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Oliguria and Acute Renal Failure in the ICU

Epidemiology

Studies estimate that 2.5 to 15% of ICU patients develop some form of AKI

In a large observational study of 29,269 ICU patients, Uchino et al. observed 5.7% patients had severe AKI requiring Renal Replacement Therapy or with severe oliguria and uremia.

Overall hospital mortality of these patients with severe AKI was 60.3%, the outcome was not significantly changed by use of RRT.

The most common cause was septic shock.

Other studies cite overall mortality up to 78% in patients requiring RRT.

It’s believed that up to 9% of AKI in critically ill patients is 2° to ATN.

The PICARD study - an observational study of 618 ICU patients – demonstrated bad prognostic factors included older age, male gender, baseline GFR, tachycardia, low UOP, and presence of co-morbid organ failure.

What is the definition of Acute Kidney Injury (AKI)?

Stage GFR** Criteria Urine Output Criteria Probability

Risk SCr† increased × 1.5orGFR decreased >25%

UO‡ < 0.5 mL/kg/h × 6 h High sensitivity (Risk >Injury >Failure)

Injury SCr increased × 2orGFR decreased >50%

UO < 0.5 mL/kg/h × 12 h

Failure SCr increased × 3orGFR decreased 75%orSCr ≥4 mg/dL; acute rise ≥0.5 mg/dL

UO < 0.3 mL/kg/h × 24 h(oliguria)oranuria × 12 h

Loss Persistent acute renal failure: complete loss of kidney function >4 wk

High specificity

ESRD* Complete loss of kidney function >3 mo

*ESRD—end-stage renal disease; **GFR—glomerular filtration rate; †SCr—serum creatinine; ‡UO—urine output 

Note: Patients can be classified either by GFR criteria or by UO criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-FC; failure is present in such cases even if the increase in SCr is less than 3-fold, provided that the new SCr is greater than 4.0 mg/dL (350 μmol/L) and results from an acute increase of at least 0.5 mg/dL (44 μmol/L). 

When the failure classification is achieved by UO criteria, the designation of RIFLE-FO is used to denote oliguria. The initial stage, "risk," has high sensitivity; more patients will be classified in this mild category, including some who do not actually have renal failure. Progression through the increasingly severe stages of RIFLE is marked by decreasing sensitivity and increasing specificity. 

Table 1. RIFLE Classification System for Acute Kidney Injury)

Oliguria definition

Urine Output < 400 ml/day or or 16ml/hr

Or more commonly <0.5ml/kg/hr (30-60 ml/hr in 70-80 kg adult)

Evaluating AKI

Pre – renal urine sodium low (<20mEq), FeNa < 1%, FeUrea < 35%, UOsm > 500, BUN/Cr ratio of > 20 may also suggest pre-renal state but none of these are absolute

Intrinsic renal – Urine sodium high (>40) FeNa>2%, FeUrea > 50%, UOsm< 350 However, there is often a mixed picture, so FeNa, Uosm etc.

does not help much.

Post renal (10%) Urine sodium high (>40) FeNa>4%, Acute – Pre-renal picture Chronic – Post-renal picture

Pre-renal Causes

Hypovolemia eg diarrhea, vomiting, GIBMechanical Ventilation (decreased venous

return)Cardiomyopathy (Decreased LVEF)Aortic StenosisDissecting Aortic AneurysmDrugs that impair renal autoregulation (eg

NSAIDS, ACEI, ARBS)Sepsis

Renal causes

Usually ATN (50% cases) or AIN caused by:Circulatory ShockSevere SepsisMulti-organ failureSurgery (Cardiac and AAA repair)Drugs and toxins (e.g. aminoglycosides,

amphotericin, cisplatin causing AIN, nephrotoxins like ethylene glycol)

Myoglobinuria, Radio-contrast dye

Post-renal Obstruction

Distal to the renal parenchyma Papillary necrosisRetroperitoneal mass – compressing uretersUrethral StrictureProstatic hypertrophyBladder stones - if 1 functional kidney

Evaluating renal causes

Break intrinsic renal causes up anatomically within nephron: glomerular, tubular, interstitial, collecting system, vascular Glomerular: glomerulonephritis – nephrotic vs. nephritis Tubular – Acute tubular necrosis – is the most common cause of

AKI in the ICU Ischemic – most common cause in ICU is septic shock Toxic contrast, pigment, meds; osmotic agents (IVIG), Cisplatin,

Amphotericin, Interstitial: Acute Interstitial Nephritis Collecting System: crystals (phosphate, ethylene glycol,

acyclovir, sulfa antibiotics, megadose Vitamin C, MTX, indinavir), stones (uric acid)

Vascular: TTP/HUS, DIC, Sickle Crisis/Papillary Necrosis, Polyarteritis Nodosa, Atheroembolic Disease (after catherization), renal artery or vein thrombosis

Work up

CVP – usually we want this 8-12. If Low i.e. less than 2, pretty sensitive for hypovolemia

BP varying with respirations or collapsing IVC with respirations – may benefit from volume

Spot urine protein to creatinine ratio (if UA positive for protein)

Serum osmoles to calculate osmolar gap

Check CPK to evaluate for rhabdomyolysis

Check bladder pressure to evaluate for abdominal compartment syndrome (concerning if>20)

Check ANCA, cryoglobulins and complements (C3 & C4) to look for MPGN or Wegnener’s associated with Hepatitis B and C respectively

HIV viral load to estimate activity of disease

Urine Microscopy

Hyaline casts – suggests pre-renalGranular casts , muddy brown casts - ATNRed cell casts, dysmorphic RBCs – acute

GlomerulonephritisOval fat bodies, maltese crosses Crystals –

calcium oxalate (ethylene glycol ingestion)White cell casts, sterile pyuria– Interstitial

nephritisEosinophils with Wright’s stain – AIN,

pyleonephritis, prostatitis, Cholesterol emboli

ATN

Pathophysiology:

Oxidative injury to renal tubular epithelial cells

Sloughing of cells into lumen of renal tubules obstruction that increases pressure in proximal tubules

Decreases filtration pressure decrease in GFR

Termed tubulo-glomerular feedback

ATN – muddy brown cast

Management

Correct underlying causeFluid challenge in pre-renal patientsDon’t use low dose dopamine – makes no

differenceFurosemide (Lasix) if they have LV

dysfunction with fluid overload

Other renal disorders: Contrast nephropathy

Iodinated radiocontrast agents can produce acute renal injury and renal failure

Contrast-induced nephropathy is considered the third leading cause of acute renal failure in hospitalized patients

Look for rising serum creatinine within 72 hours after the procedure.

Predisposing conditions : diabetes, hypertension, CKD, CHF, osmolality and volume of iodinated contrast agent used during the procedure.

Most cases resolve within 2 weeks, and few require

hemodialysis.

The mechanism of renal injury is multifactorial, and includes hyperosmolar injury to the endothelium of small vessels in the kidney, and oxidative injury to the renal tubular epithelial cells.

Prevention CIN – Contrast induced nephropathy

ERBP position statement: We recommend volume expansion with either isotonic sodium

chloride or sodium bicarbonate solutions, rather than no volume expansion, in patients at increased risk for CIN. (1A)

We suggest using the oral route for hydration, on the premise that adequate intake of fluid and salt are assured. (2C)

We suggest that, when oral intake of fluid and salt is deemed cumbersome in patients at increased risk of CIN, hydration should be performed by intravenous route. (2C)

We recommend not using oral N-acetylcysteine (NAC) as the only method for prevention of CIN. (1D)

European Renal Best Practice (ERBP) Position Statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury

Prevention CIN – Contrast induced nephropathy

A prospective randomized trial comparing i.v. fluids with oral hydration with or without sodium bicarbonate found no differences in the incidence of CIN in patients with mild CKD

 There appears to be insufficient evidence to support the universal use of NAC to prevent CIN despite its ease of administration.

To date, 7 out of the 11 meta-analyses that have been published on this subject found a net benefit for NAC in the prevention of CIN. NAC, however, has been reported to decrease SCr levels in normal volunteers with normal kidney function. This reduction in SCr was not accompanied by a change in serum cystatin C levels, suggesting an effect independent of a change in GFR, such as an increase in tubular secretion of creatinine or a decrease in creatinine production. 

In view of its low costs and the high likelihood of absence of harm, there is no objection against oral NAC administration, but this should never replace adequate fluid loading.

Cho R, Javed N, Traub D, et al. Oral hydration and alkalinization is noninferior to intravenous therapy for prevention of contrast-induced nephropathy in patients with chronic kidney disease. J Interv Cardiol 2010;23:460–466.

Fishbane S. N-acetylcysteine in the prevention of contrast-induced nephropathy. Clin J Am Soc Nephrol2008;3:281–287

AIN

In cases of drug-induced AIN, the characteristic signs of a hypersensitivity reaction (e.g., fever, rash, eosinophilia) may not be present.

The onset of renal injury usually occurs within 2 weeks after starting the drug, but delayed reactions occurring months after the onset of drug therapy have been reported.

The presence of eosinophils and leukocyte casts on urine microscopy are the most characteristic diagnostic findings. A renal biopsy can secure the diagnosis, but is rarely obtained.

In suspected cases of AIN, any possible offending agents should be discontinued.

Oral prednisone at a dose of 0.5 to 1 mg/kg daily for one to four weeks may help to speed recovery.

Complete resolution can take months.

Common culprits of AIN

Antibiotics CNS Drugs DiureticsAminoglycosides Carbamazepine

AcetazolamideAmphotericin B Phenobarbital FurosemideCephalosporins Phenytoin ThiazidesFluoroquinolones NSAIDs OthersPenicillins Aspirin

AcetaminophenSulfonamides Ibuprofen ACE InhibitorsVancomycin Ketorolac Iodinated dyesNaproxen Ranitidine

Myoglobinuric Renal Failure

Acute renal failure develops in about one-third of patients with rhabdomyolysis.

The culprit is myoglobin, which is released by the injured muscle and is capable of damaging the renal tubular epithelial cells after it is filtered through the glomerulus.

The source of cell injury may be the iron moiety in heme , which is capable of oxidative cell injury via the production of hydroxyl radicals

The common causes of rhabdomyolysis are trauma, infection, immobility (in alcoholics), drugs (e.g., lipid lowering agents) and electrolyte abnormalities (e.g., hypophosphatemia).

Myoglobinuric Renal Failure

The risk of renal failure is not related to any single abnormality, but is more likely when there is a combination of abnormalities.

For example, one study of trauma victims with rhabdomyolysis revealed that the best predictor of acute renal failure was the combination of a serum creatinine >1.5, a creatine kinase (CPK) >5,000 IU/L, a base deficit =4, and myoglobin in the urine .

The serum creatinine is not an accurate index of renal function in rhabdomyolysis because the enhanced creatine release from skeletal muscle adds to the serum creatinine.

Management: Myoglobinuric Renal Failure

The plasma levels of potassium and phosphate must be monitored carefully in rhabdomyolysis because these electrolytes are released by injured skeletal muscle

Aggressive volume resuscitation to prevent hypovolemia and maintain renal blood flow is one of the most effective measures for preventing or limiting the renal injury in rhabdomyolysis.

Alkalinizing the urine can also help to limit the renal injury, but this is difficult to accomplish and is often not necessary.

About 30% of patients who develop myoglobinuric renal failure will require dialysis

Hepatorenal syndrome

Defined as worsening renal dysfunction in a cirrhotic with a serum Cr >1.5, after adequate fluid resuscitation with albumin, being off diuretics > 2 days, absence of shock, signs of renal parenchyma disease: i.e., bland urine sediment <500 mg protein, < 50 RBCs, absence of nephrotoxic drugs, normal kidneys on renal US.

The pathophysiology involves splanchnic vasodilation causing a decreased venous return to the heart and thus decreased cardiac output and high renin-angiotension tone causing an intense afferent arteriolar vasoconstriction leading to an irreversible pre-renal state for an otherwise normal kidney.

Hepatorenal syndrome

There are 2 major types of HRS:Type I: defined as doubling Cr in < two weeks

may resolve spontaneously after resolution of infection or inciting factor or may progress to ESRD

Type 2: defined as a slower, more chronic decompensation of renal function in a cirrhotic; Type 2 HRS may benefit from simultaneous kidney and liver transplant because can be hard to distinguish HRS from ATN and often have both processes concurrently in same patient

What are indications for dialysis in ICU?

This can be very specific to patients, nephrologist and hospital factors, however general indications can be remembered by the mnemonic: A, E, I, O, U:

‐ Acid-base: acidemia pH < 7‐ Electrolytes: K > 6.5 acutely (in non- CKD patient);

Na > 155 or < 120, severe, toxic hyperphosphatemia or magnesium

‐ Intoxicants: Lithium, ethylene glycol, methanol, etc.‐ Overload: fluid overloaded state, pulmonary edema,

anasarca, etc.‐ Uremic complications: pericarditis, neuropathy,

myopathy, encephalopathy

Options for renal replacement therapies

There are two major types of renal replacement therapy: Intermittent hemodialysis vs. continuous RRT (Continuous veno-venous

hemofiltration i.e. CVVH is the most common type currently) Most studies show NO MORTALITY DIFFERENCE between CVVH vs. HD.

Although some initial studies showed better results in patients receiving CVVH this was found to be because they were able to achieve better dialysis dose (better clearance).

However if one adequately doses intermittent hemodialysis by adjusting goals and dry weight on the severity of illness in patient can similar results can be achieved.

HD Pros of Intermittent Hemodialysis: more available ; less bleeding risk, removes toxins and

electrolytes faster, cheaper. Cons of Intermittent HD: need special staffing, may be limited by patient’s hemodynamic status

(hypotension, tachycardia), poor fluid control, may achieve lower dialysis dose

CRRT Pros of CVVH: can be used in more hemodynamically unstable pts, less hypotension and

tachycardias, perhaps associated with a reduced ICU length of stay Cons: expensive

Prognosis

2013 study in Chest: Severity of Acute Kidney Injury and Two-Year Outcomes in Critically Ill Patients

Chart review of 15,048 patients, 12,399 (82.4%) survived 60 days from ICU admission

45.7% didn’t develop during ICU admission, whereas 54.3% did.

Acute Kidney Injury Network (AKIN) criteria AKIN 1, AKIN 2, and AKIN 3 developed in 37.0%, 13.0%, and 4.3%, respectively

Patients with AKIN 3 had a 61% higher mortality risk at 2 years from ICU discharge vs. patient’s without AKI.

They conclude that even 2 years after ICU admission, pt’s with AKI have significantly increased risks of death that extend beyond their high ICU mortality rates.

Chest. 2013;144(3):866-875. doi:10.1378/chest.12-2967