AZOTEMIA
Dr.Vajehallah Raeesi
Assistant Professor
Department of Internal Medicine
Birjand University of Medical Sciences
DR.VAJEHALLAH RAEESI
c
Normal kidney functions occur through numerous cellular processes to
maintain body homeostasis
The duration and severity of the disease
. The combination of these findings should permit identification of one of
the major nephrologic syndromes and will allow differential diagnoses to
be narrowed and the appropriate diagnostic evaluation and therapeutic
course to be determined
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Initial Clinical and Laboratory Data Base for
Defining Major Syndromes in Nephrology
Syndromes
Important Clues to Diagnosis
Findings That Are Common
Acute or rapidly progressive
renal failure
Anuria
Oliguria
Documented recent decline in
GFR
Hypertension, hematuria
Proteinuria, pyuria
Casts, edema
Chronic renal failure
Azotemia for >3 months
Prolonged symptoms or signs of
uremia
Symptoms or signs of renal
osteodystrophy
Kidneys reduced in size
bilaterally
Broad casts in urinary sediment
Proteinuria
Casts
Polyuria, nocturia
Edema, hypertension
Electrolyte disorders
Nephrotic syndrome
Proteinuria >3.5 g per 1.73 m2
per 24 h
Hypoalbuminemia
Edema
Hyperlipidemia
Casts
Lipiduria
DR.VAJEHALLAH RAEESI
reduction in GFR leading to azotemia
alterations of the urinary sediment and/or protein excretion

GFR is important in both the hospital and outpatient settings

GFR is the primary metric for kidney "function," and its direct measurement involves
administration of a radioactive isotope (such as inulin or iothalamate) that is filtered at
the glomerulus but neither reabsorbed nor secreted throughout the tubule

GFR is related directly to the urine creatinine excretion and inversely to the serum
creatinine (UCr/PCr).
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
Failure to account for GFR reductions in drug dosing can lead to significant
morbidity and mortality from drug toxicities (e.g., digoxin, aminoglycosides)

In patients with chronic progressive renal disease, there is an approximately
linear relationship between 1/PCr (y axis) and time (x axis).

Signs and symptoms of uremia develop at significantly different levels of
serum creatinine, depending on the ntpatie (size, age, and sex), the
underlying renal disease, the existence of concurrent diseases, and true GFR.
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CrCl = (Uvol x UCr)/(PCr x Tmin

Assessment of Glomerular Filtration Rate (GFR

radioactive isotope (such as inulin or iothalamate

Serum creatinine

Urea clearance
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
When a timed collection for creatinine clearance is not available, decisions
about drug dosing must be based on serum creatinine alone. Two formulas are
used widely to estimate kidney function from serum creatinine: (1) CockcroftGault and (2) four-variable MDRD (Modification of Diet in Renal Disease).

Cockcroft-Gault: CrCl (mL/min) = (140 – age (years) x weight (kg) x [0.85 if
female])/(72 x sCr (mg/dL)

MDRD: eGFR (mL/min per 1.73 m2) = 186.3 x PCr (e–1.154) x age (e–0.203) x
(0.742 if female) x (1.21 if black).
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can mask significant changes in GFR with small or
imperceptible changes in serum creatinine concentration

The gradual loss of muscle from chronic illness,

chronic use of glucocorticoids

malnutrition
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Serum cystatin C has been proposed to be a more sensitive
marker of early GFR decline than is plasma creatinine

however, like serum creatinine, cystatin C is
influenced by age, race, and sex and additionally
is associated with diabetes, smoking, and markers
of inflammation
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Once it has been established that GFR is reduced, the
physician must decide if this represents acute renal injuryor
chronic

clinical situation

history

laboratory data anemia, hypocalcemia, and hyperphosphatemia

Radiographic evidence of renal osteodystrophy ; urinalysis ; and renal
ultrasound
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
Patients with advanced chronic renal insufficiency ;
Proteinuria. nonconcentrated urine (isosthenuria. small kidneys on ultrasound.
increased echogenicity and cortical thinningTreatment should be directed toward
slowing the progression of renal disease and providing symptomatic relief for
edema, acidosis, anemia,
Acute renal failure; (prerenal azotemia. intrinsic renal diseases (affecting small
vessels, glomeruli, or tubules), or postrenal processes (obstruction to urine flow
in ureters, bladder, or urethra)
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1
Novel Biomarkers

BUN and creatinine are functional biomarkers of glomerular filtration rather
than tissue injury biomarkers and, therefore, may be suboptimal for the
diagnosis of actual parenchymal kidney damage

Kidney injury molecule-1 (KIM-1) :ischemia or nephrotoxins such as cisplatin

Neutrophil gelatinase associated lipocalin (NGAL, also known as lipocalin-2 or
siderocalin): 2 hours of cardiopulmonary bypass–associated AKI.

a1-Microglobulin: high levels may predict poorer outcome

Cystatin C: tubular dysfunction

Interleukin-18 (IL-18):Elevated urinary levels found to be early marker of AKI
and independent predictor of mortality in critically ill patients
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Prerenal Failure

40–80% of acute renal failure

any cause of decreased circulating blood volum

reductions in cardiac output from peripheral vasodilation (sepsis, drugs)

profound renal vasoconstriction [severe heart failure, hepatorenal syndrome,
drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs)

Patients on NSAIDs and/or ACE inhibitors/ARBs

Normal GFR is maintained in part by the relative resistances of the afferent
and efferent renal arterioles

Atherosclerosis, hypertension, and older age can lead to hyalinosis and
myointimal hyperplasia, causing structural narrowing of the intrarenal
arterioles and impaired capacity for renal afferent vasodilation
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Index
Prerenal Azotemia
Oliguric Acute Renal Failure
BUN/PCr ratio
>20:1
10-15:1
Urine sodium (UNa), meq/L
<20
>40
Urine osmolality, mosmol/L
H2O
>500
<350
Fractional excretion of
sodium
Urine/plasma creatinine
(UCr/PCr)
<1%
>2%
>40
<20
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DR.VAJEHALLAH RAEESI
Postrenal Azotemia

<5% of cases of acute renal failure

urethra or bladder outlet, bilateral ureteral obstruction, or unilateral
obstruction in a patient with a single functioning kidney

diagnosed by renal ultrasound

False-positive : diuresis, renal cysts, extrarenal pelvis

False-negative :obstruction is less than 48 hours in duration or associated with
volume contraction, staghorn calculi, retroperitoneal fibrosis, or infiltrative
renal diseases

Unilateral obstruction may cause AKI in the setting of significant underlying
CKD or in rare cases from reflex vasospasm of the contralateral kidney.
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Intrinsic Renal Disease

prerenal and postrenal azotemia have been excluded

large renal vessels, intrarenal microvasculature and glomeruli, or the
tubulointerstitium

Ischemic and toxic ATN account for 90% of cases of acute intrinsic renal
failure

Ischemic ATN : major surgery, trauma, severe hypovolemia, overwhelming
sepsis, or extensive burns.

Processes that involve the tubules and interstitium : drug (especially
antibiotics, NSAIDs, and diuretics), severe infections (both bacterial and
viral), systemic diseases (e.g., systemic lupus erythematosus), and infiltrative
disorders (e.g., sarcoid, lymphoma, or leukemia).

Occlusion of large renal vessels including arteries and veins is an uncommon
cause of acute renal failure

Diseases of the glomeruli (glomerulonephritis and vasculitis) and the renal
microvasculature (hemolytic-uremic syndromes, thrombotic
thrombocytopenic purpura, and malignanthypertension
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Nephrotoxin-Associated Aki

All structures of the kidney are vulnerable to toxic injury, including the
tubules, interstitium, vasculature, and collecting system

risk factors for nephrotoxicity include older age, chronic kidney disease
(CKD), and prerenal azotemia.

Contrast Agents: rise in SCr beginning 24–48 hours following exposure,
peaking within 3–5 days, and resolving within 1 week

Antibiotics:AKI typically manifests after 5–7 days of therapy

Chemotherapeutic Agents:Cisplatin and carboplatin -Ifosfamide may cause
hemorrhagic cystitis - mitomycin C and gemcitabine

Toxic Ingestions:Ethylene glycol-Melamine-Aristolochic acid

Endogenous Toxins: myoglobin, hemoglobin, uric acid, and myeloma light
chains
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Diagnostic Evaluation

AKI is currently defined by a rise of at least 0.3 mg/dL or 50% higher than
baseline within a 24–48-hours period

or a reduction in urine output to 0.5 mL/kg per hour for longer than 6 hours

History and Physical Examination

Urine Findings

Blood Laboratory Findings
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Oliguria and Anuria

Oliguria refers to a 24-h urine output <400 mL

anuria is the complete absence of urine formation (<100 mL)

. Anuria can be caused by total urinary tract obstruction, total renal artery or
vein occlusion, and shock .

Cortical necrosis, ATN, and rapidly progressive glomerulonephritis
occasionally cause anuria.

Oliguria can accompany any cause of acute renal failure and carries a more
serious prognosis for renal recovery in all conditions except prerenal
azotemia.
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Proteinuria

The dipstick measurement detects only albumin and gives false-positive
results when pH >7.0 and the urine is very concentrated or contaminated with
blood

proteinuria that is not predominantly albumin will be missed by dipstick
screening.

healthy individuals excrete <150 mg/d of total protein and <30 mg/d of
albumin. However, even at albuminuria levels <30 mg/d, risk for progression
to overt nephropathy or subsequent cardiovascular disease is increased

When the total daily excretion of protein is >3.5 g, hypoalbuminemia,
hyperlipidemia, and edema (nephrotic syndrome

A hypercoagulable state may arise from urinary losses of antithrombin III,
reduced serum levels of proteins S and C, hyperfibrinogenemia, and enhanced
platelet aggregation
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Hematuria

Isolated hematuria without proteinuria, other cells, or casts is often indicative of bleeding
from the urinary tract

Hematuria is defined as two to five RBCs per high-power field (HPF) and can be detected by
dipstick.

A false-positive dipstick for hematuria (where no RBCs are seen on urine microscopy) may
occur when myoglobinuria is present, often in the setting of rhabdomyolysis

Common causes of isolated hematuria include stones, neoplasms, tuberculosis, trauma, and
prostatitis. Gross hematuria with blood clots is usually not an intrinsic renal process; rather,
it suggests a postrenal source in the urinary collecting system

A single urinalysis with hematuria is common and can result from menstruation, viral illness,
allergy, exercise, or mild trauma

Persistent or significant hematuria (>3 RBCs/HPF on three urinalyses, a single urinalysis with
>100 RBCs, or gross hematuria) is associated with significant renal or urologic lesions in 9.1%
of cases
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
Even patients who are chronically anticoagulated should be investigated

The suspicion for urogenital neoplasms in patients with isolated painless
hematuria and nondysmorphic RBCs increases with age

Hematuria with pyuria and bacteriuria is typical of infection

Hypercalciuria and hyperuricosuria are also risk factors for unexplained isolated
hematuria

The RBCs of glomerular origin are often dysmorphic

The most common etiologies of isolated glomerular hematuria are IgA
nephropathy, hereditary nephritis, and thin basement membrane

Hematuria with dysmorphic RBCs, RBC casts, and protein excretion >500 mg/d
is virtually diagnostic of glomerulonephritis. Even in the absence of azotemia,
these patients should undergo serologic evaluation and renal biopsy
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


Hyperkalemia
a. Restriction of dietary potassium intake
b. Discontinuation of potassium-sparing diuretics, ACE inhibitors, ARBs,
NSAIDs

c. Loop diuretics to promote urinary potassium loss

d. Potassium binding ion-exchange resin (sodium polystyrene sulfonate)

e. Insulin (10 units regular) and glucose (50 mL of 50% dextrose) to promote
entry of potassium intracellularly

f. Inhaled beta-agonist therapy to promote entry of potassium
intracellularly

g. Calcium gluconate or calcium chloride (1 g) to stabilize the myocardium
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
Metabolic acidosis

a. Sodium bicarbonate (if pH <7.2 to keep serum bicarbonate >15 mmol/L)

b. Administration of other bases e.g., THAM

c. Renal replacement therapy

. Nephrotoxin-specific

a. Rhabdomyolysis: consider forced alkaline diuresis

b. Tumor lysis syndrome: allopurinol or rasburicase
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Cirrhosis and Hepatorenal Syndrome

Albumin may prevent AKI in those treated with antibiotics for spontaneous
bacterial peritonitis.

The definitive treatment of the hepatorenal syndrome is orthotopic liver
transplantation

Bridge therapies that have shown promise include terlipressin (a vasopressin
analog), combination therapy with octreotide (a somatostatin analog) and
midodrine (an 1-adrenergic agonist), and norepinephrine, all in combination
with intravenous albumin (25–50 mg per day, maximum 100 g/d).
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Classification of Chronic Kidney Disease (CKD
STAGE
GFR, mL/min per 1.73 m2
0
1
2
3
4
5
>90a
90b
60–89
30–59
15–29
<15
DR.VAJEHALLAH RAEESI
‫خسته نباشید‬
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