15_HST110 Introduction to Renal Disease I - AKI 2017

Question 1

What is definition of acute kidney injury (AKI)?

Answer 1

Sudden, often temporary, loss in kidney function (hours to days). An abrupt decrease in renal function

Question 2

What is the definition of chronic kidney disease (CKD)?

Answer 2

Structural or functional kidney abnormalities with or without decreased GFR for > 3 months

Question 3

What is the definition of end stage renal disease (ESRD)?

Answer 3

Total and permanent kidney failure

Question 4

AKI encompasses both (X) injury to the kidney and acute (Y). Etiology of AKI can be from within the kidney or from external stresses to the kidney

Answer 4

X = direct
Y = impairment of function

Question 5

AKI can be defined as any of the following:

Increase in Cr by ≥ (X) mg/dL within 48 hours
Increase in Cr by ≥ 1.5 times the baseline within the prior (Y) days
Urine volume < (Z) mL/kg/hour for 6 hours

Answer 5

X = 0.3
Y = 7
Z = 0.5

Question 6

What percent of hospital admissions are due to AKI?

Answer 6

5-13%

Question 7

What percent of ICU patients have AKI?

Answer 7

1-25%

Question 8

What is the mortality of AKI in ICU patients (in %)?

Answer 8

15-60%

Question 9

Recovery potential: Animal studies show permanent damage following experimentally-induced AKI, including what 2 conditions?

Answer 9

tubulointerstitial fibrosis

damage to microvasculature

Question 10

Multiple human studies show an increased risk of (X) and (Z) even after recovery from AKI

Answer 10

X = CKD
Y = ESRD

Question 11

Define Azotemia

Answer 11

Abnormally high levels of nitrogen-containing compounds (e.g., urea, creatinine) in the blood

Question 12

Define Oliguria

Answer 12

Low urine output
< 400 mL/day but >100 mL/day
Also defined as < 0.5 mL/kg/hour in adults

Question 13

Define Anuria

Answer 13

Absence of urine

<100 mL/day

Question 14

What are the 3 causes of AKI, based on location in the urinary system?

Answer 14

1) Prerenal (“before the kidney”)
2) Intrinsic Renal (“inside the kidney”)
3) Postrenal (“After the kidney”)

Question 15

Postrenal AKI is typically caused by an (X) to urinary flow, occuring at any level of the urinary tract (kidney, ureters, bladder, or urethra)

Answer 15

X = obstruction

Question 16

Why is all AKI considered postrenal until proven otherwise?

Answer 16

Early diagnosis and prompt correction of obstruction can result in minimal permanent kidney damage

Uncorrected obstruction can lead to irreversible renal failure

~10% of AKI is postrenal. Not most common, but direct intervention is possible so you want to be able to rule it out early on

Question 17

Name 3 causes of kidney-localized postrenal AKI

Answer 17

Stones
Cancer
Sloughed papilla

Question 18

Name 8 causes of ureter-localized postrenal AKI

Answer 18

Stones
Cancer
Sloughed papilla
Extrinsic tumors
Retroperitoneal fibrosis
Infection
Blood clot
Trauma

Question 19

Name 4 causes of bladder-localized postrenal AKI

Answer 19

Cancer
Blood clot
Edema/inflammation
Posterior urethral valves

Question 20

Name 3 causes of urethra-localized postrenal AKI

Answer 20

Prostate enlargement
Stones
Strictures

Question 21

How does postrenal AKI cause reduction in GFR? Use a formulaic argument

Answer 21

GFR decreases as a result of an increase in P_BS

GFR = Kf * {P_GC - (P_BS + (PI)_GC)]

Obstruction to urinary flow increases tubular pressure throughout the kidney

Increase in tubular pressure is transmitted back to the Bowman’s space and increases the hydrostatic pressure of Bowman’s space

Therefore, the forces favoring filtration will be decreased, and GFR will fall

Question 22

What abnormal anatomical features are common in a postrenal urinary obstruction?

Answer 22

Distended structures (renal calyces, renal pelvis), stones or other obstruction present, blocked ureter

Question 23

Under ultrasound, an obstruction results in what condition or appearance in the kidney, characterized by increased water retention?

Answer 23

Hydronephrosis. Dark regions were water is accumulating are evident. Thinning of the cortex is also seen

Question 24

Under CT, hydronephrosis appears as a (X) mass

Answer 24

X = bulbous, distended

Question 25

Name 3 treatment options for postrenal AKI in order of increasing severity and ascending location of obstruction

Answer 25

1) Urethra level: Foley catheter 2) Ureter level: Ureteral stent 3) Kidney level (complete bypass): Percutaneous nephrostomy tubes

Question 26

Prerenal AKI is instigated by a decrease in renal perfucion. Name 2 conditions this can result from

Answer 26

Decreased ECV | Hypotension

Question 27

Why does prerenal AKI not represent true "kidney injury?"

Answer 27

No intrinsic abnormality to the renal parenchyma is seen

Question 28

How can prerenal AKI be corrected?

Answer 28

With restoration of volume and circulatory deficits

Question 29

Name 5 causes of prerenal AKI due to ECV depletion (with DECREASED ECF)

Answer 29

``` Blood loss GI losses Renal losses Skin losses Third spacing ```

Question 30

Name 3 causes of prerenal AKI due to ECV depletion (with INCREASED ECF)

Answer 30

CHF Cirrhosis Nephrotic syndrom

Question 31

Stenosis of what blood vessel can cause prerenal AKI?

Answer 31

Renal artery

Question 32

Name 6 drugs that can cause prerenal AKI

Answer 32

``` NSAIDs ACE inhibitors ARBs Cyclosporine Tacrolimus IV contrast ```

Question 33

How does prerenal AKI cause reduction in GFR? Use a formulaic argument

Answer 33

GFR decreases as a result of an decrease in P_GC GFR = Kf * {P_GC - (P_BS + (PI)_GC)] Significant reduction in renal perfusion results in a decrease in capillary hydrostatic pressure

Question 34

What 3 drugs can cause direct afferent vasoconstriction resulting in prerenal AKI?

Answer 34

Cyclosporine Tacrolimus IV contrast

Question 35

NSAIDs inhibit afferent vasodilation, inhibiting the autoregulatory role of (X), leading to prerenal AKI

Answer 35

X = prostaglandins

Question 36

ACE inhibitors and ARBs block the efferent vasoconstrictive effects of (X), leading to prerenal AKI

Answer 36

X = angiotensin II

Question 37

Intrinsic Renal AKI can accur at what 4 levels?

Answer 37

Glomerular Tubular Interstitial Vascular

Question 38

Name 1 example of intrinsic renal AKI at each of its 4 levels

Answer 38

Glomerular: Acute glomerulonephritis Interstitial: Acute interstitial nephritis Tubular: Acute tubular necrosis Vascular: Vasculitis

Question 39

What is acute tubular necrosis (ATN), one of the most common causes of AKI, characterized by?

Answer 39

Death of tubular epithelial cells

Question 40

What are the 2 major types of ATN?

Answer 40

Ischemic (prolonged hypoperfusion of tubules) Nephrotoxic (direct toxic injury to tubules)

Question 41

Name 5 common causes of ischemic ATN

Answer 41

``` Major surgery Trauma Severe hypovolemia Sepsis Burns ```

Question 42

Name 4 major categories of the common toxic causes of ATN

Answer 42

Antimicrobials (Aminoglycosides, Amphotericin B) Chemotherapy (Cisplatin, Ifosfamide) Radiocontrast agents Heme pigments (Hemolysis, Rhabdomyolysis)

Question 43

Tubular injuries due to ATN affect the (X) and (Y) the most since both are in the outer medulla (relatively hypoxic)

Answer 43

``` X = Proximal tubule (pars recta or S3 segment) Y = TAL of LOH ``` PT is in charge of secretion of toxins. They can accumulate them as well

Question 44

What is a common morphological change seen in tubular epithelial cells in ATN before necrosis and luminal obstruction set in?

Answer 44

Loss of polarity following ischemia and reperfusion

Question 45

Under histological evaluation, ATN appears with what striking features?

Answer 45

Dilated, cystic tubules Loss of brush border Debris in tubular lumen

Question 46

How does ATN cause reduction in GFR? Use a formulaic argument

Answer 46

GFR decreases as a result of an increase in P_BS GFR = Kf * {P_GC - (P_BS + (PI)_GC)] Occlusion of the tubular lumens by cellular debris and casts and, with hemolysis or rhabdomyolysis, by precipitation of heme pigments Elevated intraluminal tubular pressure can disrupt epithelial cell tight junctions and cause backleak of tubular fluid into the circulation

Question 47

What are the 3 phases of ATN and their timeframes?

Answer 47

Initiation (hours to days) Maintenance (1-2 weeks) Recovery (variable)

Question 48

The "initiation" phase of ATN is characterized by exposure to (X). The injury is evolving but not established. ATN potentially (Y)

Answer 48

``` X = ischemia or toxin Y = preventable ```

Question 49

In the "maintenance" phase of ATN, (X) injury is established. This stage may be prolonged for as long as (Y) months

Answer 49

``` X = parenchymal Y = 1-12 ```

Question 50

In the "recovery" phase of ATN, repair and regeneration of tubules is evident. Increase in urine output (“(X)”) and fall in (Y) are typical

Answer 50

``` X = post-ATN diuresis Y = creatinine ```

Question 51

Acute interstitial nephritis (AIN), a common cause of AKI, is characterized by what condition?

Answer 51

Acute inflammation of the interstitium

Question 52

What is AIN more commonly caused by?

Answer 52

Drugs that cause hypersensitivity-type reactions. Also associated with infections (bacterial, viral, fungal, mycobacterial) and autoimmune disease (SLE, Sjögren’s)

Question 53

Name 4 common antibiotics associated with AIN

Answer 53

β-lactam antibiotics (penicillins, cephalosporins) Sulfonamides Rifampin Ciprofloxacin

Question 54

Name 3 non-antibiotic drugs associated with AIN

Answer 54

NSAIDs Diuretics (furosemide, thiazides) Proton-pump inhibitors

Question 55

AIN presents with a rise in (X) 1-2 weeks after exposure to offending drug. Can be as short as (Y) day(s) (if pre-exposed to drug) or as long as months (e.g. (Z))

Answer 55

``` X = creatinine Y = 1 Z = NSAIDs ```

Question 56

What are the 4 classic signs of drug-associated AIN?

Answer 56

Fever (36%) Arthralgias (45%) Skin rash (22%) Eosinophilia (35%)

Question 57

The classic triad of fever, skin rash, and eosinophilia for AIN is seen in less that what % of patients?

Answer 57

10-15%

Question 58

Under histolopathological evaluation, AIN presents with what features?

Answer 58

Interstitial infiltration (lymphocytes, eosinophils) Interstitial edema Tubulitis Glomeruli and vessels normal

Question 59

How does AIN cause reduction in GFR? Use a formulaic argument

Answer 59

GFR decreases as a result of a combined increase in P_BS and a decrease in P_GC GFR = Kf * {P_GC - (P_BS + (PI)_GC)] Interstitial inflammation and edema leads to compression of tubules and vasculature Occlusion of the tubular lumens elevates intraluminal tubular pressure and hydrostatic pressure in Bowman’s space Vascular occlusion reduces perfusion and capillary hydrostatic pressure

Question 60

Treatment of AIN involves discontinuation of the offending drug. Often leads to (X) of AKI. Recovery can take weeks to months Oral (Y) may have benefit if administered early (<14 days) after diagnosis

Answer 60

``` X = complete resolution Y = corticosteroids ```

Question 61

Define Acute Glomerulonephritis (GN)

Answer 61

Inflammation and proliferation of glomerular tissue

Question 62

GN can result in damage to what 3 structures?

Answer 62

GBM, mesangium, and capillary endothelium

Question 63

What 4 conditions is GN characterized by?

Answer 63

Hematuria with or without RBC casts Proteinuria Hypertension Renal impairment

Question 64

Spectrum of GN ranges from asymptomatic (X) to (Y) syndrome

Answer 64

``` X = hematuria Y = nephritic ```

Question 65

Under histolopathological evaluation, Acute GN (Diffuse proliferative GN) presents with what feature?

Answer 65

Glomerular hypercellularity (lymphocytes and neutrophils)

Question 66

Name 3 types of vascular acute kidney disease

Answer 66

Benign or malignant hypertensive nephrosclerosis Systemic vasculitis Thrombotic microangiopathy (Hemolytic uremic syndrome (HUS), Thrombotic thrombocytopenic purpura (TTP), Scleroderma)

Question 67

What is the first "Rule of 3's" related to the categories of AKI?

Answer 67

Postrenal Prerenal Intrinsic renal

Question 68

What is the second "Rule of 3's" related to noninvasive diagnostic tools?

Answer 68

History and physical exam Urinalysis with urinary electrolytes Ultrasound

Question 69

What is the third "Rule of 3's" related to the clinical maxims?

Answer 69

AKI is considered obstructive until proven otherwise Eliminate postrenal and prerenal causes prior to pursuing intrinsic renal causes Examine a fresh urine specimen whenever possible!

Question 70

Name examples of important information to acquire in the History and Exam for renal diseases

Answer 70

``` Time of onset? History of volume depletion? Difficulty voiding? Other symptoms? Medications? Recent events? (Recent eating/drinking habits and events, recent accidents) ```

Question 71

Name examples of useful physical exam findings in the History and Exam for renal diseases

Answer 71

Fever? Blood pressure (hypertension? hypotension?) Volume status? Other findings (e.g. rashes)?

Question 72

What is the time frame for appropriate urinalysis?

Answer 72

30-60 minutes after voiding

Question 73

How does one prevent contamination in specimen acquisition for urinalysis?

Answer 73

Midstream voiding and collection. For women, noting stage of menstrual cycle

Question 74

Name 6 of the important tests on a urinalysis dipstick

Answer 74

"Leukocyte esterase" detects urinary WBCs "Nitrate" detects bacteria in the urine "Protein" detects only albumin in the urine "pH" reflects degree of acidification of urine "Blood" detects heme from RBCs or free hemoglobin or myoglobin "Specific gravity" provides estimate of urine osmolality

Question 75

Urine sediment is collected and evaluated using what technique?

Answer 75

Centrifugation of urine sample and resuspension for light microscopy review

Question 76

What are normal values for urine sediment cellular counts? RBC WBC

Answer 76

RBC: 0-2/hpf | WBC 0-5/hpf

Question 77

Name 4 examples of cells found in urine sediment

Answer 77

RBC, WBC, Tubular Epithelial Cells, Squamous Epithelial Cells (skin)

Question 78

What do dysmorphic RBC look like and what causes this condition?

Answer 78

Blebbed, mishapen cells Indicates glomerular filtration barrier damage . Deformation of RBC membranes as they squeeze through the podocyte filtration slits or other barriers causes issues with shape and membrane integrity

Question 79

What is the interpretation of seeing dysmosphic RBCs in a urine sediment?

Answer 79

Acute GN Infection Stones Malignancy

Question 80

What is the interpretation of seeing WBCs in a urine sediment?

Answer 80

Infection Acute interstitial nephritis Acute glomerulonephritis Contamination

Question 81

Where do the cylindrical casts seen in the urine sediment form?

Answer 81

Distal tubule and collecting ducts

Question 82

What is the primary constituent of urine sediment casts?

Answer 82

Tamm-Horsfall protein

Question 83

What other general classes of substances can be trapped in the tubular lumen during the formation of casts?

Answer 83

Granules and cells

Question 84

Hyaline casts can be see in most renal diseases and contain only (X)

Answer 84

X = Tamm-Horsfall protein

Question 85

What non-renal disease-based conditions can result in hyaline casts?

Answer 85

Dehydration, fever, and post-physical exercise

Question 86

Granular casts are thought to represent filtered proteins trapped in (X) or cellular degeneration (Y)

Answer 86

``` X = lysosomes (fine) Y = coarse ```

Question 87

"Muddy Brown" granular casts are pathognomonic for what condition?

Answer 87

ATN

Question 88

RBC casts are a marker of bleeding within the (X). The RBCs usually originate from a damaged (Y). This condition can be seen in (Z)

Answer 88

``` X = renal parenchyma Y = parenchyma Z = acute glomerulonephritis ```

Question 89

WBC casts have (X) trapped within a cast matrix and are a marker of intense inflammation within the kidneys. These WBCs can originate from a damaged (Y) or from inflammed (Z)

Answer 89

``` X = leukocytes Y = glomerulus Z = interstitium ```

Question 90

What 2 AKI conditions can WBC casts be seen in?

Answer 90

Acute interstitial nephritis Acute glumerulonephritis

Question 91

Fractional excretion of sodium can suggest prerenal or ATN AKI based on the cutoff. What are these values?

Answer 91

FENa < 1% suggests prerenal | FENa >2% suggests ATN

Question 92

What is the equation for the fractional excretion of sodium using Creatinine to measure GFR?

Answer 92

``` FENa = Clearance(Na)/Clearance(Cr) = [(U_Na)/(P_Na)]/[U_Cr)/(P_Cr)] Valid only in oliguric AKI low FENa is NOT specific for prerenal AKI ```

Question 93

What is the preferred imaging test to evaluate urinary obstruction

Answer 93

Renal ultrasound

Question 94

What do small kidneys suggest on a renal ultrasound?

Answer 94

Chronic process (damage or lack of use/atrophy)

Question 95

What does hydronephrosis on renal ultrasound suggest?

Answer 95

Dilation of the collecting system in one or both kidneys consistent with obstruction

Question 96

What complications of AKI are common?

Answer 96

Water balance: Hard to predict depending on specific site of injury Sodium/Volume balance: Edema common Acid-base balance: Metabolic acidosis common Calcium/Phosphorus Homeostasis: Hyperphosphatemia with low calcium levels common (Ca-P complex takes up free calcium)