ACUTE KIDNEY INJURY ACUTE KIDNEY INJURY
Rapid decrease in GFR occurring over period of
Normochronic, ronic, norm no rmocy ocy tic anemia is seen se en in CKD CKD Normoch
usu ally ally late and s eldom helpful helpful in practice
hours to day s; reversible reversible damage to renal fx fxn
In CKD several months to years before dev’t of
Level of BUN (>140mg/dL) or Serum Creatinine
renal dysfunction : progressive; irreversible damage
(>10mg/dL) in patients who appear relatively well
to renal fxn
and are still non-oliguric are most likely CKD.
Clini Clinicall cally y diagnos ed by o ne of the ff: o
Increase in BUN
o
Increase in BUN and SCreatinine (SCr
o
Acute Oliguria UO <400ml/day
Urinar Urinary y sed iments iments t hat is inactive inactive with with broad casts
Acute-on-Chronic Kidney Disease
The degree of renal failure has been aggravated by some intercurrent intercurrent even t
elevation of 50% mpd or 43mg/dl)
Radiologic changes of renal osteodystrophy are
Additional decline in GFR from a superimposed proces s as :
No kno wn structu st ructural ral problem on t he A sians AKD Decrease in GFR observed in <3months,
o
Volume depletion
may lead to CKD if remain unreversed in 3 mos
o
Nephrot oxic oxic drugs
CKD Decrease in GFR GFR o bs erved in >3mont >3mont hs
o
Disease relapse
Elevation in nitregenous waste products, BUN,
o
Diseas Diseas e acce leration leration
o
Infection
o
Obstruction
o
Hypercalcemia
o
Accelerated hypertension
o
Heart failure
creatinine, volume overload, electrolyte
Potassium elevation is common hyperkalemia metabolic acidos is
Over Overv view ie w of AKI, AKI, CKD CKD and AKD AKD (inter (in terre relati lations onship) hip)
Consequence of AKI
Retention etention o f n itrogenous waste products
Expansion of ECF volume
Diso Diso rders on electrolytes and Acid-Base Acid-Base b alance ACUTE KIDNEY INJURY no ATN (ACUTE RENAL FAILURE) old name of AKI;
Acute Kidney Injury
has A TN; Not Not all pt s with ARF ARF will will oliguria
Acute Kidney Kidney Injury vs vs . Chronic Kidney Kidney Dis Di s ease eas e
ACUTE TUBULAR NECROSIS not all pt with
Most cases, the distinguishing features between the 2 is us ually ually s traight traight forward forward
History
PE
Laboratories
Ultrasound
AKI has ATN AKI AKI classi clas si fied as:
1) NONOL NONOLIGURIC IGURIC
2)
Urine output > 400ml 400ml/d /day ay (>500 o
40% 40% of patients patients h ave this
o
Better recovery
OLIGURIC alm almos t 60% of p atients
Small Small kidney s (<10cm) (<10cm)
Reduction of cortical thickness thickness
o
Fluid overload and/or hyperkalemia
Increased echogenecity
o
More s evere injury injury
Scarring
Multiple cyst
S.P.O.
3)
Urine output < 400ml/day
ANURIC
Urine output < 100ml/day
Page 1
ACUTE KIDNEY INJURY a.
Low Urine Output
SCr of 10mg/dl, hgb 80 or .27 hct, azotemia without ob vious blood loss
More s evere injury
Implication for volume overload
Electrolyte disturbances
(normal on Filipinos: 10 + or – 2 SD, so 6 or 7 is
Prognosis
sug ges tive); in AKI varies
4)
5)
Reduction in GFR
Retention of nitrogenous waste products AKI and CKD have both retention, but CKD: compensated,
Obstruction t o u rine flow Oliguria
Small bilateral kidneys < 10cm on renal UTZ
AKI uncompensated
Acu te renal failure
Recently, a consensus conference sponsored by the Acute Dialysis Quality
6)
Expansion of ECF volume late s tage(5)
Improvement Initiative (ADQI) has proposed a new definition of ARF, that
7)
Diso rders on electrolytes and acid – bas e balance
has been widely endorsed and is increasingly being used. In k eeping with th e
Etiology of AKI
spectrum of changes seen in AKI, a diagnostic classification scheme was
developed
blood
flow
reduction
or
Urine Outp ut criteria
Intrinsic Renal = 40% glomerular problem
Screa x 1.5
UO <0.5ml/kg/hr x6
Post – renal = 5% obs truction
or
hrs
GFR is dep endent o n renal BF, BF is dependen t on CO, hence Decrease in renal blood flow = decrease GFR
>25%
Screa x 2
UO
or
x12 hrs.
GFR FAILURE
55%
GFR criteria
GFR INJURY
=
hypo perfusion of kidney, most c ommon
ADQI definiti on of AKI: patient is at
R ISK
Pre-renal
>50%
<0.5ml/kg/hr
Causes of PreRenal AKI
Oliguria
Screa > 4mg/dl
UO
Acute rise >0.5mg/dl
x24 hrs.
<0.3ml/kg/hr
Anuria x 12hrs. LOSS
Persistent ARF = Complete loss of kidney function > 4weeks
ESKD
End Stage Kidney Disease (>3 Months)
*Renal replacement therapy/treatment for the last two (Loss and ESKD) Tandaan ang UO <30 if the patient is 50 kg
Rena l dysfunctio n is d efined in terms of either a rise in creatinine or a reduction in urine output , the m ore severe of the two c riteria being selected. RIFLE- F (Failure) is present even if the risk in serum creatinine is less that the threefold above baseline, provided that the new serum creatinine is greater than 4mg/dL and has risen by at least 0.5 mg/dL. When the achieve d designa tion results from ed e.g. RIFLE-F o . Similarly, a sub script “c” is used to denote the presence of preexisting ch ronic kidney disease.
Endothelin afferent constrictor Endothelin inhibitors given to AKI: unopposed NO effect ACE/ARB dilates efferent drops GFR
Features suggesting CKD
1) 2)
Symptoms lasting >3month s BUN or Creatinine documented mont hs earlier
3) Normocytic, normochromic anemia
S.P.O.
NSAIDs constricts afferent HPS production of subs that causes afferent vasoconstriction Hyperviscosity Syndrome --. Decreased renal BF
Multiple my eloma
Polycythemia
Macroglobulinema
Page 2
ACUTE KIDNEY INJURY Intrarenal / Intrinsic AKI
Prerenal AKI
characterized by renal hypoperfusion
Problem within the kidney
integrity of renal parenchymal tissu e is pres erved
Causes:
most common caus e of AKI
GFR is corrected rapidly on restoration of renal
o
Diseases of large renal vessels
Renal artery stenosis/ thrombosis/
perfus ion within 24 – 72 hours = reversible
embolism/
secondary to disease characterized by
atheros clerotic plaque
o
hypovolemia
o
low CO
o
systemic vasodilatation
o
intrarenal vasoconstriction
o
For Impaired Renal Autoregulation or Compens ation
Hypovolemia
Symp ath etic NS RAS
Release of AVP
cross
Bilateral
renal
thrombosis
/
occlusion
is high, (+)hyaline cast
Activation of
arterial
clamping
ass ociated with bland u rinary s ediments urine sp.gr
Activate Baroreceptors
Operative
obstruction/
Str et ch Receptor on ARF Arteries Triggers: Afferent Arte riolar Vasodilation via local pyogenic reflux (autoregulation) 2. Synthesize: A.a. vasodilatation a. vasodilating pro staglandins i. PGE2 ii. Prostacyclin b. Nitr ic Oxide i. Kallikrein ii. Kinins
Diseas es of renal microvas culature
Vasculiis wegener ’s
thrombotic microangiopath ies
hemolytic uremic syndrome
malignant hypertension
thrombotic
thrombocytopenic
purpura
1.
o
o
toxemia of pregnancy
HELLP syn drome, eclamps ia
Glomerular disease
AGN
RPGN
Tubulointerstitial
Acute
Interstitial
Nephritis
leptosp iros is in Phils
Norep ineph rine
Release of AVP Angiotensin II
Efferent Arteriolar 1. 2. 3.
S.P.O.
Vasoconstriction Inh ibit salt loss through sweat glands Stimulate salt and H2O appetite, restore BV and arter ial pressure
constriction
preserve GFR
Page 3
ACUTE KIDNEY INJURY Drug-induced Allergic Interstitial Nephritis Β-Lactams
NSAIDS
Other
Viral
Ampicillin Amoxic illin Carbenicillin Methicillin Naf cillin Oxacillin Pen G Cephalexin Cephalotin Cephradine Cefotaxime
Aspirin Celecoxib Fenoprof en Ibuprofen Indomethacin Mef enamic acid Naproxen Phenazone Pheny lbutazone Tolmetin
A-Methly dopa Allopurinol Azathioprine Carbamazepine Cimetidine Omeprazole Clof ibrate Clozapine Famotidine Sulfinpy razone Phenobarbita
CMV Measles Infectious Mononucleosis Rocky Mountain spotted f ever
Diuretics
Infectious Bacterial
Other Antibiotics
Chlorthalidone Furosemide Bumetanide Thiazides
Ethambutol p Aminosalic y late Rifampin Sulfonamides Trimetoprim Ciprofloxacin Levofloxacin Norf loxacin Vancomycin
Acute py elonephritis Leptospirosis Scarlet f ever Ty phoid f ever Legionnaire’s Dse,
Other
Candidiasis Toxoplasmosis Miscellaneous
Systemic dse. SLE Sjogren syn. Tubulointerstitial nephritis and uveitis syn, Cancer Lym phoma Leukemia Myeloma Sarcoidosis
Acute Tubular Necros is (ATN) Acute Kidney Injury (AKI)
Ischemia (Ischemic ATN) – 50%
Exogenous Nephrot oxins T hat are Common Cause of Acute Intrinsic Azot emia with Acute Tubular Necrosis Antibiotics Chemotherapeut ic agents Acyclovir Cisplatin Cidofovir Ifosfomide Indinavir Anti-inflammatory and Foscarnet immunosup pressive agents Pentamidine NSAIDS (including Aminoglycosides COX- 2 inhibitors) Amphotericin B Cyclosporin/tacrolimus Organic solvents Intravenous immune Ethy lene glycol globulin Toluene Radiocontrast agents Poisons Bacterial toxin Contrast mediumIVP Paraquat Snake bites Endogenous Myoglobin muscle injury Hemoglobin Uric acid Calcium INH int ake(not extrinsic) seizure rhabdomyolysis Malignancy hypercalcemia
Nephrot oxins (Nephroto xic ATN) – 35% 20-30% of patients do not have morphological evidences of tubular necrosis
Ischemic ATN
all causes of prerenal azotemia
hypo prefusion reduce ischemic injury to renal cells
recovery takes in which after normalization of renal blood flow
Renal Hypoperfusion Prerenal AKI Ischemic AKI Bilateral complete cortical necrosis Nephrot oxic Injury A TN
Kidney vulnerable to nephrotoxic renal injury
Causes of Acute Post Renal AKI
o
Rich blood supply – 25% of CO
o
Ability to concentrate toxins to high level within
medullary
interstitium
Ureteric Obstruction
and
renal
papillae, uric acid or su lfonamide crys tals, fungu s
epithelial cellsc harmful metabolites o
Important site for xenobiotic metabolism
balls
Increase in incidence: o
Elderly > 45 y.o. decreas e 0.6 GFR/year
o
Preexisting CKD DM Nephropathy
o
True or “effective” hypovolemia
o
Concommitant expos ure to o ther toxins
Intramural:
postoperative
edema
after
ureteric
surgery, BK virus-induced ureteric fibrosis in renal allograft
Extraureteric:
Iatrogenic
(ligation
during
pelvic
surgery)
S.P.O.
Intraluminal: Stones blood clot, sloughed renal
Periureteric: Hemorrhage, tumor, or fibrosis
Page 4
ACUTE KIDNEY INJURY o
2 functioning kidneys bilateral AKI
Integrins prevents cellular dysfunction
o
1 functioning kidney unilateral AKI
Clinical Features:
Bladder Neck Obstruction
Oliguria
Intraluminal: Stones , bloo d clots, slough ed papillae
S/S fluid overload/volume depletion
Intramural: bladder CA, bladder infection w/mural
S/S of underlying cau ses of ARF
edema,
S/S electrolytes imbalance, acid – base d isorders
Changes
neurogenic,
drugs
(eg
tricyclic
antidepressants, ganglion blockers) Extramural:
Prostatic
hypertrophy,
prostatic
in
sensorium
may
be
the
only
manifestation, early in AKI, Late in CKD
carcinoma Urethral Obstruction
Clinical Evaluati on of AKI:
Phimos is, congen ital valves, s tricture, tumor
History:
bilateral
o
Fluid losses and fluid intake
hydronephrosis obstructive nephropathy may lead to
o
Urine volume
CKD
o
Infection: Viral, bact eria, fungal
AKI from obstruction develops:
o
Drug/s intake
o
Radiologic procedures , Surgery
o
Symptoms of underlying disease
o
Diseases or clinical situation that leads to
*Bladder
Neck
and
Urethral
Obstruction
bladder neck urethra bilateral u reteric ob struction
development of endogenous toxins
unilateral ureteric obstruction in a pt with one functioning kidney or with significant preexisting
Renal calculi
CKD
Cardiac disease
Morphology of AKI
4 cellular fates:
Physi cal Examinati on:
Cellular death by necros is
Cellular death by apoptos is
Cellular replication and division
Signs of chronic liver disease
Cells may app ear indifferent to stres s
Skin Lesions
Edema fluid overload
Abdominal findings – (+) KP, distended UBobst.
Rectal exam enlarged prostate
Muscle tenderness/weakness
S ublethal Changes
cytoskeleton
of
hydration – BP,
HR,
JVP,
mucous
membrane, skin turgor
walang nakikita even in biopsy
Disruption of cell
State
Fla ttening of epitheli um Loss of brus h border Loss of focal c ell contact
Staging of AKI Membrane proteins redistribution
Disengagement of cells
(integrins, Na-K-
from substratum
ATPase) Intratubular obstruction Loss of cellular olarit Redistributi on of adhesi on Cell ular Dysfunction
S.P.O.
molecules
Clini cal Evaluation of volume s tatus Volume depletion: Hx – thirst , oliguria/anuria Excessive fluid losses Fluid balance I & O, daily weights PE – dry mucos a, poor skin turgor Absent axillary sweat Reduced JVP Postural tachycardia/hypotension Supine tachycardia/hypotension Current status of new urinary biomarkers for discriminating between different forms of A KI.
Page 5
ACUTE KIDNEY INJURY Biomarker name
CPB
NGAL
2h pos tCPB 6h pos tCPB 12h pos tCPB 4h pos tCPB
IL-18
KIM-1
L-FABP
Kidney tx
Prerenalwith
1-2 days pre-AKI
Sepsis or ICU setting 2 days pre-AKI
12-24 hpost-tx
urinary
Not increased
2 days pre-AKI
12-24 hpost-tx
High SCr, BUN and hyaline cast, High BUN-Crea ratio
Not tested
ATN
Not tested
urinary
Contrast nephropathy
Not tes ted
1-2 days pre-AKI
Not tes ted
Not tes ted
compensation
of
decrease
renal
flowincrease Na and H2O reabsorption in tubules low Na
and
H2O
concentrationHigh
no
compensation
of
decrease
renal
Na
and
H2O
concentrationlow
BUN and SERUM Creatini ne
*BUN alone can differentiate Prerenal from ATN. N.v. 6:1
Rapid elevation (within 24- 48 hrs)
Renal ischemia
Radiocontrast
Atheroembolism
<1.1
>8 >1.018 <10 <1
<3 <1.015 >40 >2
<1
>1
NGAL and IL- 8 detects rise or deflection of GFR in >8hrs better than the SCr; available in the Phils
Urine Sediment in the Differential Diagnosis of Acute Kidney Injury Normal or Few RBC or White Blood Cell Casts WBC Acute intes tinal Prerenal Azotemia nephritis or exudative Arterial thrombosis or glomerulonephritis embolism Sever PreglomerularVasculitis Pyelonephritis HUS or TTP Marked leukemic or Scleroderma crisis lymphomatous Postrenal Azotemia infiltration Eosinophils (>5% ) Granular casts Allergic interstitial Acute tubule necrosis nephritis(antibiotics (muddy brown) NSAIDs) Glomerulonephritis or Athereombolic vasculitis Disease Interstitial nephritis Crystalluria Acute Red Blood Cell Casts uratenephrophaty Glomerulonephritis or Calcium Oxalate vasculitis Acyclovir Malignant Hypertension Indinavir Rarely interstitial Sulfonamides nephritis Radiocontrast Agents
S.P.O.
urine
osmolaritylow urine sp gravityhigh urine sodium <10
Urine Chemis try in Acute Kidney Injury Urine Chemistry Pre-renal ATN Urine osmolality, Uosm >500 <300
>1.5
blood
flowdecrease Na and H2O reabsorption in tubules high
Mud dy brown granular cas t, low BUN-Crea ratio
Urine to plasma osmolality Urine to plasma urea Specific grav ity Urine sodium (mmol/L) Fractional sodium excretion Renal Failure index
urine
osmolarityHigh urine sp gravitylow urine sodium <10
*The times indicated (in hours) are the earliest time points at w hich the biomarker is increased significantly from baseline values. AKI:acute kidney injury, CPB:cardiopulmonary bypas s, KIM-1 kidney injury molecule-1;l-FABP; liver -type f atty acid____; NGAL: Neutrophil gelatinase-associated lipocalin; tx:transplant
(mosm/kg)
blood
o
Elevation later (10-14 d ays ) – toxins
o
Increas e in SK+, Uric acid, PO4
o
Decrease in SCa+2
o
Metabo lic Acidos is -increase An ionGap:
ethylene glycol
methanol toxicity
Laborator y evaluation of AKI
UTZ normal or inc echogenicity,hydronephrosis
X-ray, KUB, IVP, retrogade pyelography ureteral obstruction (diagnostic and therapeutic)
Ct scan – stonogram/ unenhanced helical Ct, CT angio renal artery stenosis
MRI/MRArenal artery pathology
Doppler UTZ renal artery pathology
Renal Biopsy
If the cause of intrinsic renal failure is unclear
if the caus e of glomerular diseas e is not known
in allergic interstial nephritis
pts on su ppo rtive ren al replacement for a period of 3 month s w/o evidence o f recovery
Page 6
ACUTE KIDNEY INJURY Complications
Volume overload
Electrolyte disorders
Metabolic acidosis
Hyperphos phatemia/ hypo calcemia
Anemia, bleeding time
Uremic syndrome
Infection- co mmon and accoun ts for 75%of deaths
Cardiac abnormalities: arrhythmia, AMI, pulmonary embolism
GI bleeding – 10 -30% due to stress ulceration on gas tric or small intestinal mucos a
P.S. Read on metabolic acid disorder for next meeting!
S.P.O.
Page 7
