Renal 05: Acute Kidney Injury

Front 1

What are the characteristics of Acute Kidney Injury?

Back 1

- ↓ GFR → Azotemia over days
- D/t renal ischemia or toxins
- Reversible

Front 2

What can cause Acute Kidney Injury?

Back 2

- Renal ischemia
- Toxins

Front 3

Is acute kidney injury reversible or irreversible?

Back 3

Reversible

Front 4

Are there symptoms of uremia in AKI?

Back 4

No chronic uremia (urea in blood) symptoms

Front 5

How does the size of kidneys change in AKI?

Back 5

Usually kidney size is preserved

Front 6

What are the diagnostic criteria of AKI?

Back 6

Abrupt (within 48 hours) reduction in kidney function:
- Absolute ↑ in serum creatinine level of 0.3 mg/dl
OR
- Percentage ↑ in serum creatinine level of ≥ 50% (1.5 fold from baseline)
OR
- Urine output < 500 ml in 24 hours

Front 7

Why is AKI important?

Back 7

As AKI becomes more severe (↑ serum creatinine), increased % mortality
- No AKI: mortality is 10%
- Dialysis d/t AKI: 60%

Front 8

What is Oliguria?

Back 8

Urine output < 400-500 ml/day

Front 9

What is Azotemia?

Back 9

Elevation of nitrogen waste products related to insufficient filtering of blood by kidneys

Front 10

What is Uremia?

Back 10

Illness accompanying kidney failure which results from toxic effects of abnormally high concentrations of nitrogenous substances in blood

Front 11

What do you look for in a Urinalysis, related to AKI?

Back 11

- Casts: caused by trapping of cellular elements in matrix of protein secreted by renal tubule cells
- Granular casts ("muddy brown urine") seen in cases of acute tubular necrosis

Front 12

Over what range of BP are GFR and RBF auto-regulated?

Back 12

~80-160 mmHg (remains at normal)
- Lower BP leads to lower GFR and RBF
- Higher BP leads to higher GFR and RBF

Front 13

How does auto-regulation control GFR if there is a decreased perfusion pressure?

Back 13

- Increased vasodilatory Prostaglandins dilate afferent arteriole
- Increased Angiotensin II constricts efferent arteriole
- Maintains normal GFR

Front 14

What can inhibit prostaglandins? How does this affect ability of kidney to auto-regulate GFR and RBF?

Back 14

- Increased age, NSAIDs, and CKD all inhibit effects of vasodilatory prostaglandin on afferent arteriole
- Prevents dilation of afferent arteriole
- Leads to low GFR

Front 15

What can inhibit Angiotensin II? How does this affect ability of kidney to auto-regulate GFR and RBF?

Back 15

- ACE-I and ARBs inhibit effects of Angiotensin II
- Prevents constriction of efferent arteriole
- Leads to low GFR

Front 16

What are the three categories of AKI?

Back 16

- Pre-renal
- Renal
- Post-renal

Front 17

What can cause pre-renal AKI?

Back 17

↓ Effective renal perfusion:
- Volume depletion
- Heart failure
- Liver failure

↓ GFR w/o ischemic or nephrotoxic injury to tubules

Front 18

What can cause renal AKI?

Back 18

Intrinsic renal disease (glomerular, tubular, interstitial, vascular)
** Acute Tubular Necrosis
- Interstitial Nephritis
- Glomerulonephritis
- Vascular diseases

Front 19

What can cause post-renal AKI?

Back 19

Obstruction of urinary flow from both kidneys
- Prostate
- Bladder outlet obstruction
- Ureteral obsturction
- Stones
- Tumors

Front 20

How does the kidney try to compensate for pre-renal AKI?

Back 20

Decreased effective renal perfusion →
- Leads to increased AngII and Vasopressin →
- Increased reabsorption of Na+ (at PT) and H2O →
- Conc. urine →
- Oliguria (appropriate)

Front 21

What are the characteristics of pre-renal AKI?

Back 21

- Increased reabsorption of urea → elevation of BUN out of proportion to creatinine (>20:1)
- Usually reversible within 3-4 days if underlying cause is treated

Front 22

How does BUN compare to creatinine in pre-renal AKI?

Back 22

Increased reabsorption of urea → elevation of BUN out of proportion to creatinine (>20:1)

Front 23

How do you reverse pre-renal AKI? How soon?

Back 23

Usually reversible within 3-4 days if underlying cause is treated

Front 24

What are the histological features of Pre-Renal AKI?

Back 24

Normal tubular epithelium

Front 25

What is the most common cause of Renal AKI?

Back 25

Acute Tubular Necrosis (ATN): ischemic, toxic, or both

Front 26

How does ischemia to kidneys cause reduced GFR and oliguria?

Back 26

Ischemia →
- Vasoconstriction →

- Tubule Cell Injury → Obstruction by casts or Tubular back-leak →

Both: ↓ GFR → ↓ Oliguria

Front 27

What are the mechanisms of acute tubular necrosis?

Back 27

Causes of tubular injury:
- O2 depletion
- ATP depletion
- Metabolic changes

Leads to:
- Cast obstructing lumen
- Decreased renal function

Front 28

What does this image show?

Back 28

Tubular obstruction in Acute Tubular Necrosis (Renal AKI)

Front 29

What are the morphological features of Acute Tubular Necrosis (Renal AKI)?

Back 29

- Tubular dilatation
- Attenuation (thinning) of tubular epithelium
- Loss of epithelial cell brush border
- Granular cast material in tubular lumen
- Mitotic figures (regenerative change)

Front 30

What do these images show?

Back 30

Progression:
- Normal →
- Early ATN (loss of tubular epithelial cells and debris in lumen) →
- Necrotic tubules (necrosis and flattening of tubular epithelium)

Front 31

Following Acute Tubular Necrosis (Renal AKI), what happens?

Back 31

- Tubular regeneration in coordinated fashion
- Sublethally injured tubular epithelial cells repopulate the tubules

Front 32

How do sub-lethally injured tubular epithelial cells repopulate the tubules in Acute Tubular Necrosis (Renal AKI)?

Back 32

- De-differentiation →
- Proliferation →
- Migration →
- Re-establishing cell polarity

Front 33

Do stem cells help re-populate the tubular epithelial cells in Acute Tubular Necrosis (Renal AKI)?

Back 33

No convincing evidence for direct re-population of tubules by intra-renal or extra-renal stem cells

Front 34

What needs to be ruled out in all patients w/ oliguria?

Back 34

Obstructive Uropathy (post-renal AKI)

Front 35

Is post-renal AKI reversible? How?

Back 35

Yes with relief of the obstruction

Front 36

What happens if there is post-renal AKI?

Back 36

Hydronephrosis - distension and dilation of renal pelvis calyces

Front 37

What are the most common causes of Acute Renal Failure / AKI?

Back 37

- ~ 70% ATN: 50% ischemia, 30% sepsis, 20% multifactorial
- 17.8% pre-renal

Front 38

How can you determine which type of AKI is causing the oliguria/AKI?

Back 38

- Pre-renal: FENa < 1%
- Renal: FENa >2%
- Post-renal: renal imaging (ultrasound, CT)

FENa = fractional excretion of Na

Front 39

What is FENa?

Back 39

Fractional Excretion of Na+ (FENa)
- Expressed as amount of Na+ excreted over amount of Na+ filtered by glomeruli

Front 40

What is the FENa (fractional excretion of Na) normally?

Back 40

~1% (99% of Na+ reabsorbed)

Front 41

How should FENa be affected by volume depletion (pre-renal AKI)?

Back 41

Urine Na reabsorption should be increased in PT → FENa < 1%

Front 42

How should FENa be affected by injury to proximal tubules (renal AKI)?

Back 42

Na+ reabsorption will be impaired → FENa > 2%

Front 43

How do you calculate FENa?

Back 43

Front 44

What is the purpose of calculating FENa?

Back 44

To differentiate between pre-renal azotemia and ATN (both common causes of oliguric acute renal failure)

Front 45

Case 1:
60 yo male w/ 10y hx of HTN and CKD admitted w/ uncontrolled HTN. He is on HCTZ & metoprolol. BP was 190/120 mmHg. Serum creatinine of 1.5 mg/dl and BUN of 15 mg/dl.

Started on Lisinopril and Amlodipine. Improved BP on day 2 of 150/90 mmHg and day 3 of 138/84 mmHg. Urine output of 1.8-2 L/day. Day 2 serum creatinine of 1.8 mg/dl and BUN of 26 mg/dl. Day 3 serum creatinine of 2.9 mg/dl and BUN of 38 mg/dl. Unremarkable urinalysis.

Does this patient have AKI?

Back 45

Yes, change in serum creatinine over 48 hours is consistent w/ AKI

Front 46

Case 1:
60 yo male w/ 10y hx of HTN and CKD admitted w/ uncontrolled HTN. He is on HCTZ & metoprolol. BP was 190/120 mmHg. Serum creatinine of 1.5 mg/dl and BUN of 15 mg/dl.

Started on Lisinopril and Amlodipine. Improved BP on day 2 of 150/90 mmHg and day 3 of 138/84 mmHg. Urine output of 1.8-2 L/day. Day 2 serum creatinine of 1.8 mg/dl and BUN of 26 mg/dl. Day 3 serum creatinine of 2.9 mg/dl and BUN of 38 mg/dl. Unremarkable urinalysis.

Does he have hematuria? Uremia? Oliguria? Polyuria? Azotemia?

Back 46

Azotemia
(Elevation of nitrogen waste products, BUN, related to insufficient filtering of blood by kidneys)

Front 47

Case 1:
60 yo male w/ 10y hx of HTN and CKD admitted w/ uncontrolled HTN. He is on HCTZ & metoprolol. BP was 190/120 mmHg. Serum creatinine of 1.5 mg/dl and BUN of 15 mg/dl.

Started on Lisinopril and Amlodipine. Improved BP on day 2 of 150/90 mmHg and day 3 of 138/84 mmHg. Urine output of 1.8-2 L/day. Day 2 serum creatinine of 1.8 mg/dl and BUN of 26 mg/dl. Day 3 serum creatinine of 2.9 mg/dl and BUN of 38 mg/dl. Unremarkable urinalysis.

What is the most likely cause for the change in serum creatinine?

Back 47

Impaired GFR auto-regulatory response to decrease in BP (d/t being on ACE-I and CKD)

Front 48

Case 1:
60 yo male w/ 10y hx of HTN and CKD admitted w/ uncontrolled HTN. He is on HCTZ & metoprolol. BP was 190/120 mmHg. Serum creatinine of 1.5 mg/dl and BUN of 15 mg/dl.

Started on Lisinopril and Amlodipine. Improved BP on day 2 of 150/90 mmHg and day 3 of 138/84 mmHg. Urine output of 1.8-2 L/day. Day 2 serum creatinine of 1.8 mg/dl and BUN of 26 mg/dl. Day 3 serum creatinine of 2.9 mg/dl and BUN of 38 mg/dl. Unremarkable urinalysis.

What pain medication should this patient avoid when treating his chronic knee pain?

Back 48

NSAIDs can cause further derangement of auto-regulation of GFR

Front 49

Case 2:
80 yo woman admitted w/ 4-day hx of nausea, vomiting, and diarrhea. Fluid intake has been low. Feels light-headed upon standing for last 24 hours. Passed one cup of dark yellow urine in 24 hours. Takes acetaminophen 1-2x/week, HCTZ, and simvastatin.

BP 84/60 mmHg and HR 110 bpm. Appears ill w/ poor skin turgor. Serum creatinine of 5.5 mg/dl and BUN of 87 mg/dl. 2 weeks ago her serum creatinine was 1.4 mg/dl. Urine output was 378 ml in one day.

Does this patient have AKI? Why?

Back 49

Yes - urine output is consistent w/ diagnosis of AKI

(can't say whether she meets criteria for serum creatinine because original value was 2 weeks ago, need to be within 48 hours)

Front 50

Case 2:
80 yo woman admitted w/ 4-day hx of nausea, vomiting, and diarrhea. Fluid intake has been low. Feels light-headed upon standing for last 24 hours. Passed one cup of dark yellow urine in 24 hours. Takes acetaminophen 1-2x/week, HCTZ, and simvastatin.

BP 84/60 mmHg and HR 110 bpm. Appears ill w/ poor skin turgor. Serum creatinine of 5.5 mg/dl and BUN of 87 mg/dl. 2 weeks ago her serum creatinine was 1.4 mg/dl. Urine output was 378 ml in one day.

Does she have hematuria? Uremia? Oliguria? Polyuria? Polydipsia?

Back 50

Oliguria: Urine output < 400-500 ml/day

Front 51

Case 2:
80 yo woman admitted w/ 4-day hx of nausea, vomiting, and diarrhea. Fluid intake has been low. Feels light-headed upon standing for last 24 hours. Passed one cup of dark yellow urine in 24 hours. Takes acetaminophen 1-2x/week, HCTZ, and simvastatin.

BP 84/60 mmHg and HR 110 bpm. Appears ill w/ poor skin turgor. Serum creatinine of 5.5 mg/dl and BUN of 87 mg/dl. 2 weeks ago her serum creatinine was 1.4 mg/dl. Urine output was 378 ml in one day.

What is the most likely cause of her AKI?

Back 51

Pre-renal AKI d/t extracellular fluid volume depletion

Front 52

Case 2:
80 yo woman admitted w/ 4-day hx of nausea, vomiting, and diarrhea. Fluid intake has been low. Feels light-headed upon standing for last 24 hours. Passed one cup of dark yellow urine in 24 hours. Takes acetaminophen 1-2x/week, HCTZ, and simvastatin.

BP 84/60 mmHg and HR 110 bpm. Appears ill w/ poor skin turgor. Serum creatinine of 5.5 mg/dl and BUN of 87 mg/dl. 2 weeks ago her serum creatinine was 1.4 mg/dl. Urine output was 378 ml in one day.

What would you expect her FENa to be?

Back 52

FENa < 1% because she has Pre-renal AKI d/t extracellular fluid volume depletion

Front 53

Case 2:
80 yo woman admitted w/ 4-day hx of nausea, vomiting, and diarrhea. Fluid intake has been low. Feels light-headed upon standing for last 24 hours. Passed one cup of dark yellow urine in 24 hours. Takes acetaminophen 1-2x/week, HCTZ, and simvastatin.

BP 84/60 mmHg and HR 110 bpm. Appears ill w/ poor skin turgor. Serum creatinine of 5.5 mg/dl and BUN of 87 mg/dl. 2 weeks ago her serum creatinine was 1.4 mg/dl. Urine output was 378 ml in one day.

Additional labs show: serum Na+ 144 mEq/L, urine Na+ 12 mEq/L, urine creatinine 160 mEq/L. Urine microscopy shows 1-5 WBCs / high power field. Renal ultrasound shows no hydronephrosis.

How do you interpret this new information?

Back 53

Fractional Excretion of Na+ is consistent w/ pre-renal AKI

Front 54

Case 2:
80 yo woman admitted w/ 4-day hx of nausea, vomiting, and diarrhea. Fluid intake has been low. Feels light-headed upon standing for last 24 hours. Passed one cup of dark yellow urine in 24 hours. Takes acetaminophen 1-2x/week, HCTZ, and simvastatin.

BP 84/60 mmHg and HR 110 bpm. Appears ill w/ poor skin turgor. Serum creatinine of 5.5 mg/dl and BUN of 87 mg/dl. 2 weeks ago her serum creatinine was 1.4 mg/dl. Urine output was 378 ml in one day.

Based on diagnosis of Pre-Renal AKI, what is the next best course of action?

Back 54

Administer 2L of normal saline

Front 55

Case 3:
52yo male w/ hx of liver transplant 2 yrs ago, hospitalized w/ 10-day fever, cough, and progressive lethargy. Oral intake has been poor for 3 days. Took acetaminophen before coming. Two days after admission he developed worsening HypoTN and increased respiratory distress. Intubated and mechanically ventilated. Received 20L of IV fluids for 2 days to treat shock. No NSAIDs or ACE-I.

Temp is 103.9, BP 70/44 mmHg, HR 122 bpm. Decreased breath sounds in R midlung. Serum creatinine is 3.8 mg/dl and BUN is 54 mg/dl. Liver function is normal. Serum creatinine was 1.1 mg/dl last month. Urine output was 280 ml in first 24 hours.

Does this patient have AKI? Why?

Back 55

Yes, urine output < 500 ml in 24 hours

Front 56

Case 3:
52yo male w/ hx of liver transplant 2 yrs ago, hospitalized w/ 10-day fever, cough, and progressive lethargy. Oral intake has been poor for 3 days. Took acetaminophen before coming. Two days after admission he developed worsening HypoTN and increased respiratory distress. Intubated and mechanically ventilated. Received 20L of IV fluids for 2 days to treat shock. No NSAIDs or ACE-I.

Temp is 103.9, BP 70/44 mmHg, HR 122 bpm. Decreased breath sounds in R midlung. Serum creatinine is 3.8 mg/dl and BUN is 54 mg/dl. Liver function is normal. Serum creatinine was 1.1 mg/dl last month. Urine output was 280 ml in first 24 hours.

Which of the following is present: hematuria? Uremia? Oliguria? Polyuria? Polydipsia?

Back 56

Oliguria: Urine output < 400-500 ml/day

Front 57

Case 3:
52yo male w/ hx of liver transplant 2 yrs ago, hospitalized w/ 10-day fever, cough, and progressive lethargy. Oral intake has been poor for 3 days. Took acetaminophen before coming. Two days after admission he developed worsening HypoTN and increased respiratory distress. Intubated and mechanically ventilated. Received 20L of IV fluids for 2 days to treat shock. No NSAIDs or ACE-I.

Temp is 103.9, BP 70/44 mmHg, HR 122 bpm. Decreased breath sounds in R midlung. Serum creatinine is 3.8 mg/dl and BUN is 54 mg/dl. Liver function is normal. Serum creatinine was 1.1 mg/dl last month. Urine output was 280 ml in first 24 hours.

What is the most likely cause of AKI?

Back 57

Ischemic acute tubular necrosis from septic shock

Front 58

Case 3:
52yo male w/ hx of liver transplant 2 yrs ago, hospitalized w/ 10-day fever, cough, and progressive lethargy. Oral intake has been poor for 3 days. Took acetaminophen before coming. Two days after admission he developed worsening HypoTN and increased respiratory distress. Intubated and mechanically ventilated. Received 20L of IV fluids for 2 days to treat shock. No NSAIDs or ACE-I.

Temp is 103.9, BP 70/44 mmHg, HR 122 bpm. Decreased breath sounds in R midlung. Serum creatinine is 3.8 mg/dl and BUN is 54 mg/dl. Liver function is normal. Serum creatinine was 1.1 mg/dl last month. Urine output was 280 ml in first 24 hours.

What additional findings would you expect?

Back 58

Muddy brown granular casts on urine microscopy d/t ATN

Front 59

Case 3:
52yo male w/ hx of liver transplant 2 yrs ago, hospitalized w/ 10-day fever, cough, and progressive lethargy. Oral intake has been poor for 3 days. Took acetaminophen before coming. Two days after admission he developed worsening HypoTN and increased respiratory distress. Intubated and mechanically ventilated. Received 20L of IV fluids for 2 days to treat shock. No NSAIDs or ACE-I.

Temp is 103.9, BP 70/44 mmHg, HR 122 bpm. Decreased breath sounds in R midlung. Serum creatinine is 3.8 mg/dl and BUN is 54 mg/dl. Liver function is normal. Serum creatinine was 1.1 mg/dl last month. Urine output was 280 ml in first 24 hours.

Additional testing shows serum Na+ 140 mEq/L, urine Na+ 52 mEq/L, urine creatinine 50 mEq/L. Urine microscopy shows 3-5 muddy brown casts and 1-5 WBCs per high power field. Renal ultrasound showed no hydronephrosis. How do you interpret this data?

Back 59

Fractional Excretion of Na+ is consistent w/ acute tubular necrosis (>2%)

Front 60

Case 3:
52yo male w/ hx of liver transplant 2 yrs ago, hospitalized w/ 10-day fever, cough, and progressive lethargy. Oral intake has been poor for 3 days. Took acetaminophen before coming. Two days after admission he developed worsening HypoTN and increased respiratory distress. Intubated and mechanically ventilated. Received 20L of IV fluids for 2 days to treat shock. No NSAIDs or ACE-I.

Temp is 103.9, BP 70/44 mmHg, HR 122 bpm. Decreased breath sounds in R midlung. Serum creatinine is 3.8 mg/dl and BUN is 54 mg/dl. Liver function is normal. Serum creatinine was 1.1 mg/dl last month. Urine output was 280 ml in first 24 hours.

Which of these biopsies is most consistent with his type of AKI?

Back 60

Front 61

Case 3:
52yo male w/ hx of liver transplant 2 yrs ago, hospitalized w/ 10-day fever, cough, and progressive lethargy. Oral intake has been poor for 3 days. Took acetaminophen before coming. Two days after admission he developed worsening HypoTN and increased respiratory distress. Intubated and mechanically ventilated. Received 20L of IV fluids for 2 days to treat shock. No NSAIDs or ACE-I.

Temp is 103.9, BP 70/44 mmHg, HR 122 bpm. Decreased breath sounds in R midlung. Serum creatinine is 3.8 mg/dl and BUN is 54 mg/dl. Liver function is normal. Serum creatinine was 1.1 mg/dl last month. Urine output was 280 ml in first 24 hours.

Transplant team is considering changing his immunosuppressant. They would like to start him on Rapamycin (anti-proliferative). Nephrologist suggests to wait until patient's renal function improves. Why?

Back 61

Rapamycin may impair renal tubular regeneration