Essentials of Nephrology
Chronic kidney disease (CKD) can be defined
as:
(A) Kidney damage as defined by pathologic
abnormalities or markers in blood or urine for
1 mo
(B) Kidney damage on imaging studies for 1
mo
(C) Glomerular filtration rate (GFR) 60
mL/min per 1.73 m2 for 3 mo
(D) Albumin to creatinine ratio of <30 mg of
albumin to 1 g of creatinine for 3 mo
Answer
• (C) Glomerular filtration rate (GFR) 60
mL/min per 1.73 m2 for 3 mo
Risk factors for CKD include
which of the following?
(A) Systemic lupus
(B) Bladder outlet obstruction
(C) Preeclampsia
(D) All the above
Answer
• (D) All the above
In glomerulosclerosis:
(A) Intraglomerular pressure
must be decreased to maintain
function
(B) The efferent arteriole
constricts
(C) GFR begins to decline early
in disease process
(D) The mesangium becomes
thin
Answer
• (B) The efferent arteriole constricts
When stratifying risk for
cardiovascular disease in patients
with normal GFR and
macroalbuminuria, CKD should
be
considered a myocardial
infarction equivalent.
(A) True (B) False
Answer
• (A) True
In the United Kingdom
Prospective Diabetes
Study, the _______ control
group had better renal
outcomes.
(A) Blood pressure (BP)
(B) Glycemic
Answer
• (A) Blood pressure (BP)
Which class of antihypertensive
agents appears most effective in
improving renal outcomes?
(A) Calcium channel blockers
(B) Angiotensin-converting
enzyme (ACE) inhibitors and
angiotensin receptor blockers
(ARBs)
(C) Direct renin inhibitors
(D) Beta-blockers
Answer
• (B) Angiotensin-converting
enzyme (ACE) inhibitors and
angiotensin receptor blockers
(ARBs)
A patient with CKD is started on
an ACE inhibitor to control her
BP. During the first 2 to 4 wk of
therapy, a temporary
increase in which of the
following can be expected?
(A) Serum potassium
(B) Albumin to creatinine ratio
(C) Serum creatinine
(D) GFR
Answer
• (C) Serum creatinine
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What is considered an
acceptable rise in the
creatinine after starting and
ACE inhibititor?
A. 10%
B. 20%
C. 30%
D 40%
Answer
• C. 30%
Choose the correct statement about
aliskiren.
(A) Blocks renin activity
(B) Should be used in combination
with ACE inhibitor or ARB
(C) Associated with better renal
outcomes than ACE inhibitors or
ARBs
(D) No significant effect on BP
control
Answer
• (A) Blocks renin activity
Which of the following drugs is
contraindicated in patients with
serum creatinine >1.4 mg/dL?
(A) Aliskiren
(B) Amlodipene
(C) Kayexalate
(D) Metformin
Answer
• (D) Metformin
Dietary modifications of patients
with CKD should include the
restriction of which of the
following?
(A) Protein
(B) Phosphate
(C) Salt substitutes
(D) All the above
Answer
• (D) All the above
Choose the correct statement
about acute kidney injury.
(A) Characterized by rapid rise in
creatinine over 1 mo
(B) Can be nonoliguric or
oliguric
(C) Anuria usually associated
with good prognosis
(D) Mortality rates lower in
patients who require dialysis
Answer
• (B) Can be nonoliguric or oliguric
Intrinsic renal problems that lead
to acute kidney injury are most
commonly caused by:
(A) Pelvic cancer
(B) Vomiting
(C) Congestive heart failure
(D) Medications
Answer
• (D) Medications
Values for fractional excretion of
sodium are often elevated by:
(A) Diuretic use
(B) Acute glomerulonephritis
(C) Rhabdomyolysis
(D) Sepsis
Answer
• (A) Diuretic use
Which of the following findings
on urinalysis with microscopy is
most commonly indicative of
acute interstitial nephritis?
(A) Tubular epithelial cell casts
(B) White blood cell casts
(C) Red blood cell casts
(D) Hyaline casts
Answer
• (B) White blood cell casts
A urine dipstick can detect
protein (albumin) at what level
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A. >30 mg of protein (albumin)
B. >100 mg
C. >300 mg
D. >500 mg
Answer
• C. >300 mg
Which of the following is not an
independent indication for
emergent hemodialysis?
(A) Hyperkalemia
(B) Uremic encephalopathy
(C) Abnormal serum urea
nitrogen and creatinine levels
(D) Metabolic acidosis
Answer
• (C) Abnormal serum urea nitrogen and
creatinine levels
What is indicative of ATN
• tubular epithelial cell casts
• white cell casts without bacteria
• ask nephrologist to look for >10%
eosinophils),
• red cell casts
• Hyaline casts
• oval fat bodies
Answer
• tubular epithelial cell casts
What is indicative of Nephrotic
Syndrome
• tubular epithelial cell casts
• white cell casts without bacteria
• ask nephrologist to look for >10%
eosinophils),
• red cell casts
• Hyaline casts
• oval fat bodies
Answer
• oval fat bodies
What is indicative of acute
interstitial nephritis
• tubular epithelial cell casts
• white cell casts without bacteria
• ask nephrologist to look for >10%
eosinophils
• red cell casts
• Hyaline casts
• oval fat bodies
Answer
• white cell casts without bacteria
• ask nephrologist to look for >10%
eosinophils
What is indicative of
glomerulonephritis
• tubular epithelial cell casts
• white cell casts without bacteria
• ask nephrologist to look for >10%
eosinophils),
• red cell casts
• Hyaline casts
• oval fat bodies
Answer
• red cell casts
Using diuretics to convert
oliguric renal failure to
nonoliguric renal failure may
worsen mortality.
(A) True (B) False
Answer
• (A) True
Choose the correct statement about
screening for proteinuria.
(A) Can detect kidney disease even
before changes in estimated
glomerular filtration rate (eGFR)
occur
(B) Normal urinary protein to
creatinine ratio <200 mg to 1 g
(C) 24-hr urine collection is gold
standard, but prone to error
(D) All the above
Answer
• (D) All the above
A patient with an eGFR
measurement of 45 mL/min per
1.73 m2 would most likely be
diagnosed with _______ chronic
kidney disease (CKD).
(A) Stage 1
(B) Stage 2
(C) Stage 3
(D) Stage 4
Answer
• (C) Stage 3
Prerenal is which of the
following?
• A. Anything that causes decreased effective
renal perfusion: Hypovolemia, CHF, Renal
Artery Stenosis, Sepsis, etc. Sometines
contrast-induced nephropathy
• B. ATN, AIN, Glomerulonephritides, etc
• C. Obstruction (BPH, bladder stone,
bilateral ureter obstruction
Answer
• A. Anything that causes decreased effective
renal perfusion: Hypovolemia, CHF, Renal
Artery Stenosis, Sepsis, etc. Sometines
contrast-induced nephropathy
Post renal is which of the
following?
• A. Anything that causes decreased effective
renal perfusion: Hypovolemia, CHF, Renal
Artery Stenosis, Sepsis, etc. Sometines
contrast-induced nephropathy
• B. ATN, AIN, Glomerulonephritides, etc
• C. Obstruction (BPH, bladder stone,
bilateral ureter obstruction)
Answer
• C. Obstruction (BPH, bladder stone,
bilateral ureter obstruction
Intrarenal is What?
• A. Anything that causes decreased effective
renal perfusion: Hypovolemia, CHF, Renal
Artery Stenosis, Sepsis, etc. Sometines
contrast-induced nephropathy
• B. ATN, AIN, Glomerulonephritides, etc
• C. Obstruction (BPH, bladder stone,
bilateral ureter obstruction
Answer
• B. ATN, AIN, Glomerulonephritides, etc
In patients with CKD, what is the
recommended target level of lowdensity lipoprotein?
(A) <175 mg/dL
(B) <150 mg/dL
(C) <125 mg/dL
(D) <100 mg/dL
Answer
• (D) <100 mg/dL
In patients with CKD,
angiotensin-converting enzyme
inhibitor therapy should be
discontinued if elevations in
creatinine
occur.
(A) True (B) False
Answer
• (B) False
What is high in Phosphorus?
A. MEATS, ETC
B. BREAD & STARCHES
C. DAIRY PRODUCTS
D. Fruits
E. Vegetables
F. A,B,C
Answer
• F. A,B,C
Acute kidney injury
• Consider whether problem
• Prerenal (problem of flow to kidneys)
• Postrenal (obstructive process at level of
ureter, bladder, or urethra)
• Or intrinsic (“is it the kidneys?”) 66% of
time
• Problem prerenal 10% of the time
• Postrenal 33% of time
• Intrinsic the rest of the time
Case presentation
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man 55 yr of age with diabetes, hypertension, and degenerative joint disease (DJD)
presents with 3-day history of nausea, vomiting, diarrhea, and low oral intake
becomes oliguric, anuric, confused, and complains of pruritus
medications include benazepril hydrochlorothiazide, glipizide, and ibuprofen
physical examination—dehydration; hypotension; tachycardia; tachypnea; hypoxia; confusion
dry mucous membranes; rales on lung examination; no abdominal mass
normal prostate examination; no petechiae or purpura
laboratory studies—potassium high (6 mEq/L); sodium low (129 mEq/L); CO2 low (20 mEq/L);
serum
urea nitrogen (BUN) high; creatinine high
treatment— normal saline boluses for hypotension
Foley catheter inserted to rule out obstruction (no urine excreted)
no acute changes on electrocardiography (ECG)
Hyperkalemia treated with transcellular shifting-mediated mechanism of insulin and glucose,
calcium, and sodium polystyrene to help bind potassium in gut
blood pressure (BP) medications and nonsteroidal anti-inflammatory drugs (NSAIDs) held
Urinalysis (UA) showed concentrated urine, with no red blood cells (RBCs), white blood cells
(WBCs), or tubular cell casts (acute tubular necrosis [ATN] ruled out)
renal ultrasonography (US) negative for hydronephrosis
patient's BP, urine output, mental status, BUN, and creatinine improved
Man discharged after few days with diagnosis of acute kidney injury (prerenal azotemia secondary to
acute viral gastroenteritis)
Acute kidney injury
• rapid rise in creatinine over 2 wk
• If baseline creatinine <2.5 mg/dL often defined as rise of 0.5 mg/dL
• if baseline creatinine >2.5 mg/dL, defined as increase in creatinine
>20%
• can be nonoliguric or oliguric
• (oliguria in adults, urine output of <400 mL/day; in children <0.5
mL/kg per hr)
• anuria (urine output <100 mL/day) usually associated with poorer
prognosis, except in dehydration
• mortality rates vary (25%-90%; in-hospital mortality, 50%)
• higher mortality rates usually seen in patients who require dialysis
• complications—electrolyte disorders (eg, hyperkalemia, metabolic
acidosis)
• infections
• gastrointestinal (GI) bleeding
• arrhythmia
• Myocardial infarction (MI)
• pulmonary edema
Causes of acute kidney
injury
• volume depletion—
• decreased oral intake; vomiting; diarrhea; diuretic use; anaphylaxis;
sepsis; MI; congestive heart failure (CHF); cirrhosis;
• signs of obstruction—patients often asymptomatic
• abdominal or flank pain; hematuria; sudden anuria
• weight loss or cancer symptoms (pelvic cancers lead to obstruction of
ureters, urethra, or bladder)
• agitation
• intrinsic renal problems—most commonly due to medications (eg,
intravenous [IV] contrast, aminoglycosides, amphotericin, penicillins,
cephalosporins, sulfonamides); positive family history of kidney
disease; personal renal history
• Autoimmune disease and vasculitis (eg, lupus, Sjögren’s syndrome)
• viral diseases (eg, hepatitis B or C, HIV)
Consequences of acute kidney
injury
• encephalopathy
• Uremic pericarditis
• CHF and fluid overload (eg, pulmonary or peripheral edema,
significant hypertension)
• acute platelet dysfunction
• indications for dialysis
• Physical examination: volume status; orthostatic vital signs;
• dry mucous membranes; pericardial rub (pericarditis; emergent
hemodialysis indicated)
• pulmonary edema
• Bladder distention
• petechiae might suggest uremic syndrome or thrombotic
thrombocytopenic purpura (TTP)
• Palpable purpura suggest vasculitis
• pelvic and prostate examination
Laboratory studies
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complete blood cell count (CBC)
Platelet count normal in acute kidney failure
chemistry panel (CHEM- 7)
stat ECG
UA with microscopy
urine culture and renal US helpful
serum sodium and creatinine and urinary sodium and creatinine (to
calculate fractional excretion of sodium [FENa])
x-ray of kidneys, ureter, and bladder optional
computed tomog- raphy (CT) of abdomen for masses or symptoms
suggestive of cancer
ECG in hyperkalemia—ventricular tachycardia or ventricular
fibrillation can be sudden or gradual
peaked T waves with prolonged PR intervals
with progression, P waves lost and QRS intervals widen with peaked T
waves
Top 10 items for K+
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Avocado540mg
Cantaloupe494mg
Tomatoes427mg
Crimini Mushrooms390mg
SwissChard364mg
Spinach839mg
Broccoli456mg
Celery263mg
Romaine Lettuce232mg
Collard Green220mg
Low potassium fruits
• FruitsPotassium Content (mg)Apples,
peeled & slides62Applesauce, canned78 –
92
• Apricot,1medium105
• Blueberries65Cranberry sauce36Fig (1
medium)116Fruit
cocktail114Grapes (10)116Lemon (1
medium)80Peaches (canned)118Pears
(canned)83Pineapple (diced)88Plums
(raw)118Raspberries (raw)94Watermelon
(diced)93Blackberries141Sweet cherries
(10)152Grapefruit (1/2 medium)165
Low Potassium Vegetables
• VegetablesPotassium Content (mg)Alfalfa
sprouts (raw)13Green beans76Bean
sprouts63 - 78Cabbage (raw)72 86Cauliflower125Carrots (cooked)114Colla
rds (cooked)84Collards (raw)214Corn
(cooked)114Cucumbers (sliced)84Steamed
eggplant119Endive (raw)79Leeks
(raw)94Leeks
(cooked)46Lettuce87Onions (cut into small
cubes)124Peppers (raw)89Peppers
(cooked)113
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High Phosphorus Foods
Foods High in Phosphorus (greater than 160 mg per serving):
MEATS, ETC: Fish & Seafood (3 oz.) - Bass, Catfish, Clams, Cod, Crab (real and imitation), Flounder, Halibut,
Orange Roughy, Pollack, Salmon (canned with bones), Sardines (canned with bones), Scallops (breaded and fried - 4
to 6 pieces), Shrimp (Breaded and Fried - 10 to 11 pieces), Swordfish, Trout, Tuna (canned in oil); Lamb (3 oz); Liver
(3 oz); Pork (3 oz); Turkey (3 oz); Veal (3 oz)
BREAD & STARCHES: Bulgar (1/2 cup); Cornbread (prepared from dry mix) - 1 piece; Golden Grahams (3/4 cup);
Frosted Mini-Wheats (1 cup); Kellogg's Raisin Bran (1 cup); Lentils, cooked (1/2 cup); Post Shredded Wheat (1 cup);
Trail Mix (1/2 cup).
DAIRY PRODUCTS: Buttermilk (8 oz); Chocolate Milk (8 oz); Chocolate Pudding - instant (4 oz); Egg Nog (8 oz);
Milk (8 oz.); Milkshakes (8 oz); Ricotta Cheese (1/2 cup); Swiss Cheese (1 oz); Yogurt (8 oz)
Foods Moderately High in Phosphorus (110-160 mg per serving):
MEATS, ETC: Bacon (2 slices); Beef (3 oz); Chicken (3 oz); Chicken Pot Pie (one small); Fish and Seafood (3 oz) Lobster, Oysters, Perch, Steamed Shrimp, Tuna (canned in water)
BREAD & STARCHES: Biscuits (one 4-inch biscuit from recipe); Waffle (one from mix); Pancake (one from mix);
Cheerios (1-1/4 cup); Wheaties (1 cup); Wheat CHEX (1 cup); Oatmeal (1 cup)
DAIRY PRODUCTS: Cheddar Cheese (1 oz.); Cottage Cheese (1/2 cup); Custard (1/2 cup); Fat-free Cream Cheese
(2 Tbsp.); Mozzarella Cheese (1 oz.); Provolone Cheese (1 oz.); Pudding - instant, made with milk (1/2 cup)
DRIED BEANS & PEAS: Baked Beans (1/2 cup); Black-eyed Peas (1/2 cup); Black Beans (1/2 cup); Chili Beans
(1/2 cup); Garbanzo Beans (1/2 cup); Kidney Beans (1/2 cup); Lima Beans (1/2 cup); Pinto Beans (1/2 cup); Refried
Beans (1/2 cup)
NUTS & SEEDS: Almonds (22 nuts); Cashews (18 medium nuts); Pecans (20 halves); Pumpkin Seeds (50 seeds);
Sunflower Seeds (50 seeds)
MISCELLANEOUS: Angel Food Cake (one piece); Beer (12 oz); Doughnut (one medium); Peanut Butter (2 Tbsp);
Soy Milk (8 oz)
Foods Low in Phosphorus (less
than 110 mg per serving)
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MEATS, ETC: Egg (one): Hot Dog (one); Sausage, fresh; Frozen Fish Sticks (two sticks)
BREAD & STARCHES: Bagel (one); all Bread (one slice); Biscuit (one made from refrigerated
dough); Croissant (one); all Crackers (four); Cereals, including: Cocoa Puffs (1 cup); Corn, Rice
CHEX (1 cup); Corn Flakes (1 cup); Corn Pops (1 cup); Cream of Wheat (3/4 cup); Kix (1-1/3 cup);
Rice Krispies (1-1/4 cup); Special K (1 cup); English Muffin (one); Pasta (1/2 cup); Noodles (1/2
cup); Rice (1/2 cup); Popcorn (1 cup); Tortilla (one)
VEGETABLES All Vegetables are Low in Phosphorus
FRUITS: All Fruits are Low in Phosphorus
DAIRY PRODUCTS: Brie (1 oz); Cream Cheese (2 Tbsp); Feta Cheese (1 oz); Ice Cream (1/2
cup); Half & Half (1/2 cup); Grated Parmesan Cheese (2 Tbsp); Sour Cream (2 Tbsp); Whipping
Cream (1/2 cup)
NUTS & SEEDS: Macadamia Nuts (12 nuts); Peanuts (28 nuts); Walnuts (14 halves)
MISCELLANEOUS: Cake (one piece); Coffee (6 oz); Cookie (one); Fruit Works; Hard Candy;
Jelly Beans; Nestea COOL Iced Tea (8 oz); Non-dairy Creamer (1/2 cup); Pie (one piece); Ready-toEat Pudding (1/2 cup); Unenriched Rice Milk (8 oz); Snickers bar (one 2 oz bar); Soda Pop (12 oz);
Tea (6 oz)
FENa
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FENa—indicates how well kidneys retain sodium in setting of dehydration
(urinary sodium/plasma sodium) ÷ (urinary creatinine/plasma creatinine) x 100
obtain urinary and plasma values at same time of day
<1% usually suggests prerenal etiology
(>1% usually suggests ATN)
FENa often elevated by diuretic use, or decreased due to certain intrinsic renal
problems (eg, acute glomerulonephritis, ATN, rhabdomyolysis, contrast
nephropathy, sepsis)
Patients with chronic kidney disease can have chronically elevated FENa
fractional excretion of urea—useful in patients with recent use of diuretic
(urinary urea/plasma urea) ÷ (urinary creatinine/
plasma creatinine) x 100
<35% usually suggests prerenal etiology
(>35% usually suggests ATN)
more reliable than FENa; if clinical setting suggests prerenal etiology
low urinary sodium and low fractional excretion of sodium confirm prerenal
etiology
FENa can be low in acute glomerulonephritis or vascular disorder
in intrinsic renal problems, urinary sodium high
www.mdcalc.com fractionalexcretion-of-sodium-fena
• Fractional Excretion of Sodium (FENa) = (PCr * UNa ) /
(PNa x UCr) %
• Prerenal Intrinsic Renal Postrenal UNa (mmol/L <20 >40
>40
• FENa<1% >1% >4%
• Prerenal: Anything that causes decreased effective renal
perfusion: Hypovolemia, CHF, Renal Artery Stenosis,
Sepsis, etc. Remember, contrast-induced nephropathy will
often look pre-renal.
• Intrinsic Renal: ATN, AIN, Glomerulonephritides, etc
• Postrenal: Obstruction (BPH, bladder stone, bilateral ureter
obstruction
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Acute tubular necrosis
Acute tubular necrosis is kidney injury characterized by acute tubular cell injury and dysfunction.
Common causes are hypotension causing renal hypoperfusion and nephrotoxic drugs. The condition
is asymptomatic unless it causes renal failure. The diagnosis is suspected when azotemia develops
after a hypotensive event, severe sepsis, or drug exposure and is distinguished from prerenal
azotemia by laboratory testing and response to volume expansion. Treatment is supportive.
Acute Tubular Necrosis
Causes of acute tubular necrosis (ATN) include the following:
Hypotension (ischemic ATN, common)
Nephrotoxins (common)
Sepsis (common)
Major surgery
Third-degree burns covering > 15% of BSA
The heme pigments myoglobin and hemoglobin (uncommon)
Disorders resulting in other endogenous toxins, such as tumor lysis or multiple myeloma
(uncommon)
Poisons, such as ethylene glycol (uncommon)
Herbal and folk remedies, such as ingestion of fish gallbladder in Southeast Asia (uncommon)
Common nephrotoxins include the following:
Aminoglycoside antibiotics
Amphotericin B
Cisplatin
Radiocontrast (particularly agents with osmolality > 100 mL)
NSAIDs
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Glomerulonephritis
Glomerulonephritis — an inflammation of the glomeruli — can damage your kidneys so that they lose their filtering ability,
allowing dangerous levels of fluid and waste to accumulate in your body (called kidney failure) and depriving your bloodstream
of protein, which is excreted in your urine.
Often the cause of glomerulonephritis is unknown. Known causes include:
Infections
Post-streptococcal glomerulonephritis. Glomerulonephritis may develop after a strep infection in your throat or, rarely, on your
skin (impetigo). Post-infectious glomerulonephritis is becoming less common in the United States, most likely because of rapid
and complete antibiotic treatment of most streptococcal infections.
Bacterial endocarditis. Bacteria can occasionally spread through your bloodstream and lodge in your heart, causing an infection
of one or more of your heart valves. Those at greatest risk are people with a heart defect, such as a damaged or artificial heart
valve.
Viral infections. Among the viral infections that may trigger glomerulonephritis are the human immunodeficiency virus (HIV),
which causes AIDS, and the hepatitis B and hepatitis C viruses, which primarily affect the liver.
Immune diseases
Lupus. A chronic inflammatory disease, lupus can affect many parts of your body, including your skin, joints, kidneys, blood
cells, heart and lungs.
Goodpasture's syndrome. A rare immune lung disorder that may mimic pneumonia, Goodpasture's syndrome causes bleeding
(hemorrhage) into your lungs as well as glomerulonephritis.
IgA nephropathy. Characterized by recurrent episodes of blood in the urine, this primary glomerular disease results from
deposits of immunoglobulin A (IgA) in the glomeruli. IgA nephropathy can progress for years with no noticeable symptoms. The
disorder seems to be more common in men than in women.
Vasculitis
Polyarteritis. This form of vasculitis affects small and medium blood vessels in many parts of your body, such as your heart,
kidneys and intestines.
Wegener's granulomatosis. This form of vasculitis affects small and medium blood vessels in your lungs, upper airways and
kidneys.
Conditions that cause scarring of the glomeruli
High blood pressure. Damage to your kidneys and their ability to perform their normal functions can occur as a result of high
blood pressure. Glomerulonephritis can also cause high blood pressure because it reduces kidney function.
Diabetic kidney disease. Diabetic kidney disease (diabetic nephropathy) can affect anyone with diabetes. Diabetic nephropathy
usually takes years to develop. Good control of blood sugar levels and blood pressure may prevent or slow kidney damage.
Focal segmental glomerulosclerosis. Characterized by scattered scarring of some of the glomeruli, this condition may result
from another disease or occur for no known reason.
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Acute Interstitial Nephritis
Overview of Acute Interstitial Nephritis (AIN)
The interstitium is the tissue that surrounds and imbeds the glomeruli (microscopic "filtering screens") and tubules
(long tubes that connect with each glomerulus and channel urine) within the kidneys. Acute interstitial nephritis
(AIN) is rapidly developing inflammation that occurs within the interstitium. It can produce a variety of clinical
symptoms, depending upon the severity and extent of kidney involvement.
Causes of Acute Interstitial Nephritis (AIN)
Most AIN is caused by an acute allergic reaction to a medication, including antibiotics and nonsteroidal antiinflammatory drugs (NSAIDs) such as:
Ibuprofen
Cephatholin
Cimetidine
Cyclosporine
Methicillin
Penicillins
AIN is also linked with certain infections and diseases such as Legionella pneumophila, collagen vascular diseases
(e.g., sarcoidosis), streptococcal infections, and transplant rejection.
Signs and Symptoms of Acute Interstitial Nephritis (AIN)
Indicators of AIN include a recent history of infection or the start of a new medication. Symptoms often include fever,
rash, and generalized aches and pains.
Acute Interstitial Nephritis (AIN) Diagnosis
The definitive diagnosis of AIN requires a kidney biopsy, which reveals inflammation of the renal
interstitium. Urinalysis (analysis of the urine) often reveals eosinophils—specialized white blood cells that are seen in
allergic reactions. Often one can detect increased eosinophils in the blood in patients with AIN. AIN sometimes is
diagnosed by means of a gallium scan (nuclear medicine imaging method; a radiologist injects the patient with
gallium-67, which will accumulate in areas of infection or malignancy and can be viewed with a special camera).
Treatment for Acute Interstitial Nephritis (AIN)
All medication(s) believed to be responsible for the inflammation must be discontinued. If there is significant renal
impairment, treatment with steroids typically is required for 2 to 3 months. Stronger immunosuppressive agents may
be needed if there is no response to the steroids. Each case of AIN must be reviewed by anephrologist (kidney
specialist).
UA with microscopy
• —tubular epithelial cell casts usually indicate ATN, and
sometimes acute interstitial nephritis
• white cell casts without bacteria often indicative of acute
interstitial nephritis (most commonly caused by drugs
• ask nephrologist to look for >10% eosinophils), but
sometimes seen in chronic glomerulonephritis
• red cell casts indicative of glomerulonephritis
• Hyaline casts nonspecific (often seen in prerenal cases)
• oval fat bodies indicative of nephrotic syndrome
• when urine dipstick positive for blood (eg, 1+, 2+, or 3+)
with no RBCs on UA microscopy,
• consider rhabdomyolysis (reversible cause of acute renal
failure
• irreversible if missed) and check serum creatine kinase
Treatment before
dialysis
• hyperkalemia—treat with glucose and insulin or IV
calcium
• sodium polystyrene (Kayexalate)
• Furosemide
• check ECG and monitor
• CHF—treat with O2 and diuresis
• severe acidosis—treat with sodium bicarbonate
• NSAIDs and anticoagulants contraindicated in patients
with uremic pericarditis
• avoid— potassium, potassium-sparing diuretics,
angiotensin-converting enzyme (ACE) inhibitors, NSAIDs,
and IV contrast
Postrenal causes
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Masses
Tumors
Stones
anticholinergic drugs
(eg, tricyclic antidepressants;
diphenhydramine [eg, Benadryl])
Intrinsic renal causes
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aortic dissection
90% of time, due to ATN (often induced by hypotension)
most common problems due to nephrotoxic drugs and rhabdomyolysis (treat with
hydration and IV bicarbonate)
acute interstitial nephritis—can develop as late as 10 to 30 days after last drug dose
drug history important
only 33% of patients have eosinophils in urine (diagnostic finding)
vascular—less likely
emboli from left heart
aortic atheroma
Postaortic surgery
left heart endocarditis
atrial fibrillation
Renal artery stenosis (consider in young people with refractory hypertension) or
thrombosis
Glomerulonephritis
Autoimmune diseases
renal infiltration (rare)
Nephritis
• interstitial—clinical clues include fever, rash, and eosinophilia in
blood; urine sediment; protein in urine
• consider viral testing (for, eg, cytomegalovirus [CMV], HIV, hepatitis
B virus [HBV]) and autoimmune testing (for, eg, sarcoidosis,
Sjögren’s syndrome)
• Consult nephrologist before treating
• glomerulonephritis—
• clinical clues include preexisting infection (eg, Streptococcus), rash,
arthritis
• urine sediment; RBC casts
• Protein in urine
• look for infections (eg, HIV, hepatitis B and C)
• in patients with rash or arthritis, look for cryoglobulinemia or lupus
• consider multiple myeloma in patients >40 yr of age (perform urine
and serum protein electrophoresis)
• consult nephrologist
Vasculitis
• clinical clues include fever, constitutional
symptoms, rash, respiratory symptoms
• RBC casts
• Autoimmune testing
• testing for HIV
• hepatitis B and C
Summary of acute renal failure
• adjust doses of all drugs
• choose lowest dosing
• diuretics for converting oliguric to nonoliguric renal failure
no longer used (benefits unclear and may worsen
mortality)
• no benefit of low doses of dopamine
• prevention of contrast nephropathy—in patients with risk
factors for acute renal failure (eg, advanced age, chronic
kidney or liver disease)
• hold metformin, diuretics, and NSAIDs for 2 days
• start IV fluids or advise high oral fluid intake 1 day before
• giving sodium bicarbonate 1 hr before and 6 hr after may
be beneficial (data conflicting);
• acetylcysteine (eg, Mucomyst; 600 mg bid) 1 day before
and on day of study (controversial)
Chronic
kidney
disease
(CKD)
• definition—kidney damage as defined by pathologic abnormalities or
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markers in blood or urine or on imaging studies for 3 mo
or glomerular filtration rate (GFR) <60 mL/min per 1.73 m2 for 3 mo
stage 0—presence of risk factors (eg, hypertension, diabetes), but no
evidence of kidney damage
Stages 1 to 5—progressive loss of glomerular filtration (ie, renal
function)
prevalence—in 1997, prevalence in United
States 10% (currently, 13.1% [26 million people])
worldwide—affects 50 million people (1 million patients on renal
replacement therapy [eg, dialysis, transplantation])
United States—474,000 people have had
renal replacement therapy
costs—total Medicare payments in 2007, $333 billion ($23 billion
spent on endstage renal disease)
average lifetime cost of patients on dialysis, $250,000 to $300,000
emotional burden on patient
increased demands on caregivers
Stages of Chronic Kidney Disease
• Stage 1 Slightly diminished function; Kidney damage with normal or
relatively high GFR (>90 mL/min/1.73 m2). Kidney damage is defined
as pathologic abnormalities or markers of damage, including
abnormalities in blood or urine test or imaging studies.
• Stage 2 Mild reduction in GFR (60-89 mL/min/1.73 m2) with kidney
damage. Kidney damage is defined as pathologic abnormalities or
markers of damage, including abnormalities in blood or urine test or
imaging studies.
• Stage 3 Moderate reduction in GFR (30-59 mL/min/1.73 m2). British
guidelines distinguish between stage 3A (GFR 45-59) and stage 3B
(GFR 30-44) for purposes of screening and referral.[4]
• Stage 4 Severe reduction in GFR (15-29 mL/min/1.73 m2)
Preparation for renal replacement therapy
• Stage 5 Established kidney failure (GFR <15 mL/min/1.73 m2, or
permanent renal replacement therapy (RRT)
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Symptoms of CKD
CKD is initially without specific symptoms and can only be detected as an increase in
serum creatinine or protein in the urine. As the kidney function decreases:
blood pressure is increased due to fluid overload and production of vasoactive
hormones, increasing one's risk of developing hypertension and/or suffering
from congestive heart failure
Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from
lethargy to pericarditis and encephalopathy). Urea is excreted by sweating and
crystallizes on skin ("uremic frost").
Potassium accumulates in the blood (known as hyperkalemia with a range of symptoms
including malaise and potentially fatal cardiac arrhythmias)
Erythropoietin synthesis is decreased (potentially leading to anemia, which
causes fatigue)
Fluid volume overload - symptoms may range from mild edema to lifethreatening pulmonary edema
Hyperphosphatemia - due to reduced phosphate excretion, associated
with hypocalcemia (due to vitamin D3 deficiency). The major sign of hypocalcemia
being tetany.
– Later this progresses to tertiary hyperparathyroidism, with hypercalcaemia, renal
osteodystrophy and vascular calcification that further impairs cardiac function.
Metabolic acidosis, due to accumulation of sulfates, phosphates, uric acid etc. This may
cause altered enzyme activity by excess acid acting on enzymes and also increased
excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due
to excess acid (acidemia)
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Causes
The most common causes of CKD are diabetic nephropathy, hypertension,
and glomerulonephritis.[3] Together, these cause approximately 75% of all
adult cases. Certain geographic areas have a high incidence of HIV
nephropathy.
Historically, kidney disease has been classified according to the part of the
renal anatomy that is involved, as:[citation needed]
Vascular, includes large vessel disease such as bilateral renal artery
stenosis and small vessel disease such as ischemic nephropathy, hemolyticuremic syndrome and vasculitis
Glomerular, comprising a diverse group and subclassified into
– Primary Glomerular disease such as focal segmental
glomerulosclerosis and IgA nephritis
– Secondary Glomerular disease such as diabetic nephropathy and lupus
nephritis
Tubulointerstitial including polycystic kidney disease, drug and toxin-induced
chronic tubulointerstitial nephritis and reflux nephropathy
Obstructive such as with bilateral kidney stones and diseases of the prostate
On rare cases, pin worms infecting the kidney can also cause idiopathic
nephropathy.
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Treatment
The goal of therapy is to slow down or halt the otherwise relentless progression of CKD
to stage 5. Control of blood pressure and treatment of the original disease, whenever
feasible, are the broad principles of management. Generally, angiotensin converting
enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as
they have been found to slow the progression of CKD to stage 5.[5][6] Although the use
of ACE inhibitors and ARBs represents the current standard of care for patients with
CKD, patients progressively lose kidney function while on these medications, as seen in
the IDNT[7] and RENAAL[8] studies, which reported a decrease over time in
estimated glomerular filtration rate (an accurate measure of CKD progression, as
detailed in the K/DOQI guidelines[1]) in patients treated by these conventional methods.
Currently, several compounds are in development for CKD. These include, but are not
limited to, bardoxolone methyl[9], olmesartan medoxomil,sulodexide, and avosentan[10].
Replacement of erythropoietin and vitamin D3, two hormones processed by the kidney,
is usually necessary in patients with CKD, as is calcium.Phosphate binders are used to
control the serum phosphate levels, which are usually elevated in chronic kidney
disease.
When one reaches stage 5 CKD, renal replacement therapy is required, in the form of
either dialysis or a transplant.
In some cases, dietary modifications have been proven to slow and even reverse further
progression. Generally this includes limiting protein intake.[citation needed]
The normalization of hemoglobin has not been found to be of any benefit
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Hyperparathyroidism
• The major factors responsible for stimulating parathyroid gland
function in renal failure are hypocalcemia, diminished 1,25dihydroxyvitamin D levels, and hyperphosphatemia.
• The optimal approach for treating secondary hyperparathyroidism and
mineral metabolism abnormalities in predialysis patients with stage 3,
4, and 5 chronic kidney disease (CKD) is unclear. The current
management of secondary hyperparathyroidism in patients with stage 3
to 5 CKD not yet on dialysis principally involves the administration of
some combination of dietary phosphate restriction, phosphate binders
(either calcium or non-calcium containing binders), vitamin D
analogues, calcium supplementation and/or (possibly) a calcimimetic.
However, calcimimetics are NOT currently approved for patients with
CKD not yet undergoing dialysis.
2nd Hyperparathyroidism
The elevated phosphorus level in the blood can cause deposits of calcium
and phosphorus to form in tissues, including the blood vessels.
Restricting the intake of foods that are high in phosphorus, such as
dairy products, liver, legumes, nuts, and most soft drinks, lowers the
phosphate concentration in the blood. Drugs that bind phosphate, such
as calcium carbonate
, calcium acetate, and sevelamer
, taken by mouth, may also lower the phosphorus level in the blood.
Calcium citrate should be avoided. Calcium citrate is found in many
calcium supplements and is in many products as a food additive
(sometimes called E333). Vitamin D
and similar drugs are often taken by mouth to reduce high levels of
parathyroid hormone.
2nd Hyperparathyroidism
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We suggest that the initial focus in managing secondary hyperparathyroidism
should be the management of hyperphosphatemia. Among patients with
hyperphosphatemia, we suggest restricting dietary phosphate intake.
- Among patients with hyperphosphatemia despite dietary phosphorus
restriction after two to four months, we suggest the administration of
phosphate binders. The two principal options are calcium and non-calcium
based phosphate binders. Specific interventions are based upon serum
phosphate and calcium levels.
We also suggest that treatment with ergocalciferol be initiated if vitamin D
deficiency exists, as demonstrated by a 25(OH)-vitamin D (calcidiol) level of
less than 30 ng/mL.
- If elevated PTH levels remain despite ergocalciferol and phosphate binder
therapy over a six-month period, we suggest administering a low dose active
oral vitamin D analog. If the serum level of corrected total calcium exceeds
10.2 mg/dL (2.54 mmol/L), we recommend that ergocalciferol therapy and all
forms of vitamin D therapy should be discontinued
- The next step is to decide whether phosphate binder therapy is sufficient
or whether a vitamin D analogue should be added. This is based upon calcium,
phosphate, and PTH levels that are measured when administering optimal
phosphate binder therapy.
Chronic Kidney Disease (CKD)
• Screening for CKD: screen patients with risk factors
(eg, diabetes, hypertension, age >60 yr)
• positive family history, history of recurrent urinary tract
infection (UTI) or obstruction
• or systemic illness (eg, autoimmune disease, vasculitis)
• less common risk factors
• reasons for screening—to slow disease progression
• to prevent or reduce risk for cardiovascular disease
• check BP and creatinine
• CHEM-7
• random urine sample for protein or albumin to creatinine
ratio
• UA with microscopy
Estimated glomerular
filtration rate (eGFR)
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normal GFR, 95 to 120 mL/min per 1.73 m2
GFR decreases with age
Average decline is 1 mL/min/year after age 30
Renal dysfunction can occur despite normal
creatinine
• eGFR better measure of kidneys’ ability to filter,
and helps detect early kidney disease
• calculation based on age, sex, and ethnicity (ie,
black or white)
Pathophysiology of glomerulosclerosis
• kidney exposed to insults (ie, hypertension and
hyperglycemia) and responds by dilating renal
arteries
• increased flow and increased pressure due to
underlying pathology cause mesangial cell injury,
leading to microscopic scarring within glomerulus
• other glomeruli work harder, while exposure of
nephrons to higher pressure and higher glycemic
environment and scarring continue
• over time, kidney fails to adapt and GFR begins to
decline further in disease process (early screening
and detection important)
Adaptive mechanism to increase GFR in CKD
• afferent and efferent arterioles can regulate incoming and
outgoing blood and pressure independently, or collaborate
to adjust intraglomerular pressure
• in glomerulosclerosis—intraglomerular pressure must be
increased to maintain function
• efferent arteriole constricts
• slightly dilated afferent arteriole and constricted efferent
arteriole cause increased intraglomerular pressure
• in hypovolemia—dehydration decreases intraglomerular
pressure
• afferent arteriole dilates and efferent arteriole constricts to
maintain intraglomerular pressure
• Normal adaptive mechanism in hypovolemia
• maladaptive mechanism in glomerulosclerosis, since
increasing intraglomerular pressure leads to more scarring
Pathophysiology of albuminuria
• normally, capillary bed (glomerulus) and
surrounding capsule of interdigitating
podocytes create pores that filter urea and
electrolytes, while retaining proteins and
sugar
• in glomerulosclerosis, thickening of
mesangium leads to dysfunctional
podocytes and enlarged pores, allowing
passage of albumin (sensitive marker for
early kidney damage)
Albumin to creatinine ratio
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can be performed on spot urine
best when performed on early morning urine
Compares amount of albumin in urine compared to amount of creatinine in
urine; normal, <30 mg of albumin to 1 g of creatinine
microalbuminuria, 30 to 300 mg of albumin to 1 g of creatinine
macroalbuminuria, >300 mg of albumin to 1 g of creatinine
women have higher tolerance range than Men
if abnormal for >3 mo, patient meets definition for CKD
as kidney disease worsens, albumin to creatinine ratio increases
modify therapy based on amount of excreted albumin
morphologic changes in kidney present in 50% of patients with
microalbuminuria
in 25% to 50% of patients, microalbuminuria presents before evidence of
retinopathy
albumin to creatinine ratio linearly correlated to risk for cardiovascular
disease, central nervous system disease, myocardial infarction (MI), and stroke
when risk stratifying patients with normal GFR and macroalbuminuria, CKD
should be considered as MI equivalent
Screening for proteinuria
• can detect kidney disease even before changes in eGFR occur
• proteinuria associated with more rapid decline of kidney function
• reducing proteinuria slows progression of CKD; treat with ACE
inhibitor or angiotensin receptor blocker (ARB)
• urine dipstick detects large amounts (>300 mg) of protein (albumin)
• measure albumin directly in patients with microalbuminuria
• 24-hr urine collection gold standard for protein, but inconvenient and
prone to error
• measure protein or albumin to creatinine ratio
• normal urinary protein to creatinine ratio, <200 mg to 1 g (for albumin,
<30 mg to 1 g)
• microalbuminuria, 30 to 300 mg of albumin to 1 g of creatinine
• macroalbuminuria, >300 mg of albumin to 1 g of creatinine
• in patients with protein in urine, obtain total protein to creatinine ratio
• In patients with risk factors and positive dipstick (protein >30 mg),
perform albumin or total protein to creatinine ratio
• perform 24- hr urine for patients “in extremes” (eg, extremes of age or
weight, high muscle mass) or with malnutrition, muscle diseases,
paraplegia, vegetarianism, pregnancy
Estimating GFR
• equation for calculating eGFR from Modification of Diet
and Renal Disease (MDRD) study— available for personal
digital assistants (eg, Palm Pilots)
• based on laboratory studies that do not require 24-hr urine
collection
• revised equation (CKD Epidemiology Collaboration
Equation) maintains accuracy at lower GFR (eg, <60
mL/min per 1.73 m2), but more accurate at higher GFR
(eg, 80-100 mL/min per 1.73 m2)
• MDRD equation highly accurate, except when 1) patient
emaciated due to eg, anorexia with extremely low total
body protein load (inaccuracy, 20%), or 2) patient obese
(eg, body weight >400 lb)
Diagnosing CKD
• presence of kidney damage for >3 mo (based on
abnormal structure on imaging study or abnormal
function), or eGFR <60 mL/min per 1.73 m2 for >3 mo
• end-stage renal disease—eGFR <15 mL/min per 1.73 m2
(kidney failure)
• need for dialysis or transplantation
• stages—stage 5 most severe
• stage 3, eGFR, 30 to 60 mL/min per 1.73 m2
• eGFR underestimates renal function at normal creatinine
levels
• (eg, creatinine of 0.6 mg/dL may correlate with stage 1
eGFR value
• creatinine of 0.9 mg/dL may correlate with lower eGFR)
• eGFR values <60 mL/min per 1.73 m2 reliable
Diagnosing CKD
• CKD commonly caused by diabetic kidney disease, vascular problem
(eg, hypertension, large vessel disease), and glomerular diseases (eg,
tubular interstitial disease, drug toxicities)
• in patients with risk factors for parenterally transmitted diseases
consider eg, HIV, hepatitis B and C, associated kidney diseases
• in patients with rash, consider lupus and cryoglobulinemia
• laboratory studies—recent UA
• CHEM-7
• Urine protein or albumin to creatinine ratio
• renal US—may show stones, hydronephrosis, or cysts
• small hyperechoic kidneys generally indicate CKD
• large kidneys may be associated with hydronephrosis (obstructive
process), or infiltrating process (eg, sarcoidosis or lymphoma)
• size disparity between kidneys indicates renal vascular disease (eg,
fibromuscular dysplasia or renal artery thrombosis)
• slow progression of CKD by controlling BP, glucose, and proteinuria
Evaluation
• in most patients, CKD caused by diabetes
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and hypertension
when cause of CKD unknown, consider
antinuclear antibody testing, serum protein
electrophoresis, and complete blood count
complement testing to screen for
glomerulonephritis
perinuclear antineutrophil cytoplasmic
antibody
renal ultrasonography to look for enlarged,
polycystic, or extremely small kidneys
no added value from computed tomography
Management
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blood pressure (BP) control and glycemic control
evaluate cardiovascular risk
dietary modification (consider referral to nutritionist)
anticipate complications and refer to specialist
hypertension and proteinuria— independent variables that predict long-term
decline of kidney disease
kidney disease can cause hypertension
Sclerosing and fibrosing kidney leads to systemic response of elevated BP
reduction of BP reduces cardiovascular and renal risk
reduction of proteinuria lowers cardiovascular risk and improves endothelial
cell function
Uncontrolled BP results in more rapid decline in renal function
United Kingdom Prospective Diabetes Study (UKPDS) found that patients
with BP control had better renal outcomes than patients with glycemic control
BP control—large studies show 3 to 4 medications needed
aggressive management needed
BP goal, 130/80 mm Hg (reducing BP too much can worsen renal failure)
(ACE) inhibitors and (ARBs)
• from renal standpoint, angiotensin modulation therapy more effective
than other medications
• reduce BP with better outcomes in patients with CKD
• decrease progression to macroalbuminuria
• decrease albumin excretion
• Restore ion charge and membrane permeability components to
glomerulus
• indications for ACE inhibitors—type 1 diabetes with microalbuminuria
• hypertension and type 2 diabetes with microalbuminuria
• some evidence that treating normotensive patients who have type 2
diabetes with ARB or ACE inhibitor does not affect renal outcomes
• follow-up in 1 mo
• ACE inhibitors and ARBs inhibit efferent arterioles from constricting,
leading to decreased intraglomerular pressure (reduces GFR and
increases serum creatinine)
(ACE) inhibitors and (ARBs)
• expected changes in serum creatinine—during first 2 to 4
wk of starting ACE inhibitor or ARB, creatinine may
increase due to decreased intraglomerular pressure
• increase usually not >30% above baseline, and generally
returns to baseline within 1 to 2 mo
• if increase >30%, monitor patient carefully and consider
discontinuing agent
• after serum creatinine returns to baseline, check every 6
mo
• risk for hyperkalemia— slightly increased risk with use of
ACE inhibitor or ARB
• rare; start patients on low-potassium diet and loop diuretic
• when GFR <30 mL/min per 1.73 m2, hydrochlorothiazide
ineffective
(ACE) inhibitors and (ARBs)
• counsel patients about avoiding nonsteroidal antiinflammatory drugs (NSAIDs), including ibuprofen and
cyclooxygenase-2 inhibitors
• Sodium polystyrene sulfonate (SPS; eg, Kayexalate)
sometimes used to maintain potassium
• combining ACE inhibitors and ARBs—may improve
outcomes, but Ongoing Telmisartan Alone and in
Combination with Ramipril Global Endpoint Trial
(ONTARGET) showed decline in
• outcomes (eg, cardiovascular mortality, renal outcomes)
• ACE inhibitor and ARB may be combined cautiously after
trying all other options for BP control
• monitor creatinine every 3 mo and watch patients carefully
• decline in outcomes seen in patients with congestive heart
failure (especially those on Beta-blocker therapy)
Aliskiren
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direct renin inhibitor
blocks renin activity
Effective for BP control
data about renal effects limited
recommend against combining with ACE
inhibitor or ARB
• studies show ACE inhibitors and ARBs
better agents for renal outcomes
Amlodipine
• trial found patients on amlodipine alone
had worse renal outcomes (calcium channel
blockers cause afferent arteriole to dilate
more than efferent arteriole, leading to
increased intraglomerular pressure)
• provides good BP control (especially in
black patients)
• data show good outcomes when combined
with ACE inhibitor or ARB
Nighttime dosing
• trial saw statistically significant reduction
in cardiovascular mortality with nighttime
dosing of antihypertensive agents
Prevention of overt nephropathy
• tight glycemic control important
• Diabetes Control and Complications Trial Cohort (Epidemiology of
Diabetes Interventions and Complications [EDIC] Study) showed good
outcomes and reduction in nephropathy in patients with tight glycemic
control
• continuous gradient exists between hyperglycemia and microvascular
complications (ie, retinopathy and nephropathy)
• evidence suggests glycemic control can reduce nephropathy
• Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial
and Action in Diabetes and Vascular Disease: Preterax and Diamicron
Modified Release Controlled Evaluation (ADVANCE) trial found
glycemic control not as effective as BP control (ADVANCE trial
• stopped early due to higher cardiovascular mortality in tight glycemic
control group)
• metformin contraindicated in patients with serum creatinine >1.4
mg/dL
Prevention of overt nephropathy
• in ACCORD and ADVANCE trials, tight glycemic control did not
improve overall cardiovascular outcomes, but renal outcomes
improved
• diabetes, CKD, and cardiovascular disease must be managed together;
in patients with CKD, death from cardiovascular event 10 times more
likely than dialysis
• CKD predicts cardiovascular disease (consider aspirin therapy)
• counsel patients about weight loss and tobacco cessation
• control lipids
• atorvastatin shown to improve renal function)
• dietary modifications—restrict salt intake to 2.5 to 3.5 g/day (difficult;
patients at stage 4 CKD lose sense of taste)
• protein restriction (difficult without assistance of nutritionist)
• phosphate restriction
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Complications
Hyperkalemia
Hyperphosphatemia
hypocalcemia
(secondary hyperparathyroidism)
Hyponatremia
Decreased immunoglobulins
dyslipidemia—coronary artery disease number 1 cause of
mortality in patients with CKD
• animal studies suggest dyslipidemia can worsen kidney
function
• recent meta-analysis of 13 small studies showed lipid
reduction might preserve GFR
• patients with CKD tend to have high triglycerides and
elevated low-density lipoprotein (LDL) to high-density
lipoprotein (HDL) ratios
Hyperkalemia
• During chronic kidney failure, fluid intake may need to be
restricted to prevent the sodium concentration in the blood
from becoming too low. Foods that are extremely high in
potassium, such as salt substitutes, must be avoided, and
foods that are somewhat high in potassium, such as dates,
figs, and many other fruits, should not be consumed in
excess. (See the National Kidney Foundation's Fact Sheet
on Potassium in the diet for more information.) A high
potassium level in the blood increases the risk of abnormal
heart rhythms and cardiac arrest. If the potassium level
becomes too high, drugs such as sodium polystyrene
sulfonate may help, but emergency dialysis may be
required.
Complications
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guidelines recommend aggressive targets (eg, LDL <100 mg/dL, triglycerides
<200 mg/dL)
hypertension—ACE inhibitors and ARBs preferentially lower glomerular
pressures and reduce proteinuria
in patients with normal urine protein, target BP, <130/80 mm Hg
in patients with protein in urine, target BP, <125/75 mm Hg
when starting ACE inhibitors in CKD patients, GFR initially decreases, and
creatinine increases mildly <30%
check CHEM-7 1-2 wk after initiating therapy
do not discontinue therapy unless increase does not stabilize
Monitor anemia—normochromic; normocytic; hypoproliferative;
caused by low erythropoietin
reduces quality of life
Causes fatigue and can lead to cardiomyopathy from left ventricular
hypertrophy; correction of anemia may help improve CKD;
recommended hemoglobin (Hb) target, 10 g/dL to 12 g/dL
check ferritin and supplement with iron if indicated
Give erythropoietin to predialysis patients if Hb <10 g/dL;
Complications
• Renal osteodystrophy—common
• early CKD patients have
hyperphosphatemia and increased
parathyroid hormone (PTH), resulting in
increased bone turnover, decreased bone
strength, and fractures
• check PTH and restrict dietary phosphate
intake
• treat with calcium acetate and vitamin D
• refractory patients may need surgical
treatment to remove parathyroid
Nutrition and lifestyle
• CKD patients at risk for malnutrition
• study showed patients on restricted protein
diet did not fare better
• refer patients to nutritionist and consult
nephrologist
• be aggressive about tobacco smoking
cessation
• social support and screening for depression
When to refer to nephrologist
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underlying cause unclear after work-up
need for biopsy
diagnosis unclear
stage 3 or 4 CKD rapid progression of CKD
or superimposed acute kidney failure
• www.kidney.org or www.mdrd.com useful
resources
Questions and answers
• salt substitutes—should be avoided due to high potassium
content
• management of CKD, proteinuria, and hypertension—
control BP first
• consider increasing ACE inhibitor or ARB if indicated
• Incidental finding of trace or 1+ protein on urine dipstick
in otherwise healthy patient—various proteins (eg, tubular
protein, albumin) excreted in urine
• perform albumin to creatinine ratio or urine
proteinelectrophoresis to identify protein
• whitecoat hypertension—diagnose hypertension based on
clinical findings in patients who appear unable to
provideaccurate home BP log
Questions and answers
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anemia—present in stage 3 and 4 CKD
look for other causes of anemia (eg, perform colonoscopy if indicated)
proteinuria—surrogate marker for CKD
for patients with 500 to 600 mg of protein to 1 g of creatinine, monitor efficacy of BP
treatment
refer patients in nephrotic range (>4000 mg of protein to 1 g of creatinine)
effects of NSAIDs—weigh risks and benefits
Glomerular effects tend to reverse when NSAID stopped
prostaglandin helps maintain vasodilation at afferent arteriole (blocking prostaglandin
constricts afferent arteriole, leading to hypotension within glomerulus)
stopping NSAID restores intraglomerular pressure
NSAIDs toxic at tubular level (ie, can lead to tubular necrosis; less common)
discuss risks with patient
ACE inhibitor can be restarted when patients hemodynamically stable
is one ACE inhibitor better than another?—class effect
some agents more studied than others
most ACE inhibitors (eg, enalapril, ramipril, lisinopril) and most ARBs (eg, telmisartan,
candesartan, losartan) shown beneficial
preeclampsia— risk factor for CKD