Management of Acute Renal Failure

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Management of Acute Renal Failure

• Martin Turman, MD, PhD

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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

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ARF Causes and mortality

• Primary renal disease 33
• Hemolytic uremic syndrome 88
• Obstructive uropathy
• Renal vein/artery thrombosis
• Primary glomerulonephritis (RPGN)
• Overall mortality 6
• Most primary renal diseases develop RF gradually
  and do not need emergent dialysis

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Extrarenal causes of ARF 67 of total

• Overall mortality 62!!
• In third world V/D/D-induced ATN most common
  cause of ARF

Data pooled from Ped. Nephrol. 7703, 8334,
6470, and 7434
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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
  gt 50 compared to lt 20 with non-oliguric ARF

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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

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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)

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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.

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How do you proceed from here?

• General 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?
• BUNCr 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

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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)

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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

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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

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Intrinsic Acute Renal Failure

• Acute tubular necrosis
• Prolonged prerenal azotemia of any cause
• Nephrotoxin-induced (aminoglycosides
  amphotericin)
• Primary glomerular diseases
• Hemolytic uremic syndrome
• All other forms of glomerulonephritis (RPGN)
• Intra-renal obstruction rhabdomyolysis, tumor
  lysis syndrome

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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)

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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

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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

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Urinary indices in ARF
U/P Cr
PR
40
20
ATN
FE-Na
2
FE-Na (U/PNa U/PCreatinine ) 100
1
Adopted from J. Crit. Illness 432
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Use of FE-Na

• FE-Na lt 1 Decreased effective blood volume ATN
  2o to myo- or hemo-globinuria or contrast dye
  sepsis sometimes, CSA, acute glomerulonephritis,
  hepatorenal syndrome
• FE-Na gt 2 ATN, chronic GN, diuretics,
  salt-wasting nephropathy
• Unpredictable Obstructive or reflux nephropathy,
  normal people

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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.

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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

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Assessment of case 2

• Is she in renal failure?
• Creatinine is normal, so NO!
• Why is BUN so high?

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Use of plasma BUN Cr ratio

• In pre-renal BUNCr gt 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).

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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

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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

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Fluid management in ARF

• This kid weighs 70 kg. What percent
  maintenance should you run his IV at?
• NO FLUIDS - Hep-lock it!! Hes fluid overloaded
  and hypertensive he doesnt need any fluid
• How were the maintenance calculations derived?
  What goes into the formula?
• Insensibles UOP maintenance

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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. Hes NPO though, so what fluid rate
  should you run now?
• Insensibles UOP maintenance (i.e. about ¼ to
  1/3 of a normal kids maintenance or 400 cc/M2)

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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

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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

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Back to Case 3 (nephritis)

• K 6.5,
• Bicarb 14
• Calcium 5.8, Phosphorus 9.3
• Hematocrit 30.3, Platelets 280K

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Hyperkalemia

• With 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?
• check EKG for peaked T waves, widened QRS
• Its real. Whats the first thing to do?
• Emergently stabilize membranes with calcium to
  prevent arrhythmia

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Hyperkalemia

• Whats 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
• Whats the third step?
• Remove from body with Lasix, Kayexalate, dialysis

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Hypocalcemia and hyperphosphatemia

• Ca2 x PO4 gt 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)

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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

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Acidosis

• Correct if bicarbonate is lt 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)

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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

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Indications for renal replacement therapy

• Volume overload
• Pulmonary edema, CHF, refractory HTN
• NOT for peripheral edema, esp. with cap. leak
• Hyperkalemia
• Hyperphosphatemia/Hyperuricemia in TLS
• Uremic side-effects ??mentation, sz,
  pericarditis, pleuritis
• Need to maximize nutrition

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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

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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
  1197,2000)
• Still consider if patient is volume overloaded or
  has hyperkalemia

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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
• Its an added expense
• No conclusive clinical studies demonstrating
  benefit

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Effect of low-dose Dopamine on ARF
Adopted from Alkhunaizi Schrier, Am J Kidney
Dis 28315
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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.

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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

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New potential therapies

• Calcium channel blockers
• Most studies demonstrate benefit post transplant
• One small study demonstrates improved GFR after
  malaria-induced 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

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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

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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

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New potential therapies

• Anaritide trials
• 504 patients with oliguric and non-oliguric ARF
  (NEJM 336828, 1997)
• Improved dialysis-free survival in oliguric
  patients (27 vs. 8)
• Worsened outcome for non-oliguric ARF (59 vs.
  48)
• 222 patients (AJKD 36767, 2000) with oliguric
  ARF NO benefit (21 vs. 15)

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"The great tragedy of Science - the slaying of a
beautiful hypothesis by an ugly fact."

• T.H. Huxley (1825-1895) Collected Essays

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The End

• Any questions???