital stays, and increased healthcare costs. RISK FACTORS FOR INCREASED NEPHROTOXICITY  Other toxicities associated with amphotericin B include  Diabetes mellitus thrombophlebitis, electrolyte disturbances, hypoplastic  Use of other nephrotoxic medications anemia, and systemic side effects such as fever, chills, and hypotension.  Prolonged or excessive dosing o Avoidance of nephrotoxicity is a major factor in deciding which  Repeated courses of aminoglycosides in a short period antifungal therapy to use, but clinicians must balance this with the drug’s effectiveness, cost, and spectrum of activity against fungal pathogens. NOTE: Do not use aminoglycosides for the treatment of infections unless no suitable, less nephrotoxic, therapeutic alternatives are available. LIPID FORMULATIONS  Lipid formulations of amphotericin B (e.g., liposomal IMPORTANCE OF TDM amphotericin B) have been developed to reduce  Aminoglycoside drug levels can vary significantly among nephrotoxicity while maintaining antifungal efficacy. individuals due to factors like changes in volume distribution, o These formulations are less nephrotoxic because they reduce direct renal blood flow, and filtration rate. cellular membrane interactions, limiting the damage to renal cells.  These variables can impact the risk of nephrotoxicity,  However, lipid formulations require higher doses (3 to 5 making drug level monitoring essential to ensure safe and times the dose used for deoxycholate formulations) due to effective treatment. differences in drug pharmacokinetics and distribution.  Therapeutic drug monitoring is crucial when using multiple- o While lipid formulations are less nephrotoxic, they may still cause general systemic toxicity (e.g., fever, chills, hypotension) similar to the daily aminoglycoside dosing beyond 24 hours. deoxycholate formulation.  Recommendation: Monitoring aminoglycoside drug levels  Recommendation: Using lipid formulations of amphotericin when treatment with multiple daily dosing is used for more B rather than conventional formulations of amphotericin B. than 24 hours by performing therapeutic drug monitoring o The use of lipid formulations of amphotericin B should be prioritized (TDM). over the conventional deoxycholate formulation to reduce the risk of o It ensures drug efficacy while mitigating the risk of nephrotoxicity by nephrotoxicity, especially in patients who are at higher risk for kidney keeping drug concentrations within target ranges. This practice remains injury. a cornerstone of safe aminoglycoside use, applicable to both extended- AZOLES AND ECHINOCANDINS interval and traditional dosing strategies.  Mechanisms of Action: CHALLENGES IN SPECIFIC POPULATIONS o Azoles: Inhibit the synthesis of ergosterol, a critical  Single-daily dosing can be problematic in patients with pre- component of fungal cell membranes, by blocking the existing kidney disease or fluctuating renal function, such as enzyme 14-demethylase. This leads to disrupted fungal critically ill patients. cell membrane integrity.  AHMED, CANLAS, ESGUERRA, HAPITAN, MORAL, MOSTAZA, SUGATAN, TAGUINOD, TEJARES, TOLENTINO | EBPT 1 14 o Echinocandins: Inhibits the synthesis of beta-glucan, a STAGE-BASED MANAGEMENT OF AKI key component of fungal cell walls, offering an entirely different mechanism of action from amphotericin B.  Recommendation: In the treatment of systemic mycoses or parasitic infections, we recommend using azole antifungal agents and/or the echinocandins rather than conventional amphotericin B, if equal therapeutic efficacy can be assumed. OTHER METHODS OF PREVENTION OF AKI IN THE CRITICALLY ILL ON-PUMP VS. OFF-PUMP CORONARY ARTERY BYPASS SURGERY On-Pump Coronary Artery Off-Pump Coronary Artery Bypass Surgery Bypass Surgery Involves the use of a Avoids the use of cardiopulmonary bypass cardiopulmonary bypass (CPB) machine to take over (CPB), meaning the heart the heart and lung function continues to pump blood Solid shading of gray indicates actions that are equally appropriate at all stages, whereas blue-graded shading indicates increasing priority as intensity increases. during surgery. during the surgery. CPB can cause renal ischemia Hemodynamic instability can END and systemic inflammation, occur due to ventricular which may contribute to compression when the heart is kidney damage. manipulated  Recommendation: off-pump coronary artery bypass graft surgery not be selected solely for the purpose of reducing perioperative AKI or need for RRT o The benefits of off-pump surgery in these areas remain uncertain, and decisions regarding the surgical approach should be based on other factors, such as patient-specific characteristics and the surgeon’s expertise. More research is required to establish clear recommendations in this regard. N-ACETYLCYSTEINE (NAC)  Not recommended using NAC to prevent AKI in critically ill patients with hypotension.  MOA: NAC is a precursor to glutathione, a powerful antioxidant, and it has vasodilatory properties due to enhanced nitric oxide availability.  Studies have suggested that NAC does not directly reduce creatinine levels in a way that correlates with actual changes in glomerular filtration rate (GFR). o There is also no evidence that NAC influences SCr or cystatin C in patients with chronic kidney disease (CKD), even when given in doses intended to prevent AKI. NAC IN CRITICALLY ILL PATIENTS  Not recommended using oral or I.V. NAC for prevention of postsurgical AKI. o Based on the current body of evidence, NAC is not effective in preventing postoperative AKI, whether in cardiac, abdominal vascular, or liver transplant surgery. Additionally, NAC does not provide any benefit in preventing AKI in critically ill patients with hypotension.  NAC in Cardiac Surgery: o In five studies focused on cardiac surgery. No significant difference was observed in postoperative outcomes (AKI, RRT, or mortality) between NAC and placebo groups. o Pre-existing renal dysfunction was a common inclusion criterion, but NAC did not provide a clear benefit in this population.