Transcript Background to Acute Renal Failure

RENAL FAILURE
MP 2000
14TH MAY 2009
SUMMARY
• Background to ARF
• Pathophysiology
• Classification into Pre-Renal, Renal and PostRenal ARF
• Etiology ARF
• Laboratory Studies
• Chronic Renal Failure
- Causes
- Clinical manifestations
- Specific Disorders (Anemia, Hypertension, Renal
osteodystrophy
• Concluding Remarks
Background to Acute Renal Failure
• Acute renal failure (ARF), is defined as an
abrupt or rapid decline in renal function.
• This condition is usually marked by a rise in
serum creatinine concentration or azotemia (a
rise in blood urea nitrogen [BUN] concentration).
• However, immediately after a kidney injury, BUN
or creatinine levels may be normal, and the only
sign of a kidney injury may be decreased urine
production.
• A rise in the creatinine level can result from
medications (eg, cimetidine, trimethoprim)
that inhibit the kidney’s tubular secretion.
• A rise in the BUN level can occur without
renal injury, such as in GI or mucosal
bleeding, steroid use, or protein loading
• So a careful inventory must be taken before
determining if a kidney injury is present.
Pathophysiology
• AFR may occur in 3 clinical patterns,
including the following:
• (1) as an adaptive response to severe volume
depletion and hypotension, with structurally
intact nephrons
• (2) in response to cytotoxic, ischemic, or
inflammatory insults to the kidney, with
structural and functional damage
• (3) with obstruction to the passage of urine.
• Therefore, in general terms, ARF may be
classified as:
- Pre-renal
- Intrinsic, and
- Post-renal
• The classifications are useful in establishing a
differential diagnosis
• However many pathophysiologic features are
shared among the different categories.
•
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Patients who develop ARF can be
oliguric or nonoliguric
Have a rapid or slow rise in creatinine levels
May have qualitative differences in urine
solute concentrations and cellular content.
• The reason for this lack of a uniform clinical
presentation is a reflection of the variable
nature of the injury.
• Classifying ARF as oliguric or nonoliguric based
on daily urine excretion has prognostic value
• Oliguria: daily urine volume of less than 400
mL- - has a worse prognosis,
• Anuria daily urine output of less than 100 mL/d
- if abrupt in onset, is suggestive of bilateral
obstruction or catastrophic injury to both
kidneys.
• Stratification of renal failure along these lines
helps in decision-making (e.g. timing of dialysis)
and can be an important criterion for patient
response to therapy
A: Causes of Pre-renal ARF
A: Volume depletion:
GI losses (vomiting, diarrhea)
Cutaneous losses (burns, StevensJohnson syndrome)
Hemorrhage
B: Decreased cardiac output
Heart failure
Pulmonary embolus
Acute myocardial infarction
Severe valvular disease
C: Systemic vasodilatation
Sepsis
Anaphylaxis
Anesthetics
Drug overdose
D: Vascular
Renal artery obstruction (thrombosis,
emboli, dissection, vasculitis)
Renal vein obstruction (thrombosis)
Microangiopathy (e.g. in preeclampsia)
Malignant hypertension
Transplant rejection
Atheroembolic disease
B: Causes of Intrinsic ARF (Glomerular)
Anti–glomerular basement membrane (GBM)
disease (Goodpasture syndrome)
Anti–neutrophil cytoplasmic antibody-associated
glomerulonephritis (ANCA-associated GN)
Immune complex Glomeluronephritis (lupus,
postinfectious, primary membranoproliferative
glomerulonephritis)
B: Causes of Intrinsic ARF (Tubular)
Ischemia
Cytotoxicity caused by e.g.
- Heme pigment (rhabdomyolysis,
intravascular hemolysis)
- Crystals (tumor lysis syndrome)
- Drugs (aminoglycosides, lithium,
amphotericin B, pentamidine, cisplatin,
ifosfamide, radiocontrast agents)
B: Causes of Intrinsic ARF (Interstitial)
 Drugs (penicillins, cephalosporins,
NSAIDs
Infections (pyelonephritis, viral
nephritides)
Systemic disease (Sjogren syndrome,
sarcoidosis)
C: Postrenal causes of ARF
Ureteric obstruction (stone disease,
tumor, fibrosis, ligation during pelvic
surgery)
Bladder neck obstruction (benign
prostatic hypertrophy [BPH], cancer of
the prostate [CA prostate], stone disease,
hemorrhage/clot)
Urethral obstruction (strictures, tumor,
phimosis)
Lab Studies in ARF

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•
•
•
•
•
Several laboratory tests are useful for
assessing the etiology of ARF
Can aid in proper management
These tests include:
- Urinalysis
- Serum Biochemical Tests (BUN, Serum
creatinine, Electrrolytes, Enzymes)
- CBC
- Urine Chemical Indices
Urine Output
Changes in urine output generally are
poorly correlated with changes in GFR.
Approximately 50-60% of all causes of
ARF are nonoliguric
However, categories of anuria, oliguria,
and nonoliguria may be useful in
differential diagnosis of ARF.
Presence of Anuria ( <100 mL/d) suggests ARF
due to:
- Urinary tract obstruction
- Renal artery obstruction
- Rapidly progressive glomerulonephritis
- Bilateral diffuse renal cortical necrosis
Oliguria (100-400 mL/d) is suggsetive of ARF due
to:
- Prerenal failure
- Hepatorenal syndrome
Nonoliguria (>400 mL/d) accompanies
- Acute interstitial nephritis
- acute glomerulonephritis
- partial obstructive nephropathy
Urinalysis:
Microscopic examination of urine is essential
in establishing differential diagnosis
• Normal urinary sediment without
hemoglobin, protein, cells, or casts generally
consistent with prerenal and postrenal
failure
• Granular casts - ATN, glomerulonephritis,
interstitial nephritis
• RBC casts - Glomerulonephritis, malignant
HTN
• WBC casts - Acute interstitial nephritis,
pyelonephritis
• Eosinophiluria - Acute allergic interstitial
nephritis
BUN
The urea concentration correlates poorly
with the GFR.
Because urea is highly permeable to renal
tubules, urea clearance varies with urine
flow rate.
Urea is filtered freely, but reabsorption
along the tubule is a function of urine flow
rate.
In prerenal conditions, low urine flow
rates favor BUN reabsorption out of
proportion to decreases in GFR
This results in a disproportionate rise
of BUN relative to creatinine
In prerenal failure a serum BUNcreatinine ratio >20 may be seen
BUN concentration is dependent on
nitrogen balance and renal function.
BUN concentration can rise significantly
with no decrement in GFR by increases in
urea production with steroids, trauma, or
GI bleeding.
Basal BUN concentration can be
depressed severely by malnutrition or
advanced liver disease.
Serum creatinine
 Serum creatinine provides the most
accurate and consistent estimation of GFR.
Serum creatinine level varies by method of
measurement
This becomes important when patients
present with changes in creatinine
measured in different labs.
Serum creatinine is a reflection of creatinine
clearance
Serum creatinine is a reflection of creatinine
clearance.
Serum creatinine is a function of its production
and excretion rates.
Because Creatinine production is determined
by muscle mass serum creatinine must always
be interpreted with respect to patient's weight,
age, and sex
Changes in serum creatinine reflect changes in
GFR.
Stable changes in serum creatinine correlate
with changes in GFR by the following
relationships:
• Creatinine 1.0 mg/dL - Normal GFR
• Creatinine 2.0 mg/dL - 50% reduction in GFR
• Creatinine 4.0 mg/dL - 70–85% reduction in
GFR
• Creatinine 8.0 mg/dL - 90–95% reduction in
GFR
Complete blood count
Leukocytosis is common in ARF.
Leukopenia and thrombocytopenia
suggest SLE associated ARF
Anemia and rouleaux formation suggest
multiple myeloma.
Eosinophilia suggests allergic interstitial
nephritis, polyarteritis nodosa, or
atheroemboli
Coagulation disturbances indicate liver
disease or hepatorenal syndrome.
Other Blood Tests
Creatine phosphokinase (CPK) elevations
are seen in rhabdomyolysis and myocardial
infarction.
Elevations in liver transaminases are seen
in rapidly progressive liver failure and
hepatorenal syndrome.
Hypocalcemia (moderate) is common in
ARF.
Hyperkalemia is a common complication of
ARF.
Urine chemical indices
Differentiation of prerenal azotemia from ATN
takes on a special importance in early
management of these patients
Aggressive fluid resuscitation is appropriate in
prerenal ARF.
However, rapid fluid infusion in a patient with
ATN who is unable to excrete the extra fluid
could result in life-threatening volume
overload.
Urine chemical indices in Prerenal failure
Urine indices that suggest prerenal failure
include the following:
Urine specific gravity >1.018
Urine osmolality (mOsm/kg H2O)
>500
Urine sodium (mmol/L) <15-20
Plasma BUN/creatinine ratio >20
Urine/plasma creatinine ratio >40
Urine chemical indices in ATN
Urine indices that suggest ATN include
the following:
Urine specific gravity <1.012
Urine osmolality (mOsm/kg H2O)
< 500
Urine sodium (mEq/L) >40
Plasma BUN/creatinine ratio <10-15
Urine/plasma creatinine ratio <20
CHRONIC RENAL FAILURE
• Chronic renal failure (CRF) is defined as
a permanent reduction in glomerular
filtration rate (GFR) sufficient to produce
detectable alterations in well-being and
organ function.
• This usually occurs at GFR below 25
ml/min
• Any disorder that permanently destroys
nephrons can result in chronic renal failure
Most Common Causes of CRF include:
Diabetic nephropathy
Hypertensive nephrosclerosis
Glomerulonephritis
Interstitial nephritis
Polycystic kidney disease
Clinical Manifestations
• Multiple symptoms and signs constitute the
uremic syndrome
• Neurological Disorders: Fatigue, lethargy,
sleep disturbances, headache, seizures,
encephalopathy, peripheral neuropathy including
restless leg syndrome, paraesthesia, motor
weakness, paralysis.
• Hematologic Disorders: Anemia, bleeding
tendency – due in part to platelet dysfunction.
• Cardiovascular Disorders: Pericarditis,
hypertension, congestive heart failure, coronary
artery disease, myocardiopathy
• Pulmonary Disorders: Pleuritis, uremic
lung.
• Gastrointestinal Disorders: Anorexia,
nausea, vomiting gastroenteritis, GI
bleeding, peptic ulcer.
• Metabolic-Endocrine Disorders: Glucose
intolerance, hyperllipidemia, hyperuricemia,
malnutrition, sexual dysfunction and
infertility
• Bone, Calcium, Phosphorus Disorders:
Hyperphosphatemia, hypocalcemia, tetany,
metastatic calcification, secondary
hyperparathyroidism, 1,25-dihydroxy vitamin D
deficiency, osteomalacia, osteitis fibrosa,
osteoporosis, osteosclerosis.
• Skin Disorders: Pruritus, pigmentation, easy
bruising, uremic frost.
• Psychological Disorders: Depression, anxiety,
denial, psychosis.
• Fluid and Electrolyte Disorders:
Hyponatremia, hyperkalemia,
hypermagnesemia, metabolic acidosis, volume
expansion or depletion.
Anemia:
Anemia is universal as GFR falls below 25 ml/min.; in
certain disorders it may occur with mild renal
insufficiency. Several factors contribute:
• a. Erythropoiesis is markedly depressed, mainly due to
reduced erythropoietin production; in addition, there
may be reduced end-organ response to erythropoietin
with reduced heme synthesis.
• b. Red cell survival is shortened with a mild to
moderate decrease in red cell life span, possible due to
a “uremic” toxin.
• c. Blood loss is common in uremic patients, possibly
secondary to abnormal coagulation due to decreased
platelet function.
• d. Marrow space fibrosis occurs with osteitis fibrosa of
secondary hyperparathyroidism resulting in decreased
erythropoiesis.
.
Hypertension:
• Hypertension occurs in 80% to 90% of patients with renal
insufficiency. Several factors contribute:
• a. Expansion of extracellular fluid volume; this may arise
because of reduced ability of the kidney to excrete ingested
sodium.
• b. Increased activity of the renin-angiotensin system is
common; many patients with advanced renal failure have
renin levels that are not completely suppressed by the
elevated blood pressure.
• c. Dysfunction of the autonomic nervous system occurs
with insensitive baroreceptor sensitive and with increased
sympathetic tone.
• d. Possible diminished presence of vasodilators: there may
be decreased renal generation of prostaglandins or of
factors in the kallikrein-kinin system.
PATHOGENESIS OF UREMIC SYNDROME
• Since the uremic syndrome resembles a systemic
intoxication, the search for a putative uremic toxin
has been the subject of intensive investigation
• As yet, however, no single compound has been
found to produce the clinical picture of uremia.
• Therefore it is more likely that multiple factors
contribute to the pathogenesis of this syndrome.
Retained Metabolic Products:
• Many chemical compounds have been suspected to be
responsible for the uremic syndrome.
• However, a distinct relationship between one or a combination
of these substances and the entire syndrome has not been
established in man: This theory is supported by the following
findings
• Marked symptomatic improvement occurs after
decraesing protein in the diet. This suggests that
metabolites of protein are retained in renal failure and exert
toxic effects.
• 2. Effective dialysis results in marked symptomatic
improvement even though protein continues to be
ingested. This suggests that toxic metabolites are removed
by dialysis.
• 3. Uremic plasma seriously interferes with a variety of
normal cell functions. The same plasma after dialysis has
no adverse effects.
Overproduction of Counter-regulatory
Hormones
• In CRF there is overproduction of
parathyroid hormone in response to
hypocalcemia and
• Natriuretic hormone in response to volume
overload
• These hormones have been suggested to
contribute to many aspects of the uremic
state.
Underproduction of Renal Hormones:
• Decreased erythropoietin production
causes anemia.
• Decreased 1-hydroxylation of vitamin D3
contributes to bone disease.
• Clearly, these and other such deficiencies
could play a role in the uremic state
Altered Calcium and Phosphorus Metabolism
(Renal Osteodystrophy):
• As GFR decreases there is a slight
retention of phosphorus.
• Phosphorus retention can lead to
hypocalcemia, which stimulates PTH.
• The latter causes phosphaturia, with
restoration of serum phosphorus and
calcium toward normal.
• However, this occurs only at the expense of
elevated serum PTH levels.
• This cycle repeats itself in progressive renal
failure with PTH levels increasing
progressively
• Ultimately, the renal tubule can no longer
respond to higher levels of PTH with a
further decrease in phosphorus reabsorption
• When this occurs, hyperphosphatemia
develops, hypocalcemia may become
prominent and PTH level can increase to
very high levels.
• High PTH levels cause bone disease with
severe osteitis fibrosa.
• Altered vitamin D metabolism occurs
secondary to decreased renal mass or to
phosphate retention, with decreased
synthesis of 1,25 (OH)2 D3.
• This deficiency leads to:
- Diminished intestinal absorption of calcium
- impaired suppression of PTH secretion for
any increase in serum calcium level and
altered collagen synthesis.
- With advanced renal failure, these events
can lead to secondary hyperparathyroidism
and osteomalacia.
Concluding remarks I
•
•
Normally, the kidney is site of:
fluid and electrolyte regulation
waste-product elimination.
acid-base homeostasis
hormone production and secretion
acid-base homeostasis
In the presence of renal failure, these functions are not
performed adequately and metabolic abnormalities
OCCUR (anemia, acidemia, hyperkalemia,
hyperparathyroidism, malnutrition, and hypertension)
• Uremia usually develops only after the creatinine
clearance falls to less than 10 mL/min, although some
patients may be symptomatic at higher clearance
levels, especially if renal failure acutely develops
Concluding remarks II
• Renal failure can be:
• Acute or Chronic
• The causes can be Pre-renal, Renal or Posrenal
• ARF may progress to CRF
• ARF can occur in the setting of CRF
• The clinical manifestations are due to the
derangement of normal functions of the
kidney