Acute Renal Failure - Welcome to my website :-)
Acute Renal Failure - Welcome to my website :-)
Acute Renal Failure
Anthony R Mato, MD
• Renal failure over the course of hours to
• The result will be failure to excrete
• Hard to define: in 26 studies, no two used
the same definition!!!
Classic laboratory definition
• Cr increase of .5 mg / dl.
• Increase in more than 50% over baseline Cr.
• Decreased in calculated Cr Clearance by
more than 50%.
• Any decrease in renal function that requires
Basic Differential Diagnosis
• Pre-Renal: Decreased
– ATN: Ischemic, toxic insult
to the renal tubule. Tubular
without cellular injury.
– AIN: Inflammation and
– 70% of community
– 1 cause of Intra-Renal
– GN:Injury to the filtering
the urinary outflow tract.
•Often rapidly reversible if we can identify this early.
•The elderly at high risk because of their predisposition to
hypovolemia and renal atherosclerotic disease.
•This is by definition rapidly reversible upon the restoration of
renal blood flow and glomerular perfusion pressure.
•THE KIDNEYS ARE NORMAL.
•This will accompany any disease that involves hypovolemia,
low cardiac output, systemic dilation, or selective intrarenal
– GI loss: Nausea, vomiting, diarrhea
– Renal loss: diuresis, hypo adrenalism, osmotic
– Sequestration: pancreatitis, peritonitis,trauma,
– Hemorrhage, burns, dehydration.
• Renal vasoconstriction: hyper Ca, norepi, epi,
cyclosporine, tacrolimus, ampho B.
• Systemic vasodilation: sepsis, medications,
• Cirrhosis with ascites
• Hepato-renal syndrome
• Impairment of autoregulation: NSAIDs, ACE,
• Hyperviscosity syndromes: MM, WM, PCV
• Low CO
Valvular heart disease
– Pos pressure mechanical ventillation
Reduced arterial stretch and activated
Neuro-humoral responses activated to
maintain blood volume and pressure
•Sympathetic nervous system
•AT II system
They will act together to maintain flow
to the heart and the brain at the
expense of other non-essential vascular
Renal afferent vaso-dilation is
triggered via : PGE2 (afferent), Local
myogenic reflex, ATII(efferent)
We have maximum dilation at SBP of
80 mm Hg.
Intrinsic Renal Disease
• Anatomic organization seems to work best.
ARF DOES NOT EQUAL ATN.
• 30% of cases of intrinsic renal failure will
not show any evidence of ATN on UA.
Tubules : ATN
• Ischemic Injuries to the renal tubule:
– Takes 1-2 weeks to recover from after perfusion has
– In the extreme form this can lead to bilateral renal
• Three phases:
– Initiation phase
constriction triggered by an increase in the salt delivery
sensed by the macula densa.
– Recovery phase: tubular epithelial cell repair and
regeneration. This may be associated with a marked
Low cardiac output
ATN : Toxic
ATN : Toxic facts
• ATN : Exacerbated in the elderly, CRI, hypovolemia, and
exposure to multiple toxins.
vaso-constriction: radiocontrast, cyclosporin,
tacrolimus. Initially they will look prerenal.
• Contrast – toxicity is worst in patients with CRI, DM, MM,
CHF, hypovolemia. This is dose related.
• Direct toxicity to epithelial cells: frequent offenders are :
acyclovir, foscarnet, aminoglycosides (30% of patients with
therapeutic levels will have ARF), Ampho B (causes
vasoconstriction as well as direct toxicity).
• Cisplatin (mitochondrial injury).
• Myoglobin and hemoglobin will both increase epithelial cell
oxidative stress. They also inhibit NO vasoconstriciton.
• Light chains : can form intratubular casts and are directly toxic.
UA crystal deposition.
Allergic : AIN
Allergic reaction in the tubules. IT IS
PARAMOUNT TO IDENTIFY THE
OFFENDING AGENT AND REMOVE IT.
There may be some role for steroids in the
case of AIN.
AIN : Allergic
Beta lactams / Cephalosporins
Infections: Legionella / Hanta virus
• Infection: Pyelonephritis, CMV, Candida
• Infiltration: lymphoma, leukemia, sarcoid
• Intratubular deposition and obstruction
Post Renal Causes
If we can identify this early, this can be
readily reversible. This accounts for fewer
than 5% of cases of ARF.
Prostate / Cervical cancer
Retroperitoneal fibrosis /
Neurogenic bladder /
anticholinergic drug use:
Bilateral renal calculi
Myeloma light chains
• Papillary necrosis
• Urethritis with spasm
• Intraluminal Thrombosis
system) crystal disease
• Uric acid
• Calcium oxylate
50 year old man presents to the ED
with a 1 day history of RUQ pain,
N/V. He also reports fever and
chills and decreased urine output.
PMH is a sore throat a week ago,
tx w/ an antibiotic. He is on
ibuprofen only. T = 102, HR 123,
BP 80/60. In general, he is an illappearing.
Abd: + tenderness
remainder of exam is WNL.
WBC 20 w/
Cr 1.6 (baseline is 0.7)
H and P : Prerenal
• Thirst, orthostatic dizziness, hypovolemia
on exam, tachycarida, decreased JVP, poor
skin turgor, dry mucous membranes,
reduced axillary sweating.
• Start of new medications: NSAIDs, ACE,
ARBs. Stigmata of chronic liver disease.
Advanced CHF. Signs of sepsis.
H and P: Intrinsic Renal
• Recent history or hypovolemia / septic shock.
Careful review of clinical data, pharmacy, nursing,
and radiology records for evidence of toxin
exposure. History of myeloma. Recent rhabdo.
• Flank pain (worry for arterial occlusion) : SC
nodules, livedo reticularia, hollenhorst plaques,
digital ischemia with palpable pulses. Fevers,
arthralgias, pruritis erythemetous rash: AIN.
H and P : Post renal
• Presence of suprapubic and flank pain. Pain
radiating to the groin. History of nocturia,
• History of anticholinergic medication use.
What is your differential?
What additional workup do
you want to diagnose
the etiology of his ARF /
• Dip: pH, SG, glucose,
protein, nitrite, leuk
esterase, bili, heme.
• Micro: RBCs, WBCs,
• Normal: 0-2 RBCs, 04 WBC, occasional
Urinalysis: Prerenal / Post-renal
• Sediment is acellular and
may contain hyaline casts
• This is protein that is
normally part of the urine
• Post renal : Sediment is
classically acellular and
• May also see pyuria and
hematuria. No casts.
Renal : ATN
• Muddy brown casts
– (contain tubular-epithelial cells).
• They are usually associated with
microscopic hematuria and mild
tubular proteinuria (< 1 g / d)
from impaired re-absorption.
• CASTS ARE ABSENT IN 30%
OF THE CASES OF ATN.
Renal : GN
• Red blood cell casts are
the classic finding.
• Dysmorphic RBCs.
• These indicate
• These are rarely seen in
• May also see proteinuria:
> 1 g / day.
Renal : AIN
• White cell / granular casts.
• KEEP IN MIND THAT
• Eosinophiluria (> 5%) is a
classic finding (Hansel’s
Stain) – especially in
antibiotic associated AIN.
Common UA Patterns
• Rhabdo: dip is pos for heme, neg for RBCs
• MM: dip is neg for protein, + for light
chains on UPEP
• EG: look for calcium oxylate crystals,
elevated AG, elevated osm gap.
• TLS: uric acid crystals (can also be a
normal variant of concentrated urine)
Tbili : 2.0
ALT : 44
AST : 44
UA : SG 1.02, trace ketones
Micro : No cells, No casts, No crystals
Urine Na: 10
Urine Cr: 80
Renal Failure Indices
• Fractional excretion of Na: this will relate the
clearance of Na to that of Cr.
• In the case of prerenal disease Na is actively
reabsorbed to restore intravascular volume.
• This is not the case in renal injury (absorptive
mechanisms are broken). In either case Cr is NOT
reabsorbed. So we have the makings of a
comparative ratio. The cut off is 1%.
U Na / P Na
__________ x 100% = .14% (Prerenal)
U Cr / P Cr
Keep in mind…
• Keep in mind that when pre renal patients are
receiving diuretics or have bicarbonaturia all bets
• Also salt wasting states such as CRI and adrenal
insufficiency will also alter results.
• In 15% if patients with ATN FeNa can be < 1 % :
reflecting patchy injury with partially preserved
• In GN, acute urinary post renal obstruction, and
vascular diseases the FeNa will often be < 1%.
• Urine sodium, specific gravity, urine osm, BUN :
Cr ratio are less sensitive and of limited value in
differentiating this differential.
• Peak Cr:
– In prerenal disease : may fluctuate with hemodynamics. Rise
will be rapid. This is true for contrast (5 days to peak and 7
– Atheroembolization (later peak and return to baseline), and
ischemia (later peak and return to baseline).
– Rise will be delayed in toxin exposure.
• Rhabdo: elevated K, Phos, hypocalcemia with elevations in CK
• TLS: elevated UA, K, Phos, low Ca, elevated Cr and elevated
LDH (intracellular enzyme).
• Elevated anion gap + elevated osm gap : suggests ethylene
glycol / methanol exposure.
• Anemia may suggest hemolysis, MM, or TTP.
• Eosinophillia may suggest AIN, atheroembolic disease, PAN.
Back to Ricky
• An abdominal CT with contrast
shows acute cholecystitis. He is
given an intravenous dose of
ampicillin and gentamycin, along
with normal saline.
• The next morning you note LE
edema and bibasilar crackles. His
blood pressure has improved to
110/70 and fever has resolved. His
overnight urine output was 150cc.
• Na 137, K 6.7, Cl 100, H2CO3 15,
BUN 37, Cr 2.7
Why is he hyperkalemic?
What is the management?
Does need dialysis?
• Plasma Potassium > 5.0
– Prolonged tourniquet use
– Leukostasis / Thrombocytosis
• A large meal has enough
potassium to kill us. How
will the body handle this
• Buffering system will
stimulate liver / muscle NK ATPase
The Kidney to the Rescue
• Kidney handles it in a
• It virtually reabsorbs
100% of the K in the
proximal tubule (70%)
and the loop of henle
– Solvent Drag
– Single Effect / Paracellular
• We reabsorb almost all of
the K before we reach the
The Principal Cell
• BL membrane we have a
Na/ K ATPase
• On the apical side we have
amilloride Na channels
and other channels that
allow the movement for
• Tight junctions - the
potential across the apical
membrane is – 30. The
BM is at - 70mv.
• The common
K will raise
for K inside of the cell
The Key Players
1. K concentration
4. Distal Na
6. Acid base status of the blood
• Increased intake : rare except in iatrogenesis
• Cellular release
TLS, Rhabdomyolysis, exercise, trauma
Hyperkalemic periodic paralysis
Digoxin toxicity, beta blockers
• Impaired excretion
– Renal failure
– Primary hypoaldosteronism
– Secondary hypoakdosteronism
• ACE, NSAIDs, Heparin, Type 4 RTA
– Aldo resistance
• K sparing diuretics, bactrim, pentamidine, sickle cell disease,
– Gordon’s syndrome (enhanced Cl reabsorption, less K
– Ureter Diversion to Jejunum.
Symptoms / Signs
• Flaccid paralysis
Peaked T waves
PR / QRS prolongation
AV conduction delay
Loss of P waves
Treatment : Keep the
Physiology in mind.
• EKG changes necessitate treatment:
Calcium gluconate: stabilized myocardium
Insulin / Glucose: intracellular shift
Bicarbonate: intracellular shift
Beta 2 agonists: intracellular shift
Diuretics: IV Lasix
Kayexylate: exchanges K for Na
• A : acidosis
• E : electrolytes
• I : intoxication (methanol, ethylene glycol,
isopropanol, theophylline, lithium,
• O : volume overload
• U : uremia (pericarditis, seizures,
Why did his
renal failure worsen?
U OSM 300
Muddy brown casts
U Na 80
U Cr 40
What is highest on your
How does this alter your
• Prevention is the key.
– Appropriate volume resuscitation.
– Renal dosing of potentially toxic meds
– To estimate GFR : Cockcroft-Gault Formula: takes
weight and age into account. (ONLY IN STABLE
CREATININE) MULTIPLY BY .85 IN WOMEN.
– When appropriate follow serum drug levels for dosage
– Use of NSAIDS, ACR, ARBs, diuretics should be used
sparingly in patients who are hypovolemic or have
– Allopurinol / IVFs use in patients high risk for TLS.
– Ethanol for EG toxicity / NAC for tylenol toxicity.
– Alkalinization of urine : to prevent MTX toxicity.
• IVFs: keep in mind where the loss is
coming from and administer fluids
• Inotropes, preload / after-load reduction,
anti-arrythmics, mechanical aids in CHF.
• Large volume paracentesis: to decrease
intra-abdominal pressure and increase
venous return from the kidneys.
Post Renal Treatment
5% will develop a salt wasting diuresis.
Intrinsic Renal Disease
REVERSING THERAPIES FOR ISCHEMIC
• Follow electrolytes. Avoid further insult.
• GN: may respond to steroids, alkylating agents,
• AIN: glucocorticoids may be of use.
• Malignant HTN: control of blood pressure.
• Scleroderma: HTN and ARF may responsive to
Case 2 : Fred
85 year old man with a PMHx
significant for osteoarthritis is
admitted to the hospital for
confusion. Physical exam reveals a
thin, disoriented man: T = 98, HR =
80, BP = 120/80, wt = 75 kg, and a
suprapubic mass. He takes no
medication except for naproxen.
• Labs: Na 131, K 4.8, Cl 98, HCO3 15
• BUN 65, Cr 7.3 (baseline on
What is the FeNa?
What is the baseline Cr
(140-age) x wt/(Cr x 72)
What is your differential?
The next morning
the creatinine is 2.5
and his mental
status has cleared.
45 yr old female with a
PMH for HTN presents
with “HEADACHE, ”low
back pain, and left should
pain. You decide to order
labs and discover discover
a Cr 2.0 (baseline 1.0),
Calcium 10.0, and mild
pan-cytopenia (Hb 10.0,
Pts 144). FeNa is 2.0. UA
dip is bland (no protein,
no leuks, no nitrites)
tests would you like?
The minimal criteria for the diagnosis of multiple
myeloma include a bone marrow usually containing
more than 10 percent plasma cells (or presence of a
plasmacytoma) plus at least one of the following:
• A monoclonal protein (M-protein) in the serum
(usually >3 g/dL)
• An M-protein in the urine
• Lytic bone lesions.
Additionally, at least some of the following: Anemia,
hypercalcemia, azotemia, hypoalbuminemia, bone
demineralization (THE MINOR CRITERIA)
30 year old man with diabetes,
hypertension and chronic renal
insufficiency (baseline creatinine of
2.5) presents to VA clinic for
routine follow-up. His medications
are captopril, HCTZ and insulin.
Physical exam is unremarkable.
Na= 138, K=5.8, Cl=110,
What is your differential for
What is your plan
Acid / Base : Basics
The normal renal response to acidemia
is to reabsorb all of the filtered
bicarbonate and to increase hydrogen
excretion primarily by enhancing the
excretion of ammonium ions in the
urine. Each hydrogen that is secreted
results in the regeneration of a
bicarbonate ion in the plasma.
• Reabsorption of filtered bicarbonate
predominantly occurs in the proximal
tubules primarily by Na-H exchange.
• Approximately 85 to 90 percent of the
filtered load is reabsorbed proximally.
• By comparison, 10 percent is
reabsorbed in the distal nephron
primarily via hydrogen secretion by a
proton pump (H-ATPase).
• Under normal conditions, virtually no
bicarbonate is present in the final urine.
• We need to deal with acid load from protein
• There must be sufficient buffering compounds
available to bind hydrogen ions.
• The principal buffers in the urine are ammonia
(excreted and measured as ammonium) and
phosphate (referred to and measured as
• Failure to excrete sufficient ammonium net
retention of H+ and metabolic acidosis.
• Impaired hydrogen ion secretion is the
primary defect in distal RTA while impaired
ammoniagenesis is the primary defect in type
4 RTA and renal failure.
Renal Tubular Acidosis
• Renal tubular acidosis (RTA) is a disorder of
renal acidification out of proportion to the
reduction in GFR.
• RTA is characterized by hyperchloremic
metabolic acidosis with a normal serum anion gap
[Na+– (Cl–+ HCO3–)].
• There are multiple forms of RTA, depending on
which aspects of renal acid handling have been
Type I (DISTAL)
• Distal nephron does not lower urine pH normally:
– The collecting ducts permit back-diffusion of H+ from
lumen to blood with inadequate transport of H+.
– Causes a reduction in ammonium excretion.
– [Urinary] and K conservation can be impaired.
– Chronic acidosis lowers tubule reabsorption of calcium
hypercalciuria and mild 2nd hyperparathyroidism.
– Hypercalciuria, alkaline urine, and urine citrate cause
calcium phosphate stones.
– Growth retardation is common and improves with
correction of the acidosis by alkali.
– Since the kidney does not conserve potassium or
concentrate the urine normally, polyuria and
hypokalemia occur. Sometimes fatal.
Diagnosis and Treatment
Normal AG acidosis
Urine pH > 5.5
Oral ammonium load
will worsen acidosis.
• Urine anion gap is
positive (vs. GI):
• Na + K – Cl
• Treat with
Type II RTA (Proximal)
Bicarb resorption in prox tubule is impaired.
Distal tubule resorption is overwhelmed at first.
Equilibrium is established at bicarb of 16.
Urine pH is normal / high.
Ammonium challenge does not affect urine
• Expect bicarbonaturia. FE Bicarb.
• Bicarbonate must be given in LARGE doses.
Alkali therapy can worsen hypokalemia.
Type IV RTA
• Distal secretion of K and H+ is abnormal
producing a non AG acidosis with
• Hypo aldosteronism: DM, ACE, NSAIDs, TMP,
adrenal disease (high Renin level).
• Tubular inflammation (low Renin state) with
interstitial inflammation (SSD), K sparing
diuretics (aldactone, amilloride).
• HYPERKALEMIA IS THE PRIMARY
PROBLEM. K MAY INHIB IT AMMONIA
• Do not have bicarbonaturia (vs. Type II).
• Urine is APPROPRIATELY acidic (pH < 5.5)
• Lower potassium
• Remove drugs that lower aldosterone
• High dose mineralocorticoids (beware of
• Liberal Na intake.
• Exchange resins.
Comparison of Normal Anion-Gap Acidosis
Type 1 RTA
Type 2 RTA
Type 4 RTA
GI Bicarbonate Loss
Normal anion-gap acidosis
Minimum urine pH
5 to 6
% Filtered bicarbonate excreted
Daily acid excretion
Urine anion gap
Daily bicarbonate replacement needs