02 sperati prevention and management of acute renal failure
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Prevention and Management of Acute
Renal Failure
C. John Sperati, M.D.Division of Nephrology
Johns Hopkins University [email protected]
Acute Renal Failure Sudden loss of renal function over hours to
days
Reflected by rise in creatinine and/or decrease in urine output
Epidemiology of ARF 7.2% of hospitalized patients 15.7 % CKD vs. 5.3 % nl renal function
Major Causes: Prerenal – Volume depletion, CHF ATN – ischemia or nephrotoxin or sepsis
Other causes: AIN – Drug exposure +/- Characteristic UA Obstruction – Ultrasound Glomerulonephritis – Hematuria, RBC casts, proteinuria
Nash K et al. Am J Kidney Dis. 2002 May;39(5):930-6
ARF Requiring Renal Replacement Therapy in Critically Ill Patients
Metnitz PGH, et al. Crit Care Med 2002; 30:2051-2058
0%
20%
40%
60%
80%
<40 40 - 60 > 60
Age Groups, years
Hosp
ital M
ort
ality
RRT Controls
**
*
**p < 0.001; ** p < 0.05
ICU Mortality with ARF by Era
Ympa et al, AJM August 2005
Prevention Identify that a problem even exists
Cr is an insensitive and often poor marker of renal function in ICU patients
GFR estimation requires global assessment GFR / CrCl equations (inaccurate!) Urine output I/O and daily weights Alternative markers (e.g. phosphorus) Drug clearance (e.g. vancomycin)
Approach to Acute Renal Failure— Classification
New Rise in Serum Creatinine
PrerenalDehydration CHFVasoconstriction
Intrarenal
Glomerular DiseaseGlomerulonephritisNephrotic Syndromes
Interstitial NephritisDrug-relatedOther – infection, idiopathic
Acute Tubular NecrosisIschemia – Hypovolemia, HypotensionMedication – Aminoglycoside, AmphoB, Contrast
Post-renalObstructive Uropathy
Vascular
Question
When titrating pressors in the patient with septic shock, what MAP might you target?
A. MAP > 50 mmHgB. MAP > 55 mmHgC. MAP > 60 mmHgD. MAP > 70 mmHg
Renal Autoregulation with Progressive Hypertensive Kidney Disease
Palmer NEJM 2002;347 Renal Dysfunction Complicating the Treatment of Hypertension
Glomerular Hypoperfusion
ECF volume
Effective volume (CHF, sepsis, cirrhosis)
Glomerular Hemodynamic ∆’s Vasoconstriction (pre glomerular)
NSAID/ COX-2 inhibitor Contrast Amphotericin B Cyclosporine/ tacrolimus Hypercalcemia
Efferent vasodilatation ACE inhibitors/ ARBs
ContrastCSAAmpho
ACE-IARB
NSAID
Case 1: 45 year old with Pseudomonal Pneumonia following Cholecystectomy Treated with cefipime and gentamicin for 14 days.
Normal BP without orthostasis. Urine output 1 L/day. Baseline creatinine 0.7.
Labs (POD 16) Na+ 134, K+ 4.9, CL- 108, HCO3
- 20, BUN 48, Cr 3.0, FeNa=2.4
Urinalysis shows granular casts, no white blood cells, no red blood cells
0
0.5
1
1.5
2
2.5
3
3.5
5 6 7 8 9 10 11 12 13 14 15 16
Creatinine
POD
Question: The most likely diagnosis is:
A. Acute tubular necrosisB. HypovolemiaC. Interstitial nephritisD. Post infectious GN
Case 1: 45 year old with Pseudomonal Pneumonia and ARF
Acute Tubular Necrosis
Ischemic: Prerenal ATN Nephrotoxic:
Aminoglycosides Rhabdomyolysis: cocaine, statins, trauma Contrast Ampho B, cisplatin, IVIG
U/A: granular casts Treatment: Supportive Better outcome in non-oliguria
ATN: Aminoglycoside
Duration of Rx - Usually after 5-10 days Usually non-oliguric May see electrolyte abnormalities
Mg++, K+, others Urine may show granular casts Predisposed by hypotension, concurrent
nephrotoxins and liver disease Supportive care as with most ATN Recovery usually within 3 weeks
Prerenal vs. ATN
TEST Prerenal ATNUrinalysis benign granular castsBUN/Cr > 20 < 15Urine Na < 20 > 40Urine Osm > 500 ~ 300FENa (%) < 1 > 2
( Urine Na x Serum Cr ) x 100( Serum Na x Urine Cr )
Fractional Excretion of Na+ (FENa) (Urine Na x Serum Cr) X 100 < 1% = prerenal (Serum Na x Urine Cr) > 2% = ATN
Normal renal function <1% Most accurate with oliguric ARF
Caveat: Possibly < 1% without volume depletion
Cirrhosis, severe CHF Contrast nephropathy, Acute GN Rhabdomyolysis
Possibly > 2% with prerenal state: diuretics, severe CRF Steiner AJM 1984:77:699-702
Fractional Excretion of Urea
(FEurea)
(Urine UN x Serum Cr) X 100 < 35% = prerenal (Serum UN x Urine Cr) > 50% = ATN
May be better than FENa in pts on diuretics (Carvounis et al, Kid Int 2002; 62:2223)
Rationale: Urea reabsorbed in proximal tubule + inner medulla, not affected by loop and thiazide diuretics
Caveats: Pre-renal with FEurea > 35% if problem with proximal tubule reabsorption: mannitol, hyperglycemia, acetazolamide, sickle cell
CASE 2: 50 yo man perineal prostatectomy x 6 hrs with nl BP. Nl labs pre op. POD 1: I/O 3L / 0.5L
urine output despite IVF and foley:
PE: BP 132/85, euvolemic
143 108 20 Ca2+ = 7.0 4 hrs 146 106 23 5.8 19 2.2 Phos = 6.0 6.4 14 2.6
U/A: dip - lg blood, micro – no rbcs. Muddy casts
Question: What is the next step in your evaluation?A. Obtain renal ultrasoundB. Measure urine myoglobinC. Check FeNaD. Check serum CPKE. Blood smear for hemolysis
ARF after Surgical Procedure
Rhabdomyolysis – body positioning
Hypotension and medication induced ATN are most common
Urinary tract obstruction - narcoticsPositioning for perineal prostatectomy
ATN: Rhabdomyolysis/ Myoglobinuria
Several important etiologies: Drugs – Alcohol, cocaine & heroin Trauma/Compression/Hyperthermia Medications – statins
Clues Exposures above Urinary heme without hematuria Pigmented granular casts in urine
Diagnosis Serum CPK
376 Hospitalized pts with CPK > 10,000
Derek Fine, Unpublished Data
Rate of Decline of CK is Similar Regardless of Creatinine
146 106 23
6.4 14 2.6
ATN: Rhabdomyolysis
Dangerous complications Hyperkalemia Compartment syndrome Hypocalcemia (hypercalcemia with recovery)
Treatment Early aggressive hydration with isotonic saline
May need > 10 l IVF to achieve euvolemia Trauma victims in Lebanon Ron, Arch Int Med 1984
Urine alkalinization – pH > 6.5 Forced diuresis (mannitol if urine output
adequate) – keep UO 100 - 300 ml/hr
Hyperkalemia Treatment Calcium gluconate 1Amp
Insulin 10 units reg IV + 1 Amp D50 Onset 15’, peak 1 hr K+ ~ 0.5-1.5 mEq/L in 1 hr
Albuterol neb 10-20mg (4-8 x nl dose) Use with insulin (40% failure alone) Onset rapid, peak 90’ K+ ~ 0.5-1 mEq/L in 1 hr
Bicarbonate if pH < 7.2
Kayexylate 30-60 gm in 70% sorbitol Onset 1-2 hrs, peak 2-4 hrs 60 gms K+ ~ 0.8-1.0 mEq/L/24 hrs Contraindicated with ileus
Blumberg, AJM 1988 Oct, 85(4): 507
HyperK in dialysis patients
Fever, cough, infiltrate PseudomonasTobra, Piperacillin x 2 wks, NSAIDs; CXR
improved
BUN/Cr 14/0.6 32/3.2PE now: T=38.3, RR nl, truncal rashU/A: tr prot, 2+ heme, many rbc’s, wbc’s
Case 3: 28 year old gunshot victim
Question: What is the best diagnostic study?A. Wright stain of urine B. Tobramycin levelC. 24 hr urine calcium, oxalateD. Kidney biopsyE. Peripheral eosinophil count
Acute Interstitial Nephritis: Signs (Rossert. Kid Int 60 2001 pp804-17)
Methicillin Others
Drug Induced AIN
AIN onset 3 – 5 days on second exposure Up to several weeks on first exposure
Absence of signs does not R/O AIN
Rx: Discontinue medication, ? p.o. steroids
CASE 4: 48 y.o. with CAD develops acute renal failure post cardiac catheterization Cr increase noted on day 4 post procedure
(baseline: 1.1 ; day 4: 1.5) Medications: lisinopril, metoprolol, atorvastatin,
aspirin Exam nl, labs show Cr continues to increase (now
5.0) 8 days after the procedure
Question: This patient likely has which of the following?
A. Interstitial nephritisB. Contrast induced renal failureC. Atheroembolic diseaseD. Pre-renal renal failure
ARF after Arterial Catheterization Post Contrast
ARF within 24-48 hours Prevention with hydration pre and post procedure Recent evidence of benefit of sodium bicarbonate
infusion and possibly N-acetyl cysteine
Merten et al, JAMA, May 19, 2004154 mEq/l NaHCO3
bolus 3 ml/kg/hr 1 hr before;1 ml/kg/hr infusion for 6 hours after
ARF after Arterial Catheterization If not recovering by day 5 post contrast must
consider atheroembolic disease
Can occur spontaneously or after other vascular trauma
Hollenhorst plaque, livedo reticularis and peripheral emboli
Eosinophiluria/eosinophilia, low complement, high amylase
Important to stop anticoagulation – otherwise supportive care
Classical Approach to ARF Management Conservative/Supportive
Prevent further ischemic toxic injury
Dialysis when indicated Azotemia Volume overload Acidosis Hyperkalemia Drug intoxications
Controversial Issues (or not) There is little evidence that low-dose
dopamine is of benefit in prevention or treatment of ARF
Loop diuretics do not improve outcome in ARF. May contribute to increased mortality if delays RRT
Timing of RRT initiation Early (BUN < 60 – 100) vs late (BUN > 100)
Renal Replacement Therapies
Intermittent hemodialysis (IHD) Continuous veno-venous hemofiltration
(CVVH) CVV hemodialysis (CVVHD) CVV hemodiafiltration (CVVHDF) Slow low efficiency dialysis (SLED) Peritoneal dialysis (PD) Slow continuous ultrafiltration (SCUF)
Prescribed Dialysis in ARF
Evanson JA et al. Kidney Int. 1999 Apr
CVVH Dose TrialRonco C et al. Lancet. 2000 Jul
Group 120 ml/kg/h
Group 235 ml/kg/h
Group 345 ml/kg/h
Number 146 139 140
Age 61 59 63
% Sepsis 14 12 11
Apache II 22 24 22
UF (L/24h) 32 58 72
CVVH Dose Trial – High vs Low Dose
Ronco et al: Lancet 2000; 356:26-30
Renal Replacement Therapy in ARF: Dose of CVVH
41%
57% 58%
0%
20%
40%
60%
80%
100%
Surv
ival
20 mL/kg/hr 35 mL/kg/hr 45 mL/kg/hr
Ultrafiltration Rate
Ronco et al: Lancet 2000; 356:26-30
Daily Dialysis in ARFSchiffl H et al. N Engl J Med. 2002
172 eligible patients 160 randomized
Daily dialysis vs every other day dialysis 74 pts daily vs 72 patients every other
Daily Alternate Day
Time 3.3 +/- 0.4 3.4 +/- 0.5
QB 248 +/- 45 243 +/- 25
Prescribed Kt/V 1.19 +/- 0.11 1.21 +/- 0.09
Delivered Kt/V 0.92 +/- 0.16 0.94 +/- 0.11
Frequency of Hemodialysis in ARFSchiffl H et al. N Engl J Med. 2002
Frequency of Hemodialysis in ARFComparison of Groups During Therapy
Schiffl H, et al. N Engl J Med 2002; 346:305-310
Equivalent Urea Clearance
Adapted from Casino FG et al. Nephrol Dial Transplant. 1996 Aug.
Dialysis Modality in ARF RR of death for IHD versus continuous
Tonelli AJKD 2002 40:875-885.
Dialysis Modality in ARF Continuous vs intermittent
Absence of adequately powered studies
Best modality for the unselected ICU patient is unclear
Consensus: Continuous therapy for patients with unstable hemodynamics, increased ICP
Final Thoughts Better to prevent than to treat ARF
Kidney biopsies are not contraindicated in ICU setting
Is more dialysis better? Ongoing trials underway
Best modality of RRT and optimal timing of initiation are unknown