Karen Brechbuhl – notes

Acute Kidney Injury (AKI)

1) Def. ....................................................................................................................................... 2

2) Diagnostic criteria - KDIGO................................................................................................... 2

3) Classification ........................................................................................................................ 2
A) Prerenal AKI (∼ 10% of cases).......................................................................................... 3
B) Intrinsic AKI (∼ 60% of cases) .......................................................................................... 4
C) Postrenal AKI (∼ 10% of cases) ........................................................................................ 8

5) Urianalysis in differential diagnosis of the MC causes of AKI .............................................. 9

6) Treatment ............................................................................................................................ 9

7) Prognosis ............................................................................................................................ 11

1
 Karen Brechbuhl – notes

1) Def.
u Acute kidney injury (AKI) - previously called acute renal failure - is a sudden loss of renal function with a consecutive rise in creatinine and blood urea nitrogen (BUN) (which is most often
reversible)
Note :
Creatinine
à Is the breakdown product of CREATINE (found in muscle cells)
à Has a normal serum concentration ranging from 0.6 – 1.2 mg/dL
à Once filtered, creatinine is NOT resorbed and only minorly secreted by the peritubular capillaries thus it slightly overestimatethe GFR by approximately 10% to 20%
BUN
à Comes from the urea cycle in the liver (amino acid metabolism) & pyrimidine metabolism (nitrogenous bases)
à Has a normal serum concentration ranging from 7 – 20 mg/dL
à Normally, once filtered, a ­ % is reabsorbed at the PCT [This reabsorption is ramped up during prerenal AKI as the kidney attempts to conserve water and volume when it perceives a hypoperfused state (you will undertsand that later J)]

2) Diagnostic criteria - KDIGO

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice
guideline classifies acute kidney injury (AKI) into 3 stages defined by serum
creatinine elevation or urine output decline
Serum Creatinine Urine Output (volume)
[Recent diagnostic staging criteria for AKI ; utilizes changes in serum creatinine &
urine output but not GFR except those under 18 years of age]

mildd
­ of serum creatine to 1.5-1.9 times baseline within the prior 7 days
Stage 1 OR
Reduction of urine output to
< 0.5 mL/kg/h for 6–12 h
­ of serum creatine to ≥ 0.3 mg/dL within 48 h

AKI is diagnosed when there is à ♡know at least this stage ♡

ó
The KDIGO guidelines define AKI as :
à an increase in serum creatinine by at least 0.3 mg/dL within 48 hours
OR
à an increase to 1.5x the presumed baseline value that is known, presumed to have occurred within the prior seven days
OR
à a decrease in urine volume to <0.5 mL/kg/h for 6–12 h

Reduction of urine output to

­ of serum creatine to 2–2.9 times baseline
Stage 2
< 0.5 ml/kg/h for ≥12 h

­ of serum creatine to ≥ 3 times baseline

OR Reduction of urine output to

< 0.3 mL/kg/h for ≥ 24 h
­ of serum creatine to ≥ 4 mg/dL
Stage 3 OR
OR

Initiation of renal replacement therapy,

OR Anuria for ≥ 12 h

Patients < 18 years: ¯ in GFR to < 35 mL/min/1.73 m 2

Severe

3) Classification
u AKI is most frequently caused by decreased renal perfusion [Prerenal AKI] but may also be due to direct damage to the kidneys [intrinsic AKI (involving blood vessels, glomeruli, tubule or
interstitium)] or inadequate urine drainage [Postrenal AKI]

AKI

30% Prerenal Intrinsic Posterenal 10%

Acute Tubular necrosis Acute Vascular Acute

50%
(ATN)
Tubulointerstial glomerulonephritis
nephritis

10%

Because Prerenal AKI & ATN are the MC causes, most textbooks describe how to differeiciate btw the 2 (which ofc we will see here too J)

2
Karen Brechbuhl – notes

A) Prerenal AKI (∼ 10% of cases)

Include any condition leading to decreased renal perfusion
u A1. Conditions producing HYPOTENSION leading to renal hypoperfusion
o A.2.1) All conditions mentioned above if significant & prolonged cause hypotension
o A.2.2) Septic shock1
o A.2.3) Cardiogenic shock2
o A.2.4) Severe congestive heart failure3
o A.2.5) Massive pulmonary embolism and cardiac tamponade4
u A2. Conditions producing reduced blood volume (HYPOVOLEMIA) leading to renal hypoperfusion
Symptoms of hypovolemia : hypotension, dry mucous membranes, decreased skin turgor, cool extremities, sunken eyes

o A.1.1) Loss of blood: external or internal hemorrhage

o A.1.2) Loss of plasma: extensive burns, nephrotic syndrome & cirrhosis [hypoalbunemia ∴low oncotic pressure ∴ migration of plasma to interstitium ó aka 3rd spacing5]
ü Note : Decompensated cirrhosis can cause prerenal AKI due to systemic vasodilation, splanchnic venous pooling, and ↓effective arterial volume
(3rd spacing) → ↓renal perfusion

o A.1.3) Loss of electrolytes and water: diarrhea and other gastrointestinal losses
o A.1.4) Loss of water: heat stroke & diuretics
u A3. Hepatorenal syndrome (HRS)
o A late sequela of liver cirrhosis, in HRS there is :
a) portal HTN which lead to à splanchnic vasodilation which lead to à hypotension which lead to à activation of vasoconstrictor mechanism which lead to à renal vasoconstriction = ¯ perfusion to
kidneys = HRS !!!

RBF = Renal Blood Flow

u A4. Renal vasoconstriction

o Renal artery stenosis6 [symptoms : peripheral edema & persitent HTN despite taking anti-BP medication (cause of RAAS !)]
u A5. Drug affecting glomerular perfusion
o A.5.1) NSAIDs à afferent arteriole vasoCONSTRICTION = ¯ glomerular perfusion
o A.5.2) ACE inhibitors & ARBsà efferent arteriole vasoDILATION = ¯ glomerular perfusion

NSAIDs = afferent arteriole vasoCONSTRICTION & ACE inhibitors & ARBs = cause efferent arteriole vasoDILATION

o A.5.3) Tacrolimus and Cyclosporine

§ Vasospasm leading to reduced glomerular filtration appears to be a key element in the vasculartoxicity tacrolimus and cyclosporine

1
A widespread infection causing organ failure and dangerously low blood pressure

2
Cardiogenic shock is a condition in which your heart suddenly can't pump enough blood to meet your body's needs. The condition is most often caused by a severe heart attack

3
A condition in which the heart is unable to pump enough blood to meet the metabolic needs of the body. Ventricular dysfunction results in low cardiac output, which in turn causes congestion of blood (backward failure) and poor systemic perfusion
(forward failure).
4
A compression of the heart (especially the right ventricle) caused by pericardial effusion, which leads to circulatory insufficiency

5
Third-spacing occurs when too much fluid moves from the intravascular space (blood vessels) into the interstitial or "third" space-the nonfunctional area between cells

6
A narrowing of one or both renal arteries, usually due to atherosclerosis (most commonly) OR fibromuscular dysplasia

Findings include abdominal bruits and signs of hyperaldosteronism (e.g., hypertension and hypokalemia), from activation of RAAS. Can also lead to findings of decreased kidney function secondary to ischemic renal injury

3
Karen Brechbuhl – notes

o A.5.4) Contrast media

§ The contrast media-induced vasoconstriction leads to marked reduction of oxygen delivery
§ The outer medulla is the portion of kidney mostly interested by reduced oxygen supply because it is directly vasoconstricted by contrast media and it is far from the descending vasa recta which
deliver blood to it

B) Intrinsic AKI (∼ 60% of cases)

Intrinsic causes include any disease that leads to severe direct kidney damage

u B1. Acute tubular necrosis (MC CAUSE of AKI ó ∼ 50% of cases)

o Damage to the kidney tubules caused by :
§ B.1.1) Severe ISCHEMIA (MC CAUSE) => any of the above mentionned prerenal AKI cause

OR
§ B.1.2) Nephrotoxins
• Injury secondary to substances that directly injure renal parenchyma and result in cell death
• Causes include
Mnemonic : VAACO
ü Medications
- Antibiotics à Aminoglycosides (protein synthesis inhibitor) & Vancomycin
V à Vancomycin
A à Aminoglycosides
A à Amphotericin B
Contrast induced nephropathy (CIN)
- Antifungal à Amphotericin B C à Cisplastin
- Antiviral (to treat HIV & hepatitis B) à Tenofovir O à tenOfOvir ü MC with high osmolar contrast agent [diatrizoate, iothalamate, metrizoate (no
- Chemotherapy medication à Cisplatin longer used)]
ü Radiocontrast agents (aka contrast induced nephropathy)
ü Occur within 24-48 hrs after the use of the agent
ü Pigment-induced renal failure (ó AKI occuring after day 1 or day 2 !)
à hemoglobin (hemoglobuniria à intravascular hemolysis)
& ü The rise in creatinine peaks at 3–5 days after the injury
à Myoglobin (myoglobinuria à from damage muscles órhabdomyolysis7 )
ü Obstructions ü S. creatinine returns to normal by 7-10 days (thus excellent prognosis)
• Crystals
à oxalate [especially ehtylene glycol poisoning (antifreeze – alchoholics or suicide attempt)] ü Procedure related AKI risk factors:
à uric acid [especially tumor lysis syndrome (following tx of hematologic malignancy, leukemia/lymphoma ; characterized by hyperurecemia, hyperkalemia, hyperphosphatemia & hypocalcemia)] Ä See above
Ä ↑ dose of radiocontrast
• Myeloma cast nephropathy (MCN) [in multiple myeloma]
à filtered light chains precipitate in tubule → precipitation in the tubules and to direct tubular toxicity Ä Different types of radiocontrast
à Asses for classic “CRAB” symptoms (hyperCalcemia, Renal failure, Anemia, Bone pain) Ä Multiple procedures in 72 hours
Ä Intra-arterial administration
• Atheroembolism [= dislodgement of cholesterol crystals/debris → intrinsic AKI]
à causes :
- vascular manipulation, e.g. coronary angiography, thoracic aortic aneurysm repair, etc, ü NON-procedure related AKI risk factors:
OR Ä Preexisting renal insufficiency [estimated GFR<60mL/min/1.73m2]
- spontaneous Ä Elderly
Ä Diabetes mellitus
Ä Intravascular volume depletion (ó hypotension)
Note : ATN à damage to the tubules, but to which part J ?
Ä Concomitant nephrotoxins (multiple factors of subjects causing
• ATN caused by ischemia à PCT & THE THICK ASCENDING LIMB OF THE LOOP OF HENLE are particularly affected
nephrotoxicity)
• ATN caused by nephrotoxins à PCT is particularly affected
ü Pathophysiology :
Ä It is a non-oliguric renal failure with main mechanism of pathogenesis :
- medullary hypoxia
- direct tubular injury

ü Prevention :
Ä ¯dose contrast agent
Ä Use non-ionic iso-osmolal agents
[The types of radiocontrast agents can be high osmolar, low osmolar, iso-
osmolar and are either ionic or non-ionic]
Ä Avoidance of concomitant nephrotoxins
Ä Isotonic saline at least 1h before & continued for 3-6 hrs
Ä N-acetyl cysteine & Sodium bicarbonate are often added but are of
uncertain value

ü If biopsy is done (which is usually not the case // necessary) :

à tubular epithelial cell vacuolization (especially of the PCT)

u B2. Acute Glomerulonephritis

o E.g., rapidly progressive glomerulonephritis (GN) à poststreptococcal GN, Berger GN…

▪ Rhabdomyolysis is characterized by myocyte injury with the release of intracellular muscle contents (myoglobin, electrolytes) into the circulation
▪ It is common in crush injuries, prolonged muscle activity (seizure), or drug use (cocaine)
▪ Renal injury in rhabdomyolysis results from myoglobin filtration and degradation within the glomeruli. Heme pigment is released, which causes
acute tubular necrosis by direct cytotoxicity and renal vasoconstriction.
▪ Hyperkalemia, hyperphosphatemia, and hyperuricemia also occur due to myocyte lysis.
▪ Rhabdomyolysis can present with muscle pain, weakness, dark//brown urine (myoglobinuria) & on lab exam there’s ↑serum creatine kinase (CK ≥ 1000 unitls/L)
Note also urinanalysis : dipstick positive for “blood” (heme) but no RBCs on microscopy !!!!!!

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Karen Brechbuhl – notes

u B3. Acute tubulointerstitial nephritis (AIN)

o An acute inflammation of the renal tubules and interstitium that is caused by a :
§ MOST COMMONLY : Hypersensitivity reaction to drugs (allergic interstitial nephritis)

Allergic interstitial nephritis : Type 1 or Type IV hypersensitivity reaction :

• Type I hypersensitivity reaction :
à Right after exposure
à MOA : cross-linking Ig-E on mast cells → release of proinflammatory substances

• Type IV hypersensitivity reaction :

à Delayed (1 to 3 days after exposure)
à MOA : antigen presenting cells activate TH1 helper T-cells)

!!! TO ABSOLUTELY RETAIN : NSAIDS & PROTON PUMP inhbibitor !!!

¯
Clinical findings :
à fever, maculopapular rash and symptoms of acute renal failure one to three weeks after beginning treatment
with the above mentioned drugs are highly suggestive of acute allergic intertstial nephritis!!!!!
Blood
à Eosinophilia
à Elevated BUN & creatinine
Urine:
à WBCs casts
à Eosinophiluria
à Subnephrotic proteinuria (btw 1 to 3g/day on urianalysis)
[Note also that MOST OFTEN PATIENTS ARE NOT oliguric (but sometimes oliguria can be present…) !!!!!!!]

T/:
à Symptoms almost always resolve completely after cessation of the offending medication
à Steroids [beneficial if given early, <48hrs]

§ Others :

u B4. Vascular
o B.4.1) Vasculitis8
ó
§ Small vessel vasculitis à glomerulonephritis
§ Medium vessel vasculitis (e.g. : polyarteritis nodosa (PAN) – systemic vasculitis of the small and medium-sized vessels, which leads to tissue ischemia ; MC associated with hepatitis B & C) à intrinsic AKI
§ Large vessel vasculitis à prerenal AKI
o B.4.2) Bilateral renal artery thrombosis or embolism
o B.4.3) Bilateral acute renal vein thrombosis (often associated with nephrotic syndrome àrecall : hypercoagubable state (proteinuria = loss of antithrombin III = hypercoagubale state !)
o B.4.4) Malignant hypertension9
o B.4.5) Hemolytic uremic syndrome (HUS)

A condition in which microthrombi occlude the arterioles and capillaries, which results in triad :
à thrombocytopenia (first)
à nonimmune microangiopathic hemolytic anemia (second)
àacute renal failure (hence, “uremia” in title) (third)

Predominantly affects children and most commonly occurs following dysentery due to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC)

Pathogenesis
o Toxin causes cytokine release → damages endothelium
o Microthrombi form at site of damage
§ Consumes platelets → thrombocytopenia
§ Intravascular mechanical hemolysis → schistocytes (RBC fragmented)
§ Decreases renal blood flow → acute renal failure

Epidemiology
o Most commonly in children
o Exposed to E. coli
§ raw or undercooked meat
§ unwashed fruits/vegetables
§ animals at petting zoo

o B.4.6) Thrombotic thrombocytopenic purpura (TTP)

Pathophysiology :
ü Deficiency [congenital ; mutation] or inhibition [acquired ; auto-antibodies] of metalloproteinase ADAMTS13
ü ADAMTS13 degrades vWF multimers

[Thrombocytopenia = easy bleeding & epistaxis ; neurological symptoms = confusion & seizures]
ó
Similar to HUS but with fever and neurologic symptoms

ü Deficiency → large vWF multimers → increased platelet adhesion → platelet thrombosis

8
A heterogeneous group of autoimmune diseases, all characterized by inflammation of blood vessels and potential ischemia and
damage to the organs supplied by these vessels

9
Defined as a recent significant increase over baseline BP that is associated with target organ damage

5
Karen Brechbuhl – notes

♥Because prerenal causes & ATN are the most common causes of AKI, it is clinical important to know how to differentiate//diagnose btw the 2 of them : ♥
Prerenal AKI (∼ 30% of cases) ATN (∼ 50% of cases)
u Renal blood flow decreases enough to lower the GFR

Ä Decreased blood supply to kidneys [due to : A1)hypovolemia,

A2)hypotension, A3) Hepatorenal syndrome (HRS) A4)
Renal vasoconstriction & A5) Drugs affecting glomerular perfusion], u Tubular function is significantly impaired
which leads to decreased clearance of metabolites (BUN, Cr, uremic ¯

Pathophysiology toxins) The kidneys are unable to concentrate urine effectively

u Because the renal parenchyma is undamaged, tubular function (and therefore [note also : in ATN, patchy necrosis → debris obstructing tubules and fluid
the concentrating ability) is preserved backflow → ↓ GFR]
Ä Therefore, the kidney responds appropriately, conserving as much
sodium and water as possible
ó
Decreased GFR → activation of renin-angiotensin system (RAAS) →
increased aldosterone release → increased reabsorption of Na+, H2O ∴
­urine osmolality (=concentrated urine)]
Because tubules are NOT damaged, Na+ & thus water is rebasorbed Tubular damaged
∴
∴ Poor urinary concentration
∴
Urine osmolality High urine osmolality (=concentrated urine) ­­­ urine output
∴
- low urine osmolality
-
>500 mOsm/ kg H2O 250- 300 mOsm/ kg H2O

Because tubules are NOT damaged, Na+ is rebasorbed ∴ low Urine Na+ Increased urine Na+ because Na+ is poorly reabsorbed
concentration -
Urine Urine Na+ concentration - >40 mEq/L
analysis <20 mEq/L

FeNa Increased urine Na+ because Na+ is poorly reabsorbed

[Fractional excretion of sodium(Na+)] Because tubules are NOT damaged, Na+ is rebasorbed ó reduced urinary -
excretion > 1%
-
[in some books >2%]
<1%
Assess FENa with caution cause ↓FENa in some INTRINSIC causes of AKI (glomerulonephritis,
FENa is unreliable w/ diuretic use (prerenal cause of AKI : loss of water = hypovolemia = hypotension =
vasculitis, contrast-induced nephropathy, rhabdomyolysis)
¯ renal perfusion) cause only accurate if ¯ GFR !
In this case, use FEUrea → >35% suggests intrinsic AKI !
In this case, use FEUrea → <35% suggests prerenal AKI !

FEUrea Because tubules are NOT damaged, urea is rebasorbed Tubular damaged = LESS urea is rebasorbed
- -
[Fractional Excretion of Urea]
<35% >35%

Decreased blood flow results in → ↓ GFR → oliguria

Volume Depends on which phase the patient is at – see below J !
[urine output < 500 mL in 24 hours]

Active
-
Scanty Epithelial casts
[reflect damage to tubule cells in the kidney]
- &
Muddy brown granular casts
Urine sediment Bland (Æ) [Spilled cellular contents of infarcted tubular epithelial cells]

Normal urianalysis

BUN/Creatinine ration ­ed serum BUN-to-Cr ratio ¯ed BUN-to-serum Cr ratio in comparison with prerenal failure

Both serum BUN and Cr levels are elevated (cause poor kidney job to excrete them Both BUN and Cr levels are still elevated, but less urea is reabsorbed than in
properly) but because no tubular damage, kidney can reabsorb urea! prerenal failure cause here there’s tubular damage!
- -
> 20:1 < 20:1
[in some books <15:1]
The clinical course of acute tubular necrosis is broadly divided into:
1. Incipient or initiating phase
2. Maintenance phase aka oliguric phase (corresponds to the phase of established acute tubular
Clinical course If the prerenal phase is prolonged, the renal tubules undergo necrosis necrosis)
3. Diuretic phase
4. Phase of functional recovery (post-diuretic phase)
¯
See description below J

1. Incipient or initiating phase

ü Begins with the onset of renal insult (e.g., ischemic phase of pre-renal failure or toxin exposure)
ü Lasts hours to days (usually less than 48hrs or 2 days)
ü Reflects the time from the onset of the precipitating event (e.g., ischemic phase of pre-renal failure or toxin)
ü Clinical features : there are no specific symptoms relating to renal failure during this stage

2. Maintenance phase (Oliguric Phase)

ü Begins after the initiation phase once the renal injury becomes established (when tubular necrosis has occurred)
ü Typically begins within 48 hours of the initiation phase and lasts for 10 to 14 days (May last longer)
ü During this phase the GFR and Urine output progressively decrease until they stabilize at their lowest (GFR is may be as low as 5-10ml/min and urine outplll is typically <400ml/day)
[In ATN, patchy necrosis → debris obstructing tubules and fluid backflow → ↓ GFR]
ü Clinical features :
• Signs of fluid overload (¯GFR à RAAS àNa+ and H2O retention) :
à Peripheral and pulmonary edema [symptom = dyspnea & on physical exam = crackles & wheezing]
à HTN
• Increased retention of urea and creatinine = azotemia) (¯GFR ∴¯creatine & urea are excreted)
• Uremia = clinical manifestation of azotemia
• Complications :
à Electrolytes :
- Most dangerous one àhyperkalemia [cardiac arrhythmias, muscle weakness, hyporeflexia, and gastrointestinal symptoms (e.g., constipation)]
- Others à hyperphosphatemia, hypermagnesemia, hypocalcemia
à Metabolic acidosis [¯ GFR ∴ ¯ed H+ excretion]
ü Continuous Renal Replacement Therapy (CRRT) or Dialysis should be initiated in this phase
ü The longer the patient remains in this phase, the poorer the prognosis for a return to nonnal renal function
Clinical signs and symptoms “AKI GP’s Patient Promptly Being Examinated”

ü Asterixis (is a tremor of the hand when the wrist is extended, sometimes said to resemble a bird flapping its wings - https://www.youtube.com/watch?v=YphjuZBJVkI)
ü Impaired Immunological system —uremia inhibits cellular and humoral immunity ó ­ risk of infection
ü Uremic Gastroenteritis (anorexia, nausea, vomiting)
ü Pruritus [The exact cause is unknown. However, there are a variety of hypotheses, involving accumulation of histamine, deposition of urate crystals in the skin]
ü Peripheral neuropathy : Paresthesias
ü Uremic Pericarditis [fever, pleuritic chest pain, and a pericardial friction rub heard on auscultation ; ­­­ risk of cardaic tamponade]
ü ↑ Bleeding tendency secondary to platelet dysfunction [Abnormal platelet adhesion and aggregation]
ü Encephalopathy: seizures, somnolence, coma

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Karen Brechbuhl – notes

3. Polyuric/diuretic phase
ü Begins after the oliguric phase & precedes the recovery phase
ü Typically begins 10 to 14 days after the initiation phase and lasts for about 10 days (May last longer)
ü This phase signifies recovery of glomerular filtration and partial healing of tubular lesions [Glomerular filtration returns to normal, which increases urine production (polyuria
ü ), while tubular reabsorption remains disturbed]
ü Clinical features
• Nephrons do not concentrate urine sufficiently to conserve electrolytes and water
=
Polyuria [Urine output > 2.5L/24h]
=
Dehydration
+
Loss of electrolytes [e.g.: hyponatremia (altered mental status, nausea, vomiting, muscle weakness, and hyporeflexia) & hypokalemia (pretty much the same clinical manifestations as hyperkalemia)]

• BUN and serum creatinine and potassium may remain elevated or continue to rise even

4. Phase of recovery (post-diuretic phase)

ü Begins after the diuretic Phase (roughly 3 weeks after the initiation phase)
ü May last months to years
ü The recovery phase is the period during which repair of renal tissue takes place
ü Renal tubular function is progressively restored with improvement in concentrating ability
ü Its onset usually is heralded by a gradual return of urine output towards normal and a fall in serum BUN & creatinine, indicating that the nephrons are recovering
ü The BUN and creatinine eventually returns to normal

ó
Stages of acute tubular necrosis
ü Reflects the time from the onset of the precipitating event (e.g., ischemic phase of pre-renal failure or
1. Incipient or initiating phase ü Lasts hours to days (usually less than 48hrs or 2 days) toxin)

ü Clinical features : there are no specific symptoms relating to renal failure during this stage

ü During this phase the GFR and Urine output progressively decrease until they stabilize at their lowest [GFR
is may be as low as 5-10ml/min and urine output is typically <400 – 500 ml/day (=oliguria)]
[In ATN, patchy necrosis → debris obstructing tubules and fluid backflow → ↓ GFR]

ü Clinical features : HUMAN

2. Maintenance phase (Oliguric Phase) ü Typically begins within 48 hours of the initiation phase and lasts
for 10 to 14 days (May last longer) Hyperkaliemia [¯ GFR ∴ potassium isn’t effectively removed from blood ó ¯ K+ excretion]
Note – other electrolytes disorder : hyperphosphatemia, hypermagnesemia, hypocalcemia

Uremia

Metabolic
Acidosis [pH <7.1 ; ¯ GFR ∴ ¯ed H+ excretion]

Na+ / H2O retention [thus HTN and/or pulmonary edema (symptom = dyspnea & on physical exam = crackles & wheezing)]

Note - symptoms & ¯ of GFR :

ü GFR returns to normal, which increases urine production (polyuria), while tubular reabsorption remains
3. Polyuric/diuretic phase ü Typically begins 10 to 14 days after the initiation phase and lasts disturbed]
for about 10 days (May last longer)
ü Clinical features
- Polyuria [Urine output exceeding 3 L/day] = Dehydration + Loss of electrolytes [= hypOkalemia,
hypOnatremia, hypOcalcemia, and hypOmagnesemia]
- BUN and serum creatinine and potassium may remain elevated or continue to rise even

4. Phase of recovery (post-diuretic phase) ü May last months to years ü Renal tubular function is progressively restored with improvement in concentrating ability

ü Gradual return of urine output towards normal

+
ü Fall in serum BUN & creatinine, indicating that the nephrons are recovering à eventual return to normal

Note : some textbooks put the polyuric phase into the recovery phase… (ó thus course of ATN has three stages: initiation, maintenance, and recovery phases)

ó
Main values to retain about the ≠ btw prerenal AKI and ATN :

7
Karen Brechbuhl – notes

C) Postrenal AKI (∼ 10% of cases)

Postrenal causes include any condition that results in bilateral obstruction of urinary flow from the renal pelvis to the urethra
u Urethral obstruction secondary to enlarged prostate (BPH) is the most common cause
u Others :
o Tumors [obstructing neoplasm in pelvis (bladder, cervix, prostate) or or abdomen (ureter)…]
o Stones (in both ureters OR ureter in a single functioning kidney lead to AKI)
o Hospitalizations, post-surgery (transient neurogenic bladder) or spinal cord injury, diabetes (permanent neurogenic bladder) → urinary tract obstruction

Pathophysiology
u Obstruction of any segment of the urinary tract (with intact kidney) causes increased tubular pressure (urine produced cannot be excreted), which leads to decreased GFR
[Decreased outflow results in ↓ GFR and oliguria]

u Blood supply and renal parenchyma are intact

u Note that both kidneys must be obstructed for BUN & creatinine [azotemia] to rise !!!!!!!!

u Renal function is restored if obstruction is relieved before the kidneys are damaged
o Postrenal obstruction, if untreated, can lead to ATN !!!!!
ó

e.g.: hydronephrosis is detected by USG or bilateral uretral obstruction cause of stones detected by CT…

ü Written in her book (for once I thought it was useful) :

Ä Anuria (no urine output or less than 50-100 ml/24h) occurs as a result of acute bilateral arterial or venous occlusion or
complete urinary tract obstruction
Ä Oliguria ( < 400-500 ml urine output/24 h) is present in prerenal azotemia and in acute tubular necrosis
Ä Non-oliguric AKI can be present in acute tubular necrosis [patient can directly enter the polyuria phase & skip the oliguric
phase] and in partial obstruction
Ä Polyuria ( > 2.5L/24h) occurs usually in the recovery phase of ATN

ü Renal biopsy
Ä Is not necessary in most cases, when AKI is prerenal, postrenal or an acute tubular necrosis
Ä Only indicated in the following situations:
à suspicion of acute glomerulonephritis or vasculitis
à thrombotic microangiopathies
à AKI of unknown etiology after excluding pre and postrenal causes
à Oligoanuria> 3 weeks in the absence of obstruction
à Posttransplant

8
Karen Brechbuhl – notes

5) Urianalysis in differential diagnosis of the MC causes of AKI

Acute kidney injury (AKI)
¯
­­­ BUN& Creatinine in serum:
¯
Urianalysis:

Finding Likely etiology

Hematuria
I Glomerulonephritis
RBCs casts Or
N Vasculitis
Subnephrotic proteinuria (btw 1-3g/day)
T ¯
R Perform renal biopsy
I
Granular brown muddy casts N ATN
S
Intra-tubular obstruction by drug crystals
Granular brown muddy casts
I ó
+ C ATN due to nephrotoxins
Crystals à oxalate (especially ehtylene glycol poisoning)
A à uric acid (especially tumor lysis syndrome)
K
WBCs casts
I
Eosinophils Acute interstitial nephritis
Subnephrotic proteinuria (btw 1-3g/day) ¯
hypersensitivity to drugs (MC NSAIDs or PPI)
NO oliguria

Prerenal AKI

OR

Normal urianalysis Posterenal AKI

¯
CT or USG to rule out obstruction (Postrenal AKI)

ü Note :
Ä Sometimes, an obstruction can lead to an infection & thus acute pyelonephritis à so
here may also be pyuria & WBCs casts !

ü Additional work up :
Ä Serum prostate specific antigen or PSA level which is elevated with prostatic disease-
both benign prostatic hyperplasia and prostatic cancer

6) Treatment
u General measures :
o Avoid nephrotoxic medications if possible. Use appropriate dosing, intervals, and duration of therapy
o Avoid use of intravenous contrast media when risks outweigh benefits

u Prerenal AKI
o ofc identify + treat underlying cause
&
o If the individual has signs of hypovolemia
§ IV saline àhelps restore intravascular volume & stabilize the blood pressure (goal of mean arterial pressure > 65 mm Hg)
§ If low BP persists (mean arterial pressure <65 mm Hg despite fluid resuscitation) à vasopressors like IV norepinephrine may be needed
¯
Helps to prevent development of ATN // parenchymal damage (intrinsic AKI)

!!!!!! If with IV fluids Cr does not ¯, suspect intrinsic AKI istead of prerenal !!!!!!

o If the individual has signs of cirrhosis

§ Expanding plasma volume à typically with albumin and isotonic fluids !
o If the individual has signs of HF
§ Should be treated with DIURETICS (IV furosemide) and NOT IV fluids à HF !!!!!

u Postrenal:
o Remove outflow obstructions
¯
Helps to prevent development of ATN // parenchymal damage (intrinsic AKI)

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Karen Brechbuhl – notes

u Intrinsic AKI
o Ofc identify + treat underlying cause
§ e.g.: immunosuppressive drugs such as corticosteroids and cyclophosphamide in some causes of rapidly progressive glomerulonephritis
OR
stop the offending drug in acute tubulointerstitial nephritis

+
o Temporizing measures until kidney recovers but sometimes urgent dialysis if required [During oliguric phase] :
§ Temporizing measures include :

• Hyperkalemia
• Corrected with:
ü 1st step: Myocardial membrane stabilization (if ECG changes are +ve)
Ä IV calcium gluconate
ü 2nd step : Reduce serum K+ levels by shifting K+ from extracellular to intracellular fluid
Ä IV insulin plus glucose à this is the fastest method (onset of action à within 15min)
Ä Other methods :
- Beta agonists (Albuterol) – onset of action : 30min
-Sodium bicarbonate – onset of action: at least 3 – 4hrs
rd
ü 3 step: remove K+ excess from body (excretion from the body)
Ä Diuretics (loop diuretic like furosemide)
àWorks only if patient has adequate kidnev functions
Ä Resin exchangers (E.g. polystyrene sulfonate)
àCation-exchange (removes K+ from blood into gut in exchange for an eaual amount of Na+)
àSlow acting (Requires 1-2 hrs before plasma K+ ¯es)
Ä Hemodialysis
à Definitive treatment of choice in patients with advanced renal failure and severe hvoerkalemia
ó

+
• Avoid foods high in potassium (e.g.: fruits à bananas, oranges… & vegetables à avocados, tomatoes, spinach, carrot….)

• Metabolic Acidosis (pH <7.1)

ü Resuls bicarbonate serum levels is <20 mmol/L
ü Corrected with PO or IV bicarbonate
ü Goal : maintain normal bicarbonate serum levels (22-24 mmol/L)

• Na+ / H2O retention ó Fluid overload

ü Intake of dietary sodium is restricted [<5 g/day of salt (NaCl)]
ü fluid intake should not be ­ than : 500ml/day + the equivalent of the urine output
ü Loop diuretics (e.g furosemide) may be necessary

§ Immediate therapy for the management of life-threatening abnormalities due to AKI ó indications for dialysis in acute renal failure: “HUMAN”
• Hyperkalemia (>6.5 mEq/dL) refractory to above mentionned t/
• complications of Uremia [especially pericarditis, encephalopathy & ­ risk of bleeding !!!]
• Metabolic Acidosis (pH <7.1) in whom IV bicarbonate administration is not indicated
• Na+ / H2O retention ó Fluid overload and pulmonary edema refractory to diuretics
+
• Blood urea level >200 mg/dl (BUN >100 mg/dl) or daily rise of urea >50 mg/dl (BUN >25 mg/dl)
• Serum creatinine >5 mg/dl or daily rise of creatinine >1 mg/dl

!!!! Cause of death: MC causes of death in AKI (in the absence of dialysis) are hyperkalemia (may lead to fatal arrythmias!) and pulmonary edema, followed by infection and uremia !!!!

ü Dialysis urgent access :

Ä RIGHT internal jugular vein > femoral

ü Types of Dialysis :
Ä Peritoneal dialysis (PD)
- utilizes transport properties of peritoneum as a semipermeable membrane.

Ä Hemodialysis (HD)
- Hemodialysis (HD) is purification blood outside the body (extracorporeal), and involves circulation of blood through a
hemodialyzer also known as artificial kidney. The blood is passed through the dialyzer made which is up with a semisynthetic
membrane. The nitrogenous toxins are removed from blood through this membrane and the cleansed blood is returned to
the body. The process is controlled by a dialysis machine, which pumps the blood through the extracorporeal circuit and
regulates the cleaning process

Ä Continuous Renal Replacement Therapies (CRRT) à preferred in hemodynamic unstable patient or in patients with brain injury

ü Note :

10
Karen Brechbuhl – notes

7) Prognosis
u If complete resolution if underlying cause of AKI is corrected (& t/ early)

u If permanent kidney damage occur [depends on the duration, severity10 and frequency of the episode of AKI] à chronic kidney disease (CDK)

ü Video used :

Ä https://www.osmosis.org/learn/Clinical_Reasoning:_Acute_kidney_injury

Ä https://usmle-rx.scholarrx.com/video-player;video=2503

10
Severity of AKI is assessed by the urinary output, pattern of serum creatinine increase, dialysis necessity and the presence of complications (e.g.: multiple system and organ failure)

11