Acute Kidney Injury (INC)

Question 1

What are the three types of acute kidney injuries?

Answer 1

Prerenal: something that goes into the kidney is the issue. Caused by renal hypoperfusion
Intrarenal: the kidney itself is the issue. Direct injury to 1+ renal structures
Postrenal: (rarest), there is something DOWNSTREAM of the kidney causing a problem. Caused by obstruction of urinary flow

There is some overlap though

Question 2

What is wrong with Prerenal Azotemia? What are 3 examples of these.

Answer 2

Inadequate renal perfusion

1. Hypovolemia
2. Decreased Cardiac Output (have enough blood, but the kidney is not getting enough blood)
3. Change in vascular resistance

Question 3

What are some examples of changed vascular resistance that can lead to prerenal azotemia?

Answer 3

￬ - sepsis, anaphylaxis, anesthesia
￪ - epinephrine, high-dose dopamine, renal artery stenosis
Meds that interfere with renal vascular autoregulation
NSAIDs, iodinated contrast, ACEIs/ARBs

Question 4

If there is decreased perfusion pressure, leading to less blood in kidneys, what is the body’s response?

Answer 4

Increased angiotensin 2 (constricts efferent) and increased vasodilatory prostaglandins (dilates afferent)

Both maintain GFR but work on other parts - meds can interfere with this!

Question 5

What is the MOA of NSAIDs and ACE inhibitors/ ARBs on the kidney? What is the resulting GFR?

Answer 5

NSAIDs block vasodilatory prostoglandins in the afferent arteriole, leading to an increase in the release of angiotensin II (constricting efferent), but still overall reduction in GFR

ACE inhibitors and ARBs decrease angiotensin II, leading to a slight increase in vasodilatory prostoglandin release, but still overall reduction in GFR

Both lead to reduced GFR by
1. NSAIDs leading to less vasodilation of AFFERENT and
2. ACE-I and ARBs leading to less vasoconstriction of EFFERENT

Question 6

What happens to the GFR and BUN in prerenal azotemia? What happens to sodium if oliguric?

Answer 6

￬ GFR ￪ BUN/Cr with BUN:Cr ratio > 20:1 usually

If oliguric, there should be a low fractional excretion of sodium (FENa+) in the urine - <1%

Reabsorbing urea and sodium to retain fluid (water). Remember, the kidneys are still functional, so sodium retention is possible. This leads to a Urine osmality that is normal (>500).

Question 7

What is urinary sediment in prenrenal azotemia, what can sometimes happen? What protein does this come from?

Answer 7

usually normal, may see hyaline casts (means that there is not movement of fluid, leading to highlight of tubules, normally benign)
Formed from Tamm-Horsfall mucoprotein secreted by tubule

Horsfall = hyaline

Question 8

What are the S/S of prerenal azotemia depending on the stage?

Answer 8

Uremia is possible (depending on stage)
Signs of cause - vary, may include:
Dehydration (decreased skin turgor) and/or hypovolemia
Arrhythmias, cardiomegaly (to try to pump blood)
Sepsis
Nonspecific diffuse abdominal pain and ileus (no bowel movement)
May see decreased urine output (d/t hypovolemia)

symptoms are NOT that helpful, but labs are

Question 9

What is the treatment for prerenal azotemia reliant on?

Answer 9

Resolve the underlying cause:
1. Maintain euvolemia
2. Correct abnormal electrolytes
3. Avoid nephrotoxic drugs

Question 10

Should kidney function in prerenal azotemia normalize if we restore the blood flow to the kidneys?

Answer 10

YES, because it does not directly involve dmg to the kidneys

Question 11

What do you see in postrenal obstruction? What are some common complications that can cause this?

Answer 11

Obstruction leads to elevated intraluminal pressure leading to damaged renal parenchyma

This obstruction of urethra, bladder, ureters, or renal pelvises is often d/t:

1. BPH in men (MC cause)
2. Devices Obstructed Foley catheter
3. anticholinergic medications (slows down bladder and decreases peristalsis d/t blocking parasympathetic response)

Rare things such as blood clots, stones, cancer, etc.

Question 12

What are the s/s of postrenal obstruction and what can be used to look for this?

Answer 12

S/S: Anuria or polyuria possible
May have lower abdominal pain
May see large prostate, distended bladder, pelvic/abdominal mass
Bladder catheterization and/or abdominopelvic
US can be helpful to look for hydroureter and obstruction

Question 13

What does a normal renal US look like compared to diseased?

Answer 13

The diseased kidney looks dark in areas where there is backup

Question 14

What are the lab findings for postrenal obstruction? How about urine sediment?

Answer 14

￬ GFR and ￪ BUN/Cr with BUN:Cr > 20:1 usually

Sodium varies
Urine osmolality - 400 mosm/kg or less (d/t obstruction impairing the kidney’s ability to concentrate the urine)
Urine sediment - often normal; may see RBCs, WBCs, crystals

depends on underlying condition!

Question 15

What are some areas that can lead to intrinsic kidney injury? What often leads to this?

Answer 15

Direct damage to the tubules, glomeruli, interstitium, vasculature

prerenal azotemia often leads to tubular injury because there is not enough O2 for them to survive.

Question 16

What are the 3 major forms of intrinsic kidney injury? What is the MC one of these?

Answer 16

Acute Tubular Necrosis (MC)
Acute Glomerulonephritis
Acute Interstitial Nephritis

Question 17

What are the three causes of acute tubular necrosis?

Answer 17

1. Ischemia (death d/t reduced blood flow)
2. Nephrotoxins (exogenous and endogenous, with exogenous is the worse)
3. Sepsis - causes both hypoperfusion and direct injury

Question 18

What are the exogenous nephrotoxic antimicrobials? Which is the least nephrotoxic?

Answer 18

Aminoglycosides (1/3 times patients will be nephrotoxic, typically w/in 5-7 days and damage can continue up to 30 days), streptomycin is the least though
Amphotericin B (ampho terrible)

try to use others

Question 19

What are some other exogenous nephrotoxins?

Answer 19

1. Radiographic contrast media (can increase fluid to reduce the concentration of this)
2. Chemotherapy (methotrexate, cyclosporine, cisplatin)
3. Environmental toxins in workplace hazards (heavy metals, insecticides/herbicides)

Question 20

What are some endogenous nephortoxins? What can cause this?

Answer 20

Myoglobinuria - due to rhabdomyolysis, muscle necrosis

Often crush injuries

Question 21

How do you tell the difference between mygoglobinurea and hemoglobinurea?

Answer 21

Same: Both lead to a positive urine dipstick for hemogloblin (which is a false positive in the case of myoglobinurea), both lead to dark brown urine.

Different: Myglobinurea has no RBCs on microscopy. Often seen with creatine kinase > 20,000-50,000 IU/L d/t crush injury

Question 22

How do you treat myglobinurea?

Answer 22

REHYDRATION

treatment of Hypocalcemia if symptomatic (trousseaus, twitching, etc). Typically self-corrects after hydration

possibly Hyperkalemia, hyperphosphatemia, hyperuricemia

Question 23

What are the three other endogenous nephrotoxins other than myglobinurea? How to treat

Answer 23

1. Hemoglobinuria: Tx - Reversal of underlying disorder, hydration
2. Hyperuricemia: in rapid cell turnover and lysis. Usual cause - chemo for germ cell neoplasms, leukemia, lymphoma
   Intratubular deposition of uric acid crystals
   Serum uric acid often > 15-20 mg/dL
   Medications to lower uric acid level can help
3. Bence Jones Protein, in multiple myeloma, which is directly toxic by obstructing tubule. Correct the cancer

Question 24

What are the S/S of Acute tubular necrosis (ATN)?

Answer 24

Not helpful

Signs of underlying cause
May see arrhythmias, abdominal pain, uremia
Oliguric or nonoliguric

Question 25

What are the labs of ATN? What is the urinary sediment - and how do you know that there is tubular necrosis?

Answer 25

Hyperkalemia (d/t less exchange with sodium in tubules) and hyperphosphatemia (d/t less excretion of phosphate) are common ￬ GFR and ￪ BUN/Cr with BUN:Cr < 20:1 usually Urine sodium is often elevated (d/t not being able to reabsorb) Urinary sediment - pigmented granular casts or “muddy brown” casts (think muddy drainage tube), renal tubular cells, epithelial cell casts

Question 26

What do you see for BUN:Cr ratio and urine sodium in ATN? What does this mean?

Answer 26

Decreased BUN:Cr ratio (meaning there is less urea in the blood) and high urine sodium d/t inability to reabsorb sodium and urea

Question 27

What is worse, oliguric or non-oliguric ATN? Why?

Answer 27

Oliguric, because there is concern of build up of toxins

Question 28

How do you treat ATN? What are some dietary changes?

Answer 28

Avoid volume overload (because the kidneys will have trouble processing too much fluid) Use loop diuretics if volume overloaded Dietary changes include protein restriction, ￪or ￬ dietary phosphate, calcium, magnesium depending on status

Question 29

What is the prognosis of ATN?

Answer 29

May never go back to full kidney function 20-50% mortality and up to 70% require dialysis non-oliguric have better long-term outcomes though

Question 30

What allows us to know that there are in a maintanence ATN?

Answer 30

The BUN/Cr levels off and does not get worse

Question 31

Why will they not go back to basic renal function in ATN?

Answer 31

Lost too many nephrons

Question 32

What are the five lab findings you may see in ATN

Answer 32

1. myglobinuria (endogenous nephrotoxin) 2. Uric acid crystals (endogenous nephrotoxin) 3. Bence-Jones proteins (endogenous nephrotoxin) 4. Muddy brown/ granular cells (indicative of tubular injury) 5. Renal epithelial cell casts (indicative of tubular injury)

Question 33

What often leads to Acute Glomerulonephritis?

Answer 33

It is an Intrinsic glomerular AKI Most are nephritic (involving inflammation) A few are nephrotic (minimal inflammation, proteinuria) - usually seen more in chronic cases Involve inflammatory glomerular lesions Crescent lesions - severe breaks in glomerular walls (think about the shape)

Question 34

What is the classic presentation of Acute Glomerulonephritis

Answer 34

HTN, edema (periorbital or scrotal d/t low tissue tension), and urine containing protein, RBCs, WBCs, and RBC casts (because breaks in capillary walls allow protein to cross)

Question 35

What are the 5 types of Acute Glomerulonephritis? How do you distinguish each?

Answer 35

1. Immune Complex Deposition - when antigen excess over antibody production occurs Antigen-antibody complexes lodge in glomerular basement membrane (GBM) Complement activation to resolve complexes → destruction of GBM Often lupus, endocarditis, and streptococcus 2. Anti-GBM-associated acute glomerulonephritis Autoantibodies against glomerular basement membrane (GBM) May be confined to kidney or involve lungs as well. Goodpasture’s Syndrome - renal + pulmonary involvement 3. C3 Glomerulopathy: leads to deposits. Caused by abnormalities in the alternative complement pathway (little role of Ig unlike others) happens in acute flare, so you may see normal C3 levels, but you can see low serum C3 in acute problems 4. Monoclonal Ig-Mediated Glomerulonephritis: there are so many antibodies that float around for no good reason and cause destruction of basement membrane, can use Serum Protein Electrophoresis (SPEP) can help identify, as well as other tests like immunofixation and free light chain analysis 5. Pauci-Immune Glomerulonephritis, CELLS cause the problems. Cell-mediated immune response. Other causes: hypertensive emergencies, thrombotic microangiopathies (HUS, TTP)

Question 36

What acute glomerulonephritis type involves Antigen-antibody complexes being lodge in glomerular basement membrane (GBM)? How does this result in injury? What can cause this?

Answer 36

Immune Complex Deposition - when antigen excess over antibody production occurs when these antigen-antibody complexes get lodge into the GBM, the complement system is activated to resolve this, leading to destruction of GBM Often caused by streptococcus, endocarditis, and lupus

Question 37

What acute glomerulonephritis type involves autoantibodies that directly attack the GBM? What can this lead to?

Answer 37

Anti-GBM-associated acute glomerulonephritis Can also lead to pulmonary hemorrage, known as Goodpasture’s Syndrome - having renal + pulmonary involvement (think of the autoantibodies not knowing what to target)

Question 38

What acute glomerulonephritis type involves abnormalities in the alternative complement pathway? When do you notice issues?

Answer 38

C3 glomerulopathy There is minimal role of Ig, but involves C3 deposition into the glomerulus, and overall less C3 in the blood as a result. Often seen in acute flares.

Question 39

What acute glomerulonephritis type does not involve excess antigens, but involves Ig? How do you identify this?

Answer 39

Monoclonal Ig-Mediated Glomerulonephritis - where Monoclonal Ig deposited in GBM and/or tubular basement membrane, but no excess amounts of antigen as seen in immune complex GN Serum Protein Electrophoresis (SPEP) can help identify, as well as other tests like immunofixation and free light chain analysis d/t monoclonal gammopathies

Question 40

What acute glomerulonephritis type does not involve immune complexes or Ig binding, but instead involves cell-mediated immune response? What additional manifestations can you see in this case?

Answer 40

Pauci-Immune Glomerulonephritis - small-vessel vasculitis associated with ANCAs Can see manifestations in other areas of the body (lungs, skin, upper airway)

Question 41

Other than the 5 main types of acute glomerulonephritis, what are some other causes?

Answer 41

Hypertensive emergencies, thrombotic microangiopathies (HUS, TTP)

Question 42

Why are 2 reasons that you see swelling in Acute Glomerulonephritis?

Answer 42

Retaining sodium, peeing out protein (water moves out of blood vessels into the tissues)

Question 43

What lab findings clue us into Acute Glomerulonephritis?

Answer 43

Protein in urine More RBCs Complement level differences Anti-strep titers anti-GBM antibodies SPEP P-ANCA and C-ANCA levels Other general autoimmune labs - CRP, ESR, ANA Order all of these if you suspect

Question 44

What is the treatment of Acute Glomerulonephritis?

Answer 44

Underlying issues! Steroids to calm down immune system Sometimes cytotoxic agents Plasma exchange to get rid of bad things floating around

Question 45

What is Acute Interstitial Nephritis and what is the MC cause of this?

Answer 45

10-15% of intrinsic AKI MC is meds It is an Interstitial inflammatory response

Question 46

What are the MC medications that cause Acute Interstitial Nephritis?

Answer 46

Antimicrobials (MC) diuretics, NSAIDs, rifampin, anticonvulsants, allopurinol, PPIs, H2 blockers

Question 47

Besides meds, what can cause Acute Interstitial Nephritis?

Answer 47

Infections (bacterial, viral, and fungal) Immunologic: SLE, Sjogren’s, sarcoidosis, etc. Rare others: allergic reaction, collagen vascular disease

Question 48

What is the classic triad of acute interstitial nephritis, and what percent show all three?

Answer 48

fever, rash, arthralgia All 3 only present in 10% of pts

Question 49

What does a CBC and urinary sediment show for acute interstitial nephritis? What does biopsy show?

Answer 49

CBC = eosinophilia Urine sediment: minimal protein, WBCs (95%), WBC casts Biopsy: inflammatory cells within renal interstitium

Question 50

Treatment of acute interstitial nephritis and prognosis

Answer 50

removal of cause, supportive care May use course of IV or oral corticosteroids if renal injury persists after agent is removed Urgent dialysis may be necessary in up to ⅓ of all pts Prognosis: Recovery over weeks to months May have slightly better outcomes than other AKI causes

Question 51

What imaging do you typically use for AKI? What do you typically see? What are some other imaging modalities you can use?

Answer 51

Abdominal/Pelvic US typically normal sized kidneys Can also do - Urethral Cath - r/o urethral obstruction Bladder Scan - r/o urethral obstruction

Question 52

When do you do a kidney biopsy How do you do this? What does a biopsy show?

Answer 52

Some weird glomerulonephritis, vasculitis, interstitial nephritis, etc. Numb the outside of the skin. The patterns of biopsy allow you to see what type of AKI it is.