acute renal failure in the icu. review of anatomy and physiology glomerulus -forms ultrafiltrate of...

Acute Renal Failurein the ICU

Review of Anatomy and Physiology

Glomerulus

-forms ultrafiltrate of plasma


Proximal Tubule

-reabsorbs isosmotically 65-70% of

-reclaims all the glucose, amino acids, and bicarbonate

Secretes protein bound drugs


Loop

-reabsorbs 15-25% of filtered NaCl

-Creates the gradient for the countercurrent multiplier


Distal Tubule

-reabsorbs few percent

-fine tunes- volume, osmolarity (ADH), K (aldosterone), acid-base

Background

• ARF- an abrupt reduction in renal function sufficient to result in azotemia.

Case Presentation

• 88 yo wf with MMP including: CHF, NIDDM, HTN, COPD, and CAD, presents with 3 day h/o subjective fevers, chills, headache, night sweats, flank pain, dysuria, and mild confusion.

• Vitals t 103 p120 rr13 pox 98% RA• Exam – Right flank tenderness• 140/100/50 --------------- 3.0/30/1.1

Presentation (cont)

• ER course– CXR negative– As patient appeared “ill”, arrangements made

for ICU admission for treatment of presumed urosepsis

– Prior to admission- given Toradol 40mg IM for her headache. Narcotics avoiding 2nd to concern of clouding the picture regarding her mental status changes

Glomerular Filtration Rate• Direct measure of renal function

– reduced prior to the onset of symptoms of renal failure– impairment of GFR correlates with structural

abnormalities seen on biopsy

• Normal GFR is approximately 120cc/min – Decreases with age- by age 80, GFR 80– Asymptomatic metabolic abnormalities

(hyperphosphatemia, hypocalcemia, anemia, hyperparathyroidism, osteoporosis) begin at a GFR of < 50 cc/min

– Dialysis usually initiated at GFR < 10 cc/min

Glomerular Filtration Rate

• Difficult to directly measure– as a result in clinical practice we usually

estimate from serum creatinine or creatinine clearance.

GFR vs. Serum Creatinine

0

5

10

15

20

25

30

35

120 100 80 60 40 20 15 2

Glomerular Filtration Rate

Serum

Crea

tinine

- For early disease, serum creatinine is a poor marker of GFR

-lose of 50% of function without a change in Cr

- example- transplant donor

-For late disease, serum creatinine is a poor marker of GFR

-large change in creatinine is a minimal change in GFR

- example- Cr change from 3 to 4 is a change in GFR of only a few cc/min (3cc/min in this pt)

-Serum creatinine only valid in steady-state

-ie immediately after a bilateral nephrectomy– serum creatinine initially normal

Creatinine Clearance

• Effort to improve on the poor results obtained by using serum creatinine

• Creatinine is generated from muscle metabolism of creatine– Therefore proportional to muscle mass

• Age

• Sex

• Weight

Creatinine Clearance

• Most commonly used equation is the Cockcroft Gault Equation– Attempt to account for variable muscle mass

• ((140-age) * weight (kg) ) / (72 *serum creatinine)• *.85 for females

– Derived from approximately 100 white Canadian males without renal disease

• Yet we extrapolate to everyone• As a result– average error 15%

– can be >50% off in 10% of cases– Not uncommon to have a normal serum creatinine with a GFR as

low as 20 cc/min

Our little old lady

• Her baseline serum creatinine = 1.1– “Normal” per the computer values– therefore

ER didn’t think twice about administering NSAID

– Cockcroft-Gault• Calculated CrCl of 27cc/min– or consistent with

moderate to severe renal failure

– 24hr post Toradol, Scr increased to 1.5• CrCl decreased by 25% to 20 cc/min

NSAID associated ARF

• Primarily hemodynamically mediated

• Renal physiology

Afferent

Efferent

Glomerulus

NSAID associated ARFA diseased kidney or a patient with effective

volume depletion (CHF, cirrhosis, dehydration, etc) relies upon prostaglandins to dilate the afferent arteriole to maintain adequate perfusion/GFR

Afferent

Efferent

Glomerulus

Prostaglandins

NSAID associated ARFNSAIDS block prostaglandins

-In musculoskeletal injury this limits vasodiliation and resultant swelling around sites of injury

-but unfortunately also blocks PGs in the kidney

Afferent

Efferent

Glomerulus

Prostaglandins

Afferent

Efferent

Glomerulus

Prostaglandins

NSAIDS

NSAID associated ARFNormal baseline renal function

Afferent

Efferent

Glomerulus

Afferent

Efferent

Glomerulus

Prostaglandins

NSAIDS

Because there is no baseline PG production, NSAIDS have no effect on renal function in patients with

normal volume and renal function

NSAID associated ARFBaseline abnormal renal function or baseline

PG dependent

Afferent

Efferent

Glomerulus

Prostaglandins

NSAIDS

Because there is baseline PG production which is blocked by NSAIDS, the effect is a resultant increased

creatinine

Afferent

Efferent

Glomerulus

Prostaglandins

Cirrhosis, CHF, renal disease or volume depleted

NSAID associated ARFBaseline abnormal renal function or baseline

PG dependent

• In this case the creatinine bump is analogous to angina– It is a manifestation of decreased renal blood flow

• If addressed in the early stages, it is associated with no permanent damage

– Discontinuation of NSAIDS will usually lead to a complete reversal of an increased serum creatinine

• If allowed to persist, can result in irreversible renal damage– Unfortunately, the only way to know the damage is irreversible

it to wait until it occurs

• Impact of ASA qd?

Little old Lady

• ARF noted and no further NSAIDS given• On admission, she was noted to be have

hypertension. Given her history of CHF, addition of an ACE-I was felt indicated. Lisinopril 20mg po qd added to her regimen.

• The following day, her serum creatinine was back to 1.5. Why?

ACE-I and renal function

• Like NSAIDS, the bump in serum creatinine is primarily hemodynamically mediated

Afferent

Efferent

Glomerulus

=Ace-I effect- analogous to removing the end cap from the hose

ACE-I and renal function• Unlike NSAIDS which bump the creatinine

by starving the kidney for blood, ACE-Is bump the creatinine, but in the process actually increases renal blood flow.

Afferent

Efferent

Glomerulus

=Ace-I effect- analogous to removing the end cap from the hose

Little old Lady

• As patient trending toward hypotension, ACE-I d/cd. Creatinine decreased back to 1.3.

• Urine culture positive for GNR sensitive to cipro or bactrim. To minimize the development of flouroquinolone resistance, ICU avoids levaquin and prescribes Bactrim for presumed urosepsis

• The next day the patient’s serum creatinine has again increased to 1.5

• What happened?

Bactrim and Serum creatinine

• Creatinine is removed from the body by glomerular filtration and by active transport in the proximal tubule– In patients with normal renal function,

approximately 10% of the daily load is secreted– As renal failure progresses, the proportion can

increase to up to 50%

Bactrim and Serum creatinine• Bactrim competes with creatinine for the limited number

of active transporters– Once saturated- every molecule of bactrim transported is one less

molecule of creatinine secreted– resulting in increased serum creatinine WITHOUT A CHANGE IN RENAL FUNCTION

• Minimal bump if low serum creatinine (recall you can lose 50% of function without a change in serum creatinine). But a large bump is serum creatinine already elevated (because depend on transporter to remove up to 50% of creatinine and on steep part of curve)

creatinine

creatininebactrim

creatinine

creatinine

creatinine

creatinine

creatinine

creatinine

creatinine

creatinine

bactrim

bactrim

bactrim

bactrim

bactrim

bactrim

bactrim

bactrim bactrim

Urine Space

Blood

Tubule

Little old Lady

• Remains febrile so switched to levaquin and gentamicin. Forty-hours later, Scr now elevated to 2.2 and associated with oliguria.

• Was it gentamicin nephrotoxicity?

Aminoglycoside Nephrotoxicity

• Aminoglycosides are non-protein bound and freely filtered at the level of the glomerulus. Renal excretion is the major route of elimination.

• Accumulate in the tubules where they cause toxicity– Injury visible by EM and light microscopy

Gentamicin Nephrotoxicity

• No hard and fast rule regarding toxicity– Dependent upon duration and total dose

– Risk factors- old age, volume depleted, hypomagnesemia

– Extremely rare before 72hours. Earliest onset typically at 5-7 days.

– Presents with rising BUN/creatinine associated with POLYURIA and other signs of tubular dysfunction

• Proteinuria, bicarb wasting, hypomagnesemia


• Why polyuria?

Afferent

Efferent

Glomerulus Proximal Tubule-reabsorbs 70-80% of total volume

-reabsorbs all glucose, protein, and bicarb

GFR of 120cc/min equals 173 liters of ultrafiltrate per day

If nl urine output 1 liter per day, tubules reabsorb 172/173 liters or 99.4% of the UF

If tubule damaged (by gentamicin or other nephrotoxin), even a 2% decrease in reabsorption results in an extra two liters of urine per day


• No specific therapy beyond stopping the medication

• Consider non-nephrotoxic replacement. If must have an aminoglycoside– tobramycin is less nephrotoxic

• Will take days to weeks to resolve as the gentamicin is gradually released from the tubules– Used to therapeutic advantage in treating UTIs


• Peaks and Troughs– “Peaks kill bugs, troughs kill kidneys”– Not that simple

• Mix of peaks, troughs, and overall duration• Peak studies derived using troughs of 6-7• Trough studies derived using very high peaks• My practice– if life threatening infection– aim for high troughs

(doesn’t do any good to preserve the kidneys and have the patient die). Nephrotoxicity, if it occurs won’t be for many days, by then you have either controlled the infection or lost the patient.

– Experimental nephrotoxicity- canine studies


• QD dosing

05

10152025

3035404550

6 18 30 42

TraditionalQD

Traditional therapeutic range

Post-antibiotic effect (concentration independent killing)


0

5

10

15

20

25

30

35

40Renal Insuff

QD

Traditional therapeutic range

Post-antibiotic effect (concentration independent killing)

No antibiotic coverage

Little old lady

• Continues to spike temperatures despite multiple days of broad spectrum antibiotics. What gets ordered next?

Little old lady

• Contrast CT scan to r/o peri-nephritic abscess or other intra-abdominal process

• Serum creatinine 48 hours later 3.0

Contrast Nephropathy

-Reported incidence of acute renal failure is highly variable (up to 50% depending upon the study)

-but renal failure in studies is typically defined as a bump in Scr of 50% or 0.5 mg/dl -clinically don’t care unless unless requires dialysis- incidence of dialysis is much less -Risk factors- diabetes, baseline renal dysfunction, chronic renal

insufficiency, relative volume depletion (CHF, cirrhosis, ascites, nephrosis, diarrhea)

-Risk is OVERRATED-Practically- unless serum creatinine >5.0-6.0 or diabetic with serum

creatinine >4.0, highly unlikely to experience irreversible renal dysfunction or dialysis

Contrast Nephropathy

- Traditional teaching is that multiple myeloma is at higher risk for contrast nephropathy– this is not true

- Prevention of contrast nephropathy- HYDRATION, HYDRATION, HYDRATION- NS vs.

½ NS- doesn’t matter- Non-ionic better than ionic- Minimize volume of contrast and use non-ionic contrast- Mucomyst protocol--- Jury still out. Probably doesn’t

help.

Little old Lady

• No abscess noted

• Continues to spike temperatures s/p a week on broad spectrum antibiotics– What gets added next?

Little old Lady

• Amphotericin– Polyene antibiotic that is the treatment of choice for the

majority of serious fungal infections.

– Works by attacking ergosterol in fungal membranes• Acts like a MAC of human complement- literally “punches”

holes in the cell walls leading to osmotic cell death

• Cholesterol in mammalian cell walls is very similar– Minor cross reactivity, increases with increased levels

– Where tissue is typically exposed to the highest drug levels in the human body??

Amphotericin toxicity

• What tissue is typically exposed to the highest drug concentrations? – Kidney- especially the distal tubules where

urine concentration occurs.– Therefore the cross-reactivity of amphotericin

for cholesterol is most severe in the distal tubules of the kidney.


• What are the manifestations?– All the distal tubule

functions- acid-base, volume, potassium, Mg

• What can you do to minimize?

Distal Tubule




• Minimize toxicity– NS loading

• Liposomal Amphotericin– Decreased solubilizing

agent- which causes direct nephrotoxicity

– Uptake primarily by the RES cells- lower dose with less net renal exposure

Distal Tubule



Little old Lady

Continues to spike through amphotericin and progresses to frank hypotension with pressures 60-80s for several hours

• Within 24hrs serum creatinine increased to 5.5, and continues to elevate 1 point per day

ATN

• Acute tubular necrosis– Number one etiology of renal failure in the unit setting

– Usually 2nd to hypotension

– Manifest by isosthenuric urine, course and fine granular casts in the urine sediment

– No effective therapy. Supportive treatment only

– Given no additional insults- usually reversible over a 4-6 week period

ARF in ICU

• Mortality severe– MICU- 30-50%– SICU- 50-75%

• Unchanged for 30 years- despite tremendous advances in acute dialysis and patient management.

• Why?– Patients die with renal failure, not from it.

ARF in ICUManagement

• Conversion of non-oliguric to oliguric renal failure– Not a therapeutic maneuver– prognostic only– Useful for assisting in volume management and

hyperkalemia, but no impact on ATN– Nephrectomy analogy


• Avoidance of dialysis – renal recovery will be faster and more complete if dialysis is not initiated

• Don’t exacerbate the situation– No NSAIDS, contrast, avoid hypotension etc


• Renal purpose is to maintain homeostasis- volume, acid-base, and electrolyte

• Volume– Insensible losses 500-1000cc/day– if inputs less than

that– no volume issues• KVO- even 10cc/hr (1 liter every four days—if HD only

removes one liter– that means an extra treatment each week just for the KVO)

• Obviously maximally concentrate all IVs• Sedation– use longer acting agent – volume of MSO4 is much

less than Fentanyl, BZ less volume than propofol



• Electrolytes (primarily K)– Obviously don’t give exogenous K– hidden

sources include antibiotics, Lactated ringers, unnecessary K in TPN

– Goal is < 60 meq/day for dialysis patient, none for a ARF patient



• Acid-base– Avoiding intake is not sufficient– body will generate

acid on a daily basis (2nd to protein catabolism)• Bicarbonte will decrease approximately 2 qd– anything faster

means a superimposed acidosis

• Usually drops to a minimum of 10-12– then bone buffering prevents further fall (pH 7.2ish)

• Could treat by giving bicarbonate– but a volume load



• Uremia– Due to metabolism of proteins

• Urea itself it NOT a toxin– it is a surrogate marker for other toxins which accumulate in renal failure

– Unfortunately, just like acids– cannot avoid problems merely by avoiding input

• If you don’t have protein intake, body will simply metabolize an equivalent amount of protein

– Therefore try to give an adequate amount (1gm/kg) to avoid catabolism, but no extra


• Drugs– Renally-dosed

• Texts available, but general rule of thumb

• Loading dose is unchanged

• If protein bound, less likely to require renal dosing

ARF in ICUNursing implications

• Avoid standing K or IVF orders• Dialysis access issues• Renally-dose medications• If on dialysis– try to arrange meds for after

dialysis– Especially if medications normally cleared by the

kidney

• Blood draws can be performed with dialysis (if no A-line present)

acute renal failure in the icu. review of anatomy and physiology glomerulus -forms ultrafiltrate of...

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