Transcript Acute Renal Failure - Welcome to my website :-)

Acute Renal Failure
Anthony R Mato, MD
Basic Facts
• Renal failure over the course of hours to
days.
• The result will be failure to excrete
nitrogenous
waste
and
electrolyte
imbalance.
• 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
dialysis.
Basic Differential Diagnosis
• Intra-Renal:
• Pre-Renal: Decreased
– ATN: Ischemic, toxic insult
renal perfusion
to the renal tubule. Tubular
without cellular injury.
– AIN: Inflammation and
– 70% of community
acquired cases.
– 40%
of
hospital
acquired cases.
– 1 cause of Intra-Renal
failure.
edema.
– GN:Injury to the filtering
mechanism.
• Post-Renal:
obstruction
the urinary outflow tract.
Prerenal Failure
•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
vasoconstriction.
Differential Diagnosis
• Hypovolemia
– GI loss: Nausea, vomiting, diarrhea
– Renal loss: diuresis, hypo adrenalism, osmotic
diuresis (DM)
– Sequestration: pancreatitis, peritonitis,trauma,
low albumin.
– Hemorrhage, burns, dehydration.
Differential Diagnosis
• Renal vasoconstriction: hyper Ca, norepi, epi,
cyclosporine, tacrolimus, ampho B.
• Systemic vasodilation: sepsis, medications,
anesthesia, anaphylaxis.
• Cirrhosis with ascites
• Hepato-renal syndrome
• Impairment of autoregulation: NSAIDs, ACE,
ARBs.
• Hyperviscosity syndromes: MM, WM, PCV
Differential Diagnosis
• Low CO
–
–
–
–
–
Myocardial diseases
Valvular heart disease
Pericardial disease
Tamponande
Pulmonart HTN
PE
– Pos pressure mechanical ventillation
Reduced arterial stretch and activated
baro-receptors 
Neuro-humoral responses activated to
maintain blood volume and pressure 
•Sympathetic nervous system
•AT II system
•AVP system
They will act together to maintain flow
to the heart and the brain at the
expense of other non-essential vascular
beds.
Renal afferent vaso-dilation is
triggered via : PGE2 (afferent), Local
myogenic reflex, ATII(efferent)
We have maximum dilation at SBP of
80 mm Hg.
PHYSIOLOGY OF
HYPOVOLEMIA
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.
–
–
–
–
Glomerulus
Vessels
Interstitum
Tubules
THE DIFFERENTIAL
DIAGNOSIS
Differential Diagnosis
Tubules : ATN
• Ischemic Injuries to the renal tubule:
– Takes 1-2 weeks to recover from after perfusion has
been normalized.
– In the extreme form this can lead to bilateral renal
cortical necrosis
• Three phases:
– Initiation phase
– Tubuloglomerular
feedback:
afferent
arteriole
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
diuretic phase.
ATN: Ischemic
•
•
•
•
•
Hypovolemia
Low cardiac output
Renal vasoconstriction
Systemic dilation
Hemorrhage
ATN : Toxic
• Exogenous
–
–
–
–
–
–
–
Radiocontrast
CSP
TAC
Amino glycosides
Chemotherapy
Ethylene glycol
Tylenol
• Endogenous
–
–
–
–
–
Myoglobin
Hemoglobin
Uric acid
Oxylate
Light chains
ATN : Toxic facts
• ATN : Exacerbated in the elderly, CRI, hypovolemia, and
exposure to multiple toxins.
• Intrarenal
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
Sulfinamides
TMP
NSAIDs
Diuretics
Captopril
Autoimmune diseases
Infiltrative diseases
Infections: Legionella / Hanta virus
Others
• 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.
Differential Diagnosis
•
•
•
•
•
•
•
•
BPH #1
Prostatitis
Prostate / Cervical cancer
Retroperitoneal fibrosis /
disorders
Extraluminal malignancy
Neurogenic bladder /
anticholinergic drug use:
functional obstruction
Bilateral renal calculi
Myeloma light chains
• Papillary necrosis
• Urethritis with spasm
• Inadvertent
surgical
ligature
• Intraluminal Thrombosis
• Intraluminal
(collecting
system) crystal disease
• Uric acid
• Calcium oxylate
• Acyclovir
• Sulfonamide
• MTX
Ricky’s Story
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
RUQ;
no
peritoneal
signs;
remainder of exam is WNL.
Ricky’s Story
Labs:
•
•
•
•
•
•
•
•
•
•
WBC 20 w/
16% bands
Hgb 14
Plts 300
Na 140
K 4.1
Cl 111
HCO3 22
BUN 35
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,
frequency, hesitancy.
• History of anticholinergic medication use.
What is your differential?
What additional workup do
you want to diagnose
the etiology of his ARF /
abdominal pain?
Urinalysis
• Dip: pH, SG, glucose,
protein, nitrite, leuk
esterase, bili, heme.
• Micro: RBCs, WBCs,
casts, crystals,
bacteria.
• Normal: 0-2 RBCs, 04 WBC, occasional
hyaline cast.
Urinalysis: Prerenal / Post-renal
• Sediment is acellular and
may contain hyaline casts
• This is protein that is
normally part of the urine
(Tamm-Horsfall Protein).
• Post renal : Sediment is
classically acellular and
“bland”.
• 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
glomerular injury.
• These are rarely seen in
acute ATN.
• May also see proteinuria:
> 1 g / day.
Renal : AIN
• White cell / granular casts.
• KEEP IN MIND THAT
BROAD
GRANULAR
CASTS
REFELCT
CHRONIC
RENAL
DISEASE (fibrosis).
• 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)
URINE BLING
Results
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•
Tbili : 2.0
Alk: 269
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
are off.
• 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
function.
• 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.
Additional Labs
• Peak Cr:
– In prerenal disease : may fluctuate with hemodynamics. Rise
will be rapid. This is true for contrast (5 days to peak and 7
to normal)
– 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
and UA.
• 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?
Hyperkalemia
• Plasma Potassium > 5.0
• Pseudohyperkalemia
– Prolonged tourniquet use
– Hemolysis
– Leukostasis / Thrombocytosis
Physiology
• A large meal has enough
potassium to kill us. How
will the body handle this
load initially.
• Buffering system will
stimulate liver / muscle NK ATPase
– Insulin
– Epinephrine
– Aldosterone
The Kidney to the Rescue
• Kidney handles it in a
unique way.
• It virtually reabsorbs
100% of the K in the
proximal tubule (70%)
and the loop of henle
(30%).
– Solvent Drag
– Single Effect / Paracellular
pathway
• We reabsorb almost all of
the K before we reach the
distal segments.
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
K.
• Tight junctions - the
potential across the apical
membrane is – 30. The
BM is at - 70mv.
• The common
denominator: intracellular
K will raise
electrochemical gradient
for K inside of the cell
The Key Players
1. K concentration
2. Aldosterone
3. Flow
4. Distal Na
5. ADH
6. Acid base status of the blood
Differential Diagnosis
• Increased intake : rare except in iatrogenesis
• Cellular release
–
–
–
–
–
–
–
TLS, Rhabdomyolysis, exercise, trauma
Metabolic acidosis
Insulin deficiency
Hyperkalemic periodic paralysis
Digoxin toxicity, beta blockers
Adrenal insufficiency
Succinylcholine
Differential Diagnosis
• Impaired excretion
– Renal failure
– Primary hypoaldosteronism
– Secondary hypoakdosteronism
• ACE, NSAIDs, Heparin, Type 4 RTA
– Aldo resistance
• K sparing diuretics, bactrim, pentamidine, sickle cell disease,
multiple myeloma.
– Gordon’s syndrome (enhanced Cl reabsorption, less K
secretion, HTN)
– Ureter Diversion to Jejunum.
Symptoms / Signs
• Flaccid paralysis
• Arrhythmia
–
–
–
–
–
–
Peaked T waves
PR / QRS prolongation
AV conduction delay
Loss of P waves
Sine wave
V fib
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
Dialysis
Dialysis Needs
• A : acidosis
• E : electrolytes
• I : intoxication (methanol, ethylene glycol,
isopropanol, theophylline, lithium,
salicylates)
• O : volume overload
• U : uremia (pericarditis, seizures,
encephalopathy)
Why did his
renal failure worsen?
Additional Labs
•
•
•
•
U OSM 300
Muddy brown casts
U Na 80
Calculate FeNa?
U Cr 40
What is highest on your
differential?
How does this alter your
treatment plan?
Treatment
• 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
adjustment.
– Use of NSAIDS, ACR, ARBs, diuretics should be used
sparingly in patients who are hypovolemic or have
renovascular disease.
– Allopurinol / IVFs use in patients high risk for TLS.
– Ethanol for EG toxicity / NAC for tylenol toxicity.
– Alkalinization of urine : to prevent MTX toxicity.
Prerenal disease
• IVFs: keep in mind where the loss is
coming from and administer fluids
accordingly.
• 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
•
•
•
•
Foley catheter
Nephrostomy tube
Stenting
5% will develop a salt wasting diuresis.
Intrinsic Renal Disease
• Intrinsic
renal
disease:
NO
SPECFIC
REVERSING THERAPIES FOR ISCHEMIC
AND
NEPHROTOXIC
DISEASE.
SUPPORTIVE CARE.
• Follow electrolytes. Avoid further insult.
• GN: may respond to steroids, alkylating agents,
plasmapheresis.
• AIN: glucocorticoids may be of use.
• Malignant HTN: control of blood pressure.
• Scleroderma: HTN and ARF may responsive to
ACE.
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
computer: 1.3)
What is the FeNa?
What is the baseline Cr
clearance?
Cockcroft-Gault:
(140-age) x wt/(Cr x 72)
What is your differential?
The Intervention
The next morning
the creatinine is 2.5
and his mental
status has cleared.
Geraldine
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)
What additional
tests would you like?
Multiple Myeloma
Multiple Myeloma
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)
Sam’s Case
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,
HCO3=20, BUN=30,
Cr=2.4,Glu=129
What is your differential for
elevated Potassium?
What is your plan
management 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.
Proximal Tubule
• 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.
Distal Tubule
• We need to deal with acid load from protein
catabolism.
• 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
titratable acidity).
• 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
affected.
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
Nephrocalcinosis
Oral ammonium load
will worsen acidosis.
• Urine anion gap is
positive (vs. GI):
• Na + K – Cl
• Treat with
bicarbonate.
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
acidification.
• 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
hyperchloremia.
• 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
EXCRETION.
• Do not have bicarbonaturia (vs. Type II).
• Urine is APPROPRIATELY acidic (pH < 5.5)
Treatment
• Lower potassium
• Remove drugs that lower aldosterone
production.
• High dose mineralocorticoids (beware of
CHF).
• Liberal Na intake.
• Exchange resins.
Comparison of Normal Anion-Gap Acidosis
Finding
Type 1 RTA
Type 2 RTA
Type 4 RTA
GI Bicarbonate Loss
Normal anion-gap acidosis
Yes
Yes
Yes
Yes
Minimum urine pH
>5.5
<5.5
<5.5
5 to 6
% Filtered bicarbonate excreted
<10
>15
<10
<10
Serum potassium
Low
Low
High
Low
Fanconi syndrome
No
Yes
No
No
Stones/nephrocalcinosis
Yes
No
No
No
Daily acid excretion
Low
Normal
Low
High
Urine anion gap
Positive
Positive
Positive
Negative
Daily bicarbonate replacement needs
<4 mmol/kg
>4 mmol/kg
<4 mmol/kg
Variable