Acute Kidney InjuryAcute Kidney InjuryPatho-physiological Patho-physiological

considerations considerations

Sharma Prabhakar MDSharma Prabhakar MD

DefinitionsDefinitions• Abrupt (<48 hrs) reduction of kidney Abrupt (<48 hrs) reduction of kidney

function with Scr increase of >0.3 mg/dl or function with Scr increase of >0.3 mg/dl or a reduction of urine output <0.5 ml/kg/hr a reduction of urine output <0.5 ml/kg/hr for >6 hrs)for >6 hrs)

• Acute and sustained increase in Scr >0.5 Acute and sustained increase in Scr >0.5 mg/dl if the baseline Scr is <2.5 mg/dl or mg/dl if the baseline Scr is <2.5 mg/dl or >25% increase if the baseline is >2.5 mg/dl>25% increase if the baseline is >2.5 mg/dl

• Associated often with oliguria and heavy Associated often with oliguria and heavy mortalitymortality

• Variable severity and outcomesVariable severity and outcomes

IncidenceIncidence

• Reported rates 100-620 /million/yrReported rates 100-620 /million/yr

• 5-20% of critically ill patients (5.7% 5-20% of critically ill patients (5.7% pts in BEST kidney study)pts in BEST kidney study)

• 20% of all severely septic patients20% of all severely septic patients

• 50% of all patients in septic shock50% of all patients in septic shock• Overall in-hospital incidence at least Overall in-hospital incidence at least

0.5% up to 13% 0.5% up to 13% (the PICARD study group)(the PICARD study group)

Table 1

RIFLE classification

GFR criteria Urine output criteria

Risk SCr > 1.5 times or UO < 0.5 mL/kg/h × 6h

GFR >25%

Injury SCr > 2.0 times or UO < 0.5 mL/kg/h × 12h

GFR >50%

Failure SCr > 3.0 times or UO < 0.3 mL/kg/h × 24h or

GFR >75% or anuria × 12h

SCr > 4.0 mg/dL

Loss Persistent acute renal failure= Complete loss of function for > 4 wks

ESRD End stage renal disease (ESRD) > 3 months

Table 1: RIFLE classification 3.

Abbreviations: sCr: serum creatinine; UO: urinary output; GFR: glomerular filtration

rate; ESRD: end stage renal disease.

Pre-renal azotemiaPre-renal azotemia• Most common cause of ARFMost common cause of ARF• Integrity of renal structure intactIntegrity of renal structure intact• Severe pre-renal state may lead to Severe pre-renal state may lead to

ATN (parts of a spectrum)ATN (parts of a spectrum)• ““Intermediate renal syndrome”Intermediate renal syndrome”• Result in Result in NE, Ang II and ADH levels NE, Ang II and ADH levels

splanchnic and skeletal splanchnic and skeletal vasoconstrictionvasoconstriction

• GFR preserved in mild hypoperfusion GFR preserved in mild hypoperfusion by vasodilatory renal PG, nitric oxide by vasodilatory renal PG, nitric oxide and Ang II, and kinins and Ang II, and kinins

Pre-renal azotemiaPre-renal azotemia• In moderate – severe hypoperfusion, In moderate – severe hypoperfusion,

compensatory responses overwhelmedcompensatory responses overwhelmed

• Autoregulation fails below systolic Autoregulation fails below systolic pressure of 80 mm/Hgpressure of 80 mm/Hg

• Lesser degrees of hypotension trigger Lesser degrees of hypotension trigger prerenal azotemia in elderly, prerenal azotemia in elderly, renovascular disease, DN and renovascular disease, DN and nephrosclerosisnephrosclerosis

• High levels of Ang II (CHF) cause aff High levels of Ang II (CHF) cause aff and eff constriction. and eff constriction.

Pre-renal azotemiaPre-renal azotemia• NSAID’s COX-2 inhibitors impair adaptive NSAID’s COX-2 inhibitors impair adaptive

renal responses by inhibiting renal PG renal responses by inhibiting renal PG synthesis only in hypovolemics and in CKD.synthesis only in hypovolemics and in CKD.

• ACEi and ARBs cause AKI (reversible) in ACEi and ARBs cause AKI (reversible) in patients where renal filtration pressures patients where renal filtration pressures are dependent on ANG effects such as in are dependent on ANG effects such as in hypoperfused states and in RAS.hypoperfused states and in RAS.

• Non-oliguric pre-renal ARF is seen in pts Non-oliguric pre-renal ARF is seen in pts with renal concentration defects (DI) and with renal concentration defects (DI) and solute load (glucose, urea, mannitol)solute load (glucose, urea, mannitol) Hypernatremia is a clue in these states. Hypernatremia is a clue in these states.

Classification and Major Disease Categories Causing Acute Renal Failure

DISEASE CATEGORY% OF PATIENTS WITH ACUTE RENAL FAILURE

1. Prerenal azotemia caused by acute renal hypoperfusion

55–60

2. Intrinsic renal azotemia caused by acute diseases of renal parenchyma

35–40

   Diseases involving large renal vessels  

  Diseases of small renal vessels and glomeruli  

  Acute injury to renal tubules mediated by ischemia or toxins

 

   Acute diseases of the tubulointerstitium  

3. Postrenal azotemia caused by acute obstruction of the urinary collecting system

<5

* More than 90% of cases in the intrinsic renal azotemia category in most series are caused by ischemic or nephrotoxic acute tubule necrosis

Pathophysiology of ATN-Pathophysiology of ATN-HistologyHistology

• Most severe injury in outer medulla Most severe injury in outer medulla (pars recta of the proximal tubule and (pars recta of the proximal tubule and mTAL)mTAL)

• Patchy necrosisPatchy necrosis

• Loss of tubular cells from tubulesLoss of tubular cells from tubules

• Loss of BBM in proximal tubulesLoss of BBM in proximal tubules

• Intratubular casts (THP and cells)Intratubular casts (THP and cells)

• Peritubular congestionPeritubular congestion

ATN-clinical-histological ATN-clinical-histological correlationscorrelations

• Poor structure-function correlationsPoor structure-function correlations• Recent human data suggests subtle changes Recent human data suggests subtle changes

with sublethal injury and apoptosis with sublethal injury and apoptosis contribute significantly to functional lossescontribute significantly to functional losses

• ““ATN” – a misleading term -? AKI ATN” – a misleading term -? AKI (Solez and (Solez and Racussen)Racussen)

• Animal models do not fully replicate human Animal models do not fully replicate human disease. Animals resistant to renal disease. Animals resistant to renal hypoperfusion unless very severe (<20 hypoperfusion unless very severe (<20 mm/Hg). Less severe pressures even if mm/Hg). Less severe pressures even if prolonged do not cause ARF despite PT prolonged do not cause ARF despite PT necrosis.necrosis.

Experimental models-Experimental models- Strengths and Strengths and weaknessesweaknesses

AKI- Overview of pathophysiologyAKI- Overview of pathophysiology

AKI- fate of tubular cellsAKI- fate of tubular cells

Table 27-9   -- Morphologic Differences between Apoptosis and Necrosis

MORPHOLOGIC FEATUREAPOPTOSIS NECROSIS

Cell size Decreased Increased ("oncosis")

Plasma membrane integrity Relatively normal Absent

Plasma membrane "blebbing" Characteristic Absent

Mitochondria Normal appearance Swollen, distorted cristae

Cell-cell adhesion Lost early Remains relatively intact

Cell-matrix adhesion Lost early Lost late

Exfoliation Early (as single cells) Late (as sheets of cells)

Chromatin condensation Characteristic Absent

Nuclear fragmentation Characteristic Absent

Release of cytosolic contents Absent Characteristic

Pattern of cell death in tissueIndividual scattered cells dying asynchronously

Groups of contiguous cells dying together

Tissue inflammation Absent Characteristic

Apoptotic bodies Characteristic Absent

Phagocytosis of dying cells Characteristic Absent

AKI– Oxidative StressAKI– Oxidative Stress

Sublethal tubular injurySublethal tubular injury

Endothelial injury in ATNEndothelial injury in ATN

Sepsis and ATNSepsis and ATN

Organ cross talk in AKIOrgan cross talk in AKI

Major Causes of Acute Intrinsic Renal Azotemia

Diseases Involving Large Renal Vessels

Renal arteries: thrombosis, atheroembolism, thromboembolism, dissection, vasculitis (e.g., Takayasu)

Renal veins: thrombosis, compression

Diseases of Glomeruli and the Renal Microvasculature

Inflammatory: acute or rapidly progressive glomerulonephritis, vasculitis, allograft rejection, radiation

Vasospastic: malignant hypertension, toxemia of pregnancy, scleroderma, hypercalcemia, drugs, radiocontrast agents

Hematologic: hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, hyperviscosity syndromes

Diseases Characterized by Prominent Injury to Renal Tubules Often with Acute Tubule Necrosis †

Ischemia caused by renal hypoperfusion

Exogenous toxins (e.g., antibiotics, anticancer agents, radiocontrast agents, poisons;

Endogenous toxins (e.g., myoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis;

Acute Diseases of the Tubulointerstitium

Allergic interstitial nephritis (e.g., antibiotics, nonsteroidal anti-inflammatory drugs)

Infectious (viral, bacterial, fungal)

Acute cellular allograft rejection

Infiltration ‡ (e.g., lymphoma, leukemia, sarcoid)

Clinical Course of ATNClinical Course of ATN

• Initiation Phase: exposure to Initiation Phase: exposure to ischemia/toxinischemia/toxin

• Maintenance Phase: Oliguria/azotemia 1-Maintenance Phase: Oliguria/azotemia 1-2 wks2 wks

• Recovery (diuretic) Phase : Increasing Recovery (diuretic) Phase : Increasing urine output and decrease in Scrurine output and decrease in Scr

EvaluationEvaluation

• Obstructive causes must be considered Obstructive causes must be considered and excluded especially in the elderlyand excluded especially in the elderly

• Assessment of volume status is often Assessment of volume status is often very difficultvery difficult

• Complete pelvic examination in women Complete pelvic examination in women and a rectal in men is mandatory.and a rectal in men is mandatory.

• Elicit h/o nephrotoxins, consider other Elicit h/o nephrotoxins, consider other renal parenchymal pathology . renal parenchymal pathology .

Evaluation of the progressEvaluation of the progress

• Scr depends on not only renal clearance , Scr depends on not only renal clearance , but also production and vol of but also production and vol of distribution.distribution.

• Most ATN cases increase is 0.3-0.5 Most ATN cases increase is 0.3-0.5 mg/day but slower in pre-renal AKImg/day but slower in pre-renal AKI

• BUN/cr >20 in prerenal, (unreliable)-BUN/cr >20 in prerenal, (unreliable)-exceptionsexceptions

• BUN/cr increased with low muscle mass, BUN/cr increased with low muscle mass, elderly without change in GFR.elderly without change in GFR.

AKI and CancerAKI and Cancer

• Pre-renal: Volume depletion Pre-renal: Volume depletion ( nausea, vomiting) is the most ( nausea, vomiting) is the most common cause of AKI. Others: common cause of AKI. Others: hypercalcemia, NSAIDshypercalcemia, NSAIDs

• Intrinsic renal: renal infiltration by Intrinsic renal: renal infiltration by solid and hematological cancers( 5-solid and hematological cancers( 5-10%) but clinically important in only 10%) but clinically important in only a few. Responds to chemotherapya few. Responds to chemotherapy

AKI and CancerAKI and CancerTumor lysis syndromeTumor lysis syndrome

• Following initiation of therapy for Following initiation of therapy for lympho-proliferative malignancies lympho-proliferative malignancies and solid organ tumors. Rarely and solid organ tumors. Rarely spontaneousspontaneous

• Hyperuricemia, hyperphosphatemia, Hyperuricemia, hyperphosphatemia, hypocalcemiahypocalcemia

• Tubular injury/obstruction by uric Tubular injury/obstruction by uric acid, calcium phosphate crystals.acid, calcium phosphate crystals.

AKI and CancerAKI and Cancer

• Other causes of AKI in cancer: Other causes of AKI in cancer:

- tumor associated GN- tumor associated GN

- TMA (drugs/irradiation)- TMA (drugs/irradiation)

• Multiple MyelomaMultiple Myeloma– Hypovolemia, myeloma kidney, sepsis, Hypovolemia, myeloma kidney, sepsis,

hypercalemia, ATN (drugs/TLS), hypercalemia, ATN (drugs/TLS), infiltration, amyloidosis.infiltration, amyloidosis.

AKI in Chronic liver diseaseAKI in Chronic liver disease

• HypovolemiaHypovolemia

• SepsisSepsis

• Nephrotoxins ( contrast/antibiotics)Nephrotoxins ( contrast/antibiotics)

• GI hemorrhageGI hemorrhage

• Hepatorenal syndromeHepatorenal syndrome

Hepato-renal syndromeHepato-renal syndrome• Irreversible AKI seen in the context of Irreversible AKI seen in the context of

advanced cirrhosis but also seen in acute advanced cirrhosis but also seen in acute fulminant viral/alcoholic hepatitis fulminant viral/alcoholic hepatitis

• Oliguric renal failureOliguric renal failure

• Dys-regulation of circulation : intense Dys-regulation of circulation : intense renal vasoconstriction associated systemic renal vasoconstriction associated systemic vasodilation vasodilation ECBV despite anasarcaECBV despite anasarca

• RAS and SNS activation in early diseaseRAS and SNS activation in early disease

• Role of splanchnic NO in the circulatory Role of splanchnic NO in the circulatory dysregulationdysregulation

Hepato-renal syndromeHepato-renal syndrome• Two forms of HRSTwo forms of HRS

• Type I- rapidly progressive form Type I- rapidly progressive form (Scr<2.5 mg/dl in 2 wks). Fulminant (Scr<2.5 mg/dl in 2 wks). Fulminant course- severe hyperbilirubinemia, course- severe hyperbilirubinemia, death in <monthdeath in <month

• Type II- indolent course, resistant ascitisType II- indolent course, resistant ascitis

• Diagnosis of exclusion (r/o, pre-renal, Diagnosis of exclusion (r/o, pre-renal, ATN)ATN)

• Address precipitating factors (SBP, Address precipitating factors (SBP, drugs)drugs)

Management of prerenal Management of prerenal azotemiaazotemia

• Fluid resuscitation: Type of fluid depends on Fluid resuscitation: Type of fluid depends on the nature of fluid lost (blood, isotonic the nature of fluid lost (blood, isotonic saline)saline)

• Fluid resuscitation with saline or albumin Fluid resuscitation with saline or albumin gave same results in critically ill patients gave same results in critically ill patients (SAFE study)(SAFE study)

• Once established, fluid admn must be Once established, fluid admn must be judicious since pulmonary edema could be judicious since pulmonary edema could be precipitated in patients with oliguria/anuria.precipitated in patients with oliguria/anuria.

Contrast nephropathy-Contrast nephropathy-preventionprevention

• Hydration with isotonic saline is superior Hydration with isotonic saline is superior to the routinely recommended half to the routinely recommended half isotonic saline isotonic saline (Mueller et al, 2002)(Mueller et al, 2002)

• Oral N-acetylcysteine lowers the risk of Oral N-acetylcysteine lowers the risk of CN in CKD CN in CKD ( 3 meta analyses, Birck 2003, Pannu et ( 3 meta analyses, Birck 2003, Pannu et

al 2004al 2004, , Alonso 2004, Isenbarger 2003)Alonso 2004, Isenbarger 2003)

• However the role of N-AC without However the role of N-AC without hydration is questionable ( Lin et al hydration is questionable ( Lin et al 2005)2005)

Diuretics Diuretics

• Once euvolemic, loop diuretics Once euvolemic, loop diuretics promote diuresis in some forms of AKI. promote diuresis in some forms of AKI. (Uchino et al 2004).(Uchino et al 2004). No increased mortality No increased mortality although some smaller studies showed although some smaller studies showed increased death and worsening renal increased death and worsening renal function function (Chertow et al 2004).(Chertow et al 2004).

• Mannitol is renoprotective only in the Mannitol is renoprotective only in the setting of renal transplantation setting of renal transplantation (Reddy (Reddy 2002)2002)

DopamineDopamine

• Renal dose (1-3 mcg/kg/min) of dopamine Renal dose (1-3 mcg/kg/min) of dopamine dilates renal arteries.dilates renal arteries.

• Often used alone or with furosemide in ICU Often used alone or with furosemide in ICU patients to increase urine outputpatients to increase urine output

• Meta-analysis and prospective trials do not Meta-analysis and prospective trials do not support any reno-protective role (Kellum 2001, support any reno-protective role (Kellum 2001, Bellamo 2000)Bellamo 2000)

• Fenoldopam a DA-1 receptor agonist has not Fenoldopam a DA-1 receptor agonist has not proven to be useful ( Bove 2005) in AKI after proven to be useful ( Bove 2005) in AKI after post cardiac surgerypost cardiac surgery

Calcium Channel BlockersCalcium Channel Blockers

• Prophylaxis with calcium channel Prophylaxis with calcium channel blockers protects against post blockers protects against post transplant ATN (Lamiere et al 2001)transplant ATN (Lamiere et al 2001)

• Meta-analysis- benefit unclear Meta-analysis- benefit unclear (Dishart et (Dishart et al 2000)al 2000)

• Post-surgical AKI- data more Post-surgical AKI- data more convincing convincing (Piper et al 2002)(Piper et al 2002)

• No role in established ATNNo role in established ATN

ANPANP

• In patients with established AKI, ANP In patients with established AKI, ANP given iv or intrarenally along with given iv or intrarenally along with furosemide increased GFR acutely with furosemide increased GFR acutely with lasting effects but without survival lasting effects but without survival benefit benefit (Allegren 1997) (Allegren 1997)

• Decreased need for dialysisDecreased need for dialysis• However no benefit in oliguric ATN However no benefit in oliguric ATN

patients. patients. (Sward 2004) (Sward 2004)

• Benefits inconclusiveBenefits inconclusive

IGF-1IGF-1

• IGF-1 given post-op in surgical patients IGF-1 given post-op in surgical patients with renal ischemia prevented the decline with renal ischemia prevented the decline in GFR (Franklin 1997) Incidence of AKI in GFR (Franklin 1997) Incidence of AKI was too low to validate the conclusionwas too low to validate the conclusion

• However IGF did not accelerate the renal However IGF did not accelerate the renal recovery in ICU pts with AKI when IGF was recovery in ICU pts with AKI when IGF was given within 6 days (Hirschberg 1999)given within 6 days (Hirschberg 1999)

• Effects unclearEffects unclear

ThyroxineThyroxine

• Thyroxine speeds up recovery of renal Thyroxine speeds up recovery of renal function in many animal models of AKI function in many animal models of AKI

• Human studies no benefit ( prospective Human studies no benefit ( prospective randomized controlled study of 60 randomized controlled study of 60 patients). In addition there was patients). In addition there was increased morbidity and mortality in increased morbidity and mortality in critically ill patients ( Acker 2000)critically ill patients ( Acker 2000)

Anti-inflammatory agentsAnti-inflammatory agents• Administration of ICAM-1 antibody and Administration of ICAM-1 antibody and

synthetic peptides that inhibit integrins synthetic peptides that inhibit integrins reduce AKI reduce AKI (Goligorsky 1998) (Goligorsky 1998) by decreasing by decreasing intratubular obstruction via inhibition of cell-intratubular obstruction via inhibition of cell-cell adhesion in the tubule. No human cell adhesion in the tubule. No human studies.studies.

• In renal ischemia model of AKI in rats, In renal ischemia model of AKI in rats, --MSH given in multiple doses even after 6 MSH given in multiple doses even after 6 hours, prevented structural and functional hours, prevented structural and functional damage through inhibition of IL-8, ICAM-1 damage through inhibition of IL-8, ICAM-1 and iNOS. and iNOS. (Star 2001)(Star 2001)

 Supportive Management of Intrinsic Acute Renal Failure

COMPLICATIONTREATMENT

Intravascular volume overload Restriction of salt (<1–1.5 g/day) and water (<1 L/day)

 Consider diuretics (usually loops ± thiazide) 200 mg bolus or 20 mg/hr infusion

  Ultrafiltration

Hyponatremia Restriction of oral and intravenous free water

Hyperkalemia Restriction of dietary potassium

  Discontinue K+ supplements or K+-sparing diuretics

  K+-binding resin

  Loop diuretic

  Glucose (50 mL of 50% dextrose) + insulin (10–15 U regular insulin) IV

  Sodium bicarbonate (50–100 mEq IV)

  Calcium gluconate (10 mL of 10% solution over 5 min)

  Dialysis/hemofiltration

Metabolic acidosis Restriction of dietary protein

  Sodium bicarbonate (if HCO3- <15 mEq/L)

  Dialysis/hemofiltration

 Supportive Management of Intinsic Acute Renal Failure

Hyperphosphatemia Restriction of dietary phosphate intake

 Phosphate-binding agents (calcium carbonate, calcium acetate, sevelamer)

HypocalcemiaCalcium carbonate (if symptomatic or sodium bicarbonate is to be administered)

Hypermagnesemia Discontinue magnesium-containing antacids

NutritionRestriction of dietary protein (<0.8 g/kg/day up to 1.5 g/kg/day on continuous venovenous hemodialysis) 25–30 kcal/day

  Enteral route of nutrition preferred

Drug dosageAdjust all doses for glomerular filtration rate and renal replacement modality

Absolute indications for renal replacement therapy

Clinical evidence of uremia, Intractable volume overloadHyperkalemia or severe acidosis resistant to conservative management

Dilaysis for AKIDilaysis for AKI

• Does not hasten recovery, in fact may delay if Does not hasten recovery, in fact may delay if bio-incompatible membranes are employed bio-incompatible membranes are employed

• Early/prophylactic/intensive dialysis not shown Early/prophylactic/intensive dialysis not shown to have significant benefit to have significant benefit (Bonventre NEJM 2002)(Bonventre NEJM 2002)

• Indications for initiation are evidence basedIndications for initiation are evidence based• Effect of choice of dialytic modality or intensity Effect of choice of dialytic modality or intensity

on outcomes unclear.on outcomes unclear.• Choice usually depends on resources available, Choice usually depends on resources available,

expertise of physician and patient’s profile. expertise of physician and patient’s profile.

Indications for the commencement for renal replacement therapy

Refractory fluid overlaod Hyperkalemia > 6.5 mEq/L, or hyperkalemia with electrocardiographic change Severe metabolic acidosis: pH < 7.1 Azotemia (blood urea nitrogen > 100 mg/dL) Uremia signs: pericarditis, encephalopathy, neuropathy Severe dysnatremia (sodium level > 155 mEq/L or < 120 mEq/L) Drugs overdose with dialyzable toxin

Advantage and disadvantage of intermittent (IHD) versus continuous renal replacement therapy (CRRT)

. IHD CRRT

Advantage Availability Better hemodynamic stability

Suitable for severe hyperkalemia Improved nutritional support

Lower cost Better fluid/electrolytes control

Lower risk of systemic bleeding Better cytokines removal

Disadvantage

Hemodynamic instability Vascular access problems

Inadequate dialysis dose High risk of systemic bleeding

Inadequate nutrition support Long term immobilization

Less removal of cytokines More filter problems

Complement activation by Greater cost

non-biocompatible membranes

Dialysis dosing in AKIDialysis dosing in AKI

• Dialysis to give a Ccr of 10 is reasonable initial target Dialysis to give a Ccr of 10 is reasonable initial target (12 hrs/wk) but more dosing needed for (12 hrs/wk) but more dosing needed for hypercatabolic states.hypercatabolic states.

• Kinetic urea models predict 4.4 sessions/wk needed Kinetic urea models predict 4.4 sessions/wk needed to maintain BUNof 60 mg/dl in a 50 kg pt. More to maintain BUNof 60 mg/dl in a 50 kg pt. More aggressive goals are associated with better survival aggressive goals are associated with better survival (Schiffl, NEJM 2002).(Schiffl, NEJM 2002).

Dialysis dosing in AKIDialysis dosing in AKI

• Higher Kt/V associated with improved survival in Higher Kt/V associated with improved survival in AKI except when critically ill AKI except when critically ill ( Himmelfarb 1998 )( Himmelfarb 1998 )

• Daily dialysis was associated with reduced mortality Daily dialysis was associated with reduced mortality in AKI than with in AKI than with qodqod therapy therapy ( Schiffl NEJM 2002)( Schiffl NEJM 2002) in in intermediate severity of illnessintermediate severity of illness

Dialysis dosing in AKIDialysis dosing in AKI

• Reasonable targets:Reasonable targets:– spKt/V of 1.2 or eKt/V of 1.0spKt/V of 1.2 or eKt/V of 1.0– Steady state BUN of 70 mg/dlSteady state BUN of 70 mg/dl

• Prescribed and delivered doses are Prescribed and delivered doses are differentdifferent

• VA-NIH AKI trial: VA-NIH AKI trial: Intensive therapyIntensive therapy ((6/wk) 6/wk) with target Kt/V 1.2-1.4 /tx CRRT 35 ml/kg/h with target Kt/V 1.2-1.4 /tx CRRT 35 ml/kg/h

vs. vs. conventional conventional therapy ( 3/wk) CRRT 20 therapy ( 3/wk) CRRT 20 ml/kg/hml/kg/h

 Dialytic Modalities in Acute Renal Failure

MODALITYDIALYZER PHYSICAL PRINCIPLE

UREA CLEARANCE (mL/min)

MIDDLE MOLECULE CLEARANCE

Hemodialysis

Conventional HemodialyzerIntermittent diffusive clearance and ultrafiltration (UF) concurrently

160 +

Sustained low-efficiency dialysis (SLED)

HemodialyzerIntermittent, but prolonged diffusive clearance and UF concurrently

40 +

Sequential ultrafiltration and clearance

Hemodialyzer Intermittent UF followed by diffusive clearance 160 +

Continuous arteriovenous hemodialysis (CAVHD)

HemofilterSlow diffusive clearance and UF concurrently without a blood pump

17–21 +

Continuous venovenous hemodialysis (CVVHD)

HemofilterSlow diffusive clearance and UF concurrently with a blood pump

17–21 ++

Dialytic Modalities in Acute Renal Failure

Hemofiltration

Continuous arteriovenous hemofiltration (CAVHF)

HemofilterContinuous convective clearance without a blood pump

7–10 ++

Continuous venovenous hemofiltration (CVVHF)

HemofilterContinuous convective clearance with a blood pump

15–17 +++

Continuous venovenous hemodialysis plus hemofiltration (CVVHDF)

HemofilterContinuous convective clearance plus diffusive clearance with a blood pump

25–26 +++

MODALITYDIALYZER PHYSICAL PRINCIPLE

UREA CLEARANCE (mL/min)

MIDDLE MOLECULE CLEARANCE

Dialytic Modalities in Acute Renal Failure

Ultrafiltration

Isolated UF Hemodialyzer Intermittent UF alone - -

Slow continuous UF (SCUF)

Hemofilter

Continuous arteriovenous or venovenous hemofiltration UF alone without convective or diffusive clearance

1–3  

MODALITYDIALYZER PHYSICAL PRINCIPLE

UREA CLEARANCE (mL/min)

MIDDLE MOLECULE CLEARANCE

Dialytic Modalities in Acute Renal Failure

Peritoneal Dialysis

Continuous Peritoneum

Continuous clearance and UF via exchanges performed at varying intervals

<15 +

Intermittent Peritoneum

Intermittent clearance and UF via exchanges performed at varying intervals

<15 +

+, minimal; ++, modest; +++, substantial; -, little to none.

MODALITYDIALYZER PHYSICAL PRINCIPLE

UREA CLEARANCE (mL/min)

MIDDLE MOLECULE CLEARANCE

Dialytic modality and Dialytic modality and survivalsurvival

• Conflicting reportsConflicting reports

• CVVHD vs. HD No evidence of survival CVVHD vs. HD No evidence of survival benefit benefit ( Mehta RL 2001)( Mehta RL 2001) but significant but significant differences between the groupsdifferences between the groups

• Meta-analysis of 6 studies –similar Meta-analysis of 6 studies –similar results results (Tonelli 2002)(Tonelli 2002)

• CRRT is safer in unstable pts but not shown CRRT is safer in unstable pts but not shown to give renal and patient survival benefit.to give renal and patient survival benefit.