Dr. Waleed Khairy, MDAin Shams University

There are more than 35 definitions of AKI (formerly acute renal failure) in literature!

Stage Increase in Serum Creatinine

Urine Output

1 1.5-2 times baseline OR 0.3 mg/dl increase from baseline

<0.5 ml/kg/h for >6 h

2 2-3 times baseline <0.5 ml/kg/h for >12 h

3 3 times baseline OR0.5 mg/dl increase if baseline>4mg/dlORAny RRT given

<0.3 ml/kg/h for >24 hOR Anuria for >12 h

Increase in SCr Urine output

Risk of renal injury

Injury to the kidney

Failure of kidney function

0.3 mg/dl increase

2 X baseline

3 X baseline OR

> 0.5 mg/dl increase if SCr >=4 mg/dl

< 0.5 ml/kg/hr for > 6 h

< 0.5 ml/kg/hr for >12h

Anuria for >12 h

Loss of kidney function

End-stage disease

Persistent renal failure for > 4 weeks

Persistent renal failure for > 3 months

Am J Kidney Dis. 2005 Dec;46(6):1038-48

AKI occurs in ≈ 7% of hospitalized patients. 36 – 67% of critically ill patients

(depending on the definition). 5-6% of ICU patients with AKI require

RRT.

Nash K, Hafeez A, Hou S: Hospital-acquired renal insufficiency. American Journal of Kidney Diseases 2002; 39:930-936.

Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73.

Osterman M, Chang R: Acute Kidney Injury in the Intensive Care Unit according to RIFLE. Critical Care Medicine 2007; 35:1837-1843.

Mortality increases proportionately with increasing severity of AKI (using RIFLE).AKI requiring RRT is an independent risk factor for in-hospital mortality.Mortality in pts with AKI requiring RRT 50-70%.Even small changes in serum creatinine are associated with increased mortality.

Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital

mortality in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73.

Chertow G, Levy E, Hammermeister K, et al.: Independent association between acute renal failure and mortality following cardiac surgery. American Journal of Medicine 1998; 104:343-348.

Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 294:813-818.

Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712-720.

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Inhibition of tubular creatinine secretionTrimethoprim, Cimetidine, Probenecid

Interference with creatinine assays in the lab (false elevation) acetoacetate, ascorbic acid, cefoxitinflucytosine

Increased productionGI BleedingCatabolic states (Prolonged ICU stay)CorticosteroidsProtein loads (TPN-Albumin infusion)

Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL)◦ Ann Intern Med 2008;148:810-819

Urinary Interleukin 18◦ Am J Kidney Dis 2004;43:405-414

Urinary Kidney Injury Molecule 1 (KIM-1)◦ J Am Soc Nephrol 2007;18:904-912

NGAL: ◦ Expressed in proximal and distal nephron◦ Binds and transports iron-carrying molecules◦ Role in injury and repair◦ Rises very early (hours) after injury in animals, confirmed in children having

CPB

IL-18:◦ Role in inflammation, activating macrophages and mediates ischemic renal

injury◦ IL-18 antiserum to animals protects against ischemic AKI◦ Studied in several human models

KIM-1:◦ Epithelial transmembrane protein, ?cell-cell interaction.◦ Appears to have strong relationship with severity of renal injury

Unremarkable in pre and post renal causesDifferentiates ATN vs. AIN. vs. AGN

Muddy brown casts in ATN WBC casts in AIN RBC casts in AGN

Disease Category Incidence

Prerenal azotemia caused by acute renal hypoperfusion

55-60%

Intrinsic renal azotemia caused by acute diseases of renal parenchyma: -Large renal vessels dis.

-Small renal vessels and glomerular dis.

-ATN (ischemic and toxic)

-Tubulo-interestitial dis.

-Intratubular obstruccttion

35-40%

*>90%*

Postrenal azotemia caused by acute obstruction of the urinary tract

<5%

Intravascular volume depletionbleeding, GI loss, Renal loss, Skin loss, Third space loss

Decreased cardiac outputCHF

Renal vasoconstrictionLiver Disease, Sepsis, Hypercalcemia

Pharmacologic impairment of autoregulation and GFR in specific settingsACEi in bilateral RAS, NSAIDS in any renal hypoperfusion setting

Large Renal Vessel DiseaseThrombo-embolic disease

Renal Microvasculature and Glomerular DiseaseInflammatory: glomerulonephritis, allograft rejectionVasospastic: malignant hypertension, scleroderma crisis, pre-eclampsia, contrastHematologic: HUS-TTP, DIC

Acute Tubular Necrosis (ATN)IschemicToxic

Tubulo-interestitial DiseaseAcute Interestitial Nephritis (AIN), Acute cellular allograft rejection, viral (HIV, BK virus), infiltration (sarcoid)

Intratubular Obstructionmyoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis, drugs (indinavir, acyclovir, foscarnet, oxalate in ethylene glycol toxicity)

Stones Blood clots Papillary necrotic tissue Urethral disease

anatomic: posterior valvefunctional: anticholinergics, L-DOPA

Prostate disease Bladder disease

anatomic: cancer, schistosomiasisfunctional: neurogenic bladder

History and Physical exam Detailed review of the chart, drugs administered,

procedures done, hemodynamics during the procedures.

Urinalysis SG, PH, protein, blood, crystals, infection

Urine microscopy casts, cells (eosinophils)

Urine lytes Renal imaging

US, Mag-3 scan, Retrograde Pyelogram Markers of CKD

iPTH, size<9cm, anemia, high phosphate, low bicarb

Renal biopsy

1) Obtain a thorough history and physical; review the chart in detail

2) Do everything you can to accurately assess volume status

3) Always order a renal ultrasound

4) Look at the urine

5) Review urinary indices

Recognition of underlying risk factors◦ Diabetes◦ CKD◦ Age ◦ HTN◦ Cardiac/liver dysfunction

Maintenance of renal perfusion Avoidance of hyperglycemia Avoidance of nephrotoxins

Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275.

Avoid use of intravenous contrast in high risk patients if at all possible.

Use pre-procedure volume expansion using isotonic saline (?bicarbonate).

NAC Avoid concomitant use of nephrotoxic

medications if possible. Use low volume low- or iso-osmolar contrast

Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275.

Intravenous albumin significantly reduces the incidence of AKI and mortality in patients with cirrhosis.

Albumin decreases the incidence of AKI after large volume paracentesis.

Albumin and terlipressin decrease mortality in HRS.Sort P, Navasa M, Arroyo V, et al.: Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. New England Journal of Medicine 1999; 341:403-409.

Gines P, Tito L, Arroyo V, et al.: Randomised comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 1988; 94:1493-1502.

Gluud L, Kjaer M, Christensen E: Terlipressin for hepatorenal syndrome. Cochrane Database Systematic Reviews 2006; CD005162.

Treatment is largely supportive in nature Maintain renal perfusion

Correct metabolic derangements Provide adequate nutrition ? Role of diuretics Renal Replacement therapy remains the

cornerstone of management of minority of patients with severe AKI

Human kidney has a compromised ability to autoregulate in AKI.

Maintaining haemodynamic stability and avoiding volume depletion are a priority in AKI.

Kelleher S, Robinette J, Conger J: Sympathetic nervous system in the loss of autoregulation in

acute renal failure. American Journal of Physiology 1984; 246: F379-386.

The individual BP target depends on age, co-morbidities (HTN) and the current acute illness.

A generally accepted target remains MAP ≥ 65.

Bourgoin A, Leone M, Delmas A, et al.: Increasing mean arterial pressure in patients with septic shock: Effects on oxygen variables and renal function. Critical Care Medicine 2005; 33:780-786

no statistical difference between volume resuscitation with saline or albumin in survival rates or need for RRT.

Finfer S, Bellomo R, Boyce N, et al.: A comparison of albumin and saline for fluid resuscitation in the intensive care unit. New England Journal of Medicine 2004; 350: 2247-2256.

Fluid conservative therapy decreased ventilator days and didn’t increase the need for RRT in ARDS patients.

Association between positive fluid balance and increased mortality in AKI patients.

Wiedeman H, Wheeler A, Bernard G, et al.: Comparison of two fluid management strategies in acute lung injury. New England Journal of Medicine 2006; 354:2564-2575.

Payen D, de Pont A, Sakr Y, et al.; A positive fluid balance is associated with worse outcome in patients with acute renal failure. Critical Care 2008; 12: R74

There is no evidence that from a renal protection standpoint, there is a vasopressor agent of choice to improve kidney outcome.

Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the

Intensivist. Critical Care Medicine 2010; 38:261-275.

renal dose dopamine (<5 μg/kg of body weight/min) increases RBF and, to a lesser extent, GFR. Dopamine is unable to prevent or alter the course of ischaemic or nephrotoxic AKI]. Furthermore, dopamine, even at low doses, can induce tachy-arrhythmia’s, myocardial ischaemia, and extravasation out of the vein can cause severe necrosis .Thus, the routine administration of dopamine to patients for the prevention of AKI or incipient AKI is no longer justified.

Lauschke A, Teichgraber U, Frei U, et al.: “Low-dose” dopamine worsens renal perfusion in patients with acute renal failure. Kidney 2006; 69:1669-1674.Argalious M, Motta P, Khandwala F, et al.: “Renal dose” dopamine is associated with the risk of new onset atrial fibrillation after cardiac surgery. Critical Care Medicine 2005; 33:1327-1332.

61 patients in 2 cardiothoracic ICU with post-op AKI assigned to receive recombinent ANP (50ng/kg/min) or placebo

The need for RRT before day 21 after development of AKI was significantly lower in ANP group (21% vs 47%)

The need for RRT or death after day 21 was significantly lower in ANP group (28% vs 57%)

Crit Care Med. 2004 Jun;32(6):1310-5

Dopamine-1 receptor agonist, lack of Dopamine-2, and alpha-1 receptor effect, make it a potentially safer drug than Dopamine!

Reduces in hospital mortality and the need for RRT in AKI

Reverses renal hypoperfusion more effectively than renal dose Dopamine

So far so good specially in cardiothoracic ICU patients, awaiting more powered trials in other groups!

J Cardiothorac Vasc Anesth. 2008 Feb;22(1):23-6. J Cardiothorac Vasc Anesth. 2007 Dec;21(6):847-50Am J Kidney Dis. 2007 Jan;40(1):56-68Crit Care Med. 2006 Mar;34(3):707-14

Loop diuretics may convert an oliguric into a non-oliguric form of AKI that may allow easier fluid and/or nutritional support of the patient. Volume overload in AKI patients is common and diuretics may provide symptomatic benefit in that situation. However, loop diuretics are neither associated with improved survival, nor with better recovery of renal function in AKI.

JAMA. 2002 Nov 27;288(20):2547-53Crit Care Resusc. 2007 Mar;9(1):60-8

The most recent trials seem to confirm a potential positive preventive effect of N-acetylcysteine (NAC), particularly in contrast-induced nephropathy (CIN), NAC alone should never take the place of IV hydration in patients at risk for CIN; fluids likely have a more substantiated benefit. (150 mg/kg in 500 mL saline (0.9%)] over 30 min immediately before contrast exposure and followed by 50 mg/kg in 500 mL saline (0.9%) over the subsequent 4 h )

Erythropoietin (EPO) has tissue-protective effects and prevents tissue damage during ischaemia and inflammation, and currently trials are performed with EPO in the prevention of AKI post-cardiac surgery, CIN and post-kidney transplantation.

26 yo F is involved in a MVA, with multiple fractures, blunt chest and abdominal trauma. She was briefly hypotensive on arrival to ED, received 6L NS and normalized BP. Non contrast CT showed small retroperitoneal hematoma. On day#2 her SCr is 0.9 mg/dl, lipase is elevated and tense abdominal distension is noted. US showed massive ascites. UOP drops to <20 cc/hr despite of 10 L total IV intake. On day#3, SCr is 2.1mg/dl, CVP is 17, UNa is 10 meq/L, with a bland sediment.

What is the cause of her AKI?What bedside diagnostic test and therapeutic

intervention is indicated?

Bladder pressure was 29 mmHg

UOP and SCr improved with emergent paracenthesis.

Dx: Abdominal Compartment Syndrome causing decreased renal perfusion from increased renal vein pressure.

59 yo M, s/p liver transplant in 2001 and acute on chronic rejection, now decompensated ESLD, is admitted with worsening ascites, hepatic encephalopathy and GI bleed (which is now controlled). The only medications he has been receiving are Lactulose and omeprazole. He has been hemodynamically stable with average BP~100/70 mmHg.He had a 3.5 L paracenthesis on day 2. His SCr has been slowly rising from 1.2 to 4.7 mg/dl within the 2nd to 4th day of admission and his UOP has dropped to 150 cc/day. His daily FeNa is <1% despite of 2 L fluid challenge. His Urine sediment is blend. His renal US is normal.

What is the cause of his AKI?

Patient required HD.

He had a second liver transplant and came off HD after the surgery with stable SCr of 1.4 mg/dl.

Dx: Hepatorenal Syndrome (HRS)

Major diagnostic criteria: No improvement with at least 1.5 L fluid

challengeSCr >1.5 mg/dl or GFR< 40 cc/minAbsence of proteinuria (<500 mg/d)Other causes are rouled out (obstruction,

ATN, etc.)Minor diagnostic criteria:

Urine volume < 400 cc/dayUNa < 10 meq/LSNa < 130 meq/LUrine RBC < 50/hpf

45 yo M with CHF and Bipolar Disorder on Lithium for 10 years, admitted for abdominal pain after a heavy meal, which turned out to be due to acute cholecyctitis. He was kept NPO on D5 1/2NS 50 cc/hr. Next morning he felt well but thirsty and hungry, BP=120/80, I/O=1200/4500. His SCr rose from 1.2 to 1.9 mg/dl. SNa 149 meq/L. UNa 10 meq/L. UOsm 190 mOsm/Kg.

What is the cause of his AKI?

Patients IVF was changed to ½ NS, replacing 80% of UOP per hour. SCr and SNa improved to baseline in 2 days.

Dx: Prerenal azotemia secondary to renal free water loss in DI.

54 yo F with CAD, on statin, started a new exercise program with intense weight training. She was brought to ED with neck pain, and LE weakness. VS stable, normal UOP, with dry mucosa. LE muscle strength 2/5 bilaterally. BUN 40 mg/dl, creatinine=8 mg/dl. FeNa 1.5%. Renal US normal. UA: 1.010, 3+ blood, few RBCs, few granular casts.

What would be the next test to order?What may be the cause of her AKI?

Her CPK=57,700 She was treated with IV NaHCO3 to

alkalinize urine to PH>6.5 . Her UOP remained normal but she

required HD for uremia.

Dx: ATN due to Rhabdomyolysis

72 yo M with DM, and prostate cancer metastatic to the bone, s/p radiotherapy, on hormonal therapy. He is admitted with weakness, progressive weight loss, and persistent nausea. His med list also includes Diclofenac sodium daily for hip pain. BP=150/90, 350cc of urine collection immediately after foley placement, and normal exam. BUN=107 mg/dl, creatinine=9.8 mg/dl (2.0 almost for 6 months), which remained unchanged with hydration. Uric acid=8.2 mg/dl. UA: 1.010, 1+ protein, 1+ blood, few RBCs, no cast, no WBC. US showed 10-11 cm kidneys, no hydronephrosis.

What seems to be the cause for his AKI?

Patient was initiated on HD for uremia and remained HD dependent for his symptomatic uremia.

Patient and his family were concerned about his renal recovery (outcome), so a renal Bx was done showing severe chronic interstitial nephritis, with fibrosis and glomerulosclerosis.

Dx: ESRD due to chronic tubulo-interstitial disease secondary to NSAIDs

38 yo M with post ERCP pancreatitis, is admitted to ICU, intubated for hypoxic respiratory distress, is anuric, febrile, and hypotensive, requiring massive volume resuscitation, on two vasopressors. He has received 11 L of NS and other IV meds within the last 8 hours and currently his CVP~12, has coarse crackles, and 2+ edema. His Creatinine rose from 1.2 to 3.5 the morning after the above event, FeNa > 1%, UNa 45 meq/L, UA: 1.010, no protein, no blood, moderate epithelial cells, many muddy brown granular cell casts, moderate epithelial cell casts. US showed normal sized kidneys with no hydronephrosis.

What is the cause of his AKI?

He was started on CVVH (continuous veno-venous hemofiltration )for volume control. Has had a long hospital stay complicated with polymicrobial bacteremia and VAP (Ventilator-associated pneumonia).

Dx: ATN secondary to renal ischemia and sepsis

Initiation Phase (hours to days)Continuous ischemic or toxic insultEvolving renal injuryATN is potentially preventable at this time

Maintenance Phase (typically 1-2 wks)Maybe prolonged to 1-12 monthsEstablished renal injuryGFR < 10 cc/min, The lowest UOP

Recovery PhaseGradual increase in UOP toward post-ATN diuresisGradual fall in SCr (may lag behind the onset of diuresis by several days)