Acute tubular necrosis is damage and necrosis of the renal tubule epithelial cells, usually caused by ischemia or nephrotoxic drugs. It presents with muddy brown casts or renal tubular cells in the urine and increased creatinine and BUN. Management involves treating the underlying cause, stopping nephrotoxic drugs, managing fluid balance and electrolyte abnormalities, and considering dialysis for refractory complications like fluid overload or uremia. Prognosis depends on the severity of the initial injury and development of complications.

1. Interns: Dr Parker, Dr Lakman, Dr Martin, Dr Thusi
Acute Tubular Necrosis
Presented by N4a- Internal Medicine
Consultant: Dr. P Guruvadu
MO/Reg: Dr Deenadayalu, Dr Ghobozi, Dr Moodley

2. Acute Tubular Necrosis (ATN)
Definition
Acute tubular necrosis is damage and necrosis of the
epithelial cells of the renal tubules. It is the most common
cause of Acute kidney injury (Intrinsic).

3. Causes
Ischemic-Induced Acute Tubular Necrosis
• Any factor that leads to prerenal azotemia can lead to ischemic acute tubular
necrosis.
• Some common causes include hypovolemic states such as diarrhea, vomiting,
bleeding, dehydration, burns, renal losses via diuretics or osmotic diuresis.
• Edematous states such as heart failure and cirrhosis cause reduced kidney
perfusion.

4. Causes cont.
Nephrotoxic-Induced Acute Tubular Necrosis
• Antibiotics:
• Vancomycin.
• Aminoglycosides, Colistimethate (Colistin).
• Amphotericin.
• Sulfonamides.
• Pentamidine.
• Antivirals:
• Acyclovir, ganciclovir, valacyclovir,
valganciclovir, foscarnet.
• Indinavir, cidofovir, tenofovir.
• Beta-lactams esp. nafcillin (can rarely cause
interstitial nephritis).
• ACE-inhibitors,ARBs.
• NSAIDs.
• Traditional medications
• Chemotherapeutics (carboplatin, cisplatin,
ifosfamide, methotrexate, mitomycin).
• Mannitol.
• Intravenous immunoglobulin (IVIG).
• Inflammatory bowel disease medications
(mesalamine, sulfasalazine).
• Bisphosphonates (pamidronate, zoledronic acid).
• Antiepileptics (topiramate, zonisamide).
• Sodium chloride (0.9% or 3% in large quantit

5. Causes cont
Sepsis-Induced Acute Tubular Necrosis
• Sepsis also plays a role in causing acute tubular necrosis because of systemic
hypotension and renal hypoperfusion.
• Other mechanisms that are incompletely understood include endotoxemia
leading to AKI by renal vasoconstriction and the release of
inflammatory cytokines causing enhanced secretion of reactive oxygen
species and leading to renal injury.

6. Pathophysiology
Made simple
• Damage to the kidney cells occurs due to ischaemia
or toxins.
• Decreased GFR leading to 3 possible mechanisms of
injury to the renal tubular epithelial cells:
• Afferent arteriolar vasoconstriction in response to
tubuloglomerular feedback
• Backleak of glomerular filtrate
• Tubular obstruction
• The epithelial cells have the ability to regenerate
making acute tubular necrosis reversible.
• It usually takes 7-21 days to recover.

7. Clinical Picture
Variable depending on clinical states
• Physical examination findings are often unremarkable AKI may be incidentally
detected on routine laboratory studies.
• Hypovolemia:
• Dizziness Fatigue Confusion Decreased urine output ( oliguria) Hypotension
Tachycardia Poor skin turgor Dry mucous membranes
• Hypervolemia/fluid overload
• Dyspnea Abdominal distension Swelling in the extremities Edema Crackles
• Ascites Pleural effusion Elevated jugular venous pressure (JVP) S3 heart sound

8. Investigations
Urine Analysis + Microscopy
• In prerenal disease, the UA microscopy is normal or may contain hyaline
casts.
• Shows muddy brown casts or renal tubular epithelial cells secondary to the
sloughing of tubular cells into the lumen due to ischemia or toxic injury.

9. Investigations cont.
Urine Analysis + Microscopy ➡ differential
• ATN-MuddyBrown casts
• GMNephritis -RBC casts
• AIN- WBC casts
• Pyelonephritis- WBC casts
• Rhabdo-Hb without RBCS

10. Investigations Cont
• ABG- if metabolic acidosis ➡ may signify hypoperfusion
• The FBC may reveal anemia. Erythropoietin production is decreased in AKI, and dysfunctional platelets (from uraemia) ➡ bleeding
more likely.
• Measurement of fluid balances and urine output and daily measurement of creatinine and electrolytes *** Look at the Fluid charts ***
• Initiating, maintenance and recovery phases.
• The BUN and serum creatinine concentrations are increased in AKI
• We may then use these values for AKI staging
• CXR - If fluid overloaded ➡ may show pleural effusion, Kerley lines, cardiomegaly, interstitial edema etc
• U/S
• Doppler - Renal Artery Stenosis
• Kidney Stones / Obstruction
• BPH in men

11. Severity and Staging
RIFLE + KDIGO

12. Management
• The mainstay of management is the prevention of acute tubular necrosis by identifying the patients undergoing high-risk
procedures and having comorbidities such as diabetes mellitus, heart failure, advanced malignancy, atherosclerosis, and CKD
that can potentiate the effects of acute tubular necrosis aka treating the underlying cause
• ABCs, Glucose, IV Line access
• ECG - Hyperk ( Tall T waves , Prolonged PR waves , Widened QRS)
• Stopping/Cessation of Nephrotoxic Drugs (Genta /NSAIDS etc )
• ACEI Inhibitors should be used with caution as they reduce systemic resistance
• Volume overloaded- NaCL restriction, Diuretics
• Treating any Electrolyte disturbances :
• HyperK -IV Ca Glu, K Shift
• Hypo Na - Free water restriction
• Metabolic Acidosis - Sodium Bicarb

13. Management Cont
Dialysis -Possible indications
• Acidosis refractory to IV bicarbonate.
• Electrolyte abnormalities (typically diuresis-refractory hyperkalemia).
• Fluid overload refractory to diuretics.
• Uremic symptoms.
• Early versus late initiation of dialysis remains controversial. The best
indication for earlier dialysis may be a patient who is progressively
accumulating fluid and developing severe volume overload. As
discussed above, even in the absence of frank pulmonary edema,
systemic congestion may directly harm the kidneys, perpetuating
renal dysfunction.
A- Acidosis
E- Electrolyte
emergencies
(hyperkalemia)
I- Intoxication with
dialyzable toxins
(ethylene glycol)
O- Overloaded with
volume
U- Uremia

14. Complications
• Complications related to acute tubular necrosis are the same as related to
AKI, which include acid-base and electrolyte disturbances such as
hypocalcemia, hyperkalemia related to metabolic acidosis, and
hyperphosphatemia.
• Volume overload is related to anuria or oliguria.
• Uremic complications lead to pericarditis, bleeding diathesis, altered mental
status, seizures, coma and ultimately death.

15. Prognosis
• The mortality in patients, depends on the underlying condition that leads to
ATN .
• Some factors that lead to poor survival in such patients include oliguria, poor
nutritional status, male gender, the need for mechanical ventilation, stroke,
seizures, and acute myocardial infarction.
• The mortality rate is higher in oliguric patients than in non-oliguric patients
signifying the amount of damage done leading to necrosis.
• Mortality is high (about 60%) in sepsis and surgical patients, causing multiple
organ failure.

16. Summary
ATN Is caused by : Ischemia / Nephrotoxic Drugs
• Shock Sepsis Dehydration
• Radiology contrast dye , Gentamycin, NSAIDS
UA - Muddy Brown Casts, TECs
U&E- identifies staging and therefore Kidney Function
Management
• Treat the underlying cause
• IV fluids - Ensure you choosing the correct type for your pt
• Stop nephrotoxic medications
• Treat complications
• Monitor urine output, especially in patients who are at risk for renal failure, and follow the BUN and creatinine.

17. Case study
• John C Ena, 32 yo M, Prisoner
• #HPT #Prev Covid Pneumo #RVD Neg
• #Presented w Infected Endocarditis.
• Started on IVI Ampicillin , Gentamicin,ACEI
and failure treatment -Lasix enalapril.
• Cr - 74 mmol, Urea - 7.3 mmol
• Now - Pleural effusion Elevated JVP, S3
heart sound
• Current Cr 350⬆, Urea 21⬆
• Na 126 ⬇ , K 6.2 ⬆
1. What’s the first/initial management plan for this patient?
A. Continue and lower dose of Antibiotics.
B. Request renal U/S
C. Cease all nephrotoxic drugs
D. DIALYSIS now.
2. What is your current supposition of diagnosis?
A. AKI.
B. CKD.
C. Rhabdomyolysis
D. UTI.
You then request an ECG that shows no Tall T waves nor prolonged PR
waves.
3. You then request a UA, that shows Muddy Brown Casts. What is the most
likely diagnosis?
A. Glomerular Nephritis.
B. ATN.
C. AIN.
D. Rhabdomyolysis.
4. Is this patient Indicated for emergency Dialysis?
A. Yes
B. No

18. References
• Pubmed:Early versus late initiation of renal replacement therapy in patients
with acute kidney injury-a systematic review & meta-analysis of randomized
controlled trials
• Pubmed:Acute kidney injury: Preventing acute kidney injury through
nephrotoxin management
• Pubmed:Acute Tubular Necrosis
• Medscape:Acute Tubular Necrosis Treatment & Management
• Images: https://zerotofinals.com/medicine/renal/atn/