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Residents conference
Presented by Dr Gagandeep K Heer, MD
(PGY-2)
Background
Definition: ARF is defined as an abrupt or
Background
Pathophysiology
Ischemic ATN
Ischemic ATN
Nephrotoxic ATN
At cellular level
Ischemic ATN:
Cellular ischemia results in series of alterations in energetics,
ion transport and membrane integrity that ultimately leads to cell
injury or necrosis. These changes include depletion of ATP,
inhibition of active sodium transport and transport of other
solutes, impairment of cell volume regulation, cytoskeletal
disruption and loss of cell polarity, cell-cell and cell-matrix
attachment, accumulation of intracellular calcium, altered
phospholipid metabolism, oxygen free radical formation and
peroxidation of membrane lipids.
A characteristic feature of ischemic ATN is the absence of
widespread necrosis of tubular epithelial cells. Necrosis is more
subtle and is reflected in individual necrotic cells within some
proximal or distal tubules. These single cells shed into tubular
lumen, with resulting focal denudation of the tubular basement
membrane. Interstitial edema is common.
Ischemic ATN
Histology (continued)
Nephrotoxic ATN
Frequency
History
Physical Exam
Causes of ATN
ATN is usually caused by an acute event,
either ischemic or toxic.
Exogenous toxins
Aminoglycosides:
10-30% of patients getting aminoglycosides
develop ATN.
Risk factors include preexisting liver disease,
renal disease, concomitant use of other
nephrotoxins, advanced age, shock, female sex
and a higher level 1 hr after the dose.
Toxicity presumably more common with 3
doses/day than a single daily dose (as the drug
uptake by tubules is saturable phenomenon).
Amphotericin B: The likelihood of toxicity is in
direct proportion to the total dose administered
and is more common if > 3 grams is
administered.
Exogenous Toxins
Radiocontrast media:
Endogenous toxins
Myoglobinuria
Endogenous Toxins
Crystals:
Acute crystal-induced nephropathy is encountered in
conditions where crystals are produced endogenously due
to high cellular turnover (i.e. uric acid, calcium phosphate),
as seen in certain malignancies or the treatment of these
malignancies (tumor lysis syndrome). However, this
condition is also associated with ingestion of certain toxic
substances, such as ethylene glycol.
Multiple myeloma:
This condition causes renal failure by several mechanisms,
such as prerenal azotemia due to volume contraction, cast
nephropathy due to increased light chain proteins
precipitated into the tubular lumen, hypercalcemia and uric
acid nephropathy.
Workup
Lab studies
Finding
Prerenal
Azotemia
ATN
>500
<350
<20
>40
Fraction excretion
of sodium(%)
<1
>2
Fraction excretion
of Urea(%)
<35
>50
Plasma BUN/Cr
ratio
>20
<10-15
Urine Cr/Plasma Cr
ratio
>40
<20
Bland and/or
nonspecific
Urine osmolarity
(mOsm/kg)
Urine sodium
(mmol/d)
Urine sediment
Lab (continued)
Imaging Studies
Renal biopsy
Complications
Patients with ATN can have several complications.
Electrolyte abnormalities
Hyperkalemia: Higher levels are associated with ECG
abnormalities (e.g. peaked T waves, prolonged PR interval, P
wave flattening, widened QRS) and risk of developing lifethreatening arrhythmias (e.g. ventricular tachycardia or
fibrillation, complete heart block, bradycardia, asystole).
Arrhythmias have been reported in up to 30% of patients. In
addition to these worrisome cardiac effects, hyperkalemia can
also lead to neuromuscular dysfunction and, potentially,
respiratory failure.
Hyponatremia
Hyperphosphatemia
Hypermagnesemia
Hypocalcemia: Hypocalcemia may be secondary to both
deposition of calcium phosphate and reduced levels of 1,25
dihydroxyvitamin D. It is usually asymptomatic, but
hypocalcemia may result in nonspecific ECG changes, muscle
cramps, or seizures.
Metabolic acidosis
Complications
Complications
Prevention
Ischemic ATN: Be attentive to optimizing
cardiovascular function as well as maintaining
intravascular volume, especially in patients
with preexisting risk factors or those taking
nephrotoxic medications. Medicines that
reduce systemic resistance (e.g. afterload
reducers) may cause renal vasoconstriction or
affect the kidneys autoregulatory response
(e.g. ACE inhibitors, cyclooxygenase inhibitors)
and also should be used with caution.
Dopamine, mannitol and furosemide, etc have
been tried within 24 hrs of ischemic insult to
prevent progression to ATN, but have no
proven benefit.
Prevention
Nephrotoxic ATN
Aminoglycosides: Once daily dosing of
aminoglycosides decreases the
incidence of nephrotoxicity.
Amphotericin B: Minimize the use of
this drug and assure that ECF volume
is adequate.
Cyclosporin and tacrolimus: Regular
monitoring of blood levels.
Alkalinization of the urine should be
tried in patients with marked
myoglobinuria and hemoglobinuria.
Prevention
Radiocontrast dye: Out of all the agents/modalities
that have been investigated for prevention of CIN, only
the following have been shown to be of some benefit:
1.Hydration with isotonic saline infusion has proven
benefits in prevention of contrast-induced nephropathy.
Typically, half isotonic sodium chloride solution
(0.45%) administered at a rate of 50-100 mL/h 12
hours before and 12 hours after the administration of
the dye load is most effective, especially in the setting
of prior renal insufficiency and diabetes mellitus.
2. Low osmolal and iso-osmolal nonionic contrast media
are also associated with lower incidence of CIN.
3. N-acetylcysteine has been used with success in highrisk patients to prevent contrast-induced
nephrotoxicity.
4. Using lower doses of contrast media, avoiding volume
depletion and NSAIDs, both of which can cause renal
vasoconstriction are some other useful measures.
5. A new modality recently investigated is use of
prophylactic hemofiltration in patients who need
contrast and have baseline renal insufficiency.
Treatment
General treatment
Treatment
Treatment
Dialysis treatment
In general, no clear consensus is established on when
or how often to perform hemodialysis in the setting
of ARF. Some studies have suggested that early
initiation may be beneficial, but, in one prospective
trial, aggressive dialysis did not improve recovery or
survival rates. However, hemodialysis is still
considered standard therapy in severe ARF. In
addition, continuous hemodialysis (continuous
venovenous hemofiltration [CVVHD] and continuous
arteriovenous hemofiltration with dialysis (CAVHD)
and peritoneal dialysis are also available. No
compelling studies suggest that one mode is better
than another. In general, patients with multiorgan
failure and hemodynamic instability may benefit from
a continuous mode because it is typically less taxing
on the hemodynamics.
Indications for dialysis: Clinical evidence of uremia,
intractable intravascular volume overload,
hyperkalemia or severe acidosis resistant to
conservative measures.
Treatment of Complications
Nutrition
Prognosis