Acute Renal Failure

N. SRINIVAS
 Acute Renal Failure

Defined as a sudden and sustained loss of

renal function (over several hours to
several days), ARF results in
derangements in extracellular fluid
balance, acid base, electrolytes, and
divalent cation regulation.
 Basic Facts
• Renal failure over the course of hours to days.
• The result will be failure to excrete nitrogenous
waste and electrolyte imbalance.
• An increased serum creatinine concentration,
decreased GFR, accumulation of other nitrogenous-
based waste products,and often a decline in urinary
output are the hallmarks of ARF.
• abnormal levels of K, Ca, Phosphate & hematuria
 Kidney Function decreases…

• BP raises-CHF
• Urea accumulates – azotemia, Uremia, excretes by
sweating causing Uremic Frost in skin.
• Hyperkalemia.
• Erythropoietin decreases – Anemia.
• Pulmonary edema & Hyper phosphatemia .
• Hypocalcemia due to Vitamin D3 Deficiency.
• Metabolic acidosis.
 Stages of Kidney Disease
• Abdominal Ultrasound.
• Renal Imaging with Technetium-99.
• CKD stages 1 to 5 based on GFR.
• GFR values 90, 60-90, 30-45-60, 15-30, less than
30.
• Increase in more than 50% over baseline Cr.
• Decrease in calculated Cr Clearance by more than
50%.
 EVALUATION OF ARF
• INTRAVASCULAR VOLUME STATUS IS THE
MOST IMPORTANT FACTOR

• A DECREASE IN URINARY VOLUME IS ONE

OF THE INITIAL CLINICAL FINDING IN ARF.

• The most important laboratory test is urine analysis -

Both urinary sediment and urinary indices in
combination with serum values can often be
extremely helpful in determining the cause of ARF.
 Basic Differential Diagnosis
• Pre-Renal: Decreased • Intra-Renal:
renal perfusion – ATN: Ischemic, toxic insult
to the renal tubule. Tubular
without cellular injury. – AIN: Inflammation and
– 70% of community edema.
acquired cases. – GN:Injury to the filtering
mechanism.
– 40% of hospital
acquired cases. • Post-Renal: obstruction
– 1 cause of Intra-Renal the urinary outflow tract.
failure.
 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
– Hemorrhage, burns, dehydration.
 Differential Diagnosis
• Renal vasoconstriction: hyper Ca, norepi, epi,
cyclosporine, tacrolimus, ampho B.
• Systemic vasodilation: sepsis, medications,
anesthesia, anaphylaxis.
• Impairment of autoregulation: NSAIDs, ACE,
ARBs.
 Intrinsic Renal Disease
• Anatomic organization seems to work best.
• Ischemic Injuries to the renal tubule:
– Takes 1-2 weeks to recover from after perfusion has
been normalized
• 30% of cases of intrinsic renal failure will
not show any evidence of ATN.
– Glomerulus
– Vessels
– Interstitum
– Tubules
 ATN: Ischemic
• Hypovolemia
• Low cardiac output
• Renal vasoconstriction
• Systemic dilation
• Hemorrhage
 ATN : Toxic facts
• ATN : Exacerbated in the elderly, hypovolemia, and exposure to
multiple toxins.
• Intrarenal vaso-constriction: radiocontrast, cyclosporin,
tacrolimus. Initially they will look prerenal.
• Contrast – toxicity is worst in patients with 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, 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.
 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
 Dialysis Needs
• A : acidosis
• E : electrolytes
• I : intoxication (methanol, ethylene glycol,
isopropanol, theophylline, lithium,
salicylates)
• O : volume overload
• U : uremia (pericarditis, seizures)
 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.
 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.
 Therapy of ARF
• The goal of any focused evaluation of ARF is
immediate correction of its reversible causes.
• Recognition and relief of urinary outlet obstruction
should be given the highest priority,especially for
patient with anuria.
• Support of renal perfusion with either volume
infusion or therapeutics that improve renal oxygen
delivery should be considered before any attempt to
improve urinary flow.
• Urinary indices should be examined before diuretic
intervention.
 GOALS OF MULTIORGAN
SUPPORT THERAPY

• Blood purification and renal support.

• Temperature control.
• Acid–base control.
• Fluid balance control and cardiac support.
• Protective lung support and removal of
carbondioxide.
• Protection of the brain from fluid shifts.
• Blood detoxification and liver support.
Azotemia: elevated blood urea nitrogen not
from an intrinsic renal disease

Oliguria: urine output less than

500cc/24hr.
Nonoliguria: urine output greater than
500cc/24hr.
Anuria: urine output less than
50cc/24hr.
 Mortality of ARF
• “Despite technical progress in the
management of acute renal failure over the
last 50 years, mortality rates seem to have
remained unchanged at around 50%.”

Am J Med (2005)118:827-832.
 Predictors of Dialysis in ARF
• Oliguria:
– <400cc/24hr 85% will require dialysis
– >400cc/24hr 30-40% will require dialysis
• Mechanical ventilation
• Acute myocardial infarction
• Arrhythmia
• Hypoalbuminemia
• ICU stay
• Multi-system organ failure
JASN 9(4):692-698, 1998 Arch IM 160:1309-1313, 2000
 Prevention of ARF
• Diminish risk of nosocomial infection
– conservative use of IV catheters
– judicious use of antibiotics
– hand-washing
• Prevention of nephrotoxicity
– avoid/reduce nephrotoxins
– IV NS
– N-acetylcysteine, sodium bicarbonate
– correct hypokalemia, hypomagnesemia
– correct/treat other systemic diseases
• Pharmacology
– avoid overlapping nephrotoxins
– follow drug levels closely
• Attention to fluid status
– Regular weights, I & O
 Chronic renal failure
• Chronic renal failure is a gradual and
progressive loss of the ability of the kidneys
to excrete wastes, concentrate urine, and
conserve electrolytes
• Kidney failure - chronic; Renal failure -
chronic; Chronic renal insufficiency; CRF;
Chronic kidney failure
 causes
• Unlike acute renal failure with its sudden,
reversible failure of kidney function, chronic
renal failure slowly gets worse. It most often
results from any disease that causes gradual loss
of kidney function. Progression may continue to
end-stage renal disease(ESRD).
• Chronic renal failure results in the accumulation
of fluid and waste products in the body, causing
azotemia and uremia. Azotemia is the buildup of
nitrogen waste products in the blood. It may occur
without symptoms. Uremia is the state of ill
health resulting from renal failure. Most body
systems are affected by chronic renal failure.
Fluid retention and uremia can cause many
complications.
 symptoms
• Initial symptoms may include the following:
Unintentional weight loss
• Nausea, vomiting
• General ill feeling
• Fatigue
• Headache
• Frequent hiccups
• Generalized itching
 symptoms
• Later symptoms may include the following:
• Increased or decreased urine output
• Need to urinate at night
• Easy bruising or bleeding
• May have blood in the vomit or in stools
• Decreased alertness
– drowsiness, somnolence lethargy
– confusion delirium
– coma
• Muscle twitching or cramps
• Seizures
• Uremic frost -- deposits of white crystals in and on the
skin
• Decreased sensation in the hands, feet, or other areas
 Exams & Tests
• There may be mild to severe high blood
pressure. A neurologic examination may
show polyneuropathy. Abnormal heart or
lung sounds may be heard with a
stethoscope.
A urinalysis may show protein or other
abnormalities. An abnormal urinalysis may
occur 6 months to 10 or more years before
symptoms appear.
 Exams & Tests
• Creatinine levels progressively increase
• BUN is progressively increased
• Creatinine clearance progressively
decreases
• Potassium test may show elevated levels
• Arterial blood gas and blood chemistry
analysis may show metabolic acidosis
 Exams & Tests
• Changes that indicate chronic renal failure,
including both kidneys being smaller than
normal, may be seen on:
• Renal or abdominal x-ray
• Abdominal CT scan
• Abdominal MRI
• Abdominal ultrasound
 prevention
• Call your health care provider if nausea or vomiting persists
for more than 2 weeks.
Call your health care provider if decreased urine output or
other symptoms of chronic renal failure occur.

• Treatment of the underlying disorders may help prevent or

delay development of chronic renal failure. Diabetics should
control blood sugar and blood pressure closely and should
refrain from smoking
GUIDELINE OF URINARY
INDICES
 Prerenal
• Thirst, orthostatic dizziness, hypovolemia
on exam, tachycarida, dry mucous
membranes, reduced axillary sweating.
• Start of new medications: NSAIDs, ACE,
chronic liver disease. Advanced CHF. Signs
of sepsis.
 Intrinsic Renal
• Recent history or hypovolemia / septic shock.
Careful review of clinical data, pharmacy, nursing,
and radiology records for evidence of toxin
exposure..
• Flank pain (worry for arterial occlusion) : SC
nodules, livedo reticularia, hollenhorst plaques,
digital ischemia with palpable pulses. Fevers,
arthralgias, pruritis erythemetous rash: AIN.
 Post renal
• Presence of suprapubic and flank pain. Pain
radiating to the groin. History of nocturia,
frequency, hesitancy.
• History of anticholinergic medication use.
 Urinalysis
• Dip: pH, SG, glucose,
protein, nitrite, leuk
esterase, bili, heme.
• Micro: RBCs, WBCs,
casts, crystals,
bacteria.
• Normal: 0-2 RBCs, 0-
4 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
• 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.