Management of Acute Renal Failure
Martin Turman, MD, PhD
Acute Renal Failure
Definition:
Sudden deterioration in the ability of the kidneys to maintain fluid, solute or electrolyte homeostasis Common in PICU patients (10-20%) Greater than 50% mortality ARF in PICU patients has an independent and significant impact on mortality
ARF: Causes and mortality
Primary
renal disease: 33%
– – – –
Hemolytic uremic syndrome: 88% Obstructive uropathy Renal vein/artery thrombosis Primary glomerulonephritis (RPGN)
mortality: 6% Most primary renal diseases develop RF gradually and do not need emergent dialysis
Overall
Extrarenal causes of ARF: 67% of total
Overall
Other Trauma 15% 6% Liver transplant or failure 16% Post-op heart or other heart failure 32%
mortality: 62%!!
In
Cancer related 14%
Sepsis 17%
third world: V/D/D-induced ATN most common cause of ARF
Data pooled from Ped. Nephrol. 7:703, 8:334, 6:470, and 7:434
ARF: Risk factors for mortality
Multi-organ
failure Bacterial Sepsis Fungal sepsis Hypotension/vasopressors Ventilatory support Initiation of dialysis late in hospital course Oliguria/anuria: with oliguric ARF, mortality is > 50% compared to < 20% with non-oliguric ARF
Best cure is to prevent
Have
a high index of suspicion for reversible factors - volume depletion, decreasing cardiac function, sepsis, urinary tract obstruction Be sure patient is well-hydrated when exposing patient to nephrotoxic drugs
Anticipate problems
Avoid
worsening the ARF
– Adjust medicines for renal insufficiency – Avoid nephrotoxins if possible – Avoid intravascular volume depletion (especially in third-spacing or edematous patients)
Case #1
ET
is a 3 year old who presented with abdominal pain and vomiting for 3 days. He underwent surgery for intussuception. Post-operatively he had oliguria. BUN and creatinine were 80 and 2.5. Sodium was 145. Two 5 cc/kg fluid boluses had minimal effect on urine output. He had anasarca with severe periorbital and pedal edema.
How do you proceed from here?
approach to ARF – what is the 1st question to ask in the DDx? Is it pre-renal, renal or post-renal? What labs help you decide this? BUN:Cr ratio and fractional excretion of sodium (FE-Na) What labs do you need to calculate the FE-Na? urine lytes + urine creatinine near same time as serum lytes to calculate
General
Prerenal azotemia
Decreased
effective circulatory volume
– Hypovolemia
» GI losses (V/D, ileostomy, NG drainage) » Hemorrhage (trauma, GI bleeding) » Cutaneous losses (burns) » Renal losses (diabetes insipidus or mellitus)
– Loss of fluids from intravascular space
» Third spacing » Septic (capillary leak) or anaphylactic shock » Hypoalbuminemia (Neph syndrome, protein-losing enteropathy)
Prerenal azotemia
Decreased
local blood flow to kidney
– Renal artery stenosis or RVT – Drug-induced renal vasoconstriction
» cyclosporin, tacrolimus
– Hepatorenal syndrome
Diminished
cardiac output
– Congestive Heart Failure – Arrythmias, tamponade, etc. – Cardiovascular surgery
Postrenal Failure
Kidney
stone (usually UVJ) Ureteropelvic junction (UPJ) or UVJ obstruction Bladder: "prune belly"; neurogenic bladder; fungus ball Urethra: posterior urethral valve; foreign body Iatrogenic: obstructed Foley; narcotics
Intrinsic Acute Renal Failure
Acute
tubular necrosis (aminoglycosides;
– Prolonged prerenal azotemia of any cause
Nephrotoxin-induced
amphotericin) Primary glomerular diseases
– Hemolytic uremic syndrome – All other forms of glomerulonephritis (RPGN)
Intra-renal obstruction: rhabdomyolysis, tumor lysis syndrome
Evaluation of ARF - 1
In
history, seek clues regarding secondary causes - symptoms of CHF, liver disease, sepsis, systemic vasculitis, prodromal bloody diarrhea; birth asphyxia Check for symptoms of primary renal disease - UTI sx, gross hematuria, flank pain, Hx of strept infection, drug exposure (esp. CSA, aminoglycosides and amphotericin for renal toxins or narcotics for bladder dysfunction)
Evaluation of ARF - 2
During
exam, look for secondary causes
– Causes of decreased effective circulatory volume - CHF, ascites, edema, sepsis – Signs of systemic illness - (vasculitis, SLE, HSP): rash, arthritis, purpura – Signs of RVT and obstructive uropathy: enlarged kidneys or bladder - CHECK FOLEY; Give Narcan
Evaluation for ARF - 3
Lytes,
BUN, Cr; CBC with platelets (HUS) UA: hematuria, myoglobinuria, proteinuria, RBC casts, eosinophils Urine indices Renal US (with Doppler flow to rule out renal vein thrombosis) RPGN evaluation: anti-DNase B, C3, ANA, Anti-GBM, ANCA, renal biopsy
Urinary indices in ARF
U-osm 500 350 U/P Cr U-Na PR 40 ATN 20
PR
40 ATN FE-Na ATN 20
ATN
PR
2%
1% PR
FE-Na = (U/PNa ÷ U/PCreatinine ) *100
Adopted from J. Crit. Illness 4:32
Use of FE-Na
FE-Na
< 1: Decreased effective blood volume; ATN 2o to myo- or hemoglobinuria or contrast dye; sepsis sometimes, CSA, acute glomerulonephritis, hepatorenal syndrome FE-Na > 2: ATN, chronic GN, diuretics, salt-wasting nephropathy Unpredictable: Obstructive or reflux nephropathy, normal people
Back to Case #1 (intussuception)
ET
had no proteinuria and small hematuria on urinalysis. A FE-Na was 0.1%. A serum albumin was 2.2. Thus, he had pre-renal azotemia because of loss of intravascular fluid secondary to hypoalbuminemia and third spacing. After receiving 25% albumin and further fluid resuscitation his UOP and Creatinine normalized.
Clinical Case #2
S.E.
is a 10 year-old with acute lymphocytic leukemia receiving chemotherapy Has fever, neutropenia and thrombocytopenia UOP is 1.2 cc/kg/hour On clinical exam she has very moist mucus membranes BUN and creatinine are 110 and 0.7. Albumin is 3.5
Assessment of case #2
Is
she in renal failure? is BUN so high?
– Creatinine is normal, so NO!
Why
Use of plasma BUN: Cr ratio
In
pre-renal BUN:Cr > 20 usually However, BUN may be increased disproportionately with blood products, excess amino acids in TPN, GI or other bleed; increased catabolism (treatment with steroids, fever).
Clinical Case #3
CE
is a 15 yo male who presented with URI symptoms, then headache, vomiting, abdominal pain, knee pain, edema, and a purpuric rash on his legs. He had not voided for 24 hours. What is diagnosis?
– HSP
Physical exam and labs
BP
was 152/94. He had anasarca. Heart and lung exams were normal. A urinalysis revealed hematuria and proteinuria. BUN and Creatinine were 76 and 8.0. Albumin was 3.1 He has aggressive HSP nephritis
Fluid management in ARF
This
kid weighs 70 kg. What percent “maintenance” should you run his IV at?
– NO FLUIDS - Hep-lock it!! He’s fluid overloaded and hypertensive – he doesn’t need any fluid
How
were the maintenance calculations derived? – What goes into the formula?
– Insensibles + UOP = maintenance
Fluid management in ARF
If
this kid had an albumin of 1.0 and mucus membranes were very dry, what fluids would you give him?
– Bolus of NS like any other dehydrated kid – but cautiously
Now
you have the kid euvolemic by exam but still has no UOP. He’s NPO though, so what fluid rate should you run now?
– Insensibles + UOP = maintenance (i.e. about ¼ to 1/3 of a normal kid’s maintenance or 400 cc/M2)
Management of ARF - Volume status
Water
balance
– "Maintenance" is IRRELEVANT in ARF!!! – If euvolemic, give insensibles + losses + UOP – If volume overloaded, they don't need anything (except the minimum for meds and glucose)
» concentrate all meds; limit oral intake
– Need frequent weights and BP, accurate I/O – Insensibles = 30 cc/100 kcal or 400cc/M2/day – If has any UOP, Lasix + zaroxolyn may help with fluid overload
Hypertension
Could
be from volume overload or from intrinsic renal disease If has volume overload, need to directly vasodilate (calcium channel blockers, clonidine, nicardipine drip, nitropruside, etc.) If intrinsic renal disease, ACE may work also Goal is to prevent stroke, congestive heart failure
Back to Case #3 (nephritis)
K+
6.5, Bicarb 14 Calcium 5.8, Phosphorus 9.3 Hematocrit 30.3%, Platelets 280K
Hyperkalemia
ARF, K+ will increase and will be worsened by infection, hemolysis, acidosis DON'T IGNORE A HIGH K+ just because the specimen is hemolyzed especially in a patient who could easily be hyperkalemic How can you tell if it is “real”?
With
– check EKG for peaked T waves, widened QRS
It’s
real. What’s the first thing to do?
– Emergently stabilize membranes with calcium to prevent arrhythmia
Hyperkalemia
What’s next? – Shift K+ intracellularly with: » insulin (+ glucose to prevent hypoglycemia) » bicarbonate infusion » albuterol (SQ/aerosol) – Check IV fluids to ensure no intake What happens to ionized calcium level as you correct the acidosis? – Increases albumin binding so ionized calcium decreases What’s the third step? – Remove from body with Lasix, Kayexalate, dialysis
Hypocalcemia and hyperphosphatemia
Ca+2 x
PO4 > 60-70 is risk for metastatic calcification, including in the cardiac conduction system Often are reciprocal: as PO4 Ca+ Sx of hypocalcemia: irritability, tetany, sz If hypoalbuminemic:
– check ionized Ca or – correct (0.8 increase of Ca for each 1.0 of albumin below 4)
Hypocalcemia and hyperphosphatemia
Reduce
PO4 with calcium acetate if can swallow pills, calcium carbonate if needs liquid Diet restriction Avoid exogenous PO4: Fleet's, carafate, TPN
Acidosis
Correct
if bicarbonate is < 15 Acidosis makes the kids feel terrible BUT...
– watch sodium and fluid overload – watch lowering ionized calcium levels (by increasing binding of calcium to albumin)
Anemia and uremic bleeding
Anemia
results from lack of renal erythropoietin production + increased loss Underlying disorder may also cause hemolysis (DIC, HUS, SLE) or decreased RBC production (sepsis, leukemia) Uremic PLT's do not function well, so have increased bleeding: treat with cryo-precipitate and DDAVP (causes transient improvement in PLT function; estrogen
Indications for renal replacement therapy
Volume
overload
– Pulmonary edema, CHF, refractory HTN – NOT for peripheral edema, esp. with cap. leak
Hyperkalemia
in TLS Uremic side-effects: mentation, sz, pericarditis, pleuritis Need to maximize nutrition
Hyperphosphatemia/Hyperuricemia
Modes of renal replacement therapy
CVVH,
CVVD, CVVDHF - gentle, but slower than hemodialysis; need large lines and heparin Peritoneal dialysis - also gentle and don't need heparinization but slow and catheter may leak or not work Hemodialysis - very fast, but need big lines and systemic heparinization; causes hemodynamic instability and uremic dysequilibrium symptoms
Unproven or controversial treatments
Diuretics
could decrease tubular obstruction by helping to "flush out" casts – BUT, may worsen electrolyte problems – May cause ototoxicity 126 post-op heart adult patients given Lasix drip – Creatinine 2-fold higher! (Lassnigg, JASN 11:97,2000)
Still
consider if patient is volume overloaded or has hyperkalemia
Unproven or controversial treatments
"Renal
dose" dopamine could increase renal perfusion, esp. with concurrent norepinephrine
– – – – – – Works in animal models, BUT: May depress respiratory drive May trigger arrythmias Induces a state of “hypopituitarism” It’s an added expense No conclusive clinical studies demonstrating benefit
Effect of low-dose Dopamine on ARF
Source Lindner Graziani Lumlertgul Lumlergul Duke Weisberg Type of Study Established ARF Established ARF Established ARF Established ARF Established ARF Prophylaxis IVC Severity Mod-severe Mod-severe Severe Moderate Mild Chronic Efficacy Yes Yes No Yes No No
Adopted from Alkhunaizi & Schrier, Am J Kidney Dis 28:315
Are there any new treatments?
MANY
in vitro and animal studies of ARF demonstrate improvement with various factors
– Glycine, thyroxine, anti-intercellular adhesion molecule-1 (ICAM-1), platelet-activating factor (PAF) antagonist, various growth factors, etc.
New potential therapies
Growth
factors
– Insulin-like growth factor (IGF-1), epidermal growth factor, hepatocyte growth factor » May help in recovery from ARF by improving regeneration, by protecting cells from injury or facilitating their recovery » IGF-1 trial - failed to decrease need for dialysis » GH for critically ill patients WORSENED outcome
New potential therapies
Calcium
channel blockers
– Most studies demonstrate benefit post transplant – One small study demonstrates improved GFR after malariainduced ARF – Conflicting results with contrast-induced ARF – Large meta-analysis showed no prospective placebo-controlled studies have shown benefit – only poorly designed studies did.
CVVH
to remove cytokines, etc. for patients with systemic inflammatory response syndrome
New potential therapies
Endothelin
antagonists for ATN
– Remarkably effective in animal models – Humans with radiocontrast nephrotoxicity: » Multicenter trial » ET antagonist given 30 min before contrast » Agent EXACERBATED renal insufficiency
New potential therapies
Atrial
natriuretic peptide (ANP)
– ANP dilates afferent & constricts efferent
» Leads to increased GFR
– Inhibits vasoconstrictors (endothelin, etc.) – Improves outcome in animals with ATN
New potential therapies
Anaritide
trials
– 504 patients with oliguric and non-oliguric ARF (NEJM 336:828, 1997) » Improved dialysis-free survival in oliguric patients (27% vs. 8%) » Worsened outcome for non-oliguric ARF (59% vs. 48%)
– 222 patients (AJKD 36:767, 2000) with
oliguric ARF – NO benefit (21% vs. 15%)
"The great tragedy of Science - the slaying of a beautiful hypothesis by an ugly fact."
T.H. Huxley (1825-1895) Collected Essays
The End
Any questions???