Management  of Acute Renal Failure Martin Turman, MD, PhD
Acute Renal Failure <ul><li>Definition: Sudden deterioration in the ability of the kidneys to maintain  fluid,   solute  o...
ARF: Causes and mortality <ul><li>Primary renal disease: 33% </li></ul><ul><ul><li>Hemolytic uremic syndrome: 88% </li></u...
Extrarenal causes of ARF: 67% of total <ul><li>Overall mortality: 62%!! </li></ul><ul><li>In third world: V/D/D-induced AT...
ARF: Risk factors for mortality <ul><li>Multi-organ failure </li></ul><ul><li>Bacterial Sepsis </li></ul><ul><li>Fungal se...
Best cure is to prevent <ul><li>Have a high index of suspicion for reversible factors - volume depletion, decreasing cardi...
Anticipate problems <ul><li>Avoid worsening the ARF </li></ul><ul><ul><li>Adjust medicines for renal insufficiency </li></...
Case #1 <ul><li>ET is a 3 year old who presented with abdominal pain and vomiting for 3 days.  He underwent surgery for in...
How do you proceed from here? <ul><li>General approach to ARF – what is the 1 st  question to ask in the DDx? </li></ul><u...
Prerenal azotemia <ul><li>Decreased effective circulatory volume </li></ul><ul><ul><li>Hypovolemia </li></ul></ul><ul><ul>...
Prerenal azotemia <ul><li>Decreased local blood flow to kidney </li></ul><ul><ul><li>Renal artery stenosis or RVT </li></u...
Postrenal Failure <ul><li>Kidney stone (usually UVJ) </li></ul><ul><li>Ureteropelvic junction (UPJ) or UVJ obstruction </l...
Intrinsic Acute Renal Failure <ul><li>Acute tubular necrosis </li></ul><ul><ul><li>Prolonged prerenal azotemia of any caus...
Evaluation of ARF - 1 <ul><li>In history, seek clues regarding secondary causes - symptoms of CHF, liver disease, sepsis, ...
Evaluation of ARF - 2 <ul><li>During exam, look for secondary causes </li></ul><ul><ul><li>Causes of decreased effective c...
Evaluation for ARF - 3 <ul><li>Lytes, BUN, Cr; CBC with platelets (HUS) </li></ul><ul><li>UA: hematuria, myoglobinuria, pr...
Urinary indices in ARF 40 U/P Cr 20 PR ATN FE-Na 1% 2% FE-Na  = (U/P Na  ÷  U/P Creatinine  ) *100 Adopted from J. Crit. I...
Use of FE-Na <ul><li>FE-Na < 1: Decreased effective blood volume; ATN 2 o  to myo- or hemo-globinuria or contrast dye; sep...
Back to Case #1 (intussuception) <ul><li>ET had no proteinuria and small hematuria on urinalysis. A FE-Na was 0.1%.  A ser...
Clinical Case #2 <ul><li>S.E. is a 10 year-old with acute lymphocytic leukemia receiving chemotherapy </li></ul><ul><li>Ha...
Assessment of case #2 <ul><li>Is she in renal failure? </li></ul><ul><ul><li>Creatinine is normal, so NO! </li></ul></ul><...
Use of plasma BUN: Cr ratio <ul><li>In pre-renal BUN:Cr > 20 usually </li></ul><ul><li>However, BUN may be increased dispr...
Clinical Case #3 <ul><li>CE is a 15 yo male who presented with URI symptoms, then headache, vomiting, abdominal pain, knee...
Physical exam and labs <ul><li>BP was 152/94.  He had anasarca.  Heart and lung exams were normal. </li></ul><ul><li>A uri...
Fluid management in ARF <ul><li>This kid weighs 70 kg.  What percent “maintenance” should you run his IV at? </li></ul><ul...
Fluid management in ARF <ul><li>If this kid had an albumin of 1.0 and mucus membranes were very dry, what fluids would you...
Management of ARF - Volume status <ul><li>Water balance  </li></ul><ul><ul><li>&quot;Maintenance&quot; is IRRELEVANT in AR...
Hypertension <ul><li>Could be from volume overload or from intrinsic renal disease </li></ul><ul><li>If has volume overloa...
Back to Case #3 (nephritis) <ul><li>K+ 6.5,  </li></ul><ul><li>Bicarb 14 </li></ul><ul><li>Calcium 5.8, Phosphorus 9.3 </l...
Hyperkalemia <ul><li>With ARF, K +  will increase and will be worsened by infection, hemolysis, acidosis </li></ul><ul><li...
Hyperkalemia <ul><li>What’s next? </li></ul><ul><ul><li>Shift K +  intracellularly with: </li></ul></ul><ul><ul><ul><li>in...
Hypocalcemia and hyperphosphatemia <ul><li>Ca +2  x PO 4  > 60-70 is risk for metastatic calcification, including in the c...
Hypocalcemia and hyperphosphatemia <ul><li>Reduce PO 4  with calcium acetate if can swallow pills, calcium carbonate if ne...
Acidosis <ul><li>Correct if bicarbonate is < 15 </li></ul><ul><li>Acidosis makes the kids feel terrible </li></ul><ul><li>...
Anemia and uremic bleeding <ul><li>Anemia results from lack of renal erythropoietin production + increased loss </li></ul>...
Indications for renal replacement therapy <ul><li>Volume overload  </li></ul><ul><ul><li>Pulmonary edema, CHF, refractory ...
Modes of renal replacement therapy <ul><li>CVVH, CVVD, CVVDHF - gentle, but slower than hemodialysis; need large lines and...
Unproven or controversial treatments <ul><li>Diuretics could decrease tubular obstruction by helping to &quot;flush out&qu...
Unproven or controversial treatments <ul><li>&quot;Renal dose&quot; dopamine could increase renal perfusion, esp. with con...
Effect of low-dose Dopamine on ARF Adopted from Alkhunaizi & Schrier, Am J Kidney Dis 28:315
Are there any new treatments? <ul><li>MANY in vitro and animal studies of ARF demonstrate improvement with various factors...
New potential therapies <ul><li>Growth factors </li></ul><ul><ul><li>Insulin-like growth factor (IGF-1), epidermal growth ...
New potential therapies <ul><li>Calcium channel blockers </li></ul><ul><ul><li>Most studies demonstrate benefit post trans...
New potential therapies <ul><li>Endothelin antagonists for ATN </li></ul><ul><ul><li>Remarkably effective in animal models...
New potential therapies <ul><li>Atrial natriuretic peptide (ANP) </li></ul><ul><ul><li>ANP dilates afferent & constricts e...
New potential therapies  <ul><li>Anaritide trials </li></ul><ul><ul><li>504 patients with oliguric and non-oliguric ARF (N...
&quot;The great tragedy of Science - the slaying of a beautiful hypothesis by an ugly fact.&quot; T.H. Huxley (1825-1895) ...
The End Any questions???
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11 Turman Management Of Acute Renal Failure In Picu

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11 Turman Management Of Acute Renal Failure In Picu

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

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