Transcript To “Pee” or not to “Pee”—the KIDNEY in health and disease

To “Pee” or not to “Pee”—the
KIDNEY in health and disease
Barb Bancroft, RN, MSN, PNP
CPP Associates, Inc. Chicago IL
([email protected])
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Renal diseases are responsible for a great deal of
morbidity but are not major causes of mortality.
Approximately 35,000 deaths are attributed to renal
disease per year (as compared to 750,000 deaths due
to heart disease, 400,000 due to cancer, and 200,000
due to stroke). Millions of persons are affected
annually by nonfatal kidney diseases, most notably
infections of the kidney or lower urinary tract, kidney
stones, and renal obstruction. Twenty percent of all
women have a urinary tract infection or kidney
infection at some time in their lives, and at least 1% of
the U.S. population develops kidney stones. Dialysis
and renal transplantation keep many people alive who
would formerly have died of renal failure, adding to the
pool of renal morbidity.
The kidney as an innocent
bystander…
• In addition to primary kidney disease, the
kidney is involved in many systemic
diseases and conditions
• The deadly duo--“Sugar” diabetes and
hypertension
• HF (Heart failure)
• Septic shock, hypovolemic shock
• DIC (Disseminated intravascular
coagulation)
The kidney as an innocent
bystander…
• Autoimmune diseases—lupus,
autoimmune glomerulonephritis,
Goodpasture’s disease, Wegener’s
granulomatosis, sarcoidosis
• Toxic effects of drugs—aminoglycosides,
radiocontrast agents, amphotericin,
cisplatinum, acetaminophen
• Cancer—malignant infiltration, multiple
myeloma
Let’s start at the very beginning…
• How much
embryology did you
get in nursing school?
• The sperm meets the
egg and then…
Embryology—the development of
the kidney
• The kidneys and the ears from the same
mesenchymal tissue
• The otorenal axis
• Nephrotoxic drugs and ototoxc drugs
Time to refresh your memory with a little
“gross” anatomy
• Kidneys located in the retroperitoneal
space between T12 and L3
• Right lower than the left
The kidney…retroperitoneal
space
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CVA tenderness
Acute pyelonephritis
Glomerulonephritis
Palpation? Can you palpate the kidney in
an adult?
• Not unless the kidney is HUGE…(tumor)
• Polycystic kidney disease (PKD)
Polycystic kidney disease
• Autosomal dominant polycystic kidney disease
(ADPKD)
• 1/1000; C>AA; 4-10% of patients w/ kidney
failure on dialysis or needing transplant
• 50% by age 50 have renal failure
• Kidneys can be the size of a football
Gross anatomy
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Renal capsule
Renal cortex (glomeruli)
Renal medulla (tubules)
renal papillae
the renal interstitium (columns)
renal pelvis (pyelo)/calyces
Pyelonephritis vs. glomerulonephritis
Plus the associated structures (ureters, bladder,
urethra, prostate)
Gross Anatomy—blood supply
• Aorta→renal artery→branches into
arcuate→
Blood supply to and from the
glomerulus
• Afferent arteriole delivers blood to the
• Glomerulus—a tuft of capillaries
• Blood exits via the efferent arteriole
Gross Anatomy—blood supply
• renal vein → inferior vena cava → right
atrium
What can go wrong with the blood
supply into and out of the kidney?
• Atherosclerosis of the renal artery or aorta
• Hypertension with decreased blood flow
• Diabetes with hypertension and
atherosclerosis
• Clamping the aorta above the renal artery
(AAA surgery)
• Sudden cessation with a renal artery
embolus
What can go wrong with the blood
supply to and from the kidney?
• Decreased blood pressure with acute blood loss
and hypovolemic shock, heart failure,
dehydration, septic shock
• Renal artery vasoconstriction with NSAIDs;
efferent arteriole vasodilation with ACE inhibitors
• Microthrombosis of glomeruli—DIC
(disseminated intravascular coagulation)
• Immune complex deposition in the glomerulus
triggering the inflammatory response (lupus
nephritis)
Atherosclerosis of the aorta and
renal artery
• Fatty plaques in the renal artery--chronic
decreased blood flow to the kidney
• Renal atrophy/increased release of
renin→angiotensin→
aldosterone (RAA)
• Hypertension
• CKD (chronic kidney disease)
• Which comes first?
• Who’s at risk?
Who’s at risk?
• All of the above are proatherosclerotic and
proinflammatory
• Inflammation (and oxidation) damage
endothelial cells
• LDL cholesterol is deposited in the blood vessel
and starts to form atherosclerotic plaques
• Smoking and hypertension are also
vasoconstrictive, decreasing blood flow to the
kidney
• PREVENTION
Prevention…
• Stop smoking
• Lower BP w/DASH
diet
Anti-inflammatory diet
• Decrease trans and saturated fats
• Increase fresh fruits and vegetables (high
ORAC number—the B’s)
• Omega-3 fatty acids
• Olive oil
• Nuts
How about the Cardiologist’s diet?
• “If it tastes
good, spit it
out!”
Prevention—say YES to drugs!
• Lowering blood pressure and protecting
the kidneys
• ACE inhibitors (“prils”) and/or ARBs
(“sartans”)
(ACE=angiotensin converting enzyme and
ARB=angiotensin receptor blockers)
Obviously “angie” is a problem if all we want
to do is inhibit “her”
“prils” and “sartans” to the rescue (ACE
inhibitors and angiotensin receptor blockers or
ARBS)—protect kidneys
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Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Moxepril (Univasc)
Benazepril (Lotensin)
Quinapril (Accupril)
Trandolapril (Mavik)
Ramipril (Altace)
Is there a #1 “pril”?
• losartan (Cozaar),
valsartan (Diovan),
candesartan (Atacand),
telmisartan (Micardis)
irbesartan—Avapro
olmesartan—(Benicar)
“PRILS”—The ACE inhibitors
• Who is “ACE” and why do
we want to inhibit him?
• Angiotensin Converting
Enzyme (ACE) inhibits
the conversion of AT1 to
AT2
RENIN
ANGIOTENSIN 1
ACE--
• What are the functions of
angiotensin 2?
ANGIOTENSIN 2
What does angiotensin 2 do?
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“Tenses” your “angios”—vasoconstricts
Triggers release of “AL”—aldosterone (from the
adrenal cortex to save Na+ & H2O and excrete K+)
The above 2 are normal compensatory mechanisms
in heart failure … If you block them, the heart gets a
breather…
What else does angiotensin-2 do?
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Increases inflammation in the arteries
Prothrombotic
Increases tissue resistance to insulin
Potent growth factor
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“Angie” and the healthy kidney…
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Afferent arteriole
(vasodilated via
(prostaglandins)
Blood entering
glomerulus
Glomerulus→filter
Efferent arteriole
(vasoconstricted via
(angiotensin 2)
Blood exiting
glomerulus
PG
filter
AT2
Toilet
• The pressure difference between the afferent
and the efferent arterioles sets up the glomerular
filtration pressure and determines the rate at
which the kidney filters urine (the GFR)
• The afferent arteriole is in a constant vasodilated
state—partially due to prostaglandin synthesis
• The efferent arteriole is in a constant
vasoconstricted state—due to angiotensin 2
The Diabetic Kidney…hyperglycemia/HTN (the
deadly duo)
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Afferent arteriole
(  vasodilation by
(  prostaglandins)
• Blood entering
glomerulus
• Glomerulus→filter
• Efferent arteriole
(  vasoconstriction via
(  angiotensin 2)
• Blood exiting
glomerulus
Microalbuminuria
(between 30 mg—300
mg of alb/g creatinine—
10-fold > risk of RD &
CKD)
Why is microalbuminuria a “bad”
thing?
• There is a 4-fold increase in acute coronary syndromes
in Type 1 DM greater than 35 years old;
• When microalbuminuria is present the risk is increased
by a factor of 140!
• The presence of albuminuria suggests that large vessel
walls are more permeable to lipoproteins or damage
from the local release of growth factors
• Aggressive treatment of dyslipidemia demonstrates
beneficial effects not only on macrovascular disease but
on microvascular disease as well (retinopathy and
nephropathy)
What do the “prils” and “sartans” do
in the diabetic kidney?
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Vasodilate the efferent arteriole
Decreases intraglomerular hypertension
Reduce filtration pressure
Decrease microalbuminuria
Decreases destruction of the glomerulus
(Once you lose a glomerulus, that’s it)
Prevent the progression of nephropathy
PRILS and SARTANS can decrease the decline by 50%
or MORE in the diabetic kidney
• If the HbA1C is greater than 6.2, the risk for CV disease
and renal disease starts to increase!!
Side effects…
• Hypotension
• Hyperkalemia (excreting sodium and water
and retaining potassium)
• Hypoglycemia
• Cough
• Angioedema (“Does my voice sound funny
to you?”)
What is the mechanism of the ACE inhibitorinduced angioedema?
• ACE inhibitors inhibit the breakdown of
bradykinin
• Accumulation of bradykinins have 3 results:
1) vasodilation
2) increased permeability
3) increased hereditary, acquired, and ACE
inhibitor-induced angioedema
• High-risk patients—patients with a C1 esterase
inhibitor deficiency; African Americans (4.5x  )
• Side effect has been shown to occur up to 1
year after starting ACE inhibitors
Side effects…Rx of
hyperkalemia
Hyperkalemia-- Add a thiazide diuretic to the “pril” and
voilá!
• Capozide (captopril + thiazide)
• Vaseretic (enalapril +thiazide)
• Prinizide (lisinopril + thiazide)
• Zestorectic (as above)
• Lotensin HCT (benazepril + hydrochlorothiazide)
• Decrease foods containing potassium especially
when the ACE inhibitors are combined with
spironolactone (Aldactone) or the newest potassiumsparing agent—eplerenone (Inspra)…
Adding drugs that block aldosterone—
spironolactone (Aldactone) and eprelrenone
(Inspra)
• Be really careful to check K+ levels within the
first week after adding Aldactone or Inspra
• RALES (1999) (Random Aldactone Evaluation
Study)—adding Aldactone postpones or
prevents 200 deaths/1000 people w/CHF
• BUT…For every 1000 new spironolactone RX in
heart failure patients, there are 50 more
hospitalizations for hyperkalemia
• Dose 12.5-25 mg per day of spironolactone
Decrease the intake of foods with
high potassium…
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Banana (1 m) 422 mg
Potatoes (with skin) 540 mg
French fries (1 med) 924 mg
Halibut (3 oz) 490 mg
Spinach (1c) 839 mg
Pasta sauce (1c) 940 mg
Oranges 1 m 237 mg
Prunes (elderly) 10 615 mg
Health.harvard.edu/heartextra for K+ content of 1,200
foods
Other potential K+ boosters…
• Stop taking any K+ supplements including
salt substitutes such as K+ iodide
• Go easy on the NSAIDS (decrease GFR)
with retention of fluids and electrolytes
(including K+)
• Herbal or natural remedies with hefty
doses of potassium include noni juice,
Siberian ginseng, and hawthorn berries
(Harvard Heart Letter, December 2004)
Prevention
• The “statin” drugs should also be prescribed—
decrease total cholesterol,
• Decrease LDL-cholesterol
• Shrink plaques including plaques in the renal
artery
• Prevent the formation of new plaques, and,
• Decrease inflammation in the vessels
“Statins” to the rescue to decrease
hyperlipidemia
• Hyperlipidemia is a disease-promoting
factor thought to perpetuate previous
glomerular injury. Both epithelial cells and
mesangial cells have receptors for LDL
and oxidized LDL and the statins have
been shown to inhibit mesangial
proliferation
• Who are the statin sisters?
Who are the statins?
• Lovastatin (Mevacor)
• Pravastatin (Pravachol)
• Fluvastatin (Lescol)
• Rosuvastatin (Crestor)**
• Atorvastatin (Lipitor)
** Higher HDLs=better kidneys (107 patients w/
T1DM; 42 w/ albuminuria; 65 without; the
average HDL in patients w/ albuminuria was 55
mg/dL vs. 66 mg/dL; for every 21-mg/dL
increase in HDL, people are ½ as likely to
develop albuminuria (Diabetes Care January 06)
How about the use of NSAIDS and ACE inhibitors
at the same time in a patient with renal
insufficiency?
• ACE inhibitors and ARBs vasodilate the efferent
arteriole by inhibiting the function of angiotensin
2
• NSAIDS vasoconstrict the afferent arteriole by
blocking prostaglandin synthesis
• Front door closes, back door opens
• THIS can and does, lead to acute renal failure in
patients with renal insufficiency
The anatomy of a nephron—
greater detail
• The basic functioning unit of the kidney
• The nephron—1.5 million per kidney in
normal birth weight individuals**
• Afferent arteriole → glomerulus →
basement membrane → Bowman’s
capsule → tubular system (proximal
convoluted tubule (PCT), Loop of Henle,
distal convoluted tubule (DCT), collecting
duct)
Premature babies/LBW babies
• Is your risk of hypertension related to the
number of nephrons you were born with?
• LBW babies are much more likely to
develop hypertension later on in life and it
may be due to the fact that they had less
nephrons to start with
• Autopsies on patients between 35-59
• 10 kidneys w/ known hypertension; 10 w/
normal BP
Premature babies/LBW babies
• Average number of nephrons in people w/ HBP
was fewer than ½ that of people w/ normal BP
• Couldn’t find damaged nephrons or nephrons
that had dropped out—suggesting inherited # of
nephrons
• Good prenatal nutrition and the # of nephrons—
restricting proteins ↓ # of developing nephrons
• (N Engl J Med 9 Jan 2003)
Premature babies/LBW babies
• Another implication
• Screening kidney donors for LBW may be
important when deciding who might be a
candidate as an appropriate donor
• The donor loses 50% of nephrons—if remaining
kidney has fewer #’s due to LBW, this increases
the risk of hypertension in the donor—
overworked and underpaid triggering the release
of renin-angiotensin-aldosterone
The filtration membrane
• The filtration membrane—3 layers
1) the endothelial cells of the glomerulus
2) the basement membrane between
the glomerulus and the,
3) epithelial cells of Bowman’s capsule
• Diseases—1) Lupus nephritis 2) sugar
diabetes 3) nephrotic syndrome
The glomerular filtration membrane
Glom
1.
2.
3.
The glomerular capillary wall
(endothelial cells)
The basement membrane (a
glycoprotein layer)
The fenestrated wall
(epithelial) cells of Bowman’s
capsule into the first part of
the tubule (the proximal
tubule)(epithelial cells)
1) Lupus nephritis/glomeruloneprhitis
2) diabetic nephropathy 3)
nephrotic syndrome (90% of
kids with IgE mediated disease)
1
BM
BC
PCT
3
2
3
A note on the tubules of the
kidney…
• The tubules (like Bowman’s capsule and
the PCT—proximal convuluted tubule) are
lined with epithelial cells
• The epithelial cells are extremely
vulnerable to hypoxia
• Without oxygen, the epithelial cells
become necrotic and slough into the
tubule; clogging the works resulting in
• Acute tubular necrosis (ATN)
Ethylene glycol nephrosis
• Dogs and cats love the sweet taste of antifreeze
• Crystals precipitate in the tubular lumen
resulting in intrarenal obstruction, degeneration
and necrosis of the lining of the tubular
epithelium
• Irreversible renal failure
MAJOR FUNCTIONS OF THE
KIDNEY
• Regulation of water,
solutes, electrolytes, and
acid-base balance
1) urea, creatinine
2) sodium, potassium,
calcium, phosphorus
3) hydrogen and
bicarbonate
• If the kidney FAILS…
Retention of water—edema,
weight gain, HTN
Retention of urea, creatinine
(most sensitive)
Retention of sodium,
potassium resulting in
hypertension,
hyperkalemia,
Retention of H+ ions—
metabolic acidosis
Aids in Vitamin D metabolism
• Vitamin D is necessary for the absorption of
calcium from the GI tract
• With increased phosphate retention or
decreased calcium absorption the parathyroids
increase their production of PTH
• PTH breaks down bone to replace the calcium—
secondary hyperparathyroidism
• Osteomalacia and chronic renal failure
• Phosphate binders in patients with renal failure
Some notes on Vitamin D
• 10-15 minutes of exposure to sunlight on face, hands,
and arms 2-3 days per week is required to synthesize
sufficient amounts of vitamin D (in shorts and a t-shirt,
people can soak up enough UV-B rays to produce
12,000 U of vitamin D within 20 minutes)
• Sunscreen? SPF-8?
• Food—fatty fish, cod liver oil, and egg yolks
• Fortified foods—milk, breakfast cereals, margarine,
butter, certain brands of OJ and yogurt
Secretes renin from the
juxtaglomerular apparatus
• Renin (kidney)—
angiotensin 1 (liver) –
angiotensin 2
(tissues)—
aldosterone (primarily
from the adrenal
cortex; some tissue
aldosterone
production as well)
RENIN
ANGIOTENSIN 1
ANGIOTENSIN 2
Major functions of the kidney
• Direct renin inhibitor—new antihypertensive drug known as TEKTURNA
• Renin—angiotensin—aldosterone with
increased blood pressure
• Drugs to block the system—ACE inhibitors
(“prils”), angiotensin receptor blockers
(“sartans”), and aldosterone antagonists
(spironolactone/Aldactone and eplerenone
(Inspra)
Major functions of the kidney
• Secretes erythropoietin to stimulate the bone
marrow to produce RBCs—the failing kidney
does not secrete erythropoietin
• One of the earliest signs of declining renal
function is the presence of anemia
• ~ 8 million of the 20 million have stage 3 CKD,
and almost half are anemic (Stage 3—is
characterized by a GFR of 30-60 mL/min/1.73 m)
• Anemia has been independently associated with
an increased risk of left ventricular dilation, left
ventricular hypertrophy, coronary artery disease,
heart failure
Anemia and CKD
• The link between heart failure, CKD, and renal failure is known as
cardiorenal anemia syndrome
• Synthetic erythropoietin
• ESAs (erythropoiesis stimulating agents) have been available since
1989
• Epoetin alfa (1989) and darbopoetin alfa (2001)
• BUT…fully restoring hemoglobin (greater than 13 g/dL) in patients
with CKD increases their risk of all-cause mortality, poorly controlled
BP, and AV access thrombosis…so partial restoration of Hb is
advised.
• Target Hb of 11-12 g/dL; Monitor Hb at least monthly when on ESAs
• (each 1 gm ↓ causes  LV dilation by 42%)(50% lower survival rates
with LVH)
Major functions of the kidney
• Conservation of free water (ADH receptors
on the distal tubule and collecting duct)
• Diurnal rhythm—kicks in around midnight
with water conservation and reduced
urination at night
• Early a.m. specimen is concentrated
• One of the earliest signs of renal
insufficiency is the inability to concentrate
urine at night
• OR…beer and ETOH inhibit ADH—
urinating all night
• And morphine increases ADH as well as
tightens the urinary sphincter (urinary
retention—problem after surgery)
Nocturia-what are the causes?
• Inability of the kidney to respond to ADH—immaturity?
Enuresis in kids? (DDAVP); Nephrogenic diabetes
insipidus—genetic lack of receptors
• Booze before bedtime—alcohol inhibits ADH
• “sugar” diabetes—glucose is an osmotic diuretic
• Enlarged “prostrate”
• UTI
• CHF
• Pregnancy
• Diuretics at bedtime—lasix
• Morphine increases ADH and tightens urinary sphincter
resulting in urinary retention
Now that you know what the kidney
is supposed to do…
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Accurate intake and output
Daily weights
Lab tests
Blood pressure
Check for signs of fluid retention
Check volume status—peripheral edema,
jugular vein distention, S3
Doin’ the double-dub—S3 (also listen for an
S4 with LVH; PMI displaced laterally)
Lab tests
• BUN
• Serum creatinine
• Glomerular filtration
rate as measured by
the MDRD formula
Blood urea nitrogen (BUN)
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BUN (8-18 mg/dL)—three reasons for an
elevated BUN
– decreased GFR
– increased load of urea for excretion from the
diet
– Increased tissue metabolism
What about the Atkin’s diet?
• High content of valine and lysine increases
intraglomerular pressure and can accelerate
kidney damage in impaired kidneys
• Should a diabetic go on the Atkin’s diet?
• How about an 80-year old?
• No harmful effect in young people with normal
kidneys
Serum Creatinine
• Can be influenced by age, gender, lean
body mass, diet, concomitant diseases,
circadian rhythm, and stability of renal
function, tubular secretion, & drug therapy
Serum creatinine (varies with sex and age)
newborn (0.3-1.0)
infant (0.2-0.4)
child (0.3-0.7)
Adolescent (0.5-1.0)
Adult Male (0.6-1.3)
Adult Female (0.5-1.2) (women have 15% less muscle
mass than men, hence serum creatinine is lower)
Elderly patients—decreased production due to decreased
muscle mass forming creatinine combined with
decreased filtration=serum creatinine may be WNL
Important notes…
– Starting a diabetic patient on Metformin
(Glucophage)—serum creatinine must be checked
first; do not use Metformin if the serum creatinine is
greater than 1.4 in a female and greater than 1.5 in
the male
– If a diabetic on metformin develops heart failure, stop
the metformin IMMEDIATELY; with decreased
perfusion to the kidney the metformin can build up in
the blood and cause lactic acidosis
– Metformin and radiocontrast dye—they both compete
for excretion; the dye wins, metformin is retained; stop
metformin for 48 hours AFTER a procedure with the
dye
Important notes…
– The NIH Consensus conference of 1993
recommends that patients with chronic kidney
disease be referred to a renal team when the
serum creatinine has increased to 1.5 mg/dL
in the female and 2.0 mg/dL in the male
– Most nephrologists report that patients are
usually referred to a renal healthcare team
when their serum creatinine level is 3-4 mg/dL
or greater…earlier is better!
The elderly, serum creatinine and
the GFR
– What is the glomerular filtration rate? A determination
of how much the glomerulus filters; can be
determined by how much creatinine is CLEARED into
the toilet (also known as creatinine clearance)
– GFR decreases with age—the 1% rule (a 30-year-old
has a GFR of 120 mL/min)
– 75-year-old = 1.2 mL/min x 45 years = 53 mL/min;
120-53=67 mL/min in a HEALTHY 75-year-old (not
taking into account weight, ethnicity, or gender)
Calculating the GFR
• MDRD (modification of diet in renal
disease) formula
• ml/min/1.73m2 = 170 x (SCr)-0.999x
(age)-0.176 x (BUN)-0.170 x (alb)0.318 x
(0.762 if female) x (1.180 if black)
• GFR calculators are available at:
• http://kidney.org
• http://nephron.com/cgi-bin/MDRD.cgi
Creatinine clearance
(slide switch)
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normal GFR in young adults is 120-130
mL/min/1.73 m2
a GFR of less than 60 mL/min/1.73 m2 represents a
loss of more than half of normal kidney function
GFR>90 = normal
GFR 60-89=mild renal insufficiency
30-59=moderate renal insufficiency
15-29=severe renal insufficiency
Less than 15=failure
The pitfalls of relying on serum
creatinine to evaluate renal function
• 85-year-old, 50-kg Caucasian female vs. 55-year-old,
70-kg African American Male
• SCr 1.5 in each of the patients
• CrCl as measured by the MDRD (using age, sex, color
and serum creatinine)
• 35 mL/min/173m2 in the C female (moderate renal
insufficiency)
• 63 mL/min/1.73m2 in the AA male (mild renal
insufficiency)
Functional overview
• Filtration—passive transport of material from the blood
through the glomerulus to the tubular system
• 125 ml/min or 20% of plasma; amounts to 180 L per day;
only material of a certain size of filtered
• Albumin is too big—70,000 molecular wt.
• Creatinine is filtered and not reabsorbed or changed to
any great extent, until it reaches the toilet, hence,
creatinine clearance is a test used for filtration (GFR)
• Creatinine is produced in muscle—people with large
muscle bulk have higher values; people with low muscle
bulk have lower values (the elderly—BUT…they also
have decreased filtration as a function of aging)
Functional overview
• Blood is delivered via the afferent arteriole at
approximately 60-75 mm Hg; if the blood
pressure is higher than all opposing pressures,
the filtrated is pushed through the GFM—
electrolytes, nonelectrolytes (BUN, creatinine),
and water
• If opposing forces are higher, or filtration slows
down for any reason, sodium and water are
retained, BUN and creatinine are retained (and
start rising), and urine flow decreases (oliguria)
or stops (anuria)
Functional overview
• Tubular absorption—primarily the function
of the proximal convoluted tubule;
substances are transferred from the renal
tubular lumen into the small peritubular
capillary network surrounding the tubular
system
• How much is reabsorbed?
• What is reabsorbed?
Functional overview
• The PCT reabsorbs approximately 65-80%
of the filtrate; bulk reabsorption of water
and sodium and chloride (80%)
• 100% of the glucose, potassium and
amino acids are reabsorbed
• Tm (transport maximum and glucose)
Functional overview
• Tubular secretion—involves the transport of
materials from the peritubular capillary network
surrounding he tubular system into the cells
lining the tubular lumen and into the tubular
lumen for excretion
• Primarily the function of the distal convoluted
tubule
• How much is secreted? What is secreted?
• Excess K+ and excess H+ are the two biggies
• With renal failure both of these cations are
retained—resulting in hyperkalemia and acidosis
Acute Renal Failure
• Comprises a family of syndromes that are characterized
by an abrupt (over hours or days) decrease in the GFR
• May occur in the absence of prior renal dysfunction, or it
may represent an acute exacerbation in a patient with
known stable chronic kidney disease
• Oliguria (less than 400 to 500 ml/24 h) may be a
presenting manifestation, although the urine volume may
be variable, ranging from less than 100 ml to greater
than 3 L per day
• Primary manifestation is the accumulation of nitrogenous
waste products—primarily creatinine and BUN
Classification of ARF syndromes (in
tertiary care centers)
• Prerenal—before (21%)
• Renal—within (intrinsic)(45% with ATN)
• Postrenal—after (10%)(obstructive uropathy)
• 748 cases of ARF in 13 tertiary care centers; overall
mortality 45%; 60% in patients with ATN, 35% in patients
with prerenal ARF, 27% in patients with obstructive
uropathy)
• 34% of the 748 ARF episodes occurred in ICU patients;
ATN accounted for 76% of ARF, prerenal azotemia for
18%, obstructive uropathy less than 1%)—overall
mortality in this critically ill subgroup was 71.5%
compared to 31.5% in ARF patients not requiring ICU
Prerenal ARF
• Characterized by decreased renal perfusion
resulting in a hemodynamically mediated
reduction in glomerular filtration in the absence
of injury to the renal parenchyma
• Reversal of the hemodynamic insult results in
prompt restoration of renal function
• If renal hypoperfusion is sustained, overt cellular
injury may develop with transition from prerenal
to intrinsic (intrarenal) ARF
Causes of prerenal ARF
•
•
•
•
•
•
•
Intravascular volume depletion—
GI losses
Renal—diuretics, osmotic diuresis
Cutaneous (burns)
Hemorrhage (hypovolemic shock)
3rd spacing (pancreatitis)
Decreased effective blood volume—CHF,
cirrhosis, nephrotic syndrome, sepsis,
anesthesia
Causes of prerenal ARF
• Altered intrarenal hemodynamics—such as
preglomerular (afferent) vasoconstriction (NSAIDS—
COX1, COX 2)(prescription NSAID use increases risk of
ARF in elderly by 58%)
• Cyclosporine, tacrolimus, hypercalcemia
• postglomerular (efferent) vasodilation (ACE inhibitors,
angiotensin receptor blockers)(older age, diuretic RX
and diabetics highest risk)
• Abdominal compartment syndrome—increased intraabdominal pressure with increased renal venous
pressure (trauma patients requiring massive volumes;
fluid sequestration, pancreatitis, peritonitis)
Intrinsic ARF
• Associated with renal parenchymal injury
• Most commonly results from ischemic or toxic
injury to renal tubular epithelial cells
• ATN, acute tubular necrosis
• Also includes glomerular diseases (autoimmune)
and vascular and interstitial inflammatory
processes (allergic) that are associated with
rapid loss of renal function
Causes of intrinsic ARF
• ATN
• Ischemic—hypotension, hypovolemic shock, sepsis,
cardiopulmonary arrest, cardiopulmonary bypass
• Nephrotoxic—drug-induced such as the
aminoglycosides, radiocontrast agents, amphotericin,
cisplatinum, acetaminophen
• Pigment nephropathy—intravascular hemolysis and
rhabdomyolysis (massive muscle damage—trauma,
statin drugs (rare)
Causes of intrinsic ARF
• Acute interstitial nephritis—drug-induced (penicillins,
cephalosporins, sulfonamides, rifampin, dilantin,
furosemide, NSAIDS)
• Infection-related—bacterial infections, viral, rickettsial
disease, TB
• Systemic diseases—SLE, Wegener granulomatosis
(granulomatous inflammation involving the respiratory
tract and necrotizing vasculitis of the small and medium
sized vessels; necrotizing glomerulonephritis is common)
• Malignancy—malignant infiltration, multiple myeloma
(Bence-Jone’s proteins—what are these?)
Tumor infiltration—multiple mets
from malignant melanoma
Bence-Jones proteins
• Multiple myeloma is a malignancy of the plasma
cell
• The uncontrolled plasma cell produces an
overabundance of antibodies
• The structure of an antibody is as follows:
• 2 heavy chains and 2 light chains--
Y
• The light chains are excreted in the urine and
are known as Bence-Jones proteins
•
Causes of intrinsic ARF
• Acute glomerulonephritis— postinfectious GN
(ex. Acute poststreptococcal {Group A beta
hemolytic strep} GN), endocarditis-associated
GN, Hemolytic Uremic Syndrome*, Thrombotic
Thrombocytopenic Purpura, rapidly progressive
glomerulonephritis (RPGN)
• Acute vascular syndromes—renal artery
thromboembolism, renal artery dissection, renal
vein thrombosis, atheroembolic disease
• DIC—disseminated intravascular coagulation
Meningococcemia and DIC
• DIC is characterized by microthrombi in
the small vessels
• Decreased urinary output is one of the first
signs
• Check the platelet counts and coagulation
studies (fibrinogen, thrombin time, Ddimers or fibrin split products)
E. Coli O157:H7
• Mid-70’s, mutation in Venezuela
• 3rd most deadly toxin in the world; 10-100 pathogens to make
you ill or kill you
• Shigella + E. Coli Moved up through Central America
into Southern Texas in the early ’80’s (1982 first
identified)
• The leading culprit in 2006 for food-borne illness
• 1996-1998 2.3 cases per 100,000 people from ground
beef; 2004 -- 0.9; 2006– 1.31/100,000
• 2006 presence in ground beef was 0.17%
• Cook burgers to 160° F
E. Coli O157:H7
• Very young, very old, very immunocompromised
• Acute Renal Failure in Kids
• 1993 Jack-in-the-Box in Seattle/Tacoma (500/4
deaths)
• Mickey D’s—30 outbreaks per year
• Supportive Treatment
• Bagged spinach and lettuce
Postrenal ARF
• Acute obstruction to the urinary tract from the
renal pelvis to the urethra
• However, for obstruction proximal to the urinary
bladder to result in ARF, it must be bilateral or
occur in the setting of a single functional kidney
Causes of postrenal ARF
• Intrinsic—stones, papillary necrosis, blood clot,
transitional cell carcinoma
• Extrinsic—aortic aneurysm, retroperitoneal or
pelvic malignancy
• Lower tract obstruction—urethral stricture, BPH,
prostatic cancer, transitional cell carcinoma of
the bladder, bladder stones, neurogenic bladder
Feline urologic syndrome
• Obstructive disease of the urethra—especially in
the male feline
• Pathogenesis includes the maintenance of a
constant alkaline urinary pH, increased intervals
between urination, exclusive use of dog food,
and maybe a virus thrown in
• Renal failure
Rx of acute renal failure…the
obvious
• Treat the underlying cause…
• Measure electrolytes daily, K+ restriction, diuretics and
renal replacement therapy (RRT) as necessary
• Acidosis—RRT
• Volume—I & O of course; CVP; insensible losses
• Daily weights, volume replacement
• Pulmonary edema—loop diuretics if ANY renal function
is left; if not, RRT
• Nitrates and opiates provide vasodilation in patients with
acute pulmonary edema; oxygen
• Maintain hemoglobin above 10 g/dL
Specific syndromes of ATN
• RCN—radiocontrast nephropathy is one of the most
frequent etiologies of nephrotoxic ATN accounting for
10% of all cases of hospital-acquired ARF
• Risk factors—baseline renal insufficiency (baseline
serum creatinine greater than 2.0 mg/dl), DM, CHF, large
volumes of contrast media, volume depletion, concurrent
use of NSAIDS or ACE inhibitors
• Risk with normal kidney function=negligible
• Mild to mod renal insufficiency with DM=10-40% risk
• Advanced renal insufficiency=50% risk
• Due to renal vasoconstriction and direct renal tubular
epithelial cell toxicity
RCN (radiocontrast nephropathy)
• Acute rise in serum creatinine 24-48 hours after contrast study
• Peaks 3-5 days after onset of renal failure and returns to baseline in
7-10 days
• Usually non-oliguric
• Prevention—use other imaging techniques in high-risk patients, if
possible; correct hypovolemia, discontinue NSAIDs and ACEI
• Administer saline (1 ml/kg/h from 8 a.m. on the day of the procedure
to 8 a.m. the following day—reduces RCN by 50%; especially in
women, diabetics, and patients receiving more than 250 ml of
contrast dye
• Use low-osmolality contrast media
• N-acetylcysteine (NAC) (Mucomyst)—potential therapeutic benefit
IVPs, Cardiac cath, other contrastdye procedures
Aminoglycoside nephrotoxicity
• Develops in 10-15% of patients treated for more than
several days
• Taken up by PCT where they accumulate in high
concentrations and produce cytotoxicity
• Onset of nephrotoxicity usually occurs after 7-10 days of
therapy
• Shedding of epithelial cells into urine (tubular cell casts)
• Complete recovery is possible—high risk groups are
patients with volume depletion, the elderly, cardiac
surgery, preexistent renal disease, and hepatobiliary
disease
• Once daily dosing will reduce the nephrotoxicity
Rhabdomyolysis
• Release of muscle cell constituents as the result
of traumatic or nontraumatic injury is the
principal cause of hemepigment associated ARF
(myoglobin)
• Increased CK, AST, LDH
• Severe cases result in profound hypovolemia,
metabolic acidosis, electrolyte disturbances
• Treat with aggressive volume replacement with
saline
• Renal replacement therapy may be necessary
Postoperative Acute Renal Failure
• Most commonly associated with vascular,
cardiac and major abdominal surgery, including
visceral organ transplants
• Multifactorial in origin
• Cardiogenic shock, history of renal disease with
CC less than 60 ml/min), emergency surgery,
LVEDP greater than 25 mmHg, age greater than
70, left-main coronary stenosis greater than
70%, and a history of PVD
• Decreased incidence in patients undergoing offpump bypass vs. grafting vs. bypass grafting
with cardiopulmonary bypass
Pharmacologic management of
ARF
• Prevention—optimizing vascular
hemodynamics to ensure adequate renal
perfusion with saline loading
• Discontinue drugs that increase
vasoconstriction
• Avoid nephrotoxic drugs when possible
• If unavoidable, use dosing schedules and
new preparations
Pharmacologic management of
ARF—what doesn’t work…
• Dopamine infusions—there is NO evidence that
dopamine is of benefit in the prevention or
treatment of ARF; increased risk of arrhythmias,
myocardial ischemia, intestinal ischemia…
• Loop diuretics—clinical studies do NOT support
the use for loop diuretics; outcomes are not
improved
• Atrial natriuretic peptide—the literature does not
support the use of ANP
Renal replacement therapy
• Given the lack of effective pharmacologic
therapy, the management of ARF remains
primarily supportive, with RRT the cornerstone
of treatment
• Dialysis is more difficult in ARF patients—they
are more hemodynamically unstable, more
hypercatabolic, have greater nutritional
requirements and have a a larger daily fluid
intake (vs. chronic RF patients)
• Multiple modalities to provide RRT
Renal replacement therapy
• When should it start?
• The gold standard was to initiate RRT when the
BUN hit 100 mg/dl
• 1999 study showed the early RRT with a BUN
less than 60 mg/dl vs. a BUN greater than 60
mg/dl was associated with a 39% survival as
compared to a 20.3% survival
• (Getings, LG, Reynolds HN. Outcome in post-traumatic acute renal
failure when continuous renal replacement therapy is applied early
vs. late. Intensive Care Med 25:805-813, 1999.)
Renal replacement therapy
• Intermittent hemodialysis or,
• Continuous renal replacement therapy (CRRT)?
• Insufficient data to favor intermittent vs. CRRT,
however, in hemodynamically unstable patients,
CRRT can be more safely performed due to a
lesser tendency to exacerbate hypotension
• Peritoneal dialysis (only use if nothing else is
available), or
Historical highlight
• The ancient Chinese, Roman, and
German societies frequently used urine as
mouthwash. Surprisingly, the ammonia in
urine is a good cleanser. Do not try this
unless desperate measures are
necessary.
The end.
• Barb Bancroft, RN, MSN, PNP
• CPP Associates, Inc.
• www.barbbancroft.com
• [email protected]
Bibliography
• Buhsmer J. Overview of CKD and anemia. The Director;
13(4)
• Crus DN, Perazella MA. Drug-induced acute
tubulointerstitial nephritis. Hosp Practice 1998 Feb 15;
151-164.
• Friedman JM. Ace Inhibitors and congenital anomalies.
N Engl J Med 2006 Jun 8; 2498-2500.
• Ghanasekaran I, Dimitrov H. Primary care management
of anemia in chronic kidney disease. Patient Care May
2006
Bibliography
• Palevsky P. Acute Renal Failure. Journal of the American
Society of Nephrology. March 2003; 2(2).
• Robbins and Cotran. Pathologic Basis of Disease 7th
Edition. 2006.
• Wish JB, Coyne DW. Use of Erythropoiesis-stimulating
agents in patients with anemia of chronic kidney disease:
overcoming the pharmacological and
pharmacoeconomic limitations of existing therapies.
Mayo Clin Proc. 2007 (Nov);82(11):1371-1380.