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An Approach to Management and Diagnosis of
Acute Renal Failure
Acute
Kidney
Injury
Renal
Failure
Shining a Light on Black Boxes of Understanding
Franchot van Slot MD/PhD
Multicare Health Systems, Hospitalist
Adjunct Professor, Pacific University of PA Studies
Disclosures:
No conflicts of interest to report
AKI/ARF Definitions
• Transition meant to reflect spectrum of renal
insult, increased mortality even with minor
rises, but general dfinition is the same:
• An Acute decline in GFR
• Chronic kidney disease= existing >3 months
KDIGO criteria
• Kidney Disease: Improving Global Outcomes
• Followed previous AKIN and RIFLE criteria
Criteria:
• Increase Cr ≥ 0.3 within 48 hours
• Increase Cr ≥ 1.5x baseline in <7 days
• Urine volume <0.5ml/kg/h for >6 hours
• Stage 1: 1.5-1.9x baseline or ≥0.3mg/dl
• Stage 2: 2.0-2.5x baseline or UO<0.5mg/kg/h x ≥12h
• Stage 3: 3.0x baseline or increase Cr ≥4.0 or UO
<0.3ml/kg/h x ≥24h or anuria ≥12h or RRT or if age
<18yo GFR <35ml/min/1.73m2
http://4.bp.blogspot.com/-88O6JKhocCg/Tobdp5yKiI/AAAAAAAAACw/B2VSw3OkrNM/s200/
microscope.gif
Adapted from BaileyBio.com
Adapted from:
Wikimedia Commons
https://en.m.wikipedi
a.org/wiki/File:Kidney
_Cross_Section.png
Introduction
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Shedding light on black boxes
Relatively traditional approach
Focused on management, diagnosis
A systematic approach
– Getting out of cookie-cutter mindset:
the dose and hope strategy
– Few tests required to dramatically narrow down cause
• History
• The importance of plumbing
• Medicine works best in the direction:
History, Diagnosis, Treatment
Outline
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Introduction
Epidemiology and consequences
Normal Kidney function
General, practical anatomy
Pre, intrinsic, and post renal failure and causes
Diagnosis
Treatment
New Directions
Conclusion
Epidemiology
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2 million patients per year
700,000 deaths
2-5% hospitalized patients1,2
30% may be preventable3,4,5
5-20% ICU patients1,2
Cr rise ≥ 0.5 associated with:
– 6.5 fold increased risk of death
– 3.5 day increased LOS
– $7000 increased hospital cost after adjustment7
• ICU mortality with multiorgan failure >50%8
• If RRT required mortality increasec to 80%8,9
Kidney Functions
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Volume homeostasis
Blood pressure homeostasis
Water balance
Electrolyte balance
Acid excretion, bicarbonate regeneration
Detoxification
Hematopoiesis
Vitamin D hydroxylation
AKI complications
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Volume overload
Hyperkalemia
Metabolic acidosis
Hypocalcemia
Hyperphosphatemia
Mental status changes
Hyperuricemia
Hypermagnesemia
Platelet dysfunction
Hospitalist Anatomy
Heart
Aorta
Kidney
Renal Artery
Renal Vein
Major Calyx
Ureters
Bladder
Prostate
Urethra
Urethral sphincter
-Image adapted from multiple sources see bibliography
Hospitalist Anatomy
Heart
Aorta
Kidney
Renal Artery
Renal Vein
Major Calyx
Ureter
Uterus, ovaries
Bladder
Urethra
-Image adapted from multiple sources see bibliography
Prerenal
~50-70%
(Plumbing)
Intrinsic
~10-30%
(Biochemistry)
Postrenal
~10-30%
(Plumbing)
Image adapted from multiple sources
see bibliography
History
• The Trump Card, most important factor in
diagnosis
• A good history will often reveal multiple
contributors to renal failure
• Do not allow isolated lab values to get in the
way. They count less than historical details.
Prerenal Requirements
-Cardiac Output
-Volume
-Blood Pressure
-Oxygen Carrying Capacity
-Clear path
Image adapted from multiple sources see bibliography
Prerenal Requirements:
Cardiac Output
• Cardiomyopathy
– “cardiorenal syndrome”
• Valvular disease
– Aortic stenosis
– Mitral regurgitation
• Tamponade
Prerenal Requirements:
Volume
• Direct volume losses
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–
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n/v/d
Diuretics
Osmotic diuresis (DKA/HHS)
Reactive diuresis: UTI, post-obstructive diuresis
• Insensible losses
– Sweating, tachypnea, fever, burns
• Poor PO intake
• Third spacing
– Cirrhosis
– Nephrotic syndrome
– malignancy
Prerenal Requirements:
Blood Pressure
• Severe sepsis
• Iatrogenic
– Antihypertensives
– diuretics
• Hemorrhage
– Trauma
– Surgery
– GI bleed, retroperitoneal bleed, etc
• Endogenous factors
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Cirrhosis
Hypothyroid
Adrenal insufficiency
Abdominal compartment syndrome
Prerenal Requirements:
Oxygen Carrying Capacity (Hgb)
• Acute losses
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Trauma
Surgery
Hemolysis
Phlebotomy
GI bleed, occult bleeds, etc.
• Failure of hematopoiesis
– Iron, vitamin deficiencies
– CKD
– Malignancy
• Chronic losses
– Anticoagulants
– Bruising
– PUD, esophagitis
Prerenal Requirements:
Clear Path
• Aortic dissection
• Mural thrombus
• Renal artery stenosis
– Atherosclerotic
disease
– External compression
• Proximal glomerulus
– NSAIDs
– ACEI/ARBs
Postrenal Requirements
-Clear path
Image adapted from multiple sources see bibliography
Postrenal Problems
• Ureteral
– Stones
• Bilateral or unilateral c contralateral disease
• Hemorrhage/clot
• Extrinsic compression
– Mass
– fibrosis
– Surgical
• Stent obstruction
• ligation
– Stricture
– Congenital abnormalities (valves)
Postrenal Problems
• Bladder
– Obstructed foley
– Bladder CA, outlet or
bilateral ureteral obstruction
– Bladder stone
– Neurogenic bladder (caution)
• Prostate
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BPH
Prostate CA
Prostatitis
Post surgical
• Urethra
– Stricture
– Urethritis
– Foreign body
Female and Pregnancy
• Ureteral
– Bilateral ureteral obstruction
(or unilateral c contralateral disease
• Gravid uterus
• Fibroid
• Ovarian, endometrial, cervical CA
• Bladder/urethra
– Suspensory bladder ligament laxity
• Age, multiparity, other surgery
• Prolapse: rectovaginal
– Pelvic floor relaxation
• Previous prolonged labor, multiparity age
• Post-menopausal estrogen decline
From Wikimedia commons
Hepatorenal
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Poor prognosis
Diagnosis of exclusion
Often precipitated by SBP
Pathophysiology unclear
Known prerenal component
?
– Hypoalbuminemia
– Hypotension
• Postulated Postrenal (vein)
Adapted from:
Wikimedia Commons
https://en.m.wikipedia.org/
wiki/File:Kidney_Cross_
Section.png
– Improved with agents that decrease portal HTN
– Improved with TIPS procedure
• Type I: 2x increase in Cr to >2.5 in <2 weeks
• Type II: hepatorenal syndrome not meeting Type I criteria
Intrinsic Renal Requirements
-Prerenal function
-Postrenal function
-Normal oxygenation
-Normal genetics
-Euglycemia
-Normotension
-Normal immune function
-To be kept away from doctors
Image adapted from multiple sources see bibliography
Intrinsic Renal Problems
•DM
•HTN
•ATN
•Tubulointerstitial diseases
•AIN
•Autoimmune
•Idiopathic
•Iatrogenic
•Drugs
Diabetes
-Major cause of CKD, less frequently seen acutely
-Slowly progressive, generally taking 10-15 years to be
clinically apparent
-May not always be an obvious cause
-late care
-renal failure increases half life of insulin and may be
euglycemic on presentation if renal failure is severe
-caution with long acting insulin, especially if not yet
on HD
HTN
• Often goes hand-in-hand with DM
• Like DM more typically slow, progressive
• Commonly seen as acute cause in malignant
HTN
• Results in nephrocalcinosis
ATN (acute tubular necrosis)
• Wastebasket term in many respects
• Typically reserved for ischemic causes of ARF
• Most prerenal causes left unchecked will
result in ATN
• Estimated to be present in 45-70% ICU pts6
– 35-50% of sepsis patients10
ATN Causes
• Severe sepsis
• Nephrotoxins
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Antibiotics: aminoglycosides, pentamidine, HIV drugs
Heme pigments: rhabdomyolysis, hemolysis
Chemo: cisplatin
Contrast agents: iodinated, gadolinium
IVIG
Volume expanders: mannitol, hetastarch
Synthetic drugs: cannabinoids, SPICE, K2
Tubulointerstitial Disease
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Cast nephropathy: multiple myeloma
Urate nephropathy
Sjogren’s
Polycystic kidney disease
Medullary cystic disease
Reflux nephropathy
Sarcoidosis
Nephrocalcinosis
Acute phosphate nephropathy (phos containing
bowel prep)
AIN- acute interstitial nephritis
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Perhaps best thought of as allergic interstitial nephritis
Important to think of as is very often reversible
Should give urine eosinophils, high negative predictive value
In theory any agent could cause it
Induced by a number of drugs
– Antibiotics
• Sulfa a common cause now in the wake of MRSA
• Beta-lactam (methicillin), Cephalosporins*, ciprofloxacin, ethambutol,
isoniazid, macrolides, rifampin, tetracycline, vancomycin, acyclovir
– Other drugs
• allopurinol, amlodipine, azathioprine, captopril, carbamazepine,
clofibrate, cocaine, creatine, diltiazem, famotidine, indinavir, mesalazine,
omeprazole, phenteramine, phenytoin, pranlukast, propylthioruacil,
quinine, ranitidine
• NSAIDs*
• Furosemide, thiazides, triamterene
•
Other causes
– SLE, Sjogren’s
– Etc.
Autoimmune
• Vasculitis
HUS/TTP
Scleroderma
SLE
Polyangiitis c granulomatosis (dz formerly known as Wegener’s
Antiglomerular basement membrane disease (formerly known as
Goodpasture’s)
– IgA vasculitis (disease formerly known as Henoch-Schonlein purpura)
– Polyarteritis nodosa
– Membranoproliferative glomerulonephritis:
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• IE, SLE, Hep B, C, complement dysregulation, microangiopathy
• Monoclonal immunoglobulin deposition
• Parasitic, fungal, shunt nephritis
– Mixed cryoglobulinemia
Autoimmune-Other
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Focal segmental glomerulosclerosis
Post-infectious glomerulonephritis
Thin basement membrane disease
Hereditary nephritis (Alport syndrome)
Mesangial proliferative glomerulonephritis
Fibrillary glomerulonephritis
C3 (complement) glomerulonephritis
HIVAN (HIV associated nephropathy)
Nephrotic syndrome
-Technically will not be in differential for ARF as it does not typically give Cr rise
-Distinguished from nephritic syndrome or glomerulonephritides by protein loss
(nephritis denotes inflammation, essentially requires rbc loss)
-Defined as Proteinuria>3.5g/24h, hypoalbuminemia, and peripheral edema
-without edema it is “nephrotic range proteinuria” (seen in DM, etc)
-In children minimal change disease is major cause
-In adults primary causes: FSGS, membranous nephropathy, minimal change disease
secondary causes: DM, amyloidosis, SLE
-Hyperlipidemia, thrombotic disease frequently seen due to hepatic response to low
oncotic pressure, loss of
-Higher risk of infection, sepsis
-May see malnutrition, hormone imbalance due to renal losses, anorexia, GI sx’s
-Maltese cross: fat droplets under polarized light in U/A
-fatty casts
-Treatment: Immunosuppression, ACEI/ARBs, Na restriction, diuresis, statin
Diagnosis
• Does not require many labs to dramatically
narrow diagnosis
• History is key
• Assessment of volume status
– Clinical
– Laboratory
• Imaging
Labs: CBC
• CBC
– Hgb
• anemia cause of prerenal failure itself
• Hemoconcentration can be clue to hypovolemia
– Often poor platelet function (despite normal
values in renal failure)
Labs: CMP
• CMP
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Hypo/hypernatremia give clues to volume status
Serum Na in association with other labs
K as marker for acidosis, renal clearance
HCO3 marker for acidosis
BUN is independent variable in need to be dialyzed (uremia)
Cr
Hypercalcemia as marker for hypovolemia
Phos clearance dependent on renal function
Albumin for intravascular volume status, liver function marker
• Others
– Uric acid
– Magnesium
– UPEP, SPEP
Labs: U/A
-Don’t
underestimate the power of a u/a
-Probably every inpatient should have u/a done, definitely every ARF pt
-Specific gravity very good marker of volume status
-Protein clues to diagnosis: nephrotic syndrome, DM
-no protein but elevated spot protein/Cr ratio: paraproteinemia:
paraproteins +charged, unlike albumin
-LE marker of UTI
- but +LE but sterile culture may also suggest interstitial nephritis
-occult blood without rbc’s
-hemolysis
-rhabdomyolysis
Labs: U/A
• -rbc’s:
– required for nephritis dx, need to distinguish from traumatic cath
• Dysmorphic rbc’s suggests nephritis
• History and clearance of rbc’s should demonstrate traumatic
– May point to stone, malignancy, postrenal inflammation
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-wbc’s: AIN (especially eos), glomerulonephritis
-renal tubule epithelial cells: ATN
Acanthocytes: glomerular hematuria
-Casts:
-hyaline membrane: more c/w prerenal
-muddy brown casts: more c/w ATN
-rbc: kidney inflammation, nephritic syndrome
-wbc: kidney inflammation
-fatty: c/w nephrotic syndrome
Urine Sodium
• Low in prerenal disease
• High in ATN due to impaired tubule function
• High in setting of diuretics
Starling Forces
Pi
Pc
πc
πc
Jv=Kf([Pc-Pi] – ϭ[Лc – Лi]
P= hydrostatic pressure π= oncotic pressure c= capillary
Kf = filtration constant ϭ= reflection coefficient
π= albumin, intravascular proteins, rbc component
i= interstitial
Osmolality
• Major osmolar contributors in ECF: Na, BUN,
glucose
• Calc. osmolality= 2[Na+] + [Glucose]/18 + [BUN]/2.8
• Therefore Na is major player but glucose can be
• Kidney holds on to Na, BUN in hypovolemia
BUN/Cr
• Ratio >20:1 felt to be consistent with prerenal
• Breaks down a lot
– Upper GI bleed
– Tissue breakdown
– Steroid therapy
• Probably best thought of as a poor man’s
FeNa
FeNa and FeUrea
• Fractional Excretion of Sodium (FENa)
= (PCr * UNa ) x 100 (to give %)
(PNa x UCr)
– <1% consistent with prerenal (hypovolemia)
– Limited in chronic prerenal dz, glomerulanephritis, vasculitis,
CIN
– May not give reliable result in setting of diuretics, in which case
can send:
• Fractional Excretion of Urea (FEUrea)
= (SerumCr * UUrea ) x100 (%)
(SerumUrea x UCr)
– <30-35% consistent with prerenal
Imaging
• Poor man’s u/s, rich man’s PVR: bladder scan
• (PVR)
• Ultrasound:
– Prerenal: Renal artery stenosis
– Intrinsic: echogenicity, size (<7cm definitive for CKD)
– Postrenal: hydronephrosis, stones, bladder volume
• Echo: EF, valvular dz, IE, mural thrombus, PFO
• CT:
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Prerenal: dissection
Intrinsic: radiodensity
Stones
Extrinsic intraabdominal factors e.g. Masses, post-surgical
Liver evaluation
Kidney Biopsy
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Typically reserved for intrinisic renal failure
Many cases of intrinsic failure will progress to biopsy
Generally well tolerated
Risks of bleeding, kidney loss, infection
Ideally risks are balanced against diagnostic need
– How clear is diagnosis?
– Will it change management?
– How high risk is pt to receive it?
• …But it is often easy to justify
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Considerable overlap to many intrinsic causes
Surprisingly many patients with >1 diagnosis on pathology
More than one type of renal insult with known Dx (e.g. SLE)
Major management differences depending on Dx
Treatment: Prerenal.
-All treatment with ARF geared toward treating the
cause and the resulting consequences
In prerenal:
-If hypovolemic, give IVF
-If hypervolemic (e.g. CHF), diurese
-If hypervolemic but intravascularly dry, reverse third
spacing where possible
-If severely anemic, transfuse
-And… stop the damn fool thing you’re doing: diuretics,
antihypertensives, ACEI/ARB’s
Treatment: Postrenal.
-Relieve proximal obstructions:
-ureteral stent,
-lithotripsy
-percutaneous nephrostomy
-Relieve distal obstructions:
-Foley catheter, place or replace
-suprapubic catheter
-continuous bladder irrigation
-TURP, TURBT
-dilation of stricture
-remove foreign body
-Deliver the parasite obstructing the flow
-Remove the mass
-Surgery to restore normal anatomy
-estrogen replacement (possibly as effective as abx for UTI)
Treatment: Hepatorenal
• Increase systemic blood pressure
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Midodrine
Albumin
Terlipressin, ornipressin, vasopressin
Norepinephrine
• Decrease renovascular constriction
– Clonidine acutely
• Decrease portal blood pressure
– Octreotide
– Consider TIPS, weighed against risks, contrast agent
• Dialysis for reversible liver failure or transplant candidates
Treatment: Intrinsic.
-Many cases typically irreversible
-Secondary prevention is generally the rule
-DM management
-HTN management
-improve oxygenation/hemodynamics
-For reversible causes: Stop the damn fool thing you’re doing:
-stop or change antibiotics
-stop or change chemotherapeutics if possible
-Immune modulating agents
-steroids, DMARDs, monoclonal antibodies
-Supportive care for electrolyte abnormalities, acidosis
-Hemodialysis
Acute hemodialysis Indications: AEIOU
Acidosis:
-ph <7.1 may be independent reason to dialyze as may
create hemodynamic instability, arrhythmia,
vasodilation, impaired response to catecholamine
Electrolytes:
-hyperkalemia, hypercalcemia, hyperphosphatemia
Ingestions:
-Li, methanol/ethylene glycol
Overload: volume
-CHF, pulmonary edema
Uremia:
-may cause encephalopathy, cardiac dysfunction
ESRD
• Causes*
– DM 44%
– HTN/nephrosclerosis 28%
– Glomerulonephritis 6%
– Cystic kidney disease 2%
*2012 Annual Report, US Renal Data System
New Directions
•Cystatin C
•NGAL (neutrophil gelatinase associated lipocalin
• may provide earlier diagnosis of ARF
•Interleukin 18
•KIM-1 (kidney injury molecule
•Alk Phos
•“anti-inflammatory”
•In trials to prevent tissue
damage in AKI
•3D printing
•Bladder (done)
•Kidney (coming)
http://www.cbsnews.com/
Conclusions
-Take a thorough history
-Take a systematic approach
-Consider prerenal, intrinsic, and postrenal with every evaluation
-March from heart to urethral meatus cataloging possible problems
-Remember: ~90% of the time it’s just plumbing
-Isolate your category/categories of problems
-Initial confirmatory studies: FeNa, u/a, bladder scan
-Clarify diagnosis/diagnoses:
-imaging
-specialized labs
-biopsy
-Treat the problem
Bibliography
1. Kaufman et al, Am J Kidney Dis 1991; 17: 191-198
2. Nash et al, Am J Kidney Dis 2002; 39:930–936
3. Stevens et al, QJM 2001; 94:533-40
4. Vijayan et al, Semin Nephrol 1998; 18:523-532
5. Davidson et al, Arch Int Med 1991; 151:1809-1812
6. Mehta et al, Kidney Int, 2004; 66: 1613-1621
7. Chertow et al, J. Am. Soc. Nephrol, 2005; 16:3365-3378. Liano et al, Kidney Int, 1996; 50: 811-818
9. Cosentino et al, Nephrol Dial Transp 1994; 9:179-812
10. Liangos et al, Clin J. Am. Soc. Nephrol 2006; 1:43-51
-Images adapted from following sources where not otherwise indicated
• Wikimedia Commons https://en.m.wikipedia.org/wiki/File:Kidney_Cross_Section.png
• www.medicinenet.com - by Melissa Conrad Stöppler
• http://www.urologyhealth.org
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