Nephrotube, Aki End Of Module Exam

Answer E: Norepinephrine
This patient urgently requires vasopressor therapy to achieve an adequate systemic (and renal) perfusion pressure. Norepinephrine is superior to dopamine for this purpose (Option D is incorrect, and Option E is correct) . Fenoldopam has not been proven beneficial for this purpose, and is furthermore contraindicated in the presence of profound vasodilatory shock (Option B is incorrect). ANP has not been shown to improve renal function or outcomes in septic shock, and drug-induced hypotension would also be a concern in this patient if ANP were administered (Option A is incorrect). Erythropoietin therapy has not been proven to improve renal function in patients with AKI, even with early administration (Option C is incorrect) .
1. De Backer, D, Biston, P, Devriendt, J, Madl, C, Chochrad, D, Aldecoa, C, Brasseur, A, Defrance, P, Gottignies, P, Vincent, JL: Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 362: 779-789, 2010
2. Endre, ZH, Walker, RJ, Pickering, JW, et al: Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 77:1020-1030, 2010

Answer C: She should receive crystalloid for volume resuscitation
Randomized clinical trials and a Cochrane meta-analysis of colloid versus crystalloid administration for fluid
resuscitation that have suggested that there is no benefit to colloid administration, and in general colloids are
more expensive than crystalloid solutions (D is incorrect). Furthermore, certain colloids, such as hetastarch,
have been associated with an increased rate of AKI (B is incorrect). Blood products are not routinely used for
volume resuscitation, and with a hematocrit of 37%, this patient does not meet criteria for transfusion based on
published early goal directed therapy algorithms or based on randomized clinical trials of transfusion targets in
critically ill patients (A is incorrect). Therefore, the best choice of fluid for resuscitation in this patient is an
isotonic crystalloid solution (C is correct).
1. Brunkhorst, FM, Engel, C, Bloos, F, Meier-Hellmann, A, Ragaller, M, Weiler, N, Moerer, O, Gruendling,
M, Oppert, M, Grond, S, Olthoff, D, Jaschinski, U, John, S, Rossaint, R, Welte, T, Schaefer, M, Kern, P,
Kuhnt, E, Kiehntopf, M, Hartog, C, Natanson, C, Loeffler, M, Reinhart, K: Intensive insulin therapy and
pentastarch resuscitation in severe sepsis. N Engl J Med 358:125-139, 2008

The answer is E
All of the above choices are correct (E). Uric acid is the end product of purine metabolism. It has a pKa of 5.75. At a physiologic pH of 7.4, uric acid exists as urate anion. In clinical setting, the importance of uric acid lies in its solubility. In general, uric acid is less soluble than urate, and an acidic environment reduces uric acid solubility. At a pH of 5.0, the saturation of uric acid occurs at a concentration of <10 mg/dL, whereas at a pH >7.0, the saturation occurs at a concentration of >150 mg/dL. In the distal renal tubule, the pH is <7.0. During treatment of uric acid nephropathy, it is important to alkalinize the urine pH above 7.0, so that uric acid will not precipitate in renal tubules. Volume depletion or dehydration causes tubular deposition of urate. Therefore, adequate volume repletion is necessary. Preexisting renal disease is an important precipitating factor for uric acid nephropathy. To alkalinize the urine, 100 mEq of NaHCO3 in 1 L of D5W can be used until the urine pH reaches 7 or above, and NaHCO3 infusion can be discontinued once serum uric acid returns to normal. Uric acid crystal deposition increases the tubular pressure, which opposes glomerular hydrostatic pressure with resultant increase in serum creatinine levels. Also, increased uric acid reduces renal blood flow, causing AKI.

Answer A: Intravenous crystalloid, initiated prior to hospital arrival
Several strategies have been proposed to prevent or attenuate the development of AKI in rhabdomyolysis. The most important is aggressive volume replacement. In patients with traumatic rhabdomyolysis, fluid resuscitation should be initiated in the field, even before the crushed extremity is released. Urinary alkalinization has been advocated as a means to increase the solubility of heme proteins within the tubule. It has also been suggested that alkalinization may decrease the redox cycling of myoglobin thereby reducing the generation of reactive oxygen species. The use of mannitol has also been advocated, however it has not been shown to have greater efficacy than volume expansion with saline alone. No benefit has been demonstrated for dopamine, furosemide or N-acetylcysteine in this setting.

The answer is E
Although the exact mechanisms leading to HRS are incompletely understood, the available studies so far implicate all of the above mechanisms (A–D). Thus, E is correct. Of these mechanisms, splanchnic vasodilation is widely accepted mechanism for HRS. In the initial stages of cirrhosis, inflammation of hepatocytes leads to hepatic stellate cells located in the perisinusoidal space to secrete collagen and deposition in the sinusoids, leading to portal vein resistance. With progression of liver disease, the increase in portal resistance/hypertension causes release of vasodilators such as nitric oxide (NO) by shear stress. Also, vasodilators such as cannabinoids and carbon monoxide are released. Increased shear stress also causes development of collaterals in mesenteric arteries, resulting in profound splanchnic vasodilation.
Splanchnic vasodilation causes a reduction in systemic vascular resistance because the splanchnic circulation is a major part of the peripheral circulation. In early cirrhosis, cardiac output increases with maintenance of arterial volume and BP. With advancing cirrhosis, this cardiac output may increase further, but not sufficient because of severe reduction in systemic vascular resistance. Effective circulating arterial blood volume also decreases. The result is a further increase in cardiac output, which is related to activation of sympathetic nervous system, renin-AII-aldosterone system, and nonosmotic release of ADH. Not only Na+ but also water is reabsorbed, resulting in edema and ascites. Relative hypotension develops because of increased splanchnic vasodilation despite adequate salt and water retention. Thus, circulatory dysfunction occurs in cirrhosis (A, C are correct).
Bacterial translocation from intestinal lumen to mesenteric lymph nodes occurs in cirrhotic patients. These bacteria cause inflammation and release of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. These cytokines stimulate the production of vasodilaters such as NO with accentuation of splanchnic vasodilation and further cardiac dysfunction. Thus, B is correct.
Renal cortical (arcuate and interlobular) vasoconstriction in HRS has been clearly demonstrated by imaging studies, resulting in AKI. Intense renal vasoconstriction is the result of splanchnic vasodilation and activation of sympathetic nervous and renin-AII-aldosterone system. Although the vasoconstrictive effect of sympathetic nervous and renin-AII-aldosterone system is less effective in splanchnic bed because of severe vasodilation, their effect is more pronounced on renal arteries. As a result, a decrease in renal blood flow and GFR is seen in patients with HRS (D is correct). Thus, HRS is a hemodynamically mediated abnormality rather than an intrinsic kidney disease.

Correct answer is A: Cirrhotic patient with spontaneous bacterial peritonitis.
The use of intravenous albumin in the management of hypoalbuminemic patients has been controversial.
Albumin infusions have only been shown to decrease the incidence of AKI in a very limited number of clinical situations; including initial treatment of cirrhotic patients with spontaneous bacterial peritonitis (SBP) (choice A is correct) and in association with large-volume paracentesis in patients with diuretic resistant ascites. In a randomized controlled trial of 126 patients with cirrhosis and SBP the addition of intravenous albumin infusion to standard antibiotic therapy was associated with a decrease in the incidence of AKI from 33% to 10% (p=0.002) and in in-hospital mortality from 29% to 10% (p=0.01). No reduction in the incidence of AKI has been demonstrated in the settings of nephrotic syndrome, septic shock, decompensated heart failure or closed head trauma (choices B, C, D and E are incorrect).
In patients with traumatic brain injury fluid resuscitation with albumin was associated with increased mortality as compared to saline.
• Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, Castells L, Vargas V, Soriano G, Guevara M, Ginès P, Rodés J: Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 341:403-409; 1999.
• Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline
for fluid resuscitation in the intensive care unit. N Engl J Med 350:2247-2256; 2004.
• Myburgh J, Cooper DJ, Finfer S, Bellomo R, Norton R, Bishop N, Kai Lo S, Vallance S. Saline or
albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 357:874-884;
2007.

Answer D: Decompressive laparotomy
The patient has overt abdominal compartment syndrome (ACS), and decompressive laparotomy is indicated. Intra-abdominal pressure is normally <12 mmHg but may rise in the critically ill patient due the accumulation of ascites, blood, or air in the abdominal cavity, distension of the bowel lumen due to ileus or obstruction, transmission of markedly elevated intrathoracic pressure, expansion of the retroperitoneal space or other space occupying lesion, or, most commonly, marked edema of the bowel wall.
Intra-abdominal hypertension (IAH) is defined as abdominal pressure >12 mmHg (usually measured by transduction of bladder pressure at end expiration, via a Foley catheter in a supine patient). ACS is defined by elevated intra-abdominal pressure coupled with organ dysfunction including oliguric AKI and respiratory failure with high airway pressures. It is increasingly recognized as a cause of multiorgan dysfunction in the intensive care unit. Risk factors include abdominal surgery or trauma, sepsis, burns, and large volume fluid resuscitation or massive transfusion.
Organ dysfunction results from impaired organ perfusion. Noninvasive and minimally invasive strategies to reduce IAH include adequate sedation and paralysis to improve abdominal compliance, control of positive end expiratory pressure, removal of abdominal binders, drainage of ascites, evacuation of bowel content, and optimization of volume status. Surgical decompression is the definitive management for overt ACS and can result in marked improvement in organ function.
This patient has overt ACS indicating surgical decompression. Thoracenteses and paracentesis of modest volumes will not result in persistent clinical improvement in the ACS. Adequate volume resuscitation is important in the management of ACS, but central venous pressure may be falsely elevated in ACS and is not a useful guide to volume resuscitation in this setting. The CT scan did not suggest luminal distention of the colon as a mechanism for the IAH and ACS, and therefore, placement of a colonic tube would be unlikely to be of benefit

Correct Answer C: A trial of therapy with vasopressin analogues or octreotide and midodrine should be initiated before liver transplantation.
In this patient with hepatorenal syndrome (HRS) due to chronic hepatitis C infection, a trial of therapy with terlipressin (a vasopressin analogue) or combination therapy with octreotide and midodrine should be initiated prior to liver transplantation Liver transplantation is not contraindicated in patients with HRS, although HRS is associated with an increase in peri-operative and 1-year mortality (choice A is incorrect). In a case control study, normalization of renal function with terlipressin prior to transplantation resulted in similar post-transplant outcomes as patients with normal renal function. Although terlipressin is not available in the United States, combination therapy with midodrine and octreotide is associated with similar improvement in renal function. Combined liver-kidney transplantation is not indicated in this setting as the majority of patients will recover renal function following successful liver transplantation (choice B is incorrect). The use of
transjugular intrahepatic portosystemic shunt (TIPS) may also improve renal function in patients with HRS, but is not a prerequisite to transplantation (choice D is incorrect). Although it may be appropriate to withhold renal replacement therapy in patients with HRS who are not candidates for liver transplant, renal replacement therapy is not contraindicated in patients who are active transplant candidates (choice E is incorrect).

Answer E: Zidovudine
Rhabdomyolysis is seen with increased frequency in association with HIV infection. Several factors contribute to this including a high rate of alcohol and substance abuse in this population, muscle involvement and direct drug toxicity. Although myopathy is a common complication of HIV infection, it usually does not produce severe enough muscle injury to cause myoglobinuric AKI. The antiretroviral drug zidovudine has been associated with severe myopathy and rhabdomyolysis as a result of mitochondrial DNA depletion in myocytes. None of the other agents listed are associated with rhabdomyolysis.

Correct Answer E: Infuse boluses of isotonic saline until the central venous pressure is 8 to 12 mmHg, then recheck central venous oxygen saturation.
This patient has septic shock complicated by respiratory and renal failure, and should receive early goal directed therapy. Saline boluses to achieve the target central venous pressure range of 8-12 mmHg is the best approach (Choice E). There is no proven advantage of albumin or other colloids in this setting (Choice A), even with hypoalbuminemia and acute lung injury with early pulmonary edema. There is no indication for blood transfusion at this point (Choices B and D), but this would be indicated if central venous oxygen saturation remained below 70% with a hemoglobin below 10 grams/dl when the target central venous pressure of 8-12 mmHg is achieved. Diuresis alone (Choice C) is contraindicated at this point in resuscitation
of this patient.

Answer A: Isotonic, crystalloid fluid
Isotonic and not hypotonic intravenous fluids should be used for volume resuscitation. Therefore, A is correct, and B is incorrect. Low molecular weight hetastarch solutions have been associated with an increased rate of complications, including acute kidney injury; therefore, C is incorrect. Finally, adding albumin to normal saline is not associated with any statistically significant benefit in terms of clinical outcomes, hence D is incorrect.

Answer A: The incidence of AKI is increasing, and the absolute mortality rates of AKI are decreasing
Recent trend analysis derived from cardiac surgery settings suggests that the incidence of AKI is increasing. The analysis also indicated that although the absolute mortality rates in AKI may have decreased over time, the attributable risk of death continues to increase. Therefore, A is the correct choice. Both B and D are incorrect as the incidence and mortality in AKI are not decreasing, nor is the reduction in mortality restricted to the non-dialysis subjects. Choice C is also incorrect because the rising incidence of AKI and associated mortality have been demonstrated in multiple clinical settings including cardiac surgery and after nonsurgical percutaneous coronary interventions.

Answer D: Intravenous 0.9% saline at 500 ml/h
Aggressive volume administration with isotonic saline is the best initial treatment for this patient with rhabdomyolysis. The treatment of rhabdomyolysis involves aggressive fluid administration to reduce the risk of intratubular cast formation and prevent AKI. The choice of fluids is controversial. There is a theoretical benefit to giving intravenous bicarbonate to maintain a urine pH of >6.5. Increased urine pH may prevent precipitation of the Tamm-Horsfall protein-myoglobin complex and potentially limit the reduction-oxidation cycling of myoglobin, decreasing tubular injury from lipid peroxidation. However, evidence of clear benefit is lacking. Furthermore, in patients with severe hypocalcemia, administration of high-dose bicarbonate could substantially reduce ionized calcium levels, increasing the likelihood of symptomatic hypocalcemia. Bicarbonate also promotes the deposition of calcium phosphate in the renal tubules and should be used with caution in patients with hyperphosphatemia.
Hemodialysis is not effective at removing creatine kinase and is reserved for patients with severe AKI or intractable hyperkalemia. Loop diuretics may be indicated if there was evidence of marked volume expansion.
Hypocalcemia in this setting is due to sequestration of calcium in damaged muscle cells. Rebound hypercalcemia often occurs and is exacerbated by exogenous calcium treatment. Severe vascular and visceral calcification has been reported in individuals in whom hypocalcemia was treated following an episode of rhabdomyolysis. Therefore, calcium should only be given in cases where the patient is symptomatic or where there is severe hyperkalemia with risk of arrhythmia.

Answer A: Intravenous isotonic sodium bicarbonate or sodium chloride
Recent data support the use of either intravenous isotonic sodium bicarbonate or sodium chloride infusions to decrease the risk of contrast-induced AKI. Although several randomized controlled trials showed superiority of sodium bicarbonate, these trials were underpowered, and three appropriately powered randomized trials demonstrated no difference in outcomes.
Individual studies and a pooled meta-analysis have failed to demonstrate decreased risk of contrast-induced AKI with the iso-osmolar agent iodixanol relative to “low” osmolar contrast media (600–850 mOsm/kg), whereas high osmolar contrast agents are clearly more nephrotoxic. High osmolar contrast agents are no longer used or available.
Evidence regarding the benefit of N-acetylcysteine has been equivocal, and use of intravenous N-acetylcysteine is not recommended due to the risk of anaphylaxis associated with intravenous administration. Kidney Disease Improving Global Outcomes recommends use oral N-acetylcysteine, together with intravenous isotonic crystalloids, in patients at increased risk for contrast-induced AKI, although the N-acetylcysteine guideline was a level 2D recommendation (“We suggest” with very low-quality evidence).
Hemodialysis has been shown to be of no additional benefit over intravenous crystalloid administration for preventing contrast-induced AKI, and there is risk for potential harm when it is used for prevention of contrast-induced AKI.
Enteral (oral) administration of fluid to achieve volume expansion may also provide a benefit but has not been studied rigorously and is not appropriate for an individual who is poised to have an emergency procedure.

Answer C: Vasoconstrictor therapy, infusion of albumin, and large-volume paracentesis
Large-volume paracentesis with infusion of albumin coupled with institution of vasoconstrictor therapy is the most appropriate management for this patient with tense ascites, hypotension, and acute oliguric kidney injury. Leading considerations in the differential diagnosis for this patient include prerenal azotemia, evolving acute tubular necrosis (ATN), or type I hepatorenal syndrome (HRS). A therapeutic trial of albumin 1 mg/kg at least over the initial 48 hours may ameliorate prerenal azotemia. Patients admitted to the intensive care unit with hypotension also benefit from norepinephrine titrated to raise the systolic blood pressure approximately 10 mmHg. Midodrine and octreotide (or terlipressin when available) is used rather than norepinephrine for patients managed outside of the intensive care unit. Comprehensive management includes large-volume paracentesis with the infusion of albumin to relieve intra-abdominal hypertension. The diagnosis of type I HRS would be supported by persistent kidney dysfunction despite optimization of renal perfusion in the absence of many muddy brown casts in the urine sediment. Distinguishing HRS from ATN is often difficult because epithelial cell and granular casts may be seen in the setting of hyperbilirubinemia, and the fractional excretion of sodium is often <1% in ATN in patients with advanced cirrhosis.
A TIPS is a consideration when patients fail to improve with conservative measures or suffer from recurrent variceal bleeding, but the presence of encephalopathy is a relative contraindication.
Renal replacement therapy could be considered if there is no response to standard therapy, but the prognosis of type I HRS is extremely poor even with dialytic support and is typically only used as a bridge to transplantation.
Pentoxifylline reduces the incidence of HRS in acute alcoholic hepatitis but does not reverse established HRS.
Addition of broad-spectrum antibiotics would be indicated if there was strong clinical suspicion for sepsis. This patient’s hypotension is most likely related to ongoing variceal bleeding; nonetheless, a careful search for infection including culture and analysis of ascitic fluid is indicated. Antibiotic prophylaxis with intravenous ceftriaxone, intravenous ciprofloxacin, or oral norfloxacin, however, is recommended for patients with acute variceal bleeding.

Correct answer is D: No single modality of RRT is associated with an increased probability of 28-d survival.
Multiple randomized controlled trials have been published in the last six years comparing survival in patients with AKI treated with intermittent hemodialysis and CRRT. To date, none of these studies have demonstrated survival benefit associated with modality of renal replacement therapy. No studies have been performed comparing survival with the “hybrid” modalities (e.g., SLED) to outcomes with either intermittent hemodialysis or any modality of
CRRT. Thus, current data does not support an increased probability of 28-d survival with any single modality of RRT (choice D).
• Uehlinger DE, Jakob SM, Ferrari P, Eichelberger M, Huynh-Do U, Marti HP, Mohaupt MG, Vogt B, Rothen HU, Regli B, et al: Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 20:1630-1637, 2005
• Vinsonneau C, Camus C, Combes A, Costa de Beauregard MA, Klouche K, Boulain T, Pallot JL, Chiche JD, Taupin P, Landais P, Dhainaut JF: Continuous venovenous hemodiafiltration versus intermittent hemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomized trial. Lancet 368:379-385, 2006

Answer: E. Initiate continuous venovenous hemofiltration (CVVH).
Initiation of RRT with CVVH is the most appropriate choice of intervention for this hemodynamically unstable patient with renal insufficiency, diuretic refractory oliguria, and severe volume overload. Volume overload is contributing to pulmonary dysfunction, inability to achieve sternal wound closure (with increased risk for mediastinitis), and possibly even right-sided cardiac dysfunction and shock. Even with maximal response, it is highly unlikely that diuresis can correct volume overload in a timely manner, particularly in someone refractory to furosemide infusion of 20 mg/h. Slow continuous ultrafiltration will not correct metabolic acidosis or provide therapy for evolving azotemia (GFR in this patient with anuria is 0). Mannitol
and nesiritide are of no proven benefit in this scenario and have the potential for harm by causing pulmonary edema or hypotension. Although serum creatinine has not yet increased significantly to reflect evolving acute-on-chronic renal failure in this patient, there is a strong rationale to initiate RRT at this time. Cardiac surgery patients commonly develop oliguria, acidosis, or azotemia in the perioperative period, and many groups claim superior outcomes with aggressive use of RRT in this setting. There are no adequate controlled trials to guide the timing of RRT initiation in patients with AKI after cardiac surgery, which remains a matter of clinical judgment.
● Bent P, Tan HK, Bellomo R, Buckmaster J, Doolan L, Hart G, Silvester W, Gutteridge G, Matalanis G,
Raman J, Rosalion A, Buxton BF: Early and intensive continuous hemofiltration for severe renal failure after
cardiac surgery. Ann Thorac Surg 71: 832–837, 2001

The answer is C
Several studies have shown that volume expansion (fluid overload) underestimates serum creatinine levels, and delay the initiation of diagnosing AKI and renal replacement therapies. Positive fluid balance increases the volume of creatinine distribution and lowers its levels. Both in children and adults, fluid overload (>10 %) was found to be associated with increased mortality. This patient gained 8 kg (>10 %), which underestimates her serum creatinine. Thus, C is correct.

Answer A: Measure eGFR, preoperative and postoperative albuminuria (0-6 hours after surgery)
Two separate cohort studies have shown that measurement of preoperative as well as postoperative albuminuria (measured between 0 to 6 hours after surgery) has a graded association with AKI in patients undergoing cardiac surgery. Both of these studies show that the addition of both preoperative and postoperative albuminuria improved the accuracy of prediction of AKI independent of the preoperative estimated GFR. Hence, A is the correct answer and choices B, C, and D are incorrect.

Coca SG, Jammalamadaka D, Sint K, Thiessen Philbrook H, Shlipak MG, Zappitelli M, Devarajan P, Hashim S, Garg AX, Parikh CR, Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury: Preoperative proteinuria predicts acute kidney injury in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 143: 495-502, 2012
Molnar AO, Parikh CR, Sint K, Coca SG, Koyner J, Patel UD, Butrymowicz I, Shlipak M, Garg AX: Association of postoperative proteinuria with AKI after cardiac surgery among patients at high risk. Clin J Am Soc Nephrol 7: 1749-1760, 2012

The answer is B
In ICU patients with sepsis and other conditions, hyperglycemia develops due to stress-induced insulin resistance. Intensive insulin therapy lowers glucose. Studies have shown that intensive glucose control reduces the intensity and severity of AKI. However, the degree of intensity that avoids severe hypoglycemia has not been established. Following an extensive review of literature, the KDIGO guideline recommends maintenance of serum glucose between 110 and 149 mg/dL. Thus, B is correct.

Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int (Suppl). 2:1–138, 2012.

The answer is D
Allopurinol is used prophylactically with hydration prior to chemotherapy. It inhibits xanthine oxidase, which converts xanthine to uric acid. Thus, uric acid formation and serum levels of uric acid are lowered. However, allopurinol has no direct effect on uric acid conversion to more soluble allantoin. Therefore, initiation of allopurinol in this patient does not lower uric acid levels. Thus, option A is incorrect. Colchicine reduces inflammation in gouty patients, and does not reduce uric acid levels in this patient. Also, colchicine is not indicated in tumor lysis syndrome. Thus, option B is incorrect. Losartan is an angiotensin receptor blocker, and has uricosuric properties. In this patient with elevated serum creatinine levels (acute kidney injury), losartan may not have any beneficial effect. Also, it is not the drug of choice in this patient. Therefore, option C is incorrect. Febuxostat is a novel nonpurine xanthine oxidase inhibitor, which is
recommended for prevention of hyperuricemia and gout. So far, no clinical trial results are available for its use in tumor lysis syndrome. Thus, option E is incorrect. Rasburicase is a recombinant urate oxidase. This enzyme converts urate into allantoin, which is excreted.
Human subjects lack this enzyme. Since the patient has high uric acid levels, the use of rasburicase seems appropriate in this patient, as it converts urate into allantoin. Either a single dose (0.2 mg/kg) or daily dose for 5 days lowers uric acid levels within few hours in children, adults, and elderly. Therefore, option D is correct. Rasburicase should be avoided in patients with glucose-6-phosphate dehydrogenase deficiency, as it may generate hydrogen peroxide and causes hemolytic anemia and methemoglobinemia.

The answer is D
All of the above statements are correct except for D. Indeed, most of the chemotherapeutic agents do cause AKI by a variety of mechanisms. A large Danish study reported the highest incidence of AKI in patients with renal cancer at 44 % (A is correct), followed by 33 % in patients with multiple myeloma, 31.8 % in liver cancer patients. A number of studies reported the incidence of AKI is at least threefold higher in cancer patients than in patients without cancer (B is correct). Sepsis seems to be leading cause of AKI in critically ill cancer patients (C is correct). Volume depletion due to poor oral intake causes prerenal azotemia in those with mucositis due to chemotherapeutic drugs (E is correct)

Answer A: Discontinue lisinopril now
Recent data from the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort suggest that perioperative exposure to ACEI/ARB increases the risk of functional, or prerenal, AKI (1). This prospective cohort included 1594 patients undergoing cardiac surgery who were classified as high risk for AKI based on the presence of one or more of the following: SCr > 2 mg/dl, diabetes, age > 70 years, ejection fraction <35% or grade 3-4 New York Heart Association (NYHA) Functional Classification, emergency surgery, concomitant CABG and valve surgery or prior cardiac surgery. Patients were then subclassified into 3 categories on the basis of ACEI/ARB exposure: none within the previous 30 days, chronic ACEI/ARB held on the morning of surgery, or chronic ACEI/ARB taken on the morning of surgery. Across the categories, there was a graded increase in the risk of functional AKI and percentage increase in SCr, but no increase in the risk of structural AKI (i.e., ATN) as reflected by levels of neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, or liver-fatty acid-binding protein.
In another retrospective cohort of 1358 patients who underwent cardiac surgery, preoperative use of ACEI/ARB was associated with a 27.6% increased risk of AKI (2). Of note, although all patients in this cohort were prescribed ACEI/ARB as outpatients, only exposure to these medications during admission (i.e., the immediate preoperative period) conferred increased risk.
In this patient with high risk of AKI (SCr >2 mg/dl and diabetes mellitus), discontinuing lisinopril now (A), during the month before CABG, would expose the patient to the lowest risk of functional AKI. Further studies are required to define effects on morbidity and mortality, before making more definitive recommendations regarding the perioperative use of angiotensin blockade. The remaining choices (B, C, and D) are associated with increased risk of AKI and are thus incorrect.
• Coca SG, Garg AX, Swaminathan M, Garwood S, Hong K, Thiessen-Philbrook H, Passik C, Koyner JL, Parikh CR; TRIBE-AKI Consortium: Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery. Nephrol Dial Transplant 28: 2787-2799, 2013

Answer D: Continuous venovenous hemofiltration (CVVH) is associated with improved survival as compared to peritoneal dialysis
In a study comparing CVVH to PD in 70 adult patients with infection-associated AKI (48 patients with severe falciparum malaria, 22 patients with sepsis), the mortality rate in patients treated with peritoneal dialysis was 47 % as compared to a mortality rate of 15% in patients treated with CVVH. In studies comparing CRRT to intermittent hemodialysis, no consistent survival benefit has been observed for CRRT. In the largest randomized controlled trial, CRRT was associated with a higher mortality, although this study was flawed by unbalance randomization that resulted in a higher acuity of illness in the CRRT group. There are no data to compare outcomes with either SLED or EDD to outcomes with intermittent hemodialysis or any form of CRRT. Although the mechanism of solute removal differs between CVVH (predominantly convective clearance) and CVVHD (predominantly diffusive clearance), similar degrees of solute control for urea and other low molecular weight solutes can be achieved with either modality.

• Phu NH, Hien TT, Mai NTH, et al. Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam. N Engl J Med 347:895-902; 2002
• Swartz RD, Messana JM, Orzol S, Port FK. Comparing continuous hemofiltration with hemodialysis in patients with severe acute renal failure. Am J Kidney Dis 34:424-432; 1999
• Mehta R, McDonald B, Gabbai F, Pahl M, Pascual MTA, et al. A randomized clinic trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 60:1154-1163; 2001
• Kellum JA, Angus DC, Johnson JP, Leblanc M, Grinnin M, et al. Continuous versus intermittent renal replacement therapy: a meta-analysis. Intensive Care Med 28:29-37; 2002

Answer D: Examination of the urinary sediment for casts and cells
This patient has developed AKI based on the rise in serum creatinine level of >0.3 mg/dl and the development of oliguria. This patient has important risk factors for AKI including CKD, diabetes, and recent angiography, as well as coronary artery bypass surgery complicated by postoperative hypotension. The major diagnostic consideration is to determine whether the AKI is due to renal hypoperfusion (prerenal azotemia) that will improve with volume expansion or other measures to enhance renal perfusion versus acute tubular necrosis (ATN) related to renal ischemia that will not reverse promptly with such measures.
The presence of renal tubular epithelial cells and/or granular casts has a strong positive predictive value for ATN. A low FENa (<1%) is suggestive of prerenal azotemia, but some causes of ATN present with a low FENa (such as radiocontrast nephropathy); further, furosemide may cause the FENa to be high despite renal hypoperfusion, limiting its role in this case.
Central venous pressure has not been found to be a reliable indicator of organ perfusion in this setting. Further volume challenge with colloid, although not unreasonable, could worsen pulmonary congestion if the circulation is already full. Finally, low C3 can be suggestive of atheroembolism, but it is neither specific nor sensitive for this diagnosis, and other clinical features are lacking.

Answer C: Isotonic sodium bicarbonate infusion at 100 to 150 ml/hour
N-acetylcysteine has no proven benefit for the prevention or treatment of AKI (or hemolysis) (Option B is
incorrect). Although her oliguria may respond to a volume challenge (her CVP is only 6 mmHg), the finding of
pink urine with presumed hemoglobinuria (to be confirmed with urine dipstick, and discrepancy with microscopic
urinalysis) suggests greater potential benefit with urinary alkalinisation combined with volume loading (sodium
bicarbonate), rather than the use of saline alone (Option A is incorrect, and Option C is correct) [1, 2]. If
transfusion is required, there is no indication to use of Hb threshold or target above 7 g/dl (Option D is incorrect).
Mannitol would potentially exacerbate hypovolemia, and has no proven benefit in this setting (Option E is
incorrect).
1. Vermeulen-Windsant, I, Snoeijs, M, Hanssen, S, et al: Hemolysis is associated with acute kidney injury
during major aortic surgery. Kidney Int 77:913-920, 2010