Several definitions of acute kidney injury (AKI) exist in the literature. Of all the definitions of AKI, which one of the following definitions has been validated and is considered most useful for epidemiological studies of AKI?

Before 2004, at least 30 different definitions have been reported in the literature, which were not validated or standardized. The definitions of AKI reported in options A and B were chosen by the study investigators, and were not validated. In 2004, the RIFLE classifica tion was introduced by the Acute Dialysis Quality Initiative (ADQI) group, which was subsequently validated.

The definition of AKI was further refined by the AKIN investigators. Both classifications are based on serum creatinine and urine output. Changes that were made in AKIN classification were: (1) adding an increase in serum creatinine of at least 0.3 mg/dL even this increase may not reach 50 % threshold to R in RIFLE criteria; (2) the increase in creatinine should occur within 48-h to make the diagnosis of AKI; (3) patients are included under F if they are on RRT irrespective of their creatinine or urine output at time of initiation of RRT, and finally. Loss and ESKD categories were eliminated. Table 3.1 shows both the RIFLE and AKIN classification (criteria) of AKI. Thus, option E is correct.

A 32-year-old woman is admitted to the intensive care unit (ICU) for sepsis due to pyelonephritis. Her serum creatinine is 0.5 mg/dL at time of admission. 24-h later her urine output started to decline, but her creatinine remains stable. The intensivist feels that the patient is in the process of developing acute kidney injury (AKI). Which one of the following has been clinically validated as a biomarker for the early diagnosis of AKI?

Recent studies have focused on diagnosing AKI from tubular injury prior to detectable increase in serum creatinine using novel biomarkers, such as NGAL, NAG, KIM-1, and IL-18 as well as cystatin C, liver fatty acid binding protein, and others. Of these biomarkers, NGAL has been studied extensively in both children and adults, and its serum and urine levels have been shown to increase prior to the increase in serum creatinine in the diagnosis of AKI. However, none of the above biomarkers has been validated as a sin gle marker (or markers) in clinical studies. Thus, choice E is correct.

The above patient had decreased urine output (<0.5 mL/kg/h) in 6-h, and her creatinine is gradually increasing. Which one of the following statements is TRUE regarding decreased urine output (oliguria) and AKI in this patient?

Generally oliguria is defined as urine volume <500 mL/24-h. This defi nition was proposed on the concept that a healthy individual with normal renal function can concentrate his/her urine to a maximum of 1200 mOsm/kg H ₂ O, assuming the daily intake of 600 mOsm/24-h. Therefore, the minimal amount of urine volume to excrete these 600 mOsm is 500 mL/24-h (600 mOsm/500 mL = 1200 mOsm). Any urine volume <500 mL is considered oliguria. However, this definition of oliguria has changed after the introduction of RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) and AKIN (Acute Kidney Injury Network) classification system. This classification system defines oliguria in progressive stages as <0.5 mL/kg/h for >6-h, <0.5 mL/kg/h for >12-h, and <0.3 mL/kg/h for >24-h. Therefore, <0.5 mL/kg/h indicates decreased urine output, and necessitates evaluation for oliguria.

Oliguria may be due to hypovolemia or hypotension. In these conditions, vasopressin secretion is increased with resultant reabsorption of filtered water in the kidney. Also, oliguria may be related to intrinsic disease of the kidney. Urine osmolality distinguishes these two conditions, where maximal urine concentration (osmolality >500 mOsm/kg H ₂ O) is observed with hypovolemia and isosthenuria (~300 >500 mOsm/kg H ₂ O) with diseased kidney. In one study, about 69 % of ICU patients who developed AKI were found to be oliguric, and oliguria, was found to be an indepen dent risk factor for prolonged length of hospital stay and mortality. Furthermore, there seems to be a good correlation of poor outcomes with progressive stages of oliguria. Thus, E is correct.

A 45-year-old man with no significant past medical history is admitted for nausea, vomiting and decreased urine output for 2 weeks. He is not on any medications. On physical exam, he is found to be alert, oriented, and well nourished. He has no urine output, and an ultrasound of the abdomen is consistent with hydronephrosis. A CT of abdomen shows retroperitoneal fibrosis, obstructing the ureters. Besides complete urinary tract obstruction, which one of the following conditions is ASSOCIATED with urine output <100 mL/24-h (anuria)?

In clinical practice, anuria is defined as urine output <100 mL/24-h. All of the above clinical conditions produce anuria either by severely decreased renal perfus ion or decreased GFR due to loss of glomerular function. Thus, choice E is correct.

A 55-year-old woman with type 2 diabetes, hypertension (HTN), serum creatinine of 1.4 mg/dL (eGFR 48 mL/min) and proteinuria of 800 mg/24-h is referred to you for further management of her kidney disease and HTN. Which one of the following novel risk factors is ASSOCIATED with an increased susceptibility to AKI?

The above patient has four important traditional risk factors for AKI (diabetes, HTN, CKD, and proteinuria). However, several nontraditional factors, including hyperuricemia, hypoalbuminemia, certain genetic polymorphism, and obesity, have been implicated in the genesis an d aggravation of AKI. Also, other risk factors that were found to be associated with higher incidence of AKI are chloride-rich solutions, hetastarches, and mechanical ventilation. Thus, careful management of patients with nontraditional risk factors is necessary to improve patient care and health care costs.

Regarding the incidence of AKI, which one of the following statements is CORRECT?

All of the above statements are correct. A number of population-based studies have shown that the incidence of AKI varies depending on the definition of AKI, and among community population as well as hospitalized patients. In the developed countries, AKI is predominantly a disease of hospitalized patients. Over the last decade, the incidence of AKI has increased by 11 % annually, and reported to be higher in men than women. The incidence also increases with age until ninth decade. Among hospitalized patients, the incidence of AKI is higher in critically ill patients admitted to the intensive care units.

AKI is associated with which one of the following conditions?

AKI is not a benign condition. It has several compli cations, including higher morbidity and mortality, prolonged hospital stay and resource utilization, requirement for RRT, and progression to CKD and ESRD, as compared to non-AKI patients. The financial burden was much higher for AKI patients due to longer hospital stay. The cost is higher in patients requiring RRT than uncomplicated AKI patients without RRT. Thus, E is correct.

Which one of the following statements is CORRECT regarding the epidemiology of AKI in critically ill patients globally?

All of the above statements are correct (E). The incidence of AKI is much higher in ICU than in non-ICU patients. Bacteremia/sepsis seems to be the underlying etiology for most of the patients admitted to ICU. It appears that the majority of patients admitted to ICU with AKI had previous kidney dysfunction.

AKI is a common complication following cardiac surgery. Regarding cardiac surgery-related AKI, which one of the following statements is CORRECT?

All of the above statements are correct (E). Although most of the risk factors are the same for both cardiac surgery-related and other forms of AKI, additional patient-related and procedure-related factors have been identified for AKI during and after cardiac surgery. Table 3.2 shows thes e risk factors.

A 55-year-old African American man with diabetes and severe coronary artery disease (CAD) is admitted for acute coronary syndrome. He is on several medications for his CAD, and cardiac bypass surgery (CABG) has been suggested. Which one of the following drugs needs to be discontinued before CABG to reduce the incidence of AKI?

Besides drugs such as nonsteroidal anti-inflammatory drugs, many other drugs have been shown to cause AKI. Of these drugs, the clinical implications of ACE-Is and ARBs alone have been explored in patients who require cardiac surgery because these drugs are extensively used in patients with diabetes, hypertension, and heart disease. In a meta-analysis, Yacoub et al. concluded that preoperative use of either ACE-Is or ARBs is associated with increased incidence of postoperative AKI and mortality in patients undergoing cardiac surgery. These authors suggested to discontinue ACE-Is or ARBs prior to cardiac surgery. Thus, C is correct. The effect of other drugs is little understood.

You are asked to see a 22-year-old man with congestive heart failure (CHF) with ejection fraction of 12 % for increasing serum creatinine from 1.2 to 2.6 mg/dL in 3 days. Pulmonary artery pressure is 72 mmHg. He has anasarca with increasing ascites despite adequate management of his CHF for the last 10 days. He did not receive any nephrotoxins, although he had cardiac cathet erization 4 months ago. His urine output is slowly decreasing. Which one of the following BEST describes his acute rise in creatinine and decrease in urine output?

Of all the choices, choice C best describes his acute rise in serum creatinine and a decrease in urine output. IAP, also called intra-abdominal hypertension , affects many organs, including the kidneys. Although the mechanisms for AKI are not completely understood, renal vein compression with increased venous resistance and impaired venous drainage seems to be the most important mechanism for AKI. Renal blood flow decreases even further in a decompensated CHF patient by the presence of ascites. IAP should be considered in such a patient for acute rise in serum creatinine. IAP >15 may cause oliguria, but anuria develops at a pressure >30 mmHg. Lowering IAP improves both creatinine and urine output. Other options are unlikely causes of AKI in this patient.

A 62-year-old woman with type 2 diabetes and coronary heart disease is admitted with shortness of breath and palpitations. Pertinent medications include furosemide 40 mg once daily, ramipril 10 mg once daily, and glipizide 10 mg once daily. CXR shows pulmonary congestion. On physical exam, she has increased JVD, an S₃ and 2+ pitting edema of lower extremities. The ECHO showed an ejection fraction of 20 %, and a diagnosis of acute decompensated heart failure (ADHF) was made. Labs: Na⁺ 134 mEq/L, K⁺ 3.8 mEq/L, Cl⁻ 90 mEq/L, HCO₃ ⁻ 28 mEq/L, BUN 46 mg/dL, creatinine 1.8 mg/dL (creatinine 1 week ago was 1.2 mg/dL), eGFR <60 mL/min, glucose 100 mg/dL, and HgbA1_C 7 %. Which one of the mechanisms is contributing to her decreased renal function?

This patient has type 1 cardiorenal syndrome ( CRS ). CRS is an entity that refers to the interactivity between the heart and kidney. Both organs have a cross-talk between them in health and disease. Renal dysfunction carries poor prognosis in hospitalized patients with acute decompensated heart failure. Thus, the relationship between the heart and the kidney is intricate and unavoidable. A classification of CRS has been developed to en hance our understanding of the pathophysiology of this syndrome. As shown in the following table (Table 3.3 ), CRS has been classified into five types.

The mechanisms for AKI in type 1 CRS include all of the above mechanisms (E). Of these mechanisms, a recently proposed mechanism, right-sided heart failure and renal congestion, is receiving much attention in the pathogenesis of AKI in type 1 CRS. The rise in venous pressure lowers the arteriovenous pressure gradient across the kidney, increases the renal interstitial pressure, and reduction in renal blood flow, leading to decreased GFR. Use of diuretics and RAAS inhibitors also precipitate AKI Although diuretic have been shown to activate RAAS and sympathetic tone, they are useful in improving symptoms of congestion. For this reason, loop diur etics are used in type 1 CRS.

A 56-year-old man with history of hypertension and coronary heart disease is admitted for acute decompensated heart failure (ADHF). His admission creatinine is 2.9 mg/dL, BUN 54 mg/dL. His blood pressure is 112/72 mmHg with a heart rate of 76 beats/min. Which one of the following variables is predictive of higher in-hospital mortality in patients with ADHF?

Renal dysfunction carries poor prognosis in hospitalized patients with acute decompensated heart failure. The Acute Decompensated Heart Failure National Registry (ADHERE) database study reported that of all the 39 variables the study evaluated, only high admission levels of BUN (≥43 mg/dL) followed by a systolic blood pressure <115 mmHg, and creatinine levels ≥2.75 mg/dL predicted high mortality in hospitalized patients with heart failure. Among the three variables only the admission BUN levels ≥43 mg/dL remained as the only determinator between hospital survivors and nonsurvivors. Thus, option E is correct.

A 62-year-old man with history of hypertension and type 2 diabetes is admitted for fever and acute abdominal pain. CT of abdomen with contrast is negative. He receives 2 g of vancomycin, and 4 days later his creatin ine increases to 3.4 mg/dL (admission creatinine 0.8 mg/dL). His urine output started to decrease, and subjectively developed shortness of breath (SOB). On physical exam, he has JVD and 1+ edema of his legs. Which one of the following mechanisms is responsible for cardiac dysfunction in patients with AKI?

AKI has several effects on the heart besides fluid overload and occasional hyperkalemia. In ischemia-reperfusion injury rat model of AKI, several hemodynamic changes in the heart were observed on ECHO, including left ventricular (LV) dilatation, increased LV end systolic and diastolic diameter, increased relaxation time, and decreased fractional shortening. These cardiac c hanges may be due to invasion of neutrophil and release of inflammatory cytokines. The neuroendocrine system may also play a role in altered cardiac function in type 3 CRS. Thus, option E is correct.

The above patient gradually became edematous and became more short of breath, and did not respond to either bolus or continuous intravenous (IV) furosemide and metolazone. Also, no further improvement with nesiritide, dobutamine, and milrinone. Ultrafiltration with the Aqadex System 100 (CHF solutions, Minneapolis, MN) was started. Which one of the following statements is CORRECT regarding ultrafiltration (UF) with Aquadex System 100 compared to IV diuretic therapy in patients with CHF?

All of the above statements are correct. Diuretic resistance is not uncommon in some patients with CHF. UF is recommended when pharmacologic treatment fails. In the UNLOAD (Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure) study, those participants who received UF for 48-h lost more weight, more volume, and more Na ⁺ loss than participants treated with diuretics. Also, 90-day rehospitalization rates were significantly reduced in UF than diuretic group. However, the mortality at 90 days was not significant between the groups (9 deaths in UF group and 11 in diuretic group). Thus, option E is correct.

However, it should be noted that the CARRESS-HF (The Cardio Rescue Study in Acute Decompensated Heart Failure) study reported that stepped care diuretic therapy is superior to UF in patients with acute decompensated heart failure patients. Further studies comparing UF with diuretic therapy in these patients may resolve some of these controversial issues.

In the above patient, the creatinine did not improve. Also, his serum [HCO₃ ⁻] is decreasing. His blood pressure (BP) is 110/70 mmHg. Based on BP, fluid status and electrolyte abnormalities, which one of the following renal replacement therapies (RRTs) is APPROPRIATE for this patient?

The choice of RRTs is usually based on the patient’s hemodynamics, fluid status, electrolyte abnormalities, and solute removal. Based on BP, IHD is not appropriate in this patient because it may lower BP even further without sufficient removal of fluid (A is incorrect). SCUF and CVVH may improve fluid, but do not improve electrolyte abnormalities sufficiently (B and C are incorrect). PD is a slow process, and may compromise breathing, and D is, therefore, incorrect. In this patient, CVVHDF seems appropriate because it will improve volume status, creatinine, and electrolyte abnormalities. Therefore, E is correct. It should be noted that fluid overload at the initiation of dialysis is associated with increased risk of death.

In preparation for CVVHDF, placement of a temporary catheter was ordered. Which one of the following sites is ASSOCIATED with least bacteremia and catheter dysfunction?

Studies have shown that left jugular vein catheter placement is associated with catheter dysfunction compared to right jugular vein. Also, the blood flow in left jugular and subclavian veins is erratic and lower than other sites. Earlier studies have also shown that femoral vein catheters were associated with bacteremia. However, randomized and cross-over studies showed that both femoral and jugular vein catheter placement in critically ill patients yielded similar results. Therefore, either femoral vein or jugular vein catheter placement is acceptable in the above patient (E is correct). According to KDIGO guidelines, the following are the preference sites for catheter placement:

CVVHDF was started. Which one of the following effluent (replacement) volume flow rate is recom mended in patients undergoing CVVHDF?

A study in 2000 first demonstrated an improved survival in patients with AKI who received CVVH with effluent flow rate of 35 mL/kg/h compared to those who received 20 mL/kg/h. This study led to two prospective studies that evaluated the effect of high effluent flow rate versus low effluent flow rate. In the ATN (Acute Renal Failure Trial Network) study, there was no difference in mortality at 60 days between patients who received 35 and 20 mL/kg/h. The other study, RENAL (Randomized Evaluation of Normal versus Augmented Level of Replacement Therapy), also showed no survival benefit at 90 days in patients who received effluent flow rate of either 40 or 25 mL/ kg /h during CVVHDF. Thus, no survival benefit could be achieved above 25 mL/kg/h (E is correct). Interruptions to either CVVHDF or CVVH do occur and may compromise dose; therefore, the effluent flow rate is usually recommended between 25 and 30 mL/kg/h.

You started CVVHDF in a 70-kg man for AKI and fluid overload. His INR is 2.2, and not on any anticoagulation. Both arterial and venous pressures are normal. There is no kinking of the femoral access. 24-h later, the nurse reports to you that the filter is clotted and you want to verify your orders. She gives y ou the following values:

Which one of the following is the MOST likely explanation for his filter clotting?

This patient does not need anticoagulation, as his INR is 2.2. Blo od flow is sufficient, and not low. Also, the replacement fluid is approximately 35 mL/kg/h, which is higher than the recommended dose (20–25 mL/kg/h), making options A, B, and C incorrect. High FF is the most likely cause of his filter clotting (correct answer), although replacement fluid is given before the filter (predilution).

Simply FF describes a relationship between the amount of blood flow through the filter and the rate of removal of water from blood in the filter. The FF can be calculated by the values given above and using the following formula:
where Q _UF is ultrafiltration rate (replacement volume plus fluid removal rate), which equals 2500 mL plus 150 mL = 2650 mL. Q _B is blood flow rate (190 mL/min or 11,400 mL/h) and Hct 26 % (1–0.26 = 0.74). Total denominator equals 11,400 × 0.74 = 8436 mL/h.

Therefore, increased FF is the explanation for clotting of the hemofilter. It should be noted that not only postdilution but also predilution causes increased FF. In order to lower FF, either a decrease in the dose of replacement fluid to 25–30 mL/kg/h or an increase in blood flow to 200 mL/min can lower FF to <31 %. Based on his weight of 70 kg, his replacement fluid should be 1750–2100 mL/kg/h.

Despite several adjustments during CVVHDF in the above patient, the hemofilter clotted several times. His blood pressure is 130/80 mmHg. You decide to do intermittent HD (IHD) in view of clotting and also shortage of nursing staff. Which one of the following statements is CORRECT regarding the renal replacement therapies (RRTs) on patient and renal survival?

Several studies have addressed the issue of RRTs and their effect on patient and kidney survival with different results. However, meta-analyses of these studies showed that the recovery of renal function and survival rates were similar among various RRTs. Also, a randomized study showed no difference in metabolic control, mortality, and renal function between high-volume PD and daily HD. Therefore, a real benefit of one modality over the other has not been confirmed. Thus, option E is correct.

Regarding anticoagulation in CRRT in critically ill patients, which one of the following KDIGO guideline recommendations is CORRECT?

All of the above statements are correct. Regarding the selection of anticoagulant, regional citrate anticoagulation is recommended by most of the nephrologists and intensivists in order to avoid heparin-induced bleeding and thrombocytopenia as well as preventing heparin resistance.

A 54-year-old obese African American woman with history of hypertension is admitted for acute coronary syndrome, requiring coronary catheterization and emergent CABG (coronary artery bypass grafting). She became hypotensive during surgery with decreased urine output. Her preoperative serum creatinine was 1.4 mg/dL, which increased to 3.2 mg/dL. Over the next several days, she improved her serum creatinine with fluids and inotropes. She was discharged with creatinine of 1.6 mg/dL. Which one of the following statements is CORRECT regarding AKI following CABG?

There are several studies addressing the prognostic significance of community and in-hospital acquired AKI. Coca et al. evaluated 13 cohort studies of AKI le ading to CKD, ESRD, and death, and reported the incidence of CKD and ESRD after AKI was 25.8 and 8.6 per 100 person-years, respectively. The pooled adjusted hazard ratio for mortality was 2 (CI 1.3–3.1). Also, AKI was independently associated with cardiovascular disease and congestive heart failure. Thus, D is correct.

A 63-year-old man develops AKI following knee surgery and antibiotic use. The creatinine rose from 0.9 to 6.4 mg/dL. His urine output is <200 mL in 12-h, and his serum [K⁺] is 5.5 mEq/L. Which one of the following is an absolute indication for RRT?

All of the above choices are absolute indications for initiating RRT in patients with AKI. (E is correct). In this patient, urine output <200 mL in 12-h is an indication for RRT. Using the RIFLE classification, a consensus statement was published regarding the absolute and relative indications of RRT for patients with AKI, as shown in the following table (Table 3.4 ):