Transcript Acute Renal Failure:

Acute Renal Failure:
Only three possible causes:
1. Inadequate perfusion
2. Intrinsic renal damage
3. Obstruction to the outflow of
urine
Is Renal Failure Acute or
Chronic?
• History: Get the old records
• Take a history:
–
–
–
–
Longstanding or progressive symptoms?
Underlying illnesses?
Medications, including OTC meds?
Prior MD encounters or laboratory work?
• Physical examination:
– Does the patient appear chronically ill?
– Volume status?
– Diabetic retinopathy?
• Ultrasound
• Laboratory data:
– Anemia
– Creatinine level?
Acute Renal Failure:
• Always rule out obstruction.
• Pre-renal vs. intrinsic damage.
– Urine sodium, FENa
» U/P sodium / U/P creatinine
» < 1 vs. > 1
– Urine sediment
• Caveats:
– Contrast nephropathyPigment nephropathy
– Heart failure
– Liver failure
Genesis of Acute Tubular
Necrosis
• Tubular obstruction by debris
• Backleak across damaged epithelium
• Proximal tubular damage leading to increased
delivery to the macular densa with consequent
reduction in GFR mediated by GT feedback.
Acute Renal Failure: Most
Common Causes at PHD
• Sepsis
• Post-surgical (AAA, CABG)
• Rhabdomyolysis
• Drugs:
–
–
–
–
Contrast
NSAIDs
Illicit/suicidal
All of the above
Acute Tubular Necrosis:
Reversing the Process or
Speeding Recovery?
• Diuretics
• Atrial natriuretic peptide
• Low dose dopamine
• Recombinent insulin-like growth factor
• Fenoldapam
• Volume
Diuretics in ARF
• Diuretics may increase urine output in a
patient with ARF, and if volume overload is
present be beneficial by converting an
oliguric patient to one with polyuria, but there
is not evidence that they hasten recovery.
• They will, however, make physicians feel
better and obscure the diagnosis by obviating
the value of urine electrolytes.
• If you feel compelled to give diuretics, please
obtain urine electrolytes and creatinine first.
Anaritide in acute tubular necrosis.
Auriculin Anaritide Acute Renal Failure
Study Group
The administration of anaritide did not improve the
overall rate of dialysis-free survival in critically ill
patients with acute tubular necrosis. However,
anaritide may improve dialysis-free survival in
patients with oliguria and may worsen it in patients
without oliguria who have acute tubular necrosis.
(Allgren RL; Marbury TC; Rahman SN; Weisberg LS; Fenves AZ; Lafayette RA;
Sweet RM; Genter FC; Kurnik BR; Conger JD; Sayegh MH: N Engl J Med
1997 Mar 20;336(12):828-34)
Low-dose dopamine in patients with
early renal dysfunction: a placebocontrolled randomised trial. Australian
and New Zealand Intensive Care Socity
(ANZICS) Clinical Trials Group
Administration of low-dose dopamine by
continuous intravenous infusion to critically
ill patients at risk of renal failure does not
confer clinically significant protection from
renal dysfunction.
(Bellomo R; Chapman M; Finfer S; Hickling K; Myburgh J; Lancet
2000 Dec 23-30;356(9248):2139-43)
Multicenter clinical trial of
recombinant human insulin-like
growth factor I in patients with
acute renal failure.
rhIGF-I does not accelerate the
recovery of renal function in ARF
patients with substantial
comorbidity.
(Hirschberg R; Kopple J; Lipsett P; Benjamin E; Minei J; Albertson T;
Munger M; Metzler M; Zaloga G: Murray M; Lowry S; Conger J; McKeown
W; O’shea M; Baughman R; Wood K; Haupt M; Kaiser R; Simms H;
Warnock D; Summer W; Hintz R; Myers B; Haenftling K; Capra W; et al;
Kidney Int 1999 Jun; 55(6):2423-32)
– Fenoldopam mesylate for the prevention of
contrast-induced nephropathy: a randomized
controlled trial.CONTRAST Investigators.
– Department of Cardiology, Cardiovascular Research Foundation and Lenox Hill Heart and
Vascular Institute, New York, NY 10022, USA. [email protected]
– CONTEXT: The development of contrast-induced nephropathy in patients undergoing invasive
cardiac procedures is associated with a marked increase in cardiovascular morbidity and
mortality. Fenoldopam mesylate, a specific agonist of the dopamine-1 receptor, preserves
renal blood flow after iodinated contrast administration and has shown promise in ameliorating
contrast nephropathy in previous observational and small randomized trials. OBJECTIVE: To
examine the efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive
cardiovascular procedures. DESIGN: Prospective, placebo-controlled, double-blind,
multicenter randomized trial with serial serum creatinine levels measured at a central
biochemistry laboratory (at baseline and 1, 24, 48, and 72 to 96 hours after study drug
administration) and 30-day clinical follow-up. PATIENTS AND SETTING: Between March 2001
and July 2002, 315 patients with creatinine clearance less than 60 mL/min (1.00 mL/s) at 28
centers in the United States were randomized to receive fenoldopam mesylate (n = 157) or
placebo (n = 158). INTERVENTIONS: Patients were hydrated and randomized to receive
intravenous fenoldopam (0.05 microg/kg/min titrated to 0.10 microg/kg/min) vs matching
placebo, starting 1 hour prior to angiography and continuing for 12 hours. MAIN OUTCOME
MEASURE: Contrast-induced nephropathy, defined as an increase of 25% or more in serum
creatinine level within 96 hours postprocedure. RESULTS: Mean (SD) patient age was 70 (11)
years, and 49% had diabetes mellitus. Mean (SD) baseline creatinine clearance was 29.0
(10.0) mL/min (0.48 [0.16] mL/s) (range, 7.5-56.8 mL/min [0.12-0.94 mL/s]), and 157 (108) mL
of contrast was administered during the procedures. The primary end point of contrast-induced
nephropathy occurred in 33.6% of patients assigned to receive fenoldopam vs 30.1% assigned
to receive placebo (relative risk, 1.11; 95% confidence interval, 0.79-1.57; P =.61). There were
no significant differences in the 30-day rates of death (2.0% vs 3.8%, P =.50), dialysis (2.6%
vs 1.9%, P =.72), or rehospitalization (17.6% vs 19.9%, P =.66) in fenoldopam vs placebo
randomized patients, respectively.
CONCLUSION: The selective
dopamine-1 agonist fenoldopam mesylate does not
prevent further renal function deterioration after
contrast administration in patients with chronic
renal insufficiency.
•
JAMA 290:2284-91,2003
Acute Tubular Necrosis:
Reversing the Process or
Speeding Recovery:
• Once the insult has occurred, no
pharmacologic intervention has been
demonstrated to be of any benefit.
Acute Tubular Necrosis:
Treatment
• Optimize volume
–
–
–
–
Physical examination
Chest xray
Hemodynamic measurements?
Do not be over zealous with blood pressure control
• Stop potential nephrotoxins; avoid repeated insults
– Dye studies
– Surgery
– NSAIDs
Question:
• Acute renal failure occurs on day 1 with a
creatinine of 1.2.
• On day 3, creatinine is 3.2.
• On day 6, creatinine is 7.0
• Renal function is:
– getting better?
– unchanged?
– getting worse?
Question:
• Acute renal failure occurs on day one when a
patient’s sole remaining kidney is removed
for malignancy. Creatinine is 1.2.
• On day 3, creatinine is 3.2.
• On day 7, creatinine is 7.0.
• Renal function is:
– getting better?
– staying the same?
– getting worse?
Acute Tubular Necrosis:
Treatment
• Check the MAR daily for inappropriate drugs or wrong
dosages. Do not depend on pharmacy alerts.
• Avoid hypotension and overzealous short-term blood
pressure management.
• Watch potassium.
• Meticulous general medical care.
– nursing
– line changes
• Nutritional support?
– Enteral if feasible
– Little evidence supporting benefit of TPN in an illness of
less than two weeks
– If nutritional therapy is initiated, 1.5 gm/kg of protein
Acute Tubular Necrosis:
Dialysis
• When?
–
–
–
–
Volume status and electrolytes
Etiology and anticipated course
urine output
Risk
• Biocompatible membranes
• Hemodialysis vs. CVVHD
• Is more better?
Timing of Initiation of Dialysis in
Critically Ill Patients with Acute
Kidney Injury.
• “Among critically ill patients with AKI,
initiation of dialysis at higher BUN
concentrations was associated with an
increased risk for death. Although the results
could reflect residual confounding by severity
of illness, they provide a rationale for
prospective testing of alternative dialysis
initiation strategies in critically ill patients
with severe AKI.”
• BUN <76 and >76 chosen.
– Liu, et al. Clin.J.AM.Soc.Nephrol 1:915-919, 2006.
Acute Tubular Necrosis:
Outcome
• ICU mortality = 50%
Acute Tubular Necrosis:
Prevention
• Adequate volume status prior to an anticipated insult.
– Bicarbonate?
• Drugs:
– NSAIDs
– IV contrast
» minimize dosage
» avoid multiple sequential doses
» avoid concomitant or recent NSAIDs
» Stop ACEIs or ARBs in advance
» mucomyst
• Delay surgical procedures after a possible insult.
• Avoid the second hit.
A
Prevention of Contrast-Induced Nephropathy With Sodium Bicarbonate A
Randomized Controlled Trial
Gregory J. Merten, MD; W. Patrick Burgess, MD, PhD; Lee V. Gray, MD; Jeremiah H.
Holleman, MD; Timothy S. Roush, MD; Glen J. Kowalchuk, MD; Robert M. Bersin,
MD; Arl Van Moore, MD; Charles A. Simonton III, MD; Robert A. Rittase, PharmD; H.
James Norton, PhD; Thomas P. Kennedy, MD, MPH
JAMA. 2004;291:2328-2334.
Objective To examine the efficacy of sodium bicarbonate compared with sodium
chloride for preventive hydration before and after radiographic contrast.
Interventions Patients received 154 mEq/L of either sodium chloride or sodium
bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast,
followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure.
Main Outcome Measure Contrast-induced nephropathy, defined as an increase of 25%
or more in serum creatinine within 2 days of contrast.
Results There were no significant group differences in age, sex, incidence of diabetes
mellitus, ethnicity, orcontrastvolume. Baseline serum creatinine was slightly higher
but not statistically different in patients receiving sodium bicarbonate treatment
(mean [SD], 1.71 [0.42] mg/dL [151.2 {37.1} µmol/L] for sodium chloride and 1.89
[0.69] mg/dL [167.1 {61.0} µmol/L] for sodium bicarbonate; P = .09). The primary end
point of contrast-induced nephropathy occurred in 8 patients (13.6%) infused with
sodium chloride but in only 1 (1.7%) of those receiving sodium bicarbonate(mean
difference, 11.9%; 95% confidence interval [CI], 2.6%-21.2%; P = .02). A follow-up
registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and
meeting the same inclusion criteria as the study resulted in 3 cases of contrastinduced nephropathy (1.6%; 95% CI, 0%-3.4%).
Conclusion Hydration with sodium bicarbonate before contrast exposure is more
effective than hydration with sodium chloride for prophylaxis of contrast-induced
renal failure.
MD Scientific,LLC announces
issuance of U.S. Patent
No.7,019,035
• Inventor: Burgess; W.Patrick
• “U.S.patent describing he methodology of
using bicarbonate (intravenous solution and
oral preparations) fothe reduction or
prevention of CIN was issued on March
28,2006….described in May 19,2004 article in
the JAMA….” MD Scientific news release.
• “Continued unauthorized use of the Method
after March 28,2006 constitutes patent
infringement.” letter to Mr. Hawthorne,
3/28/06.
N-Acetylcysteine and ContrastInduced Nephropathy in Primary
Angioplasty
• Intravenous and oral N-acetylcysteine may prevent
contrast-medium-induced nephropathy with a
dose-dependent effect in patients treated with
primary angioplasty and may improve hospital
outcome (NEJM 354:2773, 2006)
Facts and fallacies concerning the prevention of contrast medium-induced nephropathy.
Critical Care Medicine. 34(8):2060-2068, August 2006.
Abstract:
Objective: The aim of this article is to extract from recent medical literature and
nephrologic practice the facts and fallacies concerning the possible prophylaxis of
contrast medium-induced nephropathy.
Data Synthesis: Considerable efforts have been made to develop pharmacologic therapy for
the prevention of contrast medium-induced nephropathy, especially in patients at risk,
such as elderly subjects and those with preexisting renal impairment, hypovolemia, or
dehydration. There is general consensus that hydration protocols implemented before
and after imaging with contrast medium may be effective in preventing contrast mediuminduced nephropathy. However, definitive and convincing data related to amounts to be
infused, infusion timing, and type of solutions (half-isotonic, isotonic saline solution, or
bicarbonate) are lacking. Forced diuresis with furosemide or mannitol and use of
dopamine, together with concomitant hydration, have been proved to be ineffective or
even more risky in the event of inadequate maintenance of euvolemia. Various direct or
indirect vasodilators have been investigated (atrial natriuretic peptide, calcium channel
blockers, angiotensin-converting enzyme inhibitors, and endothelin receptor
antagonists), yet results have been inconsistent and inconclusive. Recent large metaanalyses concerning the protective role of antioxidant action of N-acetylcysteine have led
to the conclusion that the statistical significance of the results is borderline. Preventive
hemodialysis has not proved to be useful; on the contrary, it might worsen the clinical
conditions by inducing hypotension. Hemofiltration, despite some positive studies, is too
complex and cannot be used extensively.
Conclusions: It is believed that prevention is actually achieved by correcting
hypovolemia, dehydration, or both. Normalization of body fluids is probably the
true objective to be achieved by preventive measures in all patients, not only in
those at risk. Because limited data have been collected in intensive care units, at
present, no firm or specific recommendations can yet be provided for the critically
ill.
Acute Tubular Necrosis:
• ref: Diagnosis and Treatment of Acute
Tubular Necrosis. Essen ML, and Schrier RW,
Annals of Internal Medicine 137:744, 5Nov02.