categories of volume disorders intravascular/acute hemorrhage extracellular –intra- and...
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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
Intracellular25LK
Interstitial12 LNa
Plasma3 L
Protein
Total Body Water (40 L)
ECF (15 L)
Daily Fluid Balance
Total Body WaterInsensible losses200 ml/day/m2 BSA
Intake1-1.5 L (100-200 mEq Na+)
Sweat0.1 L (6 mEq Na+)
Urine1-1.5 L
(100-200 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 100BP sitting 90/50 HR 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 supineLabs: Na+ 130 K+ 2.8
HCO3- 32What 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 HyponatremiaDepartment 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
010203040506070
Volum
e Dep
letio
nCHF
SIADH
Thiaz
ide
diure
tics
Mal
ignan
cy
Alcohol
abuse
Psych
iatri
c his
tory
Multi
fact
orial
Hx Hyp
onat
rem
ia
Per centof Patients
with SymptomaticHyponatremia
27,496 Outpatients• 14% with SNa <134 mEq/L• 4% SNa < 130 mEq/L
J Am Soc Nephrol 16: 531A, 2005.
Diagnostic Evaluation of Hyponatremia
Effective Plasma Osmolality (2×Na + glucose/18)
< 275 mOsm/kgTrue Hyponatremia
Volume DepletedEdematous
Effective VolumeEuvolemic
Uosm >100 mosm/kg
Uosm >100 mosm/kg
Uosm >100 mosm/kg
Uosm <100 mosm/kg
UNa < 15meq/L(Exceptions)
True Volume Depletion
UNa < 15meq/L
CHF CirrhosisNephrosis
UNa > 25 meq/L
SIADHExclude
hypothyroidism and adrenal insufficiency
UNa < 15meq/L
Primary PolydipsiaLow Solute Intake
>290Hypertonic
Hyponatremia(Hyperglycemia) Measured Osm 275-290,
Na+ < 135 & BUN Normal
Pseudohyponatremia
Pseudohyponatremia
N Engl J Med 349: 1465-1469, 2003.
SIADH
2 4 6 8 10 12 14 16 180
140
120
1000
50
0
200
15
17
SNa+
mEq/L
Uosm
mOsm/kg
UNa+ mEq/L
ECF VolL
ADH
Water Restrict
Days
SIADH versus Volume Depletion
Favors SIADH
Serum Uric Acid < 4 mg/dL
FexUA > 10%
BUN < 5 mg/dL
FexUN > 70%
Favors Volume Depletion
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
SIADH
Pulmonary DisordersAcute respiratory failureInfectionsPositive-pressure ventilation
TumorsExtrathoracicMediastinalPulmonary
CNS DisordersAcute psychosisHemorrhageInflammatory and demyelinating diseasesMass lesionsStrokeTrauma
DrugsCarbemazepine OxytocinClofibrate PhenothiazinesCyclophosphamide NSAID’s, Cox-2 I’sDesmopressin SSRI’sNicotine TricyclicsOpiates VincristineMethylenedioxymethamphetamine (Ecstacy)
MiscellaneousHIV infectionPainPostoperative stateNausea
Vigorous exercise
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 EquationGFR 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
*Calculated with the MDRD equation.
2 patients with SCr levels of 1.5 mg/dL (0.133 mmol/L)
FemaleAge = 65 years
MaleAge = 25 years
Estimated GFR*: 73 mL/min
Estimated GFR*: 37 mL/min
Problem with Serum Creatinine in Estimating GFR
0
1
2
3
4
5
6
7
8
10 20 30 40 50 60 70 80 90 100 110 120
Ser
um
cre
atin
ine
(mg
/dL
)
0
0.088
0.176
0.264
0.352
0.44
0.528
0.616
0.704
Ser
um
cre
atin
ine
(mm
ol/
L)
Creatinine 0.5 mg/dL (0.044 mmol/L) to 0.8 mg/dL (0.071 mmol/L)GFR 100 to 60 mL/min
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
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
Nash K, et al. AJKD 2002; 39: 930-936.
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
Medication-Induced AKI in Hospitalized Patients
Nash K et al. AJKD 2002; 39: 930-936.
Medication %
Aminoglycosides 30
Nonsteroidal anti-
inflammatory drugs 21
Piperacillin/tazobactam 11
Amphotericin B 10
Trimethoprim/sulfa 10
Cyclosporine 5
Angiotensin-converting
enzyme inhibitors 3
Multiple nephrotoxins 3
Ciprofloxacin, cis-
platinum, acyclovir,
ceftazidime
1
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 30%– Intrarenal 65%– Postrenal 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 urine5) Review urinary indices
Clinical Approach to Acute Kidney Injury
HistoryVolume status
UltrasoundUrinalysis US shows
Hydronephrosis
Post-Renal
Urinalysis Normal
UrinalysisAbnormal
Tubulointerstial Disorders
Glomerular and Vascular Disorders
Pre-renal
Clinical Approach to Acute Kidney InjuryHistory
Volume StatusUltrasoundUrinalysis
Hydronephrosis
Post-Renal
Prostate disease BPH CancerPelvic malignancyStonesStrictureRetroperitoneal fibrosis
Normal Urinalysis
Pre-Renal
Low ECF Volume GI losses Hemorrhage Diuretics Osmotic diuresis
Altered renal blood flowor hemodynamics Sepsis Heart failure Cirrhosis/Hepatorenal syndrome Hypercalcemia Medications NSAIDs/Cox-2 inhibitors ACE inhibitors Angiotensin II receptor blockers Vascular disease
Vascular Disorders
TubulointerstitialDisorders
Glomerular Disorders
Tubular obstruction Crystals Calcium oxalate (Ethylene glycol, orlistat) Indinivir Acyclovir Methotrexate Tumor lysis syndrome Myeloma cast nephropathy
Acute tubular necrosis Ischemic Nephrotoxic Contrast-induced Rhabdomyolysis
Acute interstitial nephritis Medication-induced Autoimmune Sjogren syndrome Sarcoidosis Infection-related
Arterial Renal artery stenosis Renal artery thromboembolism Fibromuscular dysplasia Takayasu arteritisMedium vessel Polyarteritis nodosa Kawasaki diseaseSmall vessel Glomerulonephritis Thrombotic microangiopathies Cholesterol emboliRenal vein Renal vein thrombosis Abdominal compartment syndrome
Renal parenchymal disorders
Urinalysis abnormal
Pre-renal Azotemia
History Effective Arterial VolumeNormal Renal Ultrasound
Normal Urinalysis
Altered renal blood flowor hemodynamics Sepsis Heart failure Cirrhosis/Hepatorenal syndrome Hypercalcemia Medications NSAIDs/Cox-2 inhibitors ACE inhibitors Angiotensin II receptor blockers Vascular disease
Low ECF Volume GI losses Hemorrhage Diuretics Osmotic diuresis
Intrarenal Acute Kidney Injury
History
Nephrotoxins
Decreased perfusion
Crush injury
Other organ involvement
Volume statusECF usually normal to increased (effective arterial blood volume may be decreased)
Ultrasound Increased echotecture
UrinalysisCasts, cells
Isosthenuria with tubular injury
Urinary IndicesUosm 300-350 UNa+>40 FeNA > 4%
Glomerular disease: often mirror those of pre-renal
Acute Kidney Injury in the ICUDecreased Effect Renal Blood FlowSepsisSystemic inflammationImpaired cardiac output
NephrotoxinsAminoglycosidesAmphotericinFoscarnetRhabdomyolysisIodinated radiocontrast
Pre-renal Azotemia
Acute tubular necrosis
Nephrotoxic tubular injuryIschemic tubular injury
ATN versus Prerenal Azotemia
Indices Prerenal ATN
UNa < 20 > 40
FeNa < 1% > 4%
U/PCreat > 40 < 20
FeUN < 35% >70%
Urine SedimentPre-renalPost-renal
Normal Abnormal
RBCRBC CastsProteinuria
WBCWBC CastsEosinophils
PyelonephritisInterstitial nephritis
Allergic INAtheroemboli
Glomerulonephritis
RTE cellsPigmented casts
Tubular EpithelialInjury -ischemic -nephrotoxic aminoglycoside rhabdomyolysis
GlomerulonephritisVasculitis
Thrombotic microangiopathy
Atheroemboli
Urinalysis Findings in Acute Kidney Injury
Dysmorphic HematuriaRed cell casts
Oval fat bodiesFatty Casts
Muddy brown castsRenal tubular epithelial cells and casts
White cellsWhite cell castsEosinophiluria
MonomorphicHematuria
Crystalluria
Glomerulonephritis
Acute tubular necrosis
Acute interstitial nephritisUrinary tract infection
Obstructing tumorRenal vein thrombosisRenal infarction
Cholesterol emboli
Minimal change diseaseFocal segmental glomerulosclerosis
Thrombotic microangiopathy
Drug toxicityUrate crystals/calcium-phosphate crystals -tumor lysis syndromeCalcium oxalate crystals -ethylene glycol -orlistat
Minimal abnormalities(few cells, minimal protein)
+Blood on dipstick with noRBCs on microscopic
-Protein on dipstick with +Sulfasalicylic acid assay for protein
Pigment nephropathy(Rhabdomyolysis with ATN)
Myeloma cast nephropathy
1+ protein
3+ protein
Obstructing stone
Urinary Sediment Urine DipstickDiagnosis
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
Type of cancer
Risk
High Intermediate Low
NHLBurkitt's, lymphoblastic, B-ALL
DLBCL Indolent NHL
ALL WBC ≥100,000/microL WBC 50,000-100,000/microLWBC ≤50,000/microL
AMLWBC ≥50,000/microL, monoblastic
WBC 10,000-50,000/microLWBC ≤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 syndromeMinor Criteria
• Urine volume < 500 mL/day
• Urine sodium < 10 mEq/L
• Urine osmolality > plasma osmolality
• Urine red blood cells < 50 per high-power 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
Mehran, R. et al. J Am Coll Cardiol 2004;44:1393-1399.
Hypotension
IABP
CHF
Age > 75 years
Anemia
Diabetes
Contrast media volume
Serum creatinine > 1.5 mg/dL
OReGFR<60mL/min/1.73 m2
eGFR (mL/min/1.73 m2) =188 × (SCr)-1.154 × (Age)-0.203
× (0.742 if female) × (1.210 If African American)
Markers Integer Score
5
5
5
4
3
3
1 for each 100 mL
4
2 for 40-604 for 20-406 for < 20
Calculate
Risk
Score
Risk of CIN
Risk of
Dialysis
< 5 7.5% 0.04%
6 to 10 14.0% 0.12%
11 to 16 26.1% 1.09%
> 16 57.3% 12.6%
Risk of CIN vs. Estimated GFR
0
10
20
30
40
50
60
70
10 20 30 40 50 60 70 80 90 100 120
CIN Rate (%)
Estimated GFR (ml/min)
Modified from McCullough PA et al. Am J Cardiol 2006;98[suppl]:27K–36K.
ModerateRisk
HighRisk
DiabetesWithoutDiabetes
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 N-acetylcysteine
Moderate quality
Low risk; possible benefit
May be considered; possible impact
Iso-osmolar and low-osmolar (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 MediaAssess CIN RiskCalculate eGFR
Discontinue metforminDiscontinue NSAIDsDiscontinue diuretics
•Same strategies as eGFR 31-60 mL/min•Consider hospitalization•Nephrology consultation•Dialysis planning
•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
Good clinical practice
eGFR < 30 mL/min eGFR = 31-60 mL/min eGFR > 60 mL/min
Serum Creatinine before discharge and then in 3 days
•Serial serum creatinine and electrolytes•Initially obtain above labs daily
Modified from McCullough PA, et al.Am J Cardiol. 2006; 98:2K-4K.
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
O
NO-
H3C-N H O
N
O
O-
N
N-CH3
H O
OO
N
O
N
O
O-
N
O
O
HO
O-
O-
Gd3+ Gd3+
O
O-
O-
N
N
N
N
O
O-
O
OH
Gd3+
O
O-
O-
N
N
N
N
O
O-
OH
Gd3+
OO
Gadolinium Chelates
Gadodiamide (Omniscan) Gadopentetate dimeglumine (Magnevist)
Gadoterate meglumine (Dotarem) Gadoteridol (ProHance)
Bomgartz G. Mag Reson Mater Phy 2007;20:57-62.
Perazella, M. A. Clin J Am Soc Nephrol 2008;3:649-651
Transmetallationof Gadodiamide
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
CD34 positive staining
From Clev Clin J Med 2008;75:95-111.
Influence of Inflammation on Development of NSF
*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.
Variable Odds Ratio
No. of proinflammatory events* per patient
5.068
No. of MR examinations per patients
2.618
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?
Risk
High
Moderate
CKD: Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 DialysisGFR: > 90 60-90 30-60 15-30 < 15
CIN
NSF
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