Transcript Categories of Volume Disorders

Categories of Volume Disorders
• Intravascular/acute hemorrhage
• Extracellular
– Intra- and extravascular
– Sodium and water loss
• Diarrhea
– Sodium and water gain
• CHF with edema
• Ascites
• Total body water
– Water loss
• Diabetes insipidus
– Water retention
• SIADH
Diagnosis of Volume Disorders
• Intravascular depletion
– MAP = CO × SVR
– Clinical signs
•
•
•
•
BP HR JVP
Cool extremities
Reduced sweating
Dry mucous membranes
• ECF Depletion
– Skin turgor
– Weight
– Hemodynamic effects
Hemodynamic Truths
• Tachycardia is never a good thing.
• Hypotension is always pathologic.
• There is no such thing as normal cardiac
output.
• Central venous pressure is only elevated
in disease.
• Peripheral edema is of cosmetic concern
Pinsky.. Chest. 2007; 132:2020-2029)
Distribution of Total Body
Water
Intracellular
25L
K
Interstitial Plasma
12 L
3L
Na
Protein
Total Body Water (40 L)
ECF (15 L)
Daily Fluid Balance
Intake
1-1.5 L (100-200 mEq Na+)
Insensible losses
200 ml/day/m2 BSA
Total Body Water
Urine
1-1.5 L
(100-200 mEq Na+)
Sweat
0.1 L (6 mEq Na+)
Intravenous Crystalloid
Solutions
5% Dextrose
in Water
0.45% Saline
0.9% Saline
3% Saline
Lactated
Ringer’s
Other names
or
abbreviations
D5W
Half-normal
saline
½ NS
Normal Saline
Isotonic
Saline
NS
Hypertonic
saline
“Hot-salt”
LR
Hartman’s
solution
Dextrose
(gm/dL)
5
0
0
0
0
Na+
(mEq/L)
0
77
154
513
130
Cl(mEq/L)
0
77
154
513
109
K
(mEq/L)
0
0
0
0
4
Ca2+
(mEq/L)
0
0
0
0
3
Lactate
(mEq/L)
0
0
0
0
28
Osmolality
250 mOsm/kg
154 mOsm/kg
308 mOsm/kg
1026 mOsm/kg
274 mOsm/kg
Principles of Treatment
• How much volume?
– Need to estimate volume deficit
• Which fluid?
– Which compartment is predominantly
effected?
– Evaluate acid-base status, electrolytes and
nutrition
Case 1
A 56 y.o. male presents with massive
hematemesis.
PE: Diaphoretic
BP supine 120/70 HR 100
BP sitting 90/50HR 140
Serum Na+ 140
What is the nature of the volume deficit?
What IV fluid would you prescribe?
Case 2
An 28 y.o. intern returns from the intern
beach weekend with intractable nausea
and vomiting.
PE: BP 80/50 HR 130 supine
Labs:
Na+ 130 K+ 2.8
HCO3- 32
What is the nature of the fluid deficit?
What would happen if D5W were
administered?
Case 3
An 85 y.o. nursing home resident with
dementia and a history of diabetes
presents with confusion.
PE: BP supine 110/70 90/50 sitting.
Decreased skin turgor. Wt 60 kg
Labs:
Na+ 150 Glucose 1200
BUN 50/Creat 1.8
How would you treat this patient?
Calculation of Water Deficit
Na × Normal body water = Na × Current body water
140 × NBW = 157 × (0.5 X 60 kg)
NBW = 33.6 L
Water deficit = 33.6 L -30 L = 3.6 L
Case 4
A 40 y.o. patient with cirrhosis and ascites is
admitted with a rising creatinine.
BP 100/70 JVP 5 cm
Tense ascites No edema
BUN 12 Creat 2 Albumin 2
Urine Na 5 mEq/L
Urine volume 200 mL/24 hours
If volume depleted, how would you treat the
patient?
Case 5
A 76 y.o. male with COPD is admitted for
a COPD exacerbation. Oral intake over
the first day of hospitalization has been
poor.
PE Euvolemia
Na 140 K 3.8 BUN 13 Creat 1
What would you choose for maintenance
fluids?
Chronic Hyponatremia:
Epidemiology
• Most common electrolyte disorder,
occurring in 15-30% of hospitalized
patients
• SIADH accounts for 60% of cases of
chronic hyponatremia
Incidence of Hyponatremia
Department
Na <136 mEq/L (%)
Na < 125 mEq/L (%)
Internal medicine
36
4
Surgery
32
2
Cardiology
27
2
Pulmonary
33
3
Intensive care
38
2
Neurology
24
3
Gynecology
35
2
Urology
21
1
Ear, Nose, Throat
20
1
Psychiatry
5
0
All
30
3
Nephrol Dial Transplant 21: 70-76, 2006.
Symptomatic Hyponatremia
Per cent
of Patients
with Symptomatic
Hyponatremia
Vo
lu
m
e
D
ep
l
27,496 Outpatients
• 14% with
SNa <134 mEq/L
• 4% SNa < 130 mEq/L
et
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60
50
40
30
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10
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J Am Soc Nephrol 16: 531A, 2005.
Diagnostic Evaluation of
Hyponatremia
>290
Hypertonic
Hyponatremia
(Hyperglycemia)
Effective Plasma Osmolality (2×Na + glucose/18)
Measured Osm 275-290,
Na+ < 135
& BUN Normal
< 275 mOsm/kg
True Hyponatremia
Pseudohyponatremia
Volume Depleted
Edematous
 Effective Volume
Uosm
>100 mosm/kg
Uosm
>100 mosm/kg
UNa < 15meq/L
(Exceptions)
UNa < 15meq/L
True Volume
Depletion
CHF Cirrhosis
Nephrosis
Euvolemic
Uosm
>100 mosm/kg
UNa > 25 meq/L
SIADH
Exclude
hypothyroidism and
adrenal insufficiency
Uosm
<100 mosm/kg
UNa < 15meq/L
Primary Polydipsia
Low Solute Intake
Pseudohyponatremia
N Engl J Med 349: 1465-1469, 2003.
SIADH
ADH
Water Restrict
SNa+ 140
mEq/L
120
1000
Uosm
mOsm/kg
50
200
UNa+
mEq/L
0
17
ECF Vol
L
15
0
2
4
6
8
10
Days
12
14
16
18
SIADH versus Volume Depletion
Favors SIADH
Favors Volume Depletion
Serum Uric Acid < 4
mg/dL
FexUA > 10%
BUN < 5 mg/dL
FexUN > 70%
Serum Uric Acid > 6
mg/dL
FexUA < 10%
BUN > 15 mg/dL
FexUN < 35%
• Response to 1-2 liters of 0.9% NaCl in patients who are
not symptomatic
Causes of SIADH
Pulmonary Disorders
Acute respiratory failure
Infections
Positive-pressure ventilation
Vigorous exercise
Tumors
Extrathoracic
Mediastinal
Pulmonary
SIADH
Drugs
Carbemazepine
Oxytocin
Clofibrate
Phenothiazines
Cyclophosphamide
NSAID’s, Cox-2 I’s
Desmopressin
SSRI’s
Nicotine
Tricyclics
Opiates
Vincristine
Methylenedioxymethamphetamine (Ecstacy)
CNS Disorders
Acute psychosis
Hemorrhage
Inflammatory and
demyelinating diseases
Mass lesions
Stroke
Trauma
Miscellaneous
HIV infection
Pain
Postoperative state
Nausea
Treatment of Hyponatremia
• Treat symptomatic patients with 3% saline (and
furosemide)
• Stop therapy with 3% saline when symptoms resolve
• Do not exceed 10 mEq/L in 24 hours or 18 mEq/L in
48 hours in a symptomatic patient with chronic
hyponatremia
• Use 0.9% NaCl for asymptomatic hyponatremia due
to volume depletion
• Do not use fluid restriction alone in patients with
symptoms of brain edema
• Do not use 0.9% NaCl for symptomatic patients with
SIADH, especially when the urine osm is > 300
mOsm/kg
• Stop offending drugs whenever possible
Assessment of Renal Function –The
MDRD Equation
• GFR should be estimated by the MDRD
equation in most circumstances
• Should be applied to patients in a steady
state with respect to serum creatinine
concentration
– not valid in the setting of a rising serum creatinine
in acute kidney injury (AKI)
• Less accurate in populations with normal or
near normal GFR, extremes of age and
weight, amputees, in pregnancy and
cirrhosis
– Measure creatinine clearance in these populations
MDRD Equation
GFR in mL/min per 1.73 m2 = 175 x Cr(exp[-1.154]) ×
Age(exp[-0.203]) × (0.742 if female) x (1.21 if black)
www.kidney.org/professionals/KLS/gfr_calculator.cfm
www.nephron.com/mdrd/default.htm
Serum Creatinine (SCr) Alone Is a Poor
Indicator of Kidney Function
2 patients with SCr levels of 1.5 mg/dL (0.133 mmol/L)
Male
Age = 25 years
Female
Age = 65 years
Estimated GFR*:
73 mL/min
Estimated GFR*:
37 mL/min
*Calculated with the MDRD equation.
8
0.704
7
0.616
6
Creatinine
5
GFR
0.5 mg/dL (0.044 mmol/L) to
0.8 mg/dL (0.071 mmol/L)
100 to 60 mL/min
0.528
0.44
4
0.352
3
0.264
2
0.176
1
0.088
0
0
10
20
30
40
50
60
70
80
90
100 110 120
Serum creatinine (mmol/L)
Serum creatinine (mg/dL)
Problem with Serum Creatinine
in Estimating GFR
Cystatin C
• More sensitive in identifying milder
impairments in renal function than
serum creatinine
• Cystatin C-based equations may more
accurate in the elderly and in patients
with cirrhosis
• Levels are affected by thyroid status,
inflammation, and corticosteroids
• Clinical utility remains to be
established
Plot of GFR vs. Time in Patients with
CKD
eGFR (ml/min)
Chart
eGFR=10
Title in 4-09
40
30
20
10
0
6
7
8
5
6
7
4
5
8
0
0
0
0
0
0
0
0
0
09
0
0
0
0
0
0
0
0
0
0
2
2
2
2
2
/2 6/2
/ 2 4 /2 1/2
8
8
1/ 17/
5/ 24/ 10 /
/
/
/
/
1
1
2
/
/
/
/
/
/
8
9
6
7
2
3
4
10
11
12
Date
Key Points
• The estimated GFR should be calculated
using the MDRD equation whenever a serum
creatinine is measured in steady state
conditions
• Plots of GFR vs. time are helpful in patient
management and education
• Consider 24 hour urine collections for
creatinine clearance in the following
populations:
–
–
–
–
–
Near normal GFR
Extremes of age and weight
Amputees
Pregnant women
Cirrhotics
Etiology of Hospital Acquired AKI
Cause
% (n=377)
Mortality
Decreased renal perfusion
39
13.6
Medications
16
15
Radiographic contrast media
11
14
Postoperative
9
2.8
Sepsis
7
76
Post–liver transplantation
4
28.6
Post–heart transplantation
2
37.5
Obstruction
2
28.6
Hepatorenal
2
71.4
Rhabdomyolysis
1
25
Glomerulonephritis
1
33.3
Nash K, et al. AJKD 2002; 39: 930-936.
Medication-Induced AKI in
Hospitalized Patients
Medication
%
Aminoglycosides
30
Nonsteroidal antiinflammatory drugs
21
Piperacillin/tazobactam
11
Amphotericin B
10
Trimethoprim/sulfa
10
Cyclosporine
5
Angiotensin-converting
enzyme inhibitors
3
Multiple nephrotoxins
3
Ciprofloxacin, cisplatinum, acyclovir,
ceftazidime
1
Nash K et al. AJKD 2002; 39: 930-936.
Acute Kidney Injury
• Prevalence
– 1% all patients admitted to hospital
– 10-30% patients admitted to ICU
• Etiology
– Hemodynamic 30%
– Parenchymal 65%
• Acute tubular necrosis 55%
• Acute glomerulonephritis 5%
• Vasculopathy 3%
• Acute interstitial nephritis 2%
– Obstruction 5%
Evaluation of Renal Failure
• Is the renal failure acute or chronic?
– laboratory values do not discriminate between
acute vs. chronic
– oliguria supports a diagnosis of acute renal
failure
– small kidneys on US more common in chronic
renal failure
• What is the etiology of the renal failure?
– Prerenal
– Intrarenal
– Postrenal
30%
65%
5%
5 Key Steps in Evaluating
Acute Kidney Injury
1) Obtain a thorough history; review
the chart in detail
2) Do everything you can to
accurately assess volume status
3) Always order a renal ultrasound
4) Look at the urine
5) Review urinary indices
Clinical Approach to Acute Kidney Injury
History
Volume status
Ultrasound
Urinalysis
Urinalysis Normal
US shows
Hydronephrosis
Urinalysis
Abnormal
Post-Renal
Pre-renal
Tubulointerstial
Disorders
Glomerular and
Vascular Disorders
Clinical Approach to Acute Kidney Injury
History
Volume Status
Ultrasound
Urinalysis
Normal Urinalysis
Pre-Renal
Low ECF Volume
GI losses
Hemorrhage
Diuretics
Osmotic diuresis
Urinalysis abnormal
Altered renal blood flow
or hemodynamics
Sepsis
Heart failure
Cirrhosis/Hepatorenal syndrome
Hypercalcemia
Medications
NSAIDs/Cox-2 inhibitors
ACE inhibitors
Angiotensin II receptor blockers
Vascular disease
Tubular obstruction
Crystals
Calcium oxalate
(Ethylene glycol,
orlistat)
Indinivir
Acyclovir
Methotrexate
Tumor lysis syndrome
Myeloma cast
nephropathy
Hydronephrosis
Renal parenchymal disorders
Tubulointerstitial
Disorders
Glomerular
Disorders
Acute tubular necrosis
Ischemic
Nephrotoxic
Contrast-induced
Rhabdomyolysis
Acute interstitial nephritis
Medication-induced
Autoimmune
Sjogren syndrome
Sarcoidosis
Infection-related
Vascular Disorders
Arterial
Renal artery stenosis
Renal artery thromboembolism
Fibromuscular dysplasia
Takayasu arteritis
Medium vessel
Polyarteritis nodosa
Kawasaki disease
Small vessel
Glomerulonephritis
Thrombotic microangiopathies
Cholesterol emboli
Renal vein
Renal vein thrombosis
Abdominal compartment syndrome
Post-Renal
Prostate disease
BPH
Cancer
Pelvic malignancy
Stones
Stricture
Retroperitoneal fibrosis
Pre-renal Azotemia
History
 Effective Arterial Volume
Normal Renal Ultrasound
Normal Urinalysis
Low ECF Volume
GI losses
Hemorrhage
Diuretics
Osmotic diuresis
Altered renal blood flow
or hemodynamics
Sepsis
Heart failure
Cirrhosis/Hepatorenal syndrome
Hypercalcemia
Medications
NSAIDs/Cox-2 inhibitors
ACE inhibitors
Angiotensin II receptor blockers
Vascular disease
Intrarenal Acute Kidney Injury
History
Volume status
Nephrotoxins
Decreased perfusion
Crush injury
Other organ involvement
ECF usually normal to increased
(effective arterial blood volume may be
decreased)
Ultrasound
Increased echotecture
Urinalysis
Casts, cells
Isosthenuria with tubular injury
Urinary Indices
Uosm 300-350 UNa+>40 FeNA > 4%
Glomerular disease: often mirror those
of pre-renal
Acute Kidney Injury in the ICU
Decreased Effect Renal Blood Flow
Sepsis
Systemic inflammation
Impaired cardiac output
Nephrotoxins
Aminoglycosides
Amphotericin
Foscarnet
Rhabdomyolysis
Iodinated radiocontrast
Pre-renal Azotemia
Ischemic tubular injury
Nephrotoxic tubular injury
Acute tubular necrosis
ATN versus Prerenal Azotemia
Indices
Prerenal
ATN
UNa
< 20
> 40
FeNa
< 1%
> 4%
U/PCreat
> 40
< 20
FeUN
< 35%
>70%
Urine Sediment
Pre-renal
Post-renal
RBC
RBC Casts
Proteinuria
Glomerulonephritis
Vasculitis
Thrombotic
microangiopathy
Atheroemboli
Abnormal
Normal
WBC
WBC Casts
Eosinophils
Pyelonephritis
Interstitial nephritis
Allergic IN
Atheroemboli
Glomerulonephritis
RTE cells
Pigmented casts
Tubular Epithelial
Injury
-ischemic
-nephrotoxic
 aminoglycoside
 rhabdomyolysis
Urinalysis Findings in Acute Kidney Injury
Urinary Sediment
Dysmorphic Hematuria
Red cell casts
Oval fat bodies
Fatty Casts
Muddy brown casts
Renal tubular epithelial
cells and casts
White cells
White cell casts
Eosinophiluria
Diagnosis
Glomerulonephritis
Urine Dipstick
3+ protein
Minimal change disease
Focal segmental
glomerulosclerosis
Acute tubular necrosis
1+ protein
Acute interstitial nephritis
Urinary tract infection
Cholesterol emboli
Minimal abnormalities
(few cells,
minimal protein)
Thrombotic microangiopathy
Pigment nephropathy
(Rhabdomyolysis with ATN)
Crystalluria
Monomorphic
Hematuria
+Blood on dipstick with no
RBCs on microscopic
Drug toxicity
Urate crystals/calcium-phosphate crystals
-tumor lysis syndrome
Calcium oxalate crystals
-ethylene glycol
-orlistat
Obstructing stone
Obstructing tumor
Renal vein thrombosis
Renal infarction
Myeloma cast nephropathy
-Protein on dipstick with
+Sulfasalicylic acid assay
for protein
Key Points on Medication-induced
AKI
• Medications are the second most common
cause of cause of AKI in hospitalized
patients (pre-renal azotemia is #1)
– THINK DRUGS
• NSAIDs can result in significant
nephrotoxicity in the elderly, and in patients
with diabetes and/or CKD
• Consider AIN in patients on PPI’s with
unexplained kidney injury and pyuria
• Use of oral phosphasoda preparations for
bowel prep should be abandoned-use PEG
based preps
Renal Biopsy-When?
• Exclude pre- and post-renal failure, and
clinical findings are not typical for ATN
• Extra-renal manifestations that suggest a
systemic disorder
• Heavy proteinuria
• RBC casts
Tumor Lysis Syndrome
• Acute oliguric renal failure associated with urate
levels > 15 mg/dl and hyperphosphatemia
• Associated with overproduction and excretion of
urate and cell lysis resulting in increased release
of potassium and phosphorus in patients
undergoing chemotherapy or with a heavy tumor
burden
• Urine urate/creatinine > 1
• Urinary alkalinization may worsen calcium
phosphate precipitation and NS is as effective as
urinary alkalinization alone
• Early dialysis indicated for oliguric AKI to
decrease urate burden
Risk Stratification for TLS
Risk
Type of cancer
High
Intermediate
Low
NHL
Burkitt's, lymphoblastic, B-ALL
DLBCL
Indolent NHL
ALL
WBC ≥100,000/microL
WBC 50,000-100,000/microL
WBC
≤50,000/microL
AML
WBC ≥50,000/microL,
monoblastic
WBC 10,000-50,000/microL
WBC
≤10,000/microL
CLL
WBC 10,000-100,000/microL
treated with fludarabine
WBC
≤10,000/microL
Other
hematologic
malignancies
(including CML
and multiple
myeloma) and
solid tumors
Rapid proliferation with
expected rapid response to
therapy
Remainder of
patients
*From Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the
management of pediatric and adult tumor lysis syndrome: an evidence-based
review. J Clin Oncol. 2008; 26:2767-78.
Prevention of TLS
• If there is a concern about tumor lysis, as predicted by an
elevated serum LDH, serum uric acid, or heavy tumor burden,
the patient should be admitted for hydration and close
monitoring of kidney function, serum potassium, phosphorus
and uric acid.
• Patients with a preexisting reduction in GFR, oliguria and/or
acidic urine, and volume depletion should also be hospitalized
for hydration and observation.
• High-risk patients should be hospitalized for aggressive
intravenous hydration and prophylactic rasburicase.
• Intermediate risk patients should receive allopurinol rather than
rasburicase for prophylaxis in the absence of pretreatment
hyperuricemia.
• Patients at low risk for TLS should receive hydration, but do
not require hypouricemic therapy.
Renal Disease Associated
with Multiple Myeloma
• Myeloma cast nephropathy
– direct precipitation of casts in tubules
– Factors favoring cast precipitation:
-affinity of light chains for Tamm-Horsfall protein
-high luminal Cl-volume depletion
– Plasmapheresis may be beneficial
• Hypercalcemic nephropathy
• Glomerular lesions (MPGN, Amyloid, Light chain
deposition disease)
Acute Glomerulopathies
• RPGN most commonly seen with:
– Lupus nephritis (DPGN, class IV)
– Pauci-immune GN (ANCA associated)
– Anti-GBM disease
– less commonly: IgA, post-infectious
• Nephrotic presentations of ARF
– Collapsing FSGS (HIV nephropathy)
– Minimal change disease with ATN
• Thrombotic microangiopathies (HUS, TTP, malignant
hypertension, scleroderma kidney, pre-eclampsia)
Atheroembolic Renal Disease
• ARF in patient with erosive atherosclerosis
• Often follows aortic manipulation (angiography,
surgery, trauma) or anticoagulation
• Pattern is often an acute worsening of renal function
due to showering of emboli, followed by more
insidious progression over several weeks to months
due to ongoing embolization of atheromatous
plaques
• Livedo reticularis, Hollenhorst plaques
• Nephritic sediment, eosinophilia, eosinophiluria, low
C3
• Poor prognosis
Diagnostic Criteria for
Hepatorenal Syndrome
• Cirrhosis with ascites
• Serum creatinine >1.5 mg/dL (>133 µmol/L)
• No improvement of serum creatinine (decrease to a level of <
1.5 mg/dL) after at least 2 days with diuretic withdrawal and
volume expansion with albumin. The recommended dose of
albumin is 1 g/kg of body weight per day up to a maximum of
100 g/day.
• Absence of shock.
• No current or recent treatment with nephrotoxic drugs.
Absence of parenchymal kidney disease as indicated by
proteinuria >500 mg/day, microhematuria (>50 red blood cells
per high power field) and/or abnormal renal ultrasonography.
Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V: Diagnosis, prevention and treatment of
hepatorenal syndrome in cirrhosis. Gut 2007: 56: 1310-8.
Hepatorenal syndrome
Minor Criteria
•
•
•
•
•
Urine volume < 500 mL/day
Urine sodium < 10 mEq/L
Urine osmolality > plasma osmolality
Urine red blood cells < 50 per highpower field
Serum sodium concentration < 130
mEq/L
Vasoconstriction in Hepatorenal
Syndrome
Contrast-Induced Nephropathy
(CIN)
• Most common definitions
– absolute increase in serum creatinine level
of 0.5 to 1 mg/dL (0.044 -0.088 mmol/L)
within 48-72 hours
– 25% increase in serum creatinine level
within 48-72 hours
• Accounts for 12% of cases of acute
kidney injury
• Marker for increased mortality
Contrast-Induced Nephropathy Risk Score
in Patients Undergoing Coronary Angiography
Markers
Integer Score
Hypotension
5
IABP
5
CHF
Age > 75 years
5
Risk
Score
Risk of
CIN
Risk of
Dialysis
4
<5
7.5%
0.04%
6 to 10
14.0%
0.12%
11 to 16
26.1%
1.09%
> 16
57.3%
12.6%
Anemia
3
Diabetes
3
Contrast media volume
Serum creatinine > 1.5 mg/dL
OR
eGFR<60mL/min/1.73
m2
Calculate
1 for each 100 mL
4
2 for 40-60
4 for 20-40
6 for < 20
eGFR (mL/min/1.73 m2) =
188 × (SCr)-1.154 × (Age)-0.203
× (0.742 if female) × (1.210
If African American)
Mehran, R. et al. J Am Coll Cardiol 2004;44:1393-1399.
Risk of CIN vs. Estimated
GFR
70
60
High
50 Risk
Moderate
Risk
CIN Rate (%)
40
30
20
Diabetes
Without
Diabetes
10
0
10 20 30 40 50 60 70 80 90 100 120
Estimated GFR (ml/min)
Modified from McCullough PA et al. Am J Cardiol 2006;98[suppl]:27K–36K.
Intervention
Quality of
Evidence
Benefit
Recommendation
Volume
expansion with
normal saline
Moderate
quality
Clear
Indicated and acceptable
Volume
expansion with
NaHCO3
Moderate
quality
Clear
Indicated and acceptable
Oral Nacetylcysteine
Moderate
quality
Low risk;
possible
benefit
May be considered; possible impact
Iso-osmolar
and lowosmolar (vs.
high osmolar)
Moderate
quality
Clear
Indicated and acceptable in high risk
patients
Iso-osmolar vs.
low-osmolar
contrast
Moderate
quality
Unclear
Use of either agent in high risk
patients is acceptable based on
available evidence
Oral hydration
(vs. iv
hydration)
Low quality
Unclear
Insufficient evidence to recommend
Management of Patients Receiving Iodinated Contrast Media
Assess CIN Risk
Calculate eGFR
Discontinue metformin
Discontinue NSAIDs
Discontinue diuretics
eGFR < 30 mL/min
•Same strategies as
eGFR 31-60 mL/min
•Consider hospitalization
•Nephrology consultation
•Dialysis planning
•Serial serum creatinine
and electrolytes
•Initially obtain above labs
daily
Modified from McCullough PA, et al.
Am J Cardiol. 2006; 98:2K-4K.
eGFR = 31-60 mL/min
eGFR > 60 mL/min
•Isotonic NaCl or NaHCO3
at 1-1.5 mL/kg/hr
•Optimize cardiac output
•Use non-ionic low osmolar or
iso-osmolar contrast
•Limit contrast volume to <100 mL
•Consider NAC 600-1200 mg 2X/d
one day prior to and 2X/d on day
of study
•Avoid repeat contrast exposures
over course of next 4 weeks
when possible
Serum Creatinine before
discharge and then in 3 days
Good clinical practice
Withdrawal of Medications Around the
Time of Contrasted Studies
• NSAIDs and Cox-2 inhibitors
– Hold 1 day prior to the study until there is confirmation that
CIN has not occurred
• Metformin
– Hold 1 day prior to the study until there is confirmation that
CIN has not occurred
• Diuretics
– May be detrimental
– Hold for 1 day prior to the procedure and restart 1 day
following the procedure
• ACE inhibitors and ARBs
– No data available – reasonable to continue during the
procedure in the absence of hypotension or recent acute
change in renal function
Interventions to Limit Risk of
CIN-Key Points
• Optimize the effective circulating volume
– Delay studies in patients with volume depletion,
circulatory collapse or decompensated
congestive heart failure when possible
– Optimize congestive heart failure when possible
• Hydration with isotonic saline or sodium
bicarbonate 1-1.5 ml/kg/hr starting 3-12
hours prior to the study and continuing for at
least 12 hours after the study in moderate
risk patients
Interventions to Limit Risk of
CIN-Key Points
• N-acetylcysteine 600-1200 mg twice
daily starting one day prior to and twice
daily on the day of the study is
reasonable
• Use minimal volumes of low osmolar or
iso-osmolar non-ionic contrast
Nephrotoxicity of Gadolinium
• Ergün et al. Nephrol Dial Transplant 2006; 21: 697–
700.
– Retrospective review 473 patients with stage 3-4
CKD receiving intravenous gadolinium at a dose
of 0.2 mmol/kg body weight (gadopentetate
dimeglumine, gadodiamide and gadoterate
meglumine)
– AKI defined as a 0.5 mg/dL rise in serum
creatinine
• Frequency of AKI was 12.1%
• Older age, low baseline creatinine clearance,
diabetic nephropathy and lower hemoglobin and
albumin levels were risk factors for AKI.
Gadolinium and Nephrogenic
Systemic Fibrosis
• Gadolinium was initially thought to be safe in renal
disease and was widely used
• An unusual skin condition first identified in 1997
appeared in dialysis patients initially called
nephrogenic fibrosing dermopathy, and more
recently nephrogenic systemic fibrosis (NSF) or
gadolinium-associated systemic fibrosis
• Nearly all patients with NSF have been exposed to
gadolinium-based contrast agents and an
association was first noted in 2006
• Usually seen in patients with advanced kidney
disease
• Gadolinium has been found in tissue of patients with
NSF
Gadolinium Chelates
Gadodiamide (Omniscan) Gadopentetate dimeglumine (Magnevist)
O
O
O-
O
O
-
O
N
N
Gd3+
H3C-N
H O
O-
N-CH3
H
O
N
N
N
OH
O
N
N
O-
N
Gd3+
HO
O
O
O
O-
N
N
OH
N
O-
Gd3+
Gd3+
O-
O
O-
N
O
O
O-
O
N
O-
O
OO
N
O
Gadoterate meglumine (Dotarem) Gadoteridol (ProHance)
Bomgartz G. Mag Reson Mater Phy 2007;20:57-62.
Transmetallation
of Gadodiamide
Perazella, M. A. Clin J Am Soc Nephrol 2008;3:649-651
Nephrogenic Systemic
Fibrosis
• Plaques, papules and nodules with a brawny
wooden texture
• Starts symmetrically in legs, and may then
involve the arms and trunk. The face is
spared.
• Skin and periarticular fibrosis
• Heart, lungs, skeletal muscle and diaphragm
can be involved
• Associated with increased mortality (50% at
2 years, most deaths occurring within 6
months of diagnosis )
Nephrogenic Systemic
Fibrosis
From Clev Clin J Med 2008;75:95-111.
CD34 positive staining
Influence of Inflammation on
Development of NSF
Variable
Odds Ratio
No. of proinflammatory
events* per patient
No. of MR examinations
per patients
5.068
2.618
*Proinflammatory event defined as all processes in which the
body has sustained major tissue injury, such as vascular
surgery, transplantation surgery, or other major surgery; sepsis,
pneumonia, osteomyelitis, or other major infection; and arterial
or venous thrombosis that has caused ischemia or organ or limb
damage.
Sadowski EA et al. Radiology 2007;243:148-157.
NSF: Risk Factors
• Usually seen in stage IV-V CKD and
severe AKI, but has been described in
earlier stages (5-15% incidence and RR
10.7 in stage V disease)
• More patients with CKD have been
exposed to gadodiamide (Omniscan) at
higher doses (MRA)
• Active inflammation (recent surgery,
infection)
Dialysis and Gadolinium
• Gadolinium-chelates rapidly equilibrate
in the extracellular space and are
excreted unchanged in the glomerular
filtrate
• 65-80% is removed in a single
hemodialysis session
• Peritoneal dialysis does not efficiently
remove gadolinium-chelates
Recommendations Regarding
Gadolinium-Key Points
• Evaluate patients for renal dysfunction prior to
giving GBCA
• Avoid in patients with acute or chronic kidney
disease when the eGFR is < 30 ml/min
• Strictly avoid in the setting of hepatorenal syndrome
or in the perioperative period of liver transplant
• When use is deemed essential in high risk patients,
an agent other than gadodiamide should be used at
the lowest possible dose
• Obtain informed consent
• For ESRD patients, dialysis should be performed
within 24 hours on 2 consecutive days
Gadolinium and Iodinated Contrast:
When are they Unsafe?
High
NSF
Risk
CIN
Moderate
CKD: Stage 1
GFR: > 90
Stage 2
60-90
Stage 3
30-60
Stage 4
15-30
Stage 5
< 15
Dialysis