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Joel M. Topf,MD Clinical Nephrologist Cell 248.470.8163 Office 313.886.8787 Acute Renal Failure: a Practical Workshop

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The workbook for a workshop on acute renal failure designed for residents.


Page 1: ARF Handout

Joel M. Topf,MDClinical Nephrologist

Cell 248.470.8163 Office 313.886.8787

Acute Renal Failure:a Practical Workshop

Page 2: ARF Handout

IntroductionAcute renal failure is “The House Moment” of nephrology. The patients go from normal functioning kidneys to zero function and at that point they either recover with no significant sequelae or they die. At that branch point, between total recovery and death, is the nephrologist and she is selecting IV fluids, deploying dialysis, and determining the balance of at-oms in order to nudge the patient toward recovery.

Goals• Invention of dialysis• Definition of ARF• RIFLE Criteria• AKIN Criteria• Etiologies of inpatient versus

outpatient acute renal failure.• Pre-renal azotemia

• BUN:Cr ratio• FENa

• FEUrea• Post-renal• Intrinsic Acute Renal Failure

• U/A• ATN• Contrast nephropathy• AIN

Acute Renal Failure Joel M. Topf, MD


Page 3: ARF Handout

Table of Contents..........................................History of acute renal failure therapy 4

............................................................................Definition of ARF 5

.....................................................................................Rifle Criteria 5

...................................................................................AKIN Criteria 6

.........................Classify the following using the RIFLE Criteria 7

.....................................................................Differential Diagnosis 8

...........................................................................Pre-renal azotemia 9

......................................................................Diagnosing Pre-renal 9

...........................................................Treating Pre-renal azotemia 12

..................................................................Post-renal insufficiency 15

.................................................................Treating Post Renal ARF 16

........................................................Questions on Post-Renal ARF 17

..........................................................Intrarenal acute renal failure 18

..........................................................................................Diagnosis 18

..........................................................................Clinical Syndromes 21

...........................................................Questions on the Urinalysis 22

.....................................................Ischemic acute tubular necrosis 23

....................................................................Contrast Nephropathy 24

............................................................Acute Interstitial Nephritis 26

Acute Renal Failure Joel M. Topf, MD


Page 4: ARF Handout

History of acute renal failure therapy

Dr. Haas in his laboratory with the first human dialysis machine in 1928.

Extracorporeal dialysis for humans was first tested in the 20’s by Dr. Haas. He treated 6 patients, all of which died. In 1943, Willem Kolff, working in Nazi-occupied Holland, created the second human dialysis machine; and in 1943 he dialyzed his first patient. This young man with acute ne-phritis died during the therapy.Question: If you invented a novel and unproven technology for the treatment of a usually, but not universally, fatal condition, how many consecutive failures (patient dies during therapy) would you let occur before you considered the technique a failure?A. 5B. 10C. 15D. >20

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In 1945, a 67-year-old woman in uremic coma presented to Dr Kolff. He initiated dialysis and she regained consciousness after 11 hours of ther-apy. This was his 17th patient after 16 consecutive treatment failures. She lived another 8 years and ultimately died of community acquired pneu-monia.

Definition of ARFThe study of ARF has been ham-pered by a proliferation of defini-tions for ARF.

The classic text-book definition of acute renal failure is “An acute and sustained decrease in renal func-tion.” Unfortunately this accepted definition is hampered by ambigu-ity: How acute? How sustained? How should renal function be measured? Is the degree of renal impairment important?

As clinical scientists studied ARF they needed specific case-definitions of ARF and each re-searcher created their own. At last count there were over 35 separate definitions of ARF. This created chaos where one study couldn’t be compared to another and has hampered progress in the field of ARF.

Recently, two, related, defini-tions have gained consensus accep-tance. The first was developed by

the Acute Dialysis Quality Initia-tive, this validated definition of ARF is called the RIFLE Criteria. The second was developed by the Acute Kidney Injury Network (AKIN) and is a minor modifica-tion of the RIFLE criteria called the AKIN Criteria.

Rifle CriteriaNumerous studies have vali-

dated these criteria showing graded increases in hospital mor-tality and morbidity with increas-ing degrees of renal failure as de-fined by the RIFLE Criteria:

A university hospital in Aus-tralia1 looked at all admissions and found a stepwise increase in hospi-tal mortality as patients progressed through Risk, Injury and Failure. Importantly Failure had the same mortality regardless if it came from a tripling of Cr or Cr > 4.

The University of Pittsburgh2 found a similar step wise increase in mortality when they looked at their ICU patients.

Acute Renal Failure Joel M. Topf, MD


Page 6: ARF Handout

RIFLE Criteria Change in Cr

Oliguria Hospital mortality

AKIN Criteria

Risk1.5-2.0 X base-line

< 0.5 mL/kg/hr for more than 6 hrs



Stage 1 (in-crease in Cr 0.3 mg/dL)

Injury 2-3 X baseline

< 0.5 mL/kg/hr for more than 12 hrs


11.4%2 Stage 2


over 3 X baseline or Cr > 4 mg/dL

< 0.3 mL/kg/hr > 24 hrs or anuria for > 12 hrs



Stage 3 (in-cludes any patient who receives RRT)

Loss of func-tion

Need for dialysis for more than 4 weeks

End-Stage Renal Disease

Need for dialysis for more than 3 months

1 Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.2 Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310

AKIN CriteriaThese newer criteria come

from a different consensus group and really respond to two criti-cisms of the RIFLE criteria:

is that the last two cri-teria, loss of function

and end-stage renal disease, are actually outcomes, not measures of severity of renal injury. Re-searchers that have validated the RIFLE criteria actually ignored


Loss and End Stage and only validated the first three criteria. The AKIN criteria only divide patients based on severity of illness and do not grade patients based on duration of debility.

The second criticism is that there is docu-

mented harm associated with smaller degrees of renal failure than are recognized with Risk. Changes of creatinine as low as 0.3 mg/dL have been associated with poor outcomes. The AKIN


Acute Renal Failure Joel M. Topf, MD


Page 7: ARF Handout

criteria lower the threshold to this low limit to maximize the

sensitivity of the definition.

Classify the following using the RIFLE Criteria

A 32 year old African American hair model with a baseline creati-nine of 1.4 receives a contrasted CT scan to determine the source of bleeding following a hysterectomy. Her creatinine 2 days later is 2.2. Her urine output over the last 8 hours is 640 mL.

A 28 year old Asian bank employee is in a motor vehicle acci-dent. He goes for emergency splenectomy and repair of a liver laceration. Despite aggressive use of blood products and crystal-loids he has been anuric since a foley was placed 14 hours ago.

A 62 year old model for a national nursing home chain has arthri-tis and hypertension. She presents to her primary care doctor with symptoms of fatigue since starting ramipril for her blood pressure. Her medications include ibuprofen 800 mg tid, chlorthalidone 25 mg qd, simvastatin 40 mg qd and ramipril 10 mg qd. Her labs show a Cr of 3.2 (baseline 1.2), K of 6.6. She urinated a “normal amount” prior to coming to the office.

A 55 year old Hispanic comedian is admitted for decompensated heart failure. His baseline creatinine is 1.4. On admission his creatinine is 2.2. He is given furosemide and responds well. His oxygen requirement decreases, most of his edema improves but his creatinine has gone up to 3.2. His urine output in the last 8 hours is 460 mL.

An 82 y.o. nursing home resident with diabetic nephropathy falls. On exam he has an S3, rales and pitting edema. Labs show a creatinine of 4.8, a potassium of 7.4 and a bicarbonate of 14. His baseline creatinine is 3.4. No urine output has been recorded and the patient is unable to estimate his recent urine output.

Acute Renal Failure Joel M. Topf, MD


Page 8: ARF Handout

Differential Diagnosis

Acute renal failure can be divided into three broad etiologies: Pre-renal azotemia, intrinsic renal failure and post-renal azo-temia (obstructive uropathy).

Using these categories one is able to quickly narrow the differen-tial diagnosis of acute renal failure and determine the likely natural history of the condition. Pre- and post- renal ARF usually are quickly reversible and easy to treat. They are often obvious from the history.

When the etiology of ARF is not obvious it is helpful to be aware of the incidence of the eti-ologies in various clinical settings. Multiple studies have shown that patients with ARF upon presenta-tion to the hospital have different causes of ARF than patients who develop ARF while in the hospital.

Another clue to the etiology can be the age of the patient. Pas-cual, et al. showed that as patients age post-renal etiologies and pre-renal etiologies of ARF become more common at the expense of decreasing intrarenal causes.

Question: Why might the elderly have more pre-renal azotemia? Why do they have more post-renal failure?






<65 65-79 >79




Prerenal IntrarenalPostrenal Unknown

Acute Renal Failure Joel M. Topf, MD








Hospital acquired ARF

Outpatient acquired ARF


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Pre-renal azotemiaNo BP; No pee pee.

Volume depletion from any etiology decreases renal perfusion. The decrease in renal plasma flow (RPF), if uncompensated will de-crease GFR. We call a decrease in GFR, azotemia.

Heart failure and cirrhotic pa-tients are both edematous. These patients have total body sodium excess but the amount of fluid in

the arterial blood compart-ment, the effec-tive circulating volume, is de-creased. This

results in pre-renal azotemia de-spite the overloaded appearance.

As RPF falls the kidney com-pensates to maintain a stable GFR. There are two primary strategies for this:

Vasodilation of the affer-ent arteriole via local

prostaglandin production.

Efferent vasoconstriction via angiotensin II.

These strategies increase intra-glomerular pressure to maintain GFR despite a fall in RPF; a higher percentage of plasma is filtered. If these strategies are successful, the GFR remains constant, the creati-



nine doesn’t rise and the patient is not pre-renal. They are pre-pre-renal.

Question: What drugs antagonize afferent vasodilation? Efferent Vaso-constriction?Diagnosing Pre-renalThere are three tests you need to be facile with to separate pre-renal azotemia from intrinsic AKI: the BUN:Cr ratio, the fractional excre-tion of sodium and the fractional excretion of urea.

In volume depletion the kid-neys become sodium avid and re-tain BUN out of proportion to cre-atinine. This allows physicians to make quantitative assessments of volume depletion and make an accurate diagnosis.

BUN:Cr ratio

Acute Renal Failure Joel M. Topf, MD


Doc, I’ve had diarrhea and vomiting for the

last three days and can’t keep a thing down.

Filtration fraction = GFRRPF


Page 10: ARF Handout

A BUN to Cr ratio over twenty is a reasonably accurate indicator of volume depletion. It works be-cause the BUN:Cr ratio actually measures the filtration fraction at the glomerulus.

The increased filtration fraction means that the plasma proteins that are not filtered by the glom-erulus are diluted in less plasma (because more of that plasma went down the glomerular drain). This higher concentration of plasma proteins exert greater osmotic at-traction in the proximal tubules bringing back more plasma water, sodium and urea. Creatinine is ac-

tively secreted in the proximal tu-bule and is not affected by this os-motic movement of water. The net result is normal creatinine clear-ance and decreased urea clearance resulting in a rise in BUN out of proportion to the rise in creatinine.

The BUN:Cr calculation is easy to remember, doesn’t require a cal-culator and is surprisingly accu-rate; however the test has some

important pitfalls. One can get a falsely elevated BUN:Cr ratio with a GI bleed or in catabolic patients due to steroids or sepsis. High pro-tein tube feeds and recovery of ATN can also lead to false positive elevations in the BUN:Cr ratio. In some patients with pre-renal azo-temia the BUN:Cr is falsely low due to either liver failure or malnu-trition. This often is seen in alco-holics.

Fractional Excretion of sodium (FENa)

The fractional excretion of so-dium is the excreted sodium di-vided by the amount of sodium filtered at the glomerulus. In pre-renal azotemia less than 1% of the sodium is excreted. In intrinsic re-nal failure more than 1% of sodium is excreted.

Acute Renal Failure Joel M. Topf, MD


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FENa = X 100Urine Na x Sr CrSr Na x Urine Cr

Calculating the FENa requires the simultaneous measurement of se-rum sodium and creatinine and the urine sodium and creatinine.

FENa false negatives (High FENa in Pre-renal azotemia)

The FENa is most accurate for patients who are oliguric. The equation cannot be used in patients who have recently received diuret-ics.

FENa false positives (Low FENa in ATN)

A low FENa can be found in conditions besides pre-renal azo-temia. It also occurs with:

• Contrast nephropathy• Rhabdomyolysis• Acute GN• Hepatorenal syndrome• ATN with CHF• ATN with cirrhosis• ATN with severe burns

Acute Renal Failure Joel M. Topf, MD


Remembering the FENa EquationThe FENa is a small number (especially before you multiply it by 100). To remember the formula put all of the small numbers on the top and the big numbers on the bottom.

FENa = small x small

Big or small?1. Urine sodium big small2. Urine creatinine big small3. Serum sodium big small4. Serum creatinine big small

big x big

Page 12: ARF Handout

The Fractional Excretion of Urea

The biggest weakness of the FENa is that it fails in the face of diuretics. Patients who are prone to pre-renal azotemia are often pa-tients on diuretics. Think of CHF patients, or oliguric patients in the hospital. So in the very patients you would want to use the FENa it becomes inaccurate. Enter the FE Urea to solve this.

The equation for the FE Urea is identical to the FENa except in eve-ryplace there is sodium you replace it with urea. Instead of 1% as the line between pre-renal and intrinsic renal failure, use 35%. A FE Urea less than 35% indicates pre-renal azotemia, a FE Urea greater than

35% is indicative of intrinsic renal failure.

Though the FE Urea was de-veloped for use in patients with

previous exposure to diuretics it is just as accurate as the FENa in pa-tients without diuretic exposure. (Carvounis, Sabeeha, Nisar, Et al. Kidney Int, 2002 Vol 62. p 2223-2229)

Treating Pre-renal azotemiaThe kidneys are thirsty, give them a drink of water.

In pre-renal azotemia, nor-mally functioning kidneys are re-sponding normally to volume de-pletion. This is not pathology; it is physiology. If the patient is volume

depleted, IV replacement will fix the problem. In patients with clini-cal hypervolemia and biochemical evidence of pre-renal azotemia the therapy is more nuanced.

Acute Renal Failure Joel M. Topf, MD


FE Urea = X 100 Urine Urea x Sr Cr Sr Urea x Urine Cr

Page 13: ARF Handout

Calculate the BUN:Cr ratio, FE Na and FE Urea for the following patients and then interpret each test as indicating a true positive, false positive, true negative, false negative.

58 year old white male admitted with an exacerbation of CHF. He is treated with IV diuretics and on the third hospital day the fol-lowing labs are obtained:

Characteristic Value Interpretation




An 82 year old nursing home resident presents to the ER with obvious dehydration. The patient has a blood pressure 80/50, is oliguric and has cloudy, foul smelling urine in a Foley bag. The following labs are collected:

Characteristic Value Interpretation




Acute Renal Failure Joel M. Topf, MD


136 111 883.4 19 3.4


55 123 59


136 111 933.4 19 5.4


10 123 53


Page 14: ARF Handout

A 44 year old alcoholic presents to the ED with hematemesis. On initial labs the patient has a hemoglobin of 5 g/dL. The patient goes for emergency EGD and the bleeding is stopped. The next morning the patient has the following labs:

Characteristic Value Interpretation




An elderly gentleman is shot multiple times. While planning the surgical approach the surgeons order a contrasted CT scan. One day later the patient’s creatinine begins to rise. The patient re-mains non-oliguric. The following labs are obtained:

Characteristic Value Interpretation



FEUrea N/A

Acute Renal Failure Joel M. Topf, MD


136 111 983.4 19 3.8


62 229 22


12 N/A 67


136 111 643.4 19 3.4


Page 15: ARF Handout

Post-renal insufficiencyWhen the plumbing is clogged the kidneys fail.

Post-renal ARF is immediately intuitive. When the urinary tract is blocked renal function falls. One of the most important aspects to un-derstand is how unilateral obstruc-

tion works. In patients with two function-ing kidneys, blocking a sin-

gle kidney will not cause renal failure. Renal failure requires either bilateral obstruction or unilateral obstruction in a patient with a sin-gle functioning kidney.

The most common cause of bilateral obstruction in males is prostatic hypertrophy. In women it is cervical cancer. When people think of obstruction it is easy to solely think of physical obstruction but a neurogenic bladder from neurologic disease (MS), metabolic derangements (diabetic neuropa-thy), or drugs can be occult sources of obstruction.

Urine output is usually, but not always, decreased in obstructive uropathy. In some patients the primary symptom of obstruction is nocturia. Anuria is highly sugges-tive of bilateral obstruction.

The diagnosis can almost al-ways be made with a combination

of a renal ultrasound and Foley’s Catheter. Make sure the Foley is placed after the patient attempts to urinate and the post-void residual is recorded.

Ultrasound is considered the “gold-standard” for the diagnosis of obstructive uropathy.

Ultrasound is quick, non-invasive and painless. It is also highly sensitive and specific for the correct diagnosis. Unfortunately there a few situations where the

ultrasound can give a false nega-tive result (i.e. a normal renal ultra-

Post-Void Residual.............< 50 mL normal

..............100 mL likely abnormal...........> 200 mL very abnormal

Acute Renal Failure Joel M. Topf, MD


“Doctor, I have a hard time initiating a stream

and it only comes out like a trickle.”

Page 16: ARF Handout

sound in the presence of clinically significant obstruction):

1. Concurrent volume depletion and obstruction may not show hydronephrosis on the ultra-sound. Hydronephrosis may be visible following fluid re-suscitation.

2. Patients early in the course of obstruction may not have de-veloped hydronephrosis yet.

3. Large retroperitoneal tumors can encase the kidney and both cause the obstruction and pre-vent hydronephrosis.

4. Retroperitoneal fibrosis (idio-pathic or post-radiation ther-apy) can prevent hydroneph-rosis.

Also be careful of false posi-tives. A dilated collecting system is a normal finding in pregnancy.

One last finding which can suggest obstructive uropathy is:

hyperkalemia out of proportion to the degree of renal failure. Often patients with obstructive uropathy will have severe hyperkalemia with mild to modest renal failure.

Treating Post Renal ARFTreatment of post-renal acute

renal failure is usually simple once the diagnosis has been made. Pa-tients with neurogenic bladder will have brisk recovery after a Foley is placed. Involve urology for more

complex mechanical obstruction. Interventional radiology may be helpful by placing percutaneous nephrostomy tubes in patients with recalcitrant obstruction.

Acute Renal Failure Joel M. Topf, MD


Physical Obstruction• Phimosis• Stricture• Prostatitis• Trauma• Blood clot• Stone• BPH• Prostate / bladder cancer• Cervical cancer• Colon cancer• Sarcoidosis• Tuberculosis• Pregnant Uterus

Neurogenic Bladder• Diabetes mellitus• Spinal cord disease• Multiple Sclerosis• Parkinsons disease• Anticholinergic drugs

• diphenhydramine• Alpha-adrenergic agonists

• ephedrine• pseudoephedrine

• Calcium channel blockers• Opiates• Sedative hypnotics

Page 17: ARF Handout

Questions on Post-Renal ARF

A 58 year old white female is admitted on a friday evening from her Gyn’s office with a diagnosis of vaginal bleeding. Initial labs show:

136 111 447.8 16 2.8


What is the likely diagnosis? What problems need to be addressed immediately?

A 78 year old white male with a history of mild prostatism has been self treating for a “sinusitis” for the last few days with over the counter medications. He finally relents and comes to the doc-tor for “some antibiotics.” The PCP orders routine labs and sends him home. The patient receives a call that evening telling him to go straight to the ED. The initial labs are below:

143 111 685.4 17 4.9


A 32 year old returns to the ED because the pain from his previ-ously diagnosed kidney stone has gotten much worse and he has developed nausea and vomiting. He has been taking OTC pain medicine for this pain. A CT scan from earlier in the week revealed a 3 mm stone in the distal ureter and a 12 mm stone in the left renal pelvis. Before you arrive the ER gets a stat U/S which shows hydronephrosis on the left.

136 111 524.8 22 3.6


Acute Renal Failure Joel M. Topf, MD


31 156 29


Page 18: ARF Handout

Intrarenal acute renal failureIntrinsic acute renal failure comes in a number of flavors but this guide will only examine diagnosis and three specific etiologies: ischemic ATN, contrast nephropathy and interstitial nephritis.

Intrinsic acute renal failure is the most common cause of acute renal failure among hospitalized patients. Unlike pre- and post-renal failure there is typically no direct and easy therapy. The role of phy-sicians is relegated to supportive care as she waits for the kidneys to heal on their own. The prognosis is a classic good news/bad news:

As patients recover from their illness

the kidneys recover. Even among patients that need dialysis for sup-port during acute renal failure over 85% of survivors do not require permanent dialysis.

If patients are sick enough to require

dialysis, they often die. Commonly quoted mortality for dialysis de-pendent acute renal failure is 70%. Some series of ICU patients with sepsis quote a hospital mortality rate of 80%.

DiagnosisThe art of the Urinalysis

The cheapest objective test available is the urinalysis. It is a liquid biopsy of the kidney and can be wickedly informative. Don’t

Good news

Bad news

forget to order the U/A, don’t be “that guy” who ordered a FENa, a FEUrea a renal ultrasound but for-got the U/A.

The urinalysis is a two part analysis: a biochemical profile fol-lowed by a microscopic exam.

Biochemical assessment

• Specific gravity: look for two extremes: the concentrated urine with specific gravity greater than 1.020 and the dilute isothenic urine (1.010).★ The concentrated urine is seen

in pre-renal conditions. False positives are found in patients with ATN in the background of CHF and cirrhosis and with pigmented nephropathy or acutely following contrast administration.

★ The isothenic urine is seen with non-oliguric ATN (in-cluding recovery of ATN) and advanced CKD, including di-alysis patients. Damaged tu-bules are unable to concen-trate or dilute the urine. The tubules are on strike.

• Protein: Proteinuria is character-istic of just about any glomerular damage, from diabetes to lupus

Acute Renal Failure Joel M. Topf, MD


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nephritis. The finding of proteinuria is difficult to interpret because it is impossible to differenti-ate if it is pre-existing disease or associated with the AKI. The ab-sence of proteinuria ef-fectively rules out glom-erulonephritis.

• Hematuria is assessed in both components of the urinalysis. In the bio-chemical assessment, the assay measures heme and interprets this as blood. This will have false positives from my-oglobulinuria from rhab-domyolysis or from he-moglobinuria associated with hemolysis. The bio-chemical assessment does not differentiate glomerular blood from lower tract blood. Glom-erular blood and AKI are associated with acute GN, interstitial nephritis. Positive heme without RBC on microscopy indi-cates rhabdomyolysis or hemolysis.

Acute Renal Failure Joel M. Topf, MD


Acute Renal SuccessOne of the mysteries of ATN is why patients are oliguric. If you look at a kidney biopsy of an ATN kidney the glomerulus are completely intact with no apparent pathology. The reason these normal glomeruli are not filtering any fluid may be an adaptive response to tubular injury.The healthy glomeruli collectively filter 100 mL of plasma every minute. This means that all of the plasma in the body is filtered every 30 min-utes. Thankfully the tubules reabsorb 99% of the filtered plasma and return it to the circula-tion so the process can continue.If glomerular filtering continues but tubular re-absorption fails the kidneys would rapidly pee the patient to death. The patient would lose a liter of intravascular volume every 10 minutes.To prevent this catastrophe glomerular filtration is tightly regulated by tubular flow. At the peak of the thick ascending limb of the loop of Henle, as the tubule folds back to its originat-ing glomeruli, sodium sensors regulate GFR. If there is increased tubular sodium (indicating an abnormally high GFR or a failure of tubular reabsorption) then the sensors decrease GFR by constricting the afferent arteriole. In ATN sodium which is filtered at the glomeruli is not reabsorbed in the proximal tubule. This results in a flood of sodium at the peak of the TAL of the loop of Henle. This sodium signals the af-ferent arteriole entering the glomeruli to shut the glomeruli down. If the ATN is spotty this will shift blood flow to glomeruli with intact tubules; if, however, the ATN is more generalized then this will globally decrease GFR resulting in oliguria.This adaptive, tubular-glomerular feedback explains why patients are oliguric with ATN.

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Microscopic analysis

The microscopic analysis can iden-tify a few enormously helpful find-ings:

• Dirty brown casts are pathog-nomonic for ATN. It is com-posed of dead tubular epithelial cells.

• Red cell casts are pathogno-monic for glomerulonephritis and usually trigger a kidney bi-opsy.

• Broad waxy casts are indicative of chronic kidney disease.

• WBC casts: found with pye-lonephritis and acute interstitial nephritis.

• Hyaline casts are a normal find-ing. They are prominent in acidic urine as found with: loop diuret-ics and concentrated urine (first morning urine). Also found fol-lowing vigorous exercise.

• Red blood cells. Found with glomerular disease, tubular dis-ease, foley specimens, cystitis. Nonspecific finding that, like proteinuria, is more valuable when it is negative to rule out most types of kidney injury.

• Oval fat bodies: indicative of lipiduria found with nephrotic syndrome.

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• Bacteria useful in the diagnosis of cystitis and pyelonephritis.

Clinical SyndromesThere are two non-specific syn-dromes which are used to classify glomerular disease. These can usu-ally be identified by the history and physical and the U/A.

• Nephrotic syndrome: A non in-flammatory glomerular injury with massive proteinuria (prote-

inuria (> 10x the upper limit of normal). Patients are edematous but typically have normal blood pressure. Rarely associated with ARF.

• Nephritic syndrome: An in-flammatory glomerular injury. Patients have hematuria, prote-inuria (though not as much as with nephrotic syndrome) RBC casts (variable). Clinically the patients have renal failure and hypertension. This is an impor-tant cause of ARF.

Acute Renal Failure Joel M. Topf, MD


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Questions on the UrinalysisMatch the U/A to the patient to the diagnosis

U/A 1 U/A 2 U/A 3 U/A 4 U/A 5 U/A 6







1.025 1.010 1.014 1.010 1.012 1.040

neg 2+ 3+ 4+ 1+ 1+

neg neg 3+ 1+ 2+ 1+

hyaline casts

waxy casts

RBC Casts

oval fat bodies

WBC casts



A. 26 y.o. AA female with rash, joint pain, anemia and a Cr of 3.4 mg/dL.B. 64 y.o. white male with a history of DM and CKD stage 4 who had a

cardiac cath. 6 hours ago.C. 40 y.o. white female with a diabetic foot ulcer. She is on cefazolin for

osteomyelitis She develops a fever, rash and ARF.D. 38 y.o. with alcoholic cardiomyopathy. Patient is admitted for CHF. He

develops hospital acquired ARF on hospital day 3.E. 37 y.o. black female with AIDS. She is poorly compliant with her

HAART regimen and presents with lower extremity edema.F. 62 y.o. white male with a Cr of 2.8 mg/dl and 15 yr history of "protein"

on urinalysis.


1. Collapsing focal segmental glomerulosclerosis (FSGS)2. Early contrast nephropathy3. Pre-renal azotemia4. Acute interstitial nephritis5. Lupus nephritis6. Chronic kidney disease

Acute Renal Failure Joel M. Topf, MD


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Which of the U/As is nephritic? Nephrotic?

Ischemic acute tubular necrosisDisruptions in blood supply to the kidney cause a stereotypical acute re-nal failure called ATN. This, to a large degree, is a misnomer as there is little necrosis. A better name is acute kidney injury.

The kidneys normally receive a rich blood supply. In fact 20% of cardiac output, 1 liter per minute, is devoted to perfusing the kid-neys. Despite this abundance of perfusion, almost all of this blood goes solely to the renal cortex leav-ing the deep medullary tissue rela-tively devoid of oxygen. Much of the medulla lives in continuous ischemia at the very margin of vi-ability. Brief interruptions of perfu-sion can push these marginal tis-sues (the cells that line the renal tubules) into oxygen debt and cause them to die and slough into the urine. Once perfusion resumes the tissue regenerates and the kid-ney function is restored.

Any insult that causes a de-crease in blood pressure can cause ATN. Bleeding, sepsis, severe vol-ume depletion, ACEi and NSAIDs all can cause ATN. ATN will cause oliguria in about 70% of cases. The remainder will be non-oliguric. Patients will remain in renal failure usually for 4-14 days, though longer courses may occur. Loop diuretics can be used to increase urine output but they fail to shorten the duration of dialysis. Patients who do not have a good response to IV diuretics have a much worse prognosis than those with a good diuretic response.

Acute Renal Failure Joel M. Topf, MD


Page 24: ARF Handout

Contrast NephropathyYou were just trying to make a diagnosis and you boxed the kidneys.

Iodinated contrast agents are responsible for 12-14% of hospital acquired acute renal failure. Pa-tients with pre-existing chronic kidney disease and diabetes are at the highest risk for this complica-tion.

Contrast nephropathy is usu-ally defined as a 0.5 mg/dL or 25% increase in serum creatinine within 48 hours of administration of con-trast. The creatinine usually starts rising immediately after contrast is given and peaks on day 4. Typi-

Acute Renal Failure Joel M. Topf, MD


Page 25: ARF Handout

cally, the creatinine remains above baseline 10 days after contrast ad-ministration.

People with contrast nephropa-thy have poor prognosis. The rise in hospital mortality occurs even when patients do not require dialy-sis. In patients with the need for dialysis the condition becomes truly devastating.

Thankfully one can spare pa-tients this complication by taking some simple precautions:

• Avoid using contrast when imaging the patient. Make sure the con-trast is absolutely needed. Look-ing for an abscess? No need for contrast. Looking for a retroperi-toneal hematoma? No need for contrast. Oral contrast is safe. Angiograms can sometimes be done with CO2 rather than iodi-nated contrast agents.

Hospital Mortality









, no



, +H





• Minimize the dose of contrast. If the patient is going for a left heart catheterization, get the echo first so there is no need for a ventriculogram to asses cardiac function

• Make sure the patient is not volume depleted. IV saline is the most effective weapon to reduce con-trast nephropathy. 0.9 NS was shown to be more effective than 0.45 NS. To maximize the benefit give as much hydration as the patient can tolerate.

• Stop drugs associated with in-creased risk of contrast nephropa-thy: ★ Diuretics★ Mannitol★ ACEi/ARB★ NSAIDs.

• Consider using N-acetyl cysteine. Mucomyst has a checkered past. It likely is biologically active and is not toxic. However, there is scant data that it prevents mor-bidity or mortality. I use 1200 mg BID for 2 doses before and two doses after contrast.

• Isotonic bicarbonate after initially showing promise has recently failed a large high-profile trial and may offer no benefit to pre-venting contrast nephropathy. The correct mixture is three amps in a liter of sterile water or D5W.

Acute Renal Failure Joel M. Topf, MD


Page 26: ARF Handout

Acute Interstitial NephritisA drug induced allergic reaction that takes the kidneys down.

In most cases, the cause of acute renal failure is obvious:

• The patient received contrast

• Patient develops hy-potension

• The patient passes a liter and a half of urine after someone thinks to place a Foley

• Creatinine falls after a night of IV fluids

Then there are the exceptions, the patients whose renal function declines day after day with no obvious source of renal failure. They don’t respond to IV fluids. The patient doesn’t have a history of contrast exposure, no gentamycin on the MAR. These are the cases where a cagey neph-rologist is needed.

The differential diagnosis of occult ARF is long and complex and beyond the scope of this work-shop. One etiology I would like to highlight is acute interstitial ne-phritis (AIN).

AIN is an allergic reaction, typically to a drug which results in acute renal failure. Patients need prolonged exposure to the drug to develop their first case of AIN but

the renal failure can recur within days on subsequent exposures to the drug.

The classic presentation is re-nal failure in the presence of hema-turia, pyuria, fever and rash. The patients are almost always non-oliguric and serum potassium tends to be low rather than high.

The classic drug-class respon-sible for AIN is ß-lactam antibiotics but the list of drugs associated with AIN is long and varied (see box).

Acute Renal Failure Joel M. Topf, MD


clinical characteristics of 61 biopsy proven cases of AIN.

Page 27: ARF Handout

Most common drugs associ-ated with AIN• NSAIDs• Selective COX-2 inhibitors• Penicillins • Cephalosporins• Rifampin• Sulfonamides (Bactrim)• Furosemide, bumetanide• Thiazide-type diuretics• Ciprofloxacin and other qui-

nolones• Cimetidine• Allopurinol• Omeprazole and lansoprazole• Indinavir• Mesalamine

Therapy focuses on stopping the offending drug. Recent data suggests that high dose steroids are beneficial. The steroids should be used early to be most effective. (Gonzalez E, Et al. Kidney Interna-tional (2008) 73, 940–946)

Acute Renal Failure Joel M. Topf, MD


Page 28: ARF Handout


RIFLE: no AKI, AKIN stage 1

RIFLE: FailureAKIN stage 3

RIFLE: InjuryAKIN stage 2

RIFLE: InjuryAKIN stage 2

RIFLE: FailureAKIN stage 3

Question: Elderly with more pre-renal azotemia? Increased CKD decreases the ability to concentrate urine predisposing to fluid loss. Co-morbidities require diureticsWhy do they have more post-renal failure? Increased BPH, increased risk of Cx Ca.

Question: What drugs antagonize afferent vasodilation? NSAIDSEfferent Vasoconstriction? ACEi & ARB

Remember the FENa Eq.small, big, big, small

BUN:Cr 25.9, FENa 2.2%, FEUrea 8%, use of diuretics causes the false (–) FENa

BUN:Cr 17.2, FENa 0.7%, FEUrea 13%, malnutri t ion causes false (–) BUN:Cr

BUN:Cr 25.8, FENa 7.9%, FEUrea 40%, GI bleed causes false (+) BUN:Cr

BUN:Cr 18.8, FENa 0.4%, false (+) FENa due to contrast

Obstruction due to Cx Ca, Address hyperkalemia

Obstruction due to OTC cold medicine on top of BPH

BUN:Cr 14.4, FENa 2.8%, FEUrea 37%, ATN due to NSAIDS, obstruction is not the cause b/c it is unilateral.

Questions on urinalysisU/A 1: patient D, diagnosis 3U/A 2: patient F, diagnosis 6U/A 3: Patient A, diagnosis 5U/A 4: Patient E, diagnosis 1U/A 5: Patient C, diagnosis 4U/A 6: Patient B, diagnosis 2

Acute Renal Failure Joel M. Topf, MD


Page 29: ARF Handout

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