advances in acute renal failure acute renal failure first proposed by homer smith text book: ‘the...
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Advances in Acute renal failure
Acute renal failure first proposed by Homer Smith
Text book: ‘The Kidney Structure and Function in Health and Disease1951
35 definitions in literature(Kellum et al. Curr Opin Crit Care 2002;8:509-514)
35 definitions in literature(Kellum et al. Curr Opin Crit Care 2002;8:509-514)
Prevalence: 1 to 25% in ICUMortality: 15 to 60% Prevalence: 1 to 25% in ICUMortality: 15 to 60%
Why ‘RIFLE’ Criteria
ARDS & Sepsis: Definitions not perfect; but found to be useful
Need to classify the severity of syndrome; rather than only severest form
ARF= Dialysis dependence
Lack of single definition Held ARF research 20 years back
(Bellomo R et al. Intensive Care Med. 2001 Nov;27(11):1685-8)
Citated till now in 546 articles
Severity classes
Outcome classes
Oliguria/ARF
Decline in GFR Abrupt; 1 to 7 daysAt all levels Both UOP & S. Cr Change sustained for >24
hours.
Relationship between S. Cr & GFR Depends on the phase of recovering renal failure
Certainly steady state often not reached
Both S. Cr & GFR changes Always be considered in terms of the baseline
When baseline is unknown or confronted with a patient who has elevated S.Cr ??? Suggestion MDRD formula
Oliguria insensitive marker: many patients remain non-oliguric
Conventional definitionRapid decline hours to weeks
Decline in GFRRetention of nitrogenous waste products
1. Fails to describe dynamic process initiation, maintenance & recovery2. Emphasis on overt failure of kidneys; belies that mild decrement of renal function A/w cardiac eventsHoste et al. : Only 14% of patients of ‘F’ Received dialysis;
but 5 times hospital mortality (Crit Care 2006; 10: R73)
AKI Incidence by RIFLE : 2-10 times higher than conventional definition
No AKI Risk Injury Failure5.5% 8.8% 11.4% 26.3%
Relationship: RIFLE class V/s Outcome Six studies
Hoste EA Curr Opin Crit Care 2006; 12; 531-537
Mortality
Limitations of RIFLEUrine output
Diuretic use: sensitivity & specifictyFor accurate measurement: requires catheter
Hoste (Crit Care 2006:10:R73) Uchino (Crit Care Med 2006:34:1913-1917)
S. Cr + UOP S.CrMortality: 8.8%, 11.4%; 26.3% 15.1%; 29.2%; 41.1%
Need to know baseline S.CrNot always known
RIFLE advises to use MDRD; MDRD for CKD
RIFLE Version 1.2 or AKIN Stages
Stages 1,2 and 3 instead of R. I and F Bagshaw et al. **Increase in S. Cr at least 0.3 mg/dL even if it does not reach 50% threshold
Increase in sensitivity by 1%
A 48 hour window on first documentation of any criteria
Caution: May exclude patients that should be included in AKI diagnosis
Use of RRT, classifies patient to ‘F’ regardless of S.Cr or UOP
-
NDT 2008; 23 (5);1564-1579
**
JAMA 2005;294:813-818
29,269 patients in ICUs Largest prospective study
Period prevalence 5.7% (1.4 to 25.9%)
Median age 67 years
Contributing factors Septic shock (47.5%)Major surgery, Cardiogenic shock
Mortality 60.3%
Septic patients 70.2%
618 patients in ICUs
Mean age 59.5 years
Co-morbidities CKD 30%CAD 37%DM 29%
In-hospital mortality 37%
AKI superimposed on CKD lower mortality than AKI
Nature Reviews Nephrology 2006, 2 (7) 364
Nature Reviews Nephrology 2006, 2 (7) 364
Hospital incidence
Nature Reviews Nephrology 2006, 2 (7) 364
Disease Percentage
Pre-renal azotemia caused by acute renal hypoperfusion
55-60
Intrinsic renal azotemiaDiseases of large vessels, small vessela, glomeruli, interstititum & Tubules**ATN
35-40
Post renal azotemia due to obstruction
<5
** Accounts for 90% of intrinsic renal category
Disease categories of AKI
Diagnosis of ARFOften diagnosed Increase in S. Cr & Urea
BUN to S. Cr ratio = 15 : 1
Schrier Kid Int 1979 ; 15: 205-216
Hypercatabolic ARF Hypercatabolic ARF
LR: Likelihood ratio
Renal biopsy in ARFIndications Oliguria > 2 weeks Schrier
> 6 weeksOTCN
Anuria Flawed Patchy necrosis Angiogram to know perfusion of cortices
Systemic disease Heavy proteinuria &
haematuria Marked hypertensionNo circulatory disturbance
to account for ATN
Gomez. CJASN 3; 674: 2008
Largest registry 2281 ARF biopsies
AKI as an indication 16%
Most commonly Elderly; 32%>60y
ATN Only 5%; Intense selection bias:
Only those not presumed to be ATN clinically biopsied
What is not clarified
Initially thought to be ATN finally biopsied
Gomez. CJASN 3; 674: 2008
Modified Colapinto aspiration needle
Sheath
Protective cover
Needle
Needle + Specimen
Past = Contraindications
Interventional radiologist
25 high risk patients21 (84%) tissue adequate
17Perforation of renal capsule
6 of them coil embolization1 RVT after one week
Feasibility of transjugular biopsy well documented
Clinical benefit to be established
Previous criteria: Early v/s Late; QualitativeProposed: Quantitative; Based on RIFLE criteria
CJASN 3; 876-880; 2008
RRT: Early versus LateTiming
V. Seabra et al, AJKD, 52: 272-284; 2008Mortality
V. Seabra et al, AJKD, 52: 272-284; 2008Renal recovery
V. Seabra et al, AJKD, 52: 272-284; 2008
160 patients Randomized to daily HD v/s Alternate day HDAlt day HD Daily HD
Duration of HD (hr) 3.4 ± 0.5 3.3 ± 0.4 Kt/v (delivered) 0.94 ± 0.11 0.91 ± 0.12Mortality 46% 28%Resolution of ARF (days) 16 ± 6 9 ± 2
??? A case of inadequate dialysisMean time averaged BUN (mg/dL)
104 ± 18 60 ± 20
Mean time averaged S.Cr (mg/dL)
9.5 ± 1.2 5.3 ±1.2
Dosing
Optimal dose is 35 ml/kg/hr = 50.4 L/d
Survival rate 41% 57%** 58%**
Dosing
Intensive treatment Less Intensive treatment
IHD &/ or SLED: Six times a week
Thrice a week
CVVH: 35 ml/kg/hr 20 ml/kg/hr
Allowed patient transition from one mode to another as long as they stayed within the intensive or less intensive
groups
Palevsky et al.Dosing
Dosing
1. 6 days delay in initiation of treatment2. 219 protocol deviations Isolated UF in less
intensive group3. SLED more in intensive group4. Treatment for 28 d only. Mortality At 60 d; 10%
of patients received extra dialysis
CORRESPONDENCE
Dosing
1508 patients randomized CVVHDF 40 ml/kg/hour 25 ml/kg/hour
Deaths at 90 d 44.7% 44.7%RRT dependence
at 90 d6.8% 4.4%
Hypophosph-otemia
65%** 54%
Bellomo et al.
Dosing
Bellomo et al.Dosing
Mortality: No difference 2010 Vol. 38, No.5; 1360
RecommendationsDialysis dose: Kt/V: 1.4 & effluent volume
25 to 30 ml/kg/hourDaily monitoring of delivered dose
Nutrition & drug dosing monitored
Eight RCTs in last decadeAt present Four discussed
Steep correlation bet the dose & survival
Plateau: no further benefit
What is unknown even after VA/NIH ATN?1.Breaking point2.BP for diff modes of dialysis
What is gainedVA/NIH ATN1.Not to risk under dialysis2.Dialysis dose monitoring
CRRT v/s IHD: Six RCTs Last 10 years; In Europe & US
CRRT IHD
John S et al. NDT 16; 320-327, 2001
No difference in mortality 70% in both
Mehta et al. KI 60; 1154-1163; 2001
MortalityICU: 59%Hospital: 65%
41%47%After covariate adjustment:
No differenceAugustine JJ AJKD 2004; 44: 1000-1007 No difference in mortality
Greater haemodynamic stability in CRRT
Uhelinger DE et al.NDT 2005; 20:1630-1637
Mortality: 34% 38% p= NS
Gasporvic et al.Renal fail 25; 855-866;2003
No difference in mortality
Hemodiafe studyVinsonneau et al, Lancet, 368, 379-385, 2006
No difference in mortality
Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: A meta-analysisBagshaw, Sean M. MD, MSc; Berthiaume, Luc R. MD; Delaney, Anthony MBBS, MSc; Bellomo, Rinaldo MD
Crit Care Med, 36: 610-617; 2008CRRT v/s IHD
Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: A meta-analysisBagshaw, Sean M. MD, MSc; Berthiaume, Luc R. MD; Delaney, Anthony MBBS, MSc; Bellomo, Rinaldo MD
Crit Care Med, 36: 610-617; 2008
There was suggestion that continuous RRT had fewer episodes of hemodynamic instability and
better control of fluid balance.
In the context of these limitations, the initial RRT modality did not seem to affect mortality or
recovery to RRT independence
CRRT v/s IHD
Death Renal recovery
Intermittent, continuous and hybrid techniques offer specific advantages
All are part of a medley race in dialysis of critically ill
Prospective RCT Hypercatabolic patients87 patientsCEPD & TPD cross over trail 12 hour wash out after initial dialysis Baxter dialysate bags & Cycler machines
CEPD TPDWeekly Kt/V 1.80 ± 0.32 2.43 ± 0.87
“Just fell short of dialysis adequacy”
Higher clearances Less expensive (Rs.7165)
Both Reasonable options for the treatment of ARF
NEJM 347; 12: 895; 2004
Hemofiltration versus Acute PD78 patients48 Malaria; 22 Sepsis
MortalityAcute PD : 47%Haemofiltration: 15%
John T Daugirdas
1.Predominance of malaria2.Comparison of state of art CVVH with
rustic PD3.CVVH was low intensity; still
patients recovered fast
Kid Int 2008; 73: 587- 593
120 patients randomized HVPD Tenckhoff catheter placed by a nephrologist
7 days a week Dianeal solutionHome choice (Baxter)Weekly Kt/V= 3.6 ± 0.6
DHD 3 hour session6 days a week Weekly Kt/V= 4.7 ± 0.6
Kid Int 2008; 73: 587- 593
SummaryRIFLE Criteria Single standard definition
Severity of class MortalityAKIN criteria Impact not yet knownEpidemiology Incidence of ARF
Mortality relatively static>6 RTEC & GC LR of ATN highTransjugular biopsy Possible to do; Utility unknownEarly dialysis EffectiveIntense dialysis No effective;
Not to risk under dialysisDose Kt/V=1.4; CRRT 25-30 ml/kg/hr
Daily monitoringCRRT v/s HD No differencePD Reasonable option
Biomarkers
Qualities
Accurate, reliable
Relatively non-invasive/acceptable to patients
Rapidly measurable, standardized assay
Sensitive/specific with reproducible cutoff values
Neutrophil gelatinase assosciated lipocalin (NGAL)25 kDa, proteinExpressed in neutrophilsKidney, lungs, trachea, stomach, colonIncreased in PT—after injury
KIM-1First novel renal biomarker discovered (Han WK et al. Kid Int. 2002; 62: 237–44)
A transmembrane protein in PT
IL-18Role in inflammation, Activating macrophagesMediates ischemic renal injury
Cystatin CNon-glycosylated LMW(13.4 kDa) cystine proteaseSynthesized at constant rate by all nucleated cells (Grubb AO Adv. Clin. Chem. 2000; 35: 63–99.)
Freely filtered glomerulusCompletely reabsorbed PTReadily assayed Automated immunonephelometric (Herget-Rosenthal S Clin. Nephrol. 2005; 64: 41–6)
As a GFR measurementrobust than S Cr
Urine
Urine
Biomarker Sample Source
Cardiac surgery
CIN Sepsis RT
NGAL Plasma Early Early Early Early
NGAL Urine Early Early Early Early
Cystatin C Plasma Intermediate Intermediate Intermediate Intermediate
IL-18* Urine Intermediate Absent Intermediate Intermediate
KIM-1* Urine Intermediate Not tested Not tested Not tested
* Commercial test not yet available
Current status of AKI biomarkers
Devarajan P Contrib Nephrol 2007, 156, 203-212
Acute versus ChronicHistoryVague ill healthNocturiaPruritusSkin pigmentation‘Bit of protein’ in urine‘Bit of problem in kidneys’
Suggests chronicity
Kidney sizes USG standardSize: 3.7 ± 0.4 cm times of L2 VB
Broad waxy casts Chronic renal failure or rapidly progressive; never ARF
Carbamylated Hb (expressed as µg carbamyl valine per gram (CV/g) Hb)
CRF: 129.0 ±8.1ARF: 55.6±6.2Normal: 31.6±1.3 **
Anemia, Hypocal, Hyperphos, Hyperuricemia
Present in both
** Alian Wynckel Nephrol Dial Transplant (2000) 15: 1183-1188
Fractional Excretion of Sodium (Fe Na)
Pre-renal azotemia ATN
Na+Reabsorbed avidlyD/t Suppression of ANPActivation of R-AT-Aldo
Na+ Reabsorption is inhibited as tubule is damaged
Creatinine reabsorption smaller extent than Cr in both conditions
<1% >1%
Ratio of Na+ clearance to the Cr. ClearanceUNa+ / PNa+ X PCr / UCr X 100
FeNA > 1.0 in pre-renal azotemia
FeNa < 1.0 in ATN
Diuretics Milder form of ATNs intermediate syndrome
Underlying salt losing nephropathy
Damage only to cortico medullary junction; preservation of LOH
Adrenal insuffficiency Ischemia, Rhabdomyolysis, AGs, RCA, HRS
Espinel JAMA 236; 579-581, 1976
Pre-renal azotemia with FeNA >1 d/t diuretic use
Fractional excretion of Lithium & UA remains low
PrognosisOliguric patients with
ARF with Fe Na <1%High likelihood of response to diuretics
Pre renal azotemia ATNFeNa (%) <1 >1Renal failure index UNa/Ucr/Pcr <1 >1Urinary Na+ concentration (mEq/L) <10 >20Plasma BUN/creatinine ratio >20 <10–15Fe UA (%) <7 >15Fe Lithium (%) <7 >20Urinary creatinine/plasma creatinine ratio >40 <20
Urinary urea nitrogen/plasma urea nitrogen ratio
>8 <3
Urine specific gravity >1.018 <1.012Urine osmolality (mOsm/kg H2O) >500 <250Urine sediment Hyaline casts RTECs & casts,
Muddy brown granular casts
Renal failure indices
Treatment Usually started on same lines whether it is pre-renal azotemia or ATN
DOSINGMEHTA R., McDONALD KI 2001166 patients randomized84 to CRRT, 82 to IHDPatients with Mean Arterial Pressure (MAP) < 70 mm Hg
excluded
Mortality CRRT IHD P ICUpatients 59% 41% Significant
Hospital patients 65% 47% Significant
The mortality was worse in CRRT group, but on subgroup analysis the renal recovery was better on CRRTCriticism: Patients with MAP < 70 mm Hg have been excluded
Percentage 1965 to 1974 1981 to 1986Diarrhoeal diseases
23 10
Sepsis & drugs 37 50Obstretic 22 9Surgical causes 11 31 d/t ↑
obstructive uropathy
Changing Trends in Acute Renal Failure in Third-world Countries — Chandigarh Study
K. S. Chugh et al. Q J M 1989; 73:1117-1123
Epidemiologic Trend Changes in Acute Renal Failure—A Tertiary Center Experience from South India M. Jayakumar, Renal failure, (5 ) 2006 , 405 - 410
Number of patients 1112 between 1994 to 2004 Mean age 37.08 ± 3.4 yrsMales 669 (60.1%) MedicalObstetric Surgical
87.6 %8.9% 3.4 %
Most common medical cause
Diarrhoeal disease
Other causes Lepto, Malaria, DrugsRRT 69%Mortality 19.6%Dialysis depedence 8.18%
RIFLE3 Severity classes 2 Outcome classes
Risk
Injury
Failure
Loss
End stage kidney disease
Based on changes in S.Cr or UOP Worst of each criteria to be used
Duration of loss of kidney function
Hoste et al. : Only 14% of patients of ‘F’ Received dialysis; but 5 times hospital
mortality (Crit Care 2006; 10: R73)
Optimal dose is 35 ml/kg/hr = 50.4 L/d
Survival rate 41% 57%** 58%**