Prevention and Management of Acute

Renal Failure

C. John Sperati, M.D.Division of Nephrology

Johns Hopkins University SOMjsperati@jhmi.edu

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%

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40%

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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