Acute Tubular Necrosis

Afternoon Delight 9.23.10

Clinical Scenario
A 79-year-old F with DM, HTN, hypothyroidism

presents to the ED with AMS from her nursing home. Nurses noticed that she was not herself for the past 1-2 days. She has had an increased cough with mildly productive sputum for the past 3 days. No reported fevers, chills, or SOB. Hg, HR 101/min, RR 18/min. Cardiopulmonary examination reveals warm extremities with bounding pulses, and decreased breath sounds in the R lung base.

On physical examination, T 38.1 C, BP 88/60 mm

Clinical Scenario
Patients CXR reveals a moderate infiltrate in the RLL

consistant with an aspiration PNA.

In the ED, the patients AMS continues to worsen,

and the MICU team is called to admit her for septic shock. resuscitation and over the next 12 hours the patients mental status and hemodynamics improve.

Broad spectrum antibiotics are started as well as IVF

48 hours later on MICU rounds. . .

Intern reports that the patient

has developed AKI with a serum creatinine of 2.5 mg/dL, up from 1.0 on her day of admission. sized kidneys and no hydronephrosis.

Kidney ultrasound shows normal-

Urinalysis: Specific gravity 1.011; pH 5.5;

1+ protein; no blood; 2-5 erythrocytes/hpf; no leukocyte esterase

Muddy brown casts

Which of the following is the most likely cause of this patients findings?

A) Acute interstitial nephritis B) Acute tubular necrosis C) Pre-renal azotemia D) Post-renal AKI

What exactly happened to cause this?

Acute Tubular Necrosis (ATN)

DEFINITION: clinicopathologic entity

characterized morphologically by destruction of tubular epithelial cells and clinically by acute suppression of renal function hospitalized patients

Accounts for some 50% of cases of AKI in ATN is a reversible renal lesion that arises in a

variety of clinical settings

Types of ATN
ISCHEMIC ATN: Period of inadequate blood NEPHROTOXIC ATN: Caused by a multitude of

flow to the peripheral organs

drugs:

Accompanied by severe

Gentamicin Antibiotics Radiographic contrast Poisons Heavy metals (mercury) Oragnic solvents

hypotension and shock virtue of its rich blood supply, 25% of cardiac output

Kidney is vulnerable by

Types of ATN
Combinations of BOTH can occur:

exemplified by mismatched blood transfusions other hemolytic crises causing hemoglobinuria and skeletal muscle injuries causing myoglobinuria. Such injuries result in characteristic intratubular hemoglobin or myoglobin casts, respectively; the toxic iron content of these globin molecules contributes to the ATN

What Happened?

#1

#2

#3

#4

#5

Infection

Hypotension Shock

AKI recognition

Recovery

Diuresis

#1- Infection
# 1 Increased NO (cytokine released) #6 Renal vasoconstriction #5 Increased reninangiotensin #4 Increased sympathetic tone

#2 Arterial Vasodilatation

#3 Arterial underfilling

#2 Hypotension/Shock

#1

#2

#3

#4

#5

Infection

Hypotension Shock

AKI recognition

Recovery

Diuresis

#2 Perfusion

Glomerular capillary pressure is determined by the resistance of both the afferent and efferent arterioles

Autoregulation: -decrease in renal-artery pressure from the drop in afferent arteriole resistance -This drop SUSTAINS glomerular cap pressure = driving force of filtration -Glomerular cap pressure partly supported by an increase in efferent arteriolar resistance

#3 AKI Recognition

#1

#2

#3

#4

#5

Infection

Hypotension Shock

AKI recognition

Recovery

Diuresis

Clinical Course
48 hours after admission to MICU Intern

reports that the patient has developed AKI with a serum creatinine of 2.5 mg/dL, up from 1.0 on her day of admission.

Muddy brown casts seen on her U/A Oliguria Anuria

Elevated Cr Casts Oliguria

ISCHEMIA

Renal perfusion drops

Endogenous vasoconstrict ors increase afferent arteriole resistance

Reduced glomerular capillary pressure and GFR

Perfusion to the tubules diminished

Increased duration and severity of ischemia causes structural tubular damage

Postulated sequence of ATN

Critical events:

Tubular cell injury AND Persistant severe disturbances in blood flow

REVERSIBLE injury: cellular swelling, loss of brush border, cell detachment, and loss of polarity (results in increased Na to distal tubules) Intrarenal vasoconstriction = reduced glomerular plasma flow + reduced O2 delivery (especially to the outer medulla) Why vasoconstriction?

glomerulotubular feedback (RA system) sublethal endothelial injury direct toxic effect

Patterns of tubular damage

Histopathology

#4 Recovery

#1

#2

#3

#4

#5

Infection

Hypotension Shock

AKI recognition

Recovery

Diuresis

#4 Recovery
Patchiness of injury and the maintenance of the basement

membrane in some areas, allow for repair of the necrotic foci and recovery if the the precipitating event is removed. epithelial cells to proliferate and differentiate.

Repair dependent on the capacity of reversibly injured

Re-epithelialization is mediated by growth factors and

cytokines produced by the tubular cells or by inflammatory cells in the area. shown to help tubular repair. been disappointing.

EGF, TGF-alpha, Insulin-like GF, hepatocyte GF have been

Trials with the use of GF as therapeutic agents in AKI have

ClassificationSchemeforAcute RenalDysfunction

#5 Diuresis

#1

#2

#3

#4

#5

Infection

Hypotension Shock

AKI recognition

Recovery

Diuresis

Clinical Course: 3 Stages

Initiating: Lasting for 36 hrs Dominated by inciting event (medical, surgical or

obstetric) Only indication of renal involvement is slight decline in UOP, rise in BUN Oliguria explained by decrease blood flow to kidneys Up to 50% of patients may not have oliguria (usually nephrotoxic type)

Maintenance: Sustained decrease in UOP (40-400ml/day) Salt and water overload Rising BUN, hyperkalemia, metabolic acidosis, UREMIA

Stage 3: Recovery phase

Recovery:
Steady increase in urine volume that may reach up

to 3L/day

Tubules are still damaged, so large amounts of HYPOKALEMIA Increased risk of infection

water, sodium and potassium lost in the urinary flood

Slowly the ability to concentrate the urine is restored Subtle tubular functional impairment may persist for

MONTHS, but most pts who reach this phase eventually recover completely

Conclusion
79 F admitted to MICU with RLL PNA, septic shock,

developed ATN on hospital day 3 anuria.

Cr peaked at 5.7 (from 1.0) with correlating oliguria Patient was resucitated and her septic shock resolved

with antibiosis and IVF in first 24hrs. hypokalemia.

Significant post-ATN diuresis (~4L/day) and Close monitoring, electrolyte repletion Cr slowly normalized on hospital day 8

THANKS FOR COMING!

Hopefully the next time

you hear about muddy brown casts you think about all the pathophysiology behind them!