MEDICINE 2

NEPHROLOGY|ACUTE KIDNEY INJURY

Alsun S. Cabarles, M.D. 20 Apr 2022 | S04.T02

OUTLINE
I. Definition IV. Diagnosis
II. Stages and Epidemiology V. Management and Prognosis
III. Classification and VI. References
Pathophysiology VII. Appendix

I. DEFINITION
Figure 2.1. Similarities of AKI and CKD
A. ACUTE KIDNEY INJURY
• Previously known as Acute Renal Failure
• Defined as sudden impairment of kidney function leading to
retention of nitrogenous waste products and other wastes
→ Aside from creatinine, other wastes excreted by the kidney
cannot be measured as of now
→ This would also lead to a decrease in urine volume excretion
• Designation for a heterogenous group of conditions
• Common diagnostic features:
→ Increase in blood urea nitrogen (BUN)
→ Increase in serum creatinine (SCr)
→ Reduction in urine volume
• A clinical diagnosis (dysfunctional capacity of the kidneys) and
NOT a structural one Figure 2.2. Conceptual model for AKI
• According to the Kidney International Supplements (2012)
•

• Reversibility/recovery is possible from normal stages to kidney

criteria, AKI is defined as any of the following:
failure
→ Increase in SCr by >0.3 mg/dl (>26.5 umol/L) within 48 hrs;
• GFR decreases as kidney damage occurs; it is defined by SCr
OR
and urine output (surrogates for GFR)
→ Increase in SCr to >1.5 times baseline, which is known or
• For kidney damage, markers used as surrogates are NGAL, KIM-
presumed to have occurred within the prior 7 days; OR
1, and IL-18.
→ Urine volume <0.5 ml/kg/hr for 6 hrs
▪ Used when results of serum creatinine are not yet available B. PHASES
▪ May ask the patient to estimate urine output
• GFR from normal levels goes down in a stiff manner, staying
II. STAGES AND EPIDEMIOLOGY there from quite some time in a low state, then eventually
increases.
A. STAGES
Initiation
Table 2.1. Stages of AKI
• Renal tubular epithelial cell injury is a key feature
Stages Serum Creatinine Urine Output
• RBF decreases to a level resulting in severe cellular ATP
1 • 1.5-1.9 baseline; OR <0.5 ml/kg/hr for 6-
depletion leading to acute cell injury and dysfunction
• >0.3 mg/dl (>26.5 umol/L) 12 hrs
→ Processes happening inside the cell can be supported by the
increase low ATP, low oxygen
2 • 2.0-2.9 times baseline <0.5 ml/kg/hr for • Renal ischemia induces structural & functional alterations in renal
>12 hrs proximal tubular epithelial cells
• Disruption of the ability of renal tubular epithelial cells and renal
3 • 3.0 times baseline; OR Anuria for >12 hrs
vascular endothelial cells to maintain normal renal function
• Increase in SCr to >4.0 → Experience loss of polarity of renal tubular cells → Na/K
mg/dl (>353.6 umol/l); OR ATPase usually solely found in basolateral but may be also be
• Initiation of renal inserted in the apical/luminal membrane → instead of Na+
replacement therapy; OR reabsorbed, some are excreted in luminal side
• In patients <18 yrs:
decrease in eGFR to <35 Extension
ml/min per 1.73m2 • Ushered in by two major events: continued hypoxia following
•
the initial ischemic event and an inflammatory response
• In cases wherein serum creatinine and urine output is not along
• More pronounced in the corticomedullary junction (CMJ), or
the same stage (eg., SCr = 1.5 baseline, UO = <0.5 ml/kg/hr for
outer medullary region
>12 hrs), use the HIGHER staging (in the example, the patient
→ There are parts of the kidney not highly perfused → only rely
would be stage 2 AKI)
on diffusion of oxygen/sugar excess of other segments
• Patients who are at the higher stages of AKI, particularly stage 3,
• Renal vascular endothelial cell damage likely plays a key role in
they are at higher risk of developing CVS diseases, progressing
the continued ischemia of the renal tubular epithelium
to CKI, and at higher risk of having sudden cardiac death.
• Cells continue to undergo injury and death in the outer medulla
• Both AKI and CKD can occur at the same time.
• In contrast, the proximal tubule cells in the outer cortex, where
• Most common cause of mortality for both AKI and CKD are the
blood flow has returned to near normal levels now undergo
CVS events (MI, sudden cardiac death, arrythmias, etc.)
cellular repair and improve morphologically
• GFR continues to fall
• Continued production and release of chemokines and cytokines

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 Maintenance → Community-acquired AKI
• Creatinine levels will remain high, GFR levels will remain low ▪ Volume depletion
• Cells undergo repair, migration, apoptosis and proliferation ▪ Adverse effects of medications
in an attempt to reestablish and maintain cellular and tubule ▪ Obstruction of the urinary tract
integrity → Hospital-acquired AKI (most common clinical settings)
→ Will take a long time (2-3 weeks) ▪ Sepsis
• The GFR is stable ▪ Major surgical procedures
→ Will highly depend on the residual renal capacity of the patient ▪ Critical illness involving heart or liver failure
• Slowly improving cellular function and sets the stage for ▪ Intravenous iodinated contrast administration
improvement in organ function ▪ Nephrotoxic medication administration
• Blood flow returns toward normal and epithelial cells establish • In the developing world:
intracellular and intercellular homeostasis → AKI is a major medical complication
→ Epidemiology differs from that in developed countries due to
Recovery differences in demographics, economics, geography, and
• Cellular differentiation continues, epithelial polarity is comorbid disease burden
reestablished and normal cellular and organ function returns → Many etiologies for AKI are region-specific such as:
• Minsan mauuna dumami yung ihi ng patient bago bumaba yung ▪ Envenomation from snakes, spiders, caterpillars, bees
creatinine ▪ Infectious causes such as malaria and leptospirosis
• It’s a sign when you have an increasing volume of urine that the ▪ Crush injuries and resultant rhabdomyolysis from
kidneys are now in the recovery phase earthquakes
Table 2.2. Major Risk Factors for AKI
Patient Medications & Procedures
Factors Agents
Pre-existing NSAIDs Cardiopulmonary
renal bypass procedures
dysfunction
Sepsis Surgery involving
aortic clamp
Old age (>75) COX-2 inhibitors Increased intra-
abdominal
pressure
Diabetes Cyclosporine or Large arterial
tacrolimus* catheter placement
with risk for
atheroembolization
Hepatic failure ACE inhibitors Liver
transplantation
Atherosclerosis ARBs Kidney
transplantation
Chronic
hypertension
Perioperative Use of venous or
cardiac arterial radiocontrast
dysfunc-tion agents
Hypercalcemia
Renal artery
stenosis
*Cyclosporine & tacrolimus has to be maintained at a certain trough level; at higher
doses, they can induce toxicity to kidneys, presenting as tubular atrophy, tubular
changes, etc.

III. CLASSIFICATION AND PATHOPHYSIOLOGY

A. PRERENAL AZOTEMIA
Figure 2.3. Clinical Phases of AKI with cellular changes. [CMJ = corticomedullary
junction; BBM = brush border membrane] • Also called prerenal acute kidney injury
• Most common form of AKI (40-50%)
C. EPIDEMIOLOGY • Due to kidney hypoperfusion due to reductions in effective
• Complicates 5 – 7% of acute hospital care admission and 30% of arterial blood volume (EABV) [Cabarles, 2022]
ICU admission → True hypovolemia
• 4x increase in incidence in the United States since 1988 ▪ Decrease volume intravascularly
• Estimated yearly incidence of 500 per 100,000 population ▪ Loss of blood
• Markedly increased risk of death in hospitalized individuals with ▪ Dehydration
mortality rate exceeds 50% → Independent of volume status
• Increases the risk for the development or worsening of chronic ▪ “3rd spacing”
kidney disease (CKD) ▪ Fluid extravasate into the interstitium
• Survivor of severe AKI requiring dialysis → increased risk for later ▪ Not counted as effective blood volume
development of dialysis-requiring ESRD ▪ Ascites, pleural effusion etc.
• May be community-acquired or hospital-acquired

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 • Drugs that can affect the compensatory changes evoked to
maintain GFR:
→ NSAIDs – inhibit renal prostaglandin production, limiting
renal afferent vasodilation
→ ACE-I and ARBs – limit renal efferent vasoconstriction
that is particularly pronounced in patients with bilateral
renal artery stenosis or unilateral renal artery stenosis
→ Combined use of NSAIDs with ACE-Is or ARBs poses a
particularly high risk for developing prerenal azotemia
• Hepatorenal Syndrome: individuals with advanced cirrhosis
resembles prerenal azotemia despite total-body volume
overload
→ Systemic vascular resistance is markedly reduced due to
primary arterial vasodilation in the splanchnic circulation
activation of vasoconstrictor responses similar to those
Figure 3.1. Pathophysiology of prerenal acute kidney injury seen in hypovolemia
• Rise in SCr or BUN due to inadequate renal plasma flow and → AKI is a common complication triggered by volume
intraglomerular hydrostatic pressure to support normal depletion and spontaneous bacterial peritonitis
glomerular filtration → Two types:
• Most common clinical conditions ▪ Type 1 – AKI without an alternate cause (e.g. shock
→ Hypovolemia and nephrotoxic drugs) persists des pite volume
▪ Can be further classified as volume responsive and non- administration and withholding of diuretics. Poorer
volume responsive prognosis.
▪ May be caused by ▪ Type 2 – less severe form characterized mainly by
− Hemorrhage refractory ascites
− GI losses (nausea, vomiting)
− Renal losses (Diuretics, substances with diuretic-like
effects like alcohol)
− 3rd spacing
→ Decreased cardiac output
→ Medications that interfere with renal autoregulatory
responses:
▪ NSAIDs, ACEIs, ARBs
− These meds vasodilate afferent arteriole
• May coexist with other form of intrinsic AKI
• Prolonged prerenal azotemia ischemic injury called Acute
Tubular Necrosis (ATN)
• No parenchymal damage to the kidney, rapidly reversible once
• intraglomerular hemodynamics are restored
→ Since the problem is more on the volume

Figure 3.3. Breakdown of prevalence of different classifications and causes of

AKI.

Figure 3.2. Other organ systems that can contribute to dec. EABV. There is no
true volume depletion in these examples. These may be reversible by
medications. However, at the point wherein they cannot be regulated, AKI will
continue.

From previous transes:

• Even in healthy adults, renal autoregulation usually fails once
the systolic blood pressure falls below 80 mmHg
• A number of factors determine the robustness of the
autoregulatory response and the risk of prerenal azotemia
→ Atherosclerosis
→ Long-standing hypertension
Figure 3.4. Normal perfusion pressure
→ Older age can lead to hyalinosis
• In CKD, renal afferent vasodilation may be operating at
maximal capacity in order to maximize GFR in response to
reduced functional renal mass
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 Table 3.1. Summary of intrarenal mechanisms for autoregulation of the GFR
under decreased perfusion and reduction of the GFR by drugs
PG Afferent AiI Efferent GFR
Dec.
 Dilate  Constrict N
Perfusion
w/
 Constrict  Constrict 
NSAIDs
w/ ACEIs Slight
Dilate  Dilate 
/ ARBs 
PG- Prostaglandins; AII- Angiotensin II
• Autoregulation
→ Myogenic reflex, Tubuloglomerular feedback, RAAS activation
→ Autoregulation is achieved only at a certain point
▪ If MAP falls below 75-80mmHg, autoregulation is impaired
From previous transes:
• COUNTERREGULATORY MECHANISMS TO MAINTAIN
GFR:
→ Myogenic reflex
Figure 3.5. Decreased perfusion pressure within the autoregulatory range. → Tubuloglomerular feedback
Normal glomerular capillary pressure is maintained by afferent vasodilation and → RAAS activation
efferent vasoconstriction.
• Myogenic reflex
→ Within the afferent arteriole
→ Dilation in the setting of low perfusion pressure, thereby
maintaining glomerular perfusion
→ Intrarenal biosynthesis of vasodilator prostaglandins
(prostacyclin, prostaglandin E2), kallikrein and kinins, and
possibly nitric oxide (NO) also increase in response to low
renal perfusion pressure
• Tubuloglomerular feedback
• Decreases in solute delivery to the macula densa (specialized
cells within the distal tubule) elicit dilation of the juxtaposed
afferent arteriole in order to maintain glomerular perfusion
• Vasodilation mechanism mediated in part by NO
• RAAS activation
→ Mild degrees of hypovolemia and reductions in cardiac
output compensatory renal physiologic changes to
maintain BP and intravascular volume
▪ Renal vasoconstriction
▪ Salt and water reabsorption
Figure 3.6. Decreased perfusion pressure with NSAIDs. Loss of vasodilatory → Mediators
prostaglandins increases afferent resistance. This causes the glomerular ▪ Angiotensin II (acts on efferent arteriole)
capillary pressure to drop below normal values and the GFR to decreases.
Therefore, NSAID should be removed.
− Maintains glomerular capillary hydrostatic pressure
closer to normal
• Change medications
− Prevents marked reductions in GFR if renal blood
→ For pain: e.g., morphine or morphine derivatives
flow reduction is not excessive
▪ Norepinephrine
▪ Vasopressin
B. INTRINSIC AKI
• Most common causes:
→ Nephrotoxins
▪ Endogenous
▪ Exogenous
→ Sepsis
→ Ischemia
• If not treated, especially hypovolemic in origin, may lead to ATN
but biopsy is lacking in most cases
• Process of inflammation, apoptosis, and altered regional
perfusion
• The four major structures of the kidney when considering
etiologies of intrinsic renal failure:
→ Tubules
→ Glomeruli
→ Interstitium
Figure 3.7. Decreased perfusion pressure with ACE inhibitor or an ARB. Loss of → Intrarenal blood vessels
Angiotensin II action reduces efferent resistance. This causes the glomerular
capillary pressure to drop below normal values and the GFR to decrease.
Remember that AKI is not a clinical diagnosis but a pathologic one.
• Change medications TEMPORARILY
→ To non- ACE/ARB
→ Maintain perfusion but not compromising blood pressure
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 From previous transes:
I. Acute Tubular Necrosis
→ Acute tubular necrosis (ATN) is the term used to designate
AKI resulting from damage to the tubules. If there is
persistent hypoperfusion of the kidneys, not only filtration
of glomerulus but also blood supply of the tubules.
→ The two major causes of ATN are:
▪ Ischemic – resulting from severe or protracted
decrease in renal perfusion.
▪ Nephrotoxic – resulting from a variety of exogenous
compounds (e.g., aminoglycosides, amphotericin B, cis-
platinum, radiocontrast media) and endogenous
compounds (e.g., hemoglobin in hemolysis, myoglobin
in rhabdomyolysis) that are toxic or potentially toxic to
the kidney. Figure 3.8. Pathophysiology of Sepsis-associated AKI
→ Historically, classic ATN goes through an oliguric (urine Iscemia-Associated AKI
output ≤ 400 mL/24 hours) phase of 1–2 weeks followed by
a nonoliguric (urine output > 400 mL/day) phase of 10–14 • Kidneys
days with eventual recovery of renal function. → 20% of Cardiac Output
II. Acute Glomerulonephritis → 10% of resting O2 consumption
→ AKI from glomerular damage occurs in severe cases of → 0.5% body mass
acute glomerulonephritis (GN). → Site of ONE OF THE MOST HYPOXIC REGIONS in the body
→ Acute GN can be due to a primary renal disease such as ▪ Renal medulla
an idiopathic rapidly progressive GN or as part of a → S3 segment of PT is metabolically active and depends on
systemic disease such as systemic lupus erythematosus, oxidative metabolism for survival
bacterial endocarditis, or Wegener’s granulomatosis ▪ They don’t have direct arterial supply because PT only
→ Least affected relies on the diffusion of oxygen and nutrients (Cabarles, 2022)
→ Increased serum creatinine and presence of inflammatory ▪ During impaired perfusion, S3 segment will undergo
process in the patient anaerobic metabolism and eventually lead to ischemia and
apoptosis (Cabarles, 2022)
III. Acute Interstitial Nephritis
• The four major structures of the kidney when considering
→ AKI from interstitial damage can result from acute
etiologies of intrinsic renal failure:
interstitial nephritis due to an allergic reaction to a variety
medications → Tubules → Interstitium
→ Commonly antibiotics - penicillins, cephalosporins, → Glomeruli → Intrarenal blood vessels
sulfonamides, sometimes fluoroquinolones • ISCHEMIA ALONE in normal kidney is NOT SUFFICIENT to
→ An infection - bacterial illnesses such as leptospirosis, cause severe AKI
legionella, rarely pyelonephritis and viral illnesses such as • AKI develops in the context of
Hanta virus) → Limited renal reserve (CKD, old age)
IV. Vascular Damage → Coexisting insults (sepsis, vasoactive or nephrotoxic drugs,
→ AKI from vascular damage occurs because injury to rhabdomyolysis, SIRS associated with burns and pancreatitis)
intrarenal vessels decreases renal perfusion and • Prerenal azotemia and ischemia-associated AKI represent a
diminishes GFR continuum of the manifestation of renal hypoperfusion
→ Causes of vascular injury include malignant hypertension, Pathophysiology
atheroembolic disease, preeclampsia/eclampsia, and
hemolytic uremic syndrome (HUS)/thrombotic
thrombocytopenia purpura (TTP)

Sepsis-Associated AKI
• AKI complicates >50% of cases of severe sepsis
•  risk of death
• Typically occur in setting of hemodynamic collapse →
vasopressor support requiring
• Pathogenesis:
→ Tubular injury → (+) tubular debris and cast in urine
→ Inflammation
→ Mitochondrial dysfunction
→ Interstitial edema
• Pathophysiology
→ Generalized arterial vasodilation mediated by cytokines that Figure 3.9. Pathophysiology of Ischemic Acute Renal Failure
upregulate the inducible NO synthase in vasculature→  GFR
▪ Excessive vasodilation of EFFERENT artery (early) OR
Acute Tubular Necrosis (Carbales, 2022)
▪ Vasoconstriction from activation of SNS, RAAS, ADH,
endothelin • Acute tubular necrosis (ATN) is the term used to designate AKI
→ May also lead to endothelial damage resulting from damage to the tubules. If there is persistent
hypoperfusion of the kidneys, not only filtration of glomerulus
but also blood supply of the tubules.
→ Ischemic – resulting from severe or protracted decrease in
renal perfusion.
→ Nephrotoxic – resulting from a variety of exogenous
compounds (e.g., aminoglycosides, amphotericin B, cis-
platinum, radiocontrast media) and endogenous compounds

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 (e.g., hemoglobin in hemolysis, myoglobin in • May develop abdominal compartment syndrome
rhabdomyolysis) that are toxic or potentially toxic to the
kidney.
• Historically, classic ATN goes through an oliguric (urine output
≤ 400 mL/24 hours) phase of 1–2 weeks followed by a
nonoliguric (urine output > 400 mL/day) phase of 10–14 days
with eventual recovery of renal function.

Figure 3.12. Pathogenesis of abdominal compartment syndrome

Diseases of Microvasculature Leading to Ischemia
Figure 3.10. Pathophysiology of Acute Tubular Necrosis
• Thrombotic microangiopathies (APAS, radiation nephritis,
Carbales, 2022: malignant nephrosclerosis, TTP-HUS)
• ATN is related in a continuum with hypovolemia during the • Scleroderma
prerenal phase • Atheroembolic disease
• As the clinical phases progresses, the figure above shows what Large Vessel Diseases
happens during ATN at the cellular level over time
• Renal artery dissection • Thrombosis
• If the hypovolemia is persistent to the point of hypoperfusion
causing ischemia to the tubules, then they would result in ATN • Thromboembolism • Renal Vein Compression
• ATN is a histopathologic diagnosis in which it could be detected Nephrotoxin-Associated AKI
through the characteristics of the urine • Kidney has very high susceptibility to nephrotoxicity
Postoperative AKI → Extremely high blood perfusion
• Operations involving significant blood loss and intraoperative → High concentration of circulating substances
hypotension • ALL structures of the kidneys are vulnerable to toxic injury,
• MOST COMMONLY ASSOCIATED PROCEDURES including the tubules, interstitium, vasculature, and collecting
→ Cardiac Surgery with cardiopulmonary bypass system
→ Vascular procedures with aortic clamping • Risk factors: old age, CKD, prerenal azotemia,
hypoalbuminemia (inc free circulating drug conc -> inc toxicity
→ Intraperitoneal procedures
effect on the kidney)
• Severe AKI requiring dialysis ~1% of cardiac and vascular
procedures Contrast Agents
• Pathophysiology: MULTIFACTORIAL • Iodinated contrast agents used for CV and CT imaging
• Risk factors: → Leading cause of AKI
→ Older age → Risk is negligible with normal renal function
→ CKD → Risk increases markedly and even need for dialysis among
→ DM CKD
→ CHF • Doc: “majority of the referrals from cardiology or radiology is for
These are conditions that can be screened prior to surgery, so if clearances of patients to undergo radiocontrast procedure
these conditions exists, patients must be optimized first or must because upon evaluation of patients they have elevated
be provided with prophylactic medications (Cabarles, 2022) creatinine; hydration status of the patient should be evaluated
→ Emergency procedures because if contrast concentrate in the kidneys, they can
▪ Cardiac surgery precipitate and block the tubules which may cause toxicity
→ Nephrotoxic agents especially for patients with CKD” (2022 Trans)
▪ Iodinated contrast • Nomenclatures used:
→ Non pulsatile flow of extracorporeal circuits → Contrast-induced AKI (CN AKI)
→ Longer duration of cardiac bypass → Post contrast AKI (PC AKI)- now the commonly used term
Burn and Pancreatitis • Most common clinical course of contrast nephropathy:
→ Rise in SCr beginning 24-48 hrs following exposure
• Extensive losses into the extravascular compartments
→ Peak within 3-5 days
• AKI complicates of burns affecting 25% with ≥10% BSA
→ Resolving within 1 week
involvement
• Lead to dysregulated inflammation, increased risk of sepsis,
acute lung injury

Figure 3.11. Pathogenesis of Burns and Pancreatitis to the Development of AKI

Figure 3.13. Clinical Course of Contrast Nephropathy

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 Ifosfamide • Hemorrhagic cystitis
• Most vulnerable for severe AKI (HD requiring): • Tubular toxicity
→ Pre-existing CKD • Type II RTA (Fanconi’s syndrome)
→ CHF • Polyuria
→ Ischemic-associated AKI • Hypokalemia
→ Multiple Myeloma • Modest decline in GFR
→ Renal disease Bevacizumab Thrombotic microangiopathy (injury to
• Results in combination of factors: the glomerular microvasculature) →
→ Hypoxia in the outer renal medulla due to perturbations in proteinuria and hypertension
renal microcirculation and occlusion of small vessels Mitomycin C Thrombotic microangiopathy with
→ Cytotoxic damage to the tubules or via generation of Gemcitabine resultant AKI
oxygen free radicals, especially because the concentration of
the agent within the tubule is markedly increased Toxic Ingestions
Table 3.4. Toxic Ingestions and Its Renal Effects
→ Transient tubule obstruction w/ precipitated contrast
material Chemical Effects
• Examples: compound
→ Gadolinium in MRI Melamine Nephrolithiasis and AKI
▪ WARNING: Nephrogenic systemic fibrosis contamination Doc: there was a case report of patient
▪ Difference with iodinated contrast: iodinated contrast can who developed AKI due to melamine
be removed by dialysis whereas gadolinium cannot found in milk used in milk tea
▪ Deposition of gadolinium contrast in the subcutaneous Aristolochic acid Chinese herb nephropathy or Balkan
tissues can lead to nephrogenic systemic fibrosis nephropathy
(manifests about 1 to 10 years) Ethylene glycol Metabolized to oxalic acid,
▪ Weigh the consequences especially in using this in patients glycoaldehyde and glyoxylate → AKI
with renal insufficiency through direct tubular toxicity
→ Sodium phosphate solutions (aka phospha soda) as bowel Diethylene glycol Industrial agent which caused
purgatives: phosphate nephropathy outbreaks of severe AKI around the
▪ Alternative: soap suds enemas or lactulose (but these are world
not as good as phospha soda in clearing the bowel) 2-hydroxyacetic Thought to be responsible for tubular
acid (HEAA) injury
Antibiotics
Table 3.2. Antibiotics and its Renal Effects Endogenous Toxins
Antibiotics Effects • AKI may be caused by a number of endogenous compounds
Vancomycin • Risk: including:
→ High trough level → Myoglobin: can be released by injured muscle cells
→ Used with other nephrotoxic drugs → Hemoglobin: can be released during massive hemolysis
Aminoglycoside • Tubular necrosis leading to pigment nephropathy
• Occurs even at therapeutic range → Uric acid
(nonoliguric AKI) → Myeloma light chains
• Accumulate in the renal cortex Table 3.5. Endogenous Toxins and Its Renal Effects
• AKI typically manifests after 5-7 days of Pigment • Due to massive myoglobin and
therapy even when d/c nephropathy hemoglobin release
• Clue: hypomagnesemia Rhabdomyolysis • Results to: intrarenal vasoconstriction,
Amphotericin B • Causes vasoconstriction and direct direct PT toxicity and mechanical
tubular toxicity obstruction of the distal nephron lumen
• Dose and duration dependent with Tamm-Horsfall protein
• Clue: polyuria, hypomagnesemia, • Uromodulin is the most common
hypocalcemia and NAGMA (non-anion protein in urine
gap metabolic acidosis)
• TRIAD: myalgias, weakness, darkened
Acyclovir • Precipitate in tubules and causes
urine
obstruction
• Risk factors:
Tumor lysis • Post cytotoxic therapy when massive
syndrome release of uric acid (serum levels
→ High dose (500mg/m2)
>15mg/dL) leads to its precipitation in
→ Hypovolemia
the tubules
Foscarnet • Causes tubular toxicity
Pentamidine • Can also occasionally occur
Tenofovir spontaneously or with treatment for
Cidofovir multiple myeloma and solid tumor
Penicillin • Causes acute interstitial nephritis • CLUE: hyperkalemia,
Cephalosporins hyperphosphatemia
Fluroquinolones Light chain • Myeloma → light chain deposition
Sulfonamides deposition disease (LCDD)
disease (LCDD)
Rifampin • LC bind to Tomm-Horsfall protein to
form obstructing intratubular cast
• CLUE: hypercalcemia (may cause AKI
Chemotherapeutic Agents by intense renal vasoconstriction and
Table 3.3. Chemotherapeutic Agents and Its Renal Effects volume depletion)
Chemotherapeutic Effects • Note: Tamm-Horsfall protein cannot be
Agents detected via urinalysis
Cisplatin Accumulated by proximal tubule cells
Carboplatin → PT cell necrosis and apoptosis

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Allergic Acute Tubulointerstitial Disease
• Drugs that associated with allergic response characterized by
inflammatory infiltrate and peripheral and urinary
eosinophilia
• May be caused by severe infections and infiltrative diseases
• Diseases of the glomeruli or vasculature can lead to AKI by
compromising blood flow within the renal circulation
Glomerulonephritis and Vasculitis
• Less common causes
• Involves either the glomerular podocytes, mesangial and
endothelial cells
• Important to know the disease early before requiring timely
treatment
• Immunosuppressive agent or plasma exchange
C. POSTRENAL AKI
• Pathophysiology (Doc Cabarles PPT, 2022):
→ Hemodynamic alteration triggered by abrupt increase in
intratubular pressures
→ Initial hyperemia from affarteriolar dilatation
→ Followed by intrarenal vasoconstriction from ATII, TXA2,
ADH, and NO reduction
Figure 3.14. Pathophysiology of Postrenal AKI
• Occurs when unidirectional urine flow is acutely blocked,
either partially or totally
• Leads to increased retrograde hydrostatic pressure and
interference with the GFR
• Normal urinary flow rate does not rule out the presence of
partial obstruction because the GFR is normally two orders of
magnitude higher than the urinary flow rate
• For AKI to occur in healthy individuals:
→ Obstruction must affect both kidneys unless only one kidney
is functional, in which case unilateral obstruction can cause
AKI
→ Unilateral obstruction may cause AKI in the setting of
significant underlying CKD or, in rare cases, from reflex
vasospasm of the contralateral kidney
• Obstruction to urinary flow may be caused by functional or
structural derangements anywhere from the renal pelvis to the
tip of the urethra
• Ureteric obstruction can occur from:
→ Intraluminal obstruction (e.g., calculi, blood clots, sloughed
renal papillae)
→ Infiltration of the ureteric wall (e.g., neoplasia)
→ External compression (e.g., retroperitoneal fibrosis,
neoplasia, abscess, or inadvertent surgical damage)
MED 2 Nephrology | Acute Kidney Injury
• Bladder neck obstruction
→ Common cause due to prostate disease, neurogenic bladder
or anticholinergic drugs
• Other lower tract causes: obstructed indwelling Foley catheter
blood clots, calculi and urethral strictures
• Pathophysiology: hemodynamic alteration triggered by abrupt
increase in intratubular pressure
• An initial period of hyperemia from afferent arteriolar dilation is
followed by intrarenal vasoconstriction from generation of
angiotensin II, thromboxane A2, and vasopressin, and reduction
in NO production
• Reduced GFR is due to under perfusion of glomeruli and,
possibly, changes in the glomerular ultrafiltration coefficient
Figure 3.15. Obstruction to urinary flow
IV. DIAGNOSIS
• First, determine if the kidney problem is acute or chronic.
• When ARF diagnosis is established, determine etiology
→ Rule of thumb: AKI can be treated by treating the underlying
cause (if px needs hydration, hydrate them, relieve
obstruction, etc.)
• AKI Definition (from 2021 trans)
→ Elevation of serum creatinine by at least 0.3mg/dL withing 48
hours
→ The elevation must be 50% higher than the patients baseline
taken within one week prior to the elevation
• Suggestive of AKI: increasing trend of serum creatinine during
serial testing.
→ If serum creatinine decreases after immediate intervention,
then you can fully confirm AKI.
• Some patients with AKI will not exhibit tubular or glomerular
change.
• Suggestive of CKD:
→ Radiologic: shrunken (<10cm) kidneys with cortical thinning
on renal UTZ (<1cm thick), with evidence of renal
osteodystrophy
▪ Docs note: Filipinos naturally have smaller kidneys, so rely
more on the presence of renal osteodystrophy over the
kidney size
→ Endocrine: secondary hyperparathyroidism with increased
phosphate, and decreased calcium
▪ [2022 Trans: normocytic anemia is omitted even though
ppt, and 2021 trans mentions it since doc said that it occurs
in both CKD and AKI naman so hindi siya useful]
A. HISTORY AND PHYSICAL EXAMINATION
• Urine Volume and Fluid Intake
• Symptomatology
• Family history red flags, such as:
→ Hypertension → Stones
→ DM → Relatives who did dialysis/kidney
transplant
8 of 16
• Medication History Table 4.1. Urine sediment with associated manifestation
→ Dose → Duration Cast/Sediment Manifestation
→ Use → Including over the counter and herbal medication seen
• Cases where AKI may occur Normal Urine or • Pre or Postrenal azotemia
→ Pregnancy – preeclampsia may contribute to AKI Hyaline Casts • Thrombus/Embolus in artery
→ Acute abdominal compartment syndrome- if tense abdomen • Preglomerular vasculitis
is present. • HUS/TTP
▪ Requires bladder pressure measurement • Scleroderma
→ Rhabdomyolysis – in presence of limb ischemia Increased RBC or • Postrenal
Prerenal Azotemia Hx/PE
RBC casts • Glomerulonephritis
• Rule of thumb: anything that decreases blood flow or volume = • Vasculitis
decreases GFR = prerenal • Malignant Hypertension
• Past medical History: Associated with CHF, Liver disease, • Thrombotic microangiopathy
nephrotic syndrome, atheroembolic disease (if seen with Increased • Interstitial nephritis
matching livedo reticularis and DVT), and extensive vascular WBC/WBC casts • Pyelonephritis
disease (if asymmetric kidneys) • Allograph rejection
• Medication History: diuretic use, NSAIDS, ACEi’s/ARBs • Malignant infiltration of kidney
• Other pertinent causes: Vomiting, diarrhea, glycosuria leading Renal Tubular • Acute Tubular Necrosis
to polyuria, sepsis Epithelium Cells • Tubulointerstitial Nephritis
• Pertinent PE findings: (RTE), RTE casts • Acute cellular graft rejection
→ Hypotension → Reduced Skin turgor or Pigmented • Myoglobinuria
→ Tachycardia → Dry Mucous Membranes Casts • Hemoglobinuria
→ Reduced Granular casts • Acute Tubular Necrosis (muddy brown
JVP granular casts due to pigment)
Postrenal Azotemia Hx/Pe • Glomerulonephritis
• Rule of thumb: anything that obstructs the flow of urine past the • Vasculitis
kidneys • Tubulo-interstitial nephritis
• Past medical History: Prostate disease (BPH!), Nephrolithiasis, Eosinophiluria • Allergic Interstitial Nephritis
Pelvic/Aortic mass pushing on the urinary tract • Atheroembolic disease
• Associated Symptoms: • Pyelonephritis
→ Colicky pain in flank radiating to the groin- indicative of • Glomerulonephritis
obstruction Crystalluria • Acute uric acid nephropathy (urate
→ Nocturia, Hesitancy, Abdominal Fullness, Suprapubic Pain = crystals)
Prostate disease or bladder enalrgement • Tumor lysis Syndrome (Urate &
• Other pertinent causes: Vomiting, diarrhea, glycosuria leading oxalate)
to polyuria, sepsis • Ethylene Glycol (antifreeze)
B. LABORATORY AND IMAGING intoxication (Calcium Oxalate Crystals)
• Drugs: acyclovir, indinavir,
Important Urine Findings sulfadiazine, amoxicillin
• Volume per 24 hours Blood Chemistry
→ Anuria is <100mL per 24 hours • Serum Creatinine
▪ Complete anuria is common in
→ Prerenal azotemia – Modest increase, that return to baseline
− Urinary tract obstruction with improvement in the hemodynamic status
− Overwhelming septic shock → Due to Imaging Contrast – rises within 24-48 hours, peak
− Severe ischemia within 3-5 days, and returns to normal within 5-7 days
− Severe proliferative glomerulonephritis → Atheroembolic Disease – subacute increase only
→ Oliguria is <400 mL per 24 hours → Epithelial Cell toxins such as aminoglycosides and
▪ Indicative of more severe AKI cisplatin – The increase is delayed by 3-14 days after
→ Polyuria is >3000mL per 24 hours exposure
▪ Occurs in diabetes insipidus and post-obstructive states. • Anion Gap
▪ So, refill the patients fluid after removal of obstruction so → Increased in ethylene glycol (antifreeze) poisoning
the px doesn’t run out of water
→ Decreased in Multiple Myeloma
• Urinalysis red flags
• Important indicators in Rhabdomyolysis
→ Urine Sediments (Table Below, detailed image in appendix)
→ Increased serum Creatine Kinase, Uric Acid, PO4,
→ Proteinuria (Nephrotic if more than 3.5g/ 24 hours)
→ Decreased Ca
▪ <1g/d increase in ischemia or nephrotoxins
• FeNa (fractional Sodium excretion)
▪ Larger damage indicates glomerular ultrafiltration barrier
damage/excretion of myeloma light chains, confirm with → Prerenal azotemia <1% (also seen in glomerulonephritis,
sulfosalicylic acid test or immunoelectrophoresis sepsis, rhabdomyolysis, and contrast nephropathy)
▪ Possible Atheroemboli → CKD >1%
→ Hematuria • Tumor Lysis Syndrome
→ Hgb (+) but no RBCs in urine → Increased PO4, uric acid
▪ Rhabdomyolysis or hemolysis → Unchanged, or slightly higher creatine kinase
→ Red or brown urine: → Hypocalcemia
▪ May be seen even without gross hematuria. • Glomerulonephritis, Vasculitis
▪ Consider rhabdomyolysis if the color persists even after → Decreased Complement
centrifugation. This is indicative of pigment nephropathy. → Increased ANAs, ANCAs, Anti-GBM and cryoglobulins

MED 2 Nephrology | Acute Kidney Injury 9 of 16

 Hematologic Findings (CBC) → CKD: kidneys are usually smaller unless the patient has
→ Anemia, usually normocytic -common in AKI a diabetic nephropathy, HIV-associated nephropathy, or
→ Eosinophilia – indicative of interstitial nephritis, infiltrative disease
atheroembolic disease, polyarthritis nodosa, and Church- → AKI: normal sized kidneys
Strauss vasculitis → Acute interstitial nephritis or arterial obstruction: enlarged
→ Severe anemia, but no bleeding – possibly hemolysis, kidneys
multiple myeloma, thrombotic microangiopathy (HUS/TTP) • MRI with gadolinium-based contrast should be avoided in severe
Table 4.2. manifestations of Prerenal vs renal AKI AKI due to possibility of inducing nephrogenic system fibrosis
Prerenal Renal Indications for Biopsy
Drugs or toxin • When patient is already stable, and yet high serum crea
GI, urinary, skin
exposure, • Infection ruled out as etiology, culture negative and not showing
History volume loss, blood
hemodynamic clinical manifestations
loss or third spacing
change • Clues from labs:
Clinical Hypotension or No specific → Decreased C3
presentation volume depletion symptoms or signs → Increased ASO titer
Labs → Hepa profile indicative if Hepa infection
BUN/Crea • If the cause of AKI is not apparent based on the clinical context,
>20 <20 physical examination, lab studies, and radiologic evaluation
Ratio
(2021 trans)
Normal to few casts,
“muddy brown” • Can provide definitive diagnostic and prognostic information.
Sediment and usually hyaline
casts (2021 trans)
casts • Never 100% safe, bleeding is a risk.
Urine mOsm → Worst case scenario, nephrectomy may become necessary.
>500 <350
(mmol/kg) → Before biopsy, make sure the patient is not suffering from
Proteinuria None to trace Mild to moderate coagulopathy (do PT/PTT/CBC with platelet count/CT/BT)
→ (I mean, at least complete yung specimen)
Urine Sodium
<20 >40 • Usually used to definitively diagnose glomerulonephritis,
(mmol/l)
vasculitis immune complex, or anti GMB disease
FENa (%) <1 >1
C. COMPLICATIONS
FEUrea (%) <35 >35 • Uremia
Urine Crea/ → Elevated BUN
>40 <20
Serum Crea → Hallmark of AKI
KIM-1, cystatin C, → Generally benign if under <100mg/dL
Novel → In higher concentrations, mental status changes and bleeding
none NGAL, CYR61,
biomarkers complications arise
others
→ Always useful to compare BUN and serum Creatinine
Novel Biomarkers for Renal AKI • Hyper/Hypovolemia
• Kidney Injury Molecule-1 (KIM-1) → Hypervolemia -Impaired excretion leads to fluid buildup,
→ Exclusively expressed in proximal tubule cells injured by leading to weight gain, dependent edema, increased jugular
ischemic attack or nephrotoxicity (such as nephrotoxic drug venous pressure, and pulmonary edema
cisplatin) → Hypovolemia – occurs during recovery, or removal of
• Neutrophil Gelatinase Associated Lipocalin (NGAL) obstruction. Volume is depleted through polyuria.
→ Iron siderophore binding neutrophil granule component ▪ Polyuric phase of recovery may be due to an osmotic
→ Protective of proximal tubule cells diuresis from retained urea and other waste products as
→ Increased in: well as delayed recovery of tubular reabsorptive functions
▪ Inflammation • Hyponatremia
▪ Kidney injury → Inability to retain sodium
▪ 2 hours after cardiopulmonary bypass-associated AKI → Dysfunctional kidney has limited ability to regulate electrolyte
→ Only NGAL is locally available balance
→ Manifests faster than creatinine, allowing for faster dx → Could be iatrogenic through excess giving of hypotonic
• Interleukin 18 (IL-18) – inflammatory marker in proximal tubule crystalloid / isotonic dextrose
insult ▪ Leads to both being hypo-osmolar and hyponatremic
[Transer’s note: IL-18 po daw talaga, not IL8, confirmed by ▪ This leads to seizures
recording] • Hyperkalemia
• L-type fatty acid binding protein – present in ischemic proximal → Common in rhabdomyolysis, hemolysis, tumor lysis syndrome
tubule cells → Evident though muscle weakness
Imaging-Based Diagnosis [2021 Trans] → Serious complication: fatal arrhythmia
• Renal ultrasound or CT should be undertaken to investigate • Acidosis
obstruction in individuals with AKI → Metabolic acidosis alongside increased anion gap in AKI
→ Dilation of the collecting system and hydroureteronephrosis ▪ Could further aggravate existing acidosis like in diabetic
ketoacidosis, sepsis, or respiratory acidosis
• antegrade/retrograde pyelography – indicated in obstruction
without radiologic abnormalities in the setting of volume • Hyperphosphatemia alongside Hypocalcemia
depletion, retroperitoneal fibrosis, encasement with tumor, early → Hyperphosphatemia occurs in rhabdomyolysis, hemolysis, or
course of obstruction tumor lysis syndrome, as well as in patients with high
→ High index of suspicion 🡪 antegrade/retrograde catabolism
pyelography → Hypocalcemia occurs through metastatic deposition of
• Kidney size and echogenicity calcium phosphate, or derangements in the Vitamin D-
fibroblast growth factor 23 axis
▪ May present with perioral paresthesia, muscle cramps,
seizures, carpopedal spasms, QT interval prolongation
MED 2 Nephrology | Acute Kidney Injury 10 of 16
 → Calcium levels should be corrected for the degree of • Hyperphosphatemia
hypoalbuminemia, if present, or ionized calcium levels should → Restrict dietary phosphate intake
be followed → Administer phosphate binding agents (calcium acetate,
→ Mild, asymptomatic hypocalcemia does not require treatment sevelamer hydrochloride, aluminum hydroxide)
• Bleeding • Hypocalcemia
→ Exacerbated by coexisting disease processes such as sepsis, → Calcium carbonate/Calcium gluconate, when symptomatic
liver diseases, or DIC • Hypermagnesemia
→ AKI is associated with decreased EPO and platelet → Discontinue antacids with magnesium (Such as MgOH-AlOH)
dysfunction • Hyperuricemia
• Infections → No need for treatment unless in case of tumor lysis syndrome
→ Common precipitant of AKI and also a dreaded complication • Nutrition
of AKI → Protein energy wasting is common in AKI, particularly in the
→ Impaired immunity is commonly associated in end-stage renal setting of multisystem organ failure
disease, but can occur in severe AKI. → Inadequate nutrition may lead to starvation ketoacidosis and
• Cardiac Complications protein catabolism
→ Arrythmia → Excessive nutrition may increase the generation of
→ Pericarditis nitrogenous waste and lead to worsening azotemia
→ Pericardial effusion → Ensure sufficient protein and nitrogen intake
→ Further complicated by volume overload and uremia, leading ▪ 0.8-1g/kg per day
to impaired function and further injury ▪ BUT 1.0-1.7g/kg per day if dialysis patient
→ In animal studies, cellular apoptosis and capillary vascular → Patients with AKI should achieve a total energy intake of 20-
congestion as well as mitochondrial dysfunction have been 30 kcal/kg per day
described in the heart after renal ischemia reperfusion → Supplement with trace elements and water-soluble vitamins
• Malnutrition → Should be provided via the enteral route if possible
→ Due to the AKI’s severely hypercatabolic stage ▪ Total parenteral nutrition requires large volumes of fluid
administration and may complicate efforts at volume control
V. MANAGEMENT AND PREVENTION
• Drug Dosing
General Issues → Pay careful attention to dosages and frequency of
• Fluid resuscitation and vasopressors – for optimal administration of drugs and adjust accordingly to the level of
hemodynamic stability renal failure
• Eliminate nephrotoxic agents when possible: ACEi/ARBs, → Note that serum creatinine concentration may overestimate
NSAIDS, Aminoglycosides renal function in the non-steady state characteristic of patents
• Renal replacement therapy – when needed. with AKI
Specific Issues • Hypovolemia
• Nephrotoxins → In severe cases, furosemide given as bolus and subsequent
→ Rhabdomyolysis – aggressive IV fluids; consider forced iv drop
alkaline diuresis → In decompensated heart failure, give low dose dopamine
→ Tumor lysis syndrome- aggressive IV fluids; • Anemia
allopurinol/rasubicase → Not usually improved by Erythropoiesis stimulating agents
• Volume overload → Uremic Bleeding – responsive to desmopressin or estrogens
→ Restrict Salt and water intake ▪ But if severe, dialysis
→ Diuretics → PPI/H2 receptor blockers for GI prophylaxis
→ Ultrafiltration → Venous thromboembolism prophylaxis is important and
• Hyponatremia should be tailored to the clinical setting
→ Restriction of IV free water intake, as well as other hypotonic → Avoid LMW heparins and factor Xa inhibitors, as they
IV solutions, including those containing dextrose exacerbate bleeding.
→ Hypertonic saline is rarely necessary in AKI. Vasopressin Prerenal Azotemia Management
antagonists are generally not needed • Optimize Renal Perfusion
• Hyperkalemia • Blood loss
→ Restrict dietary potassium → pRBC in severe cases
→ Discontinue potassium-sparing diuretics, ACEi, ARBs, → in other cases, isotonic crystalloid/colloid
NSAIDs • Volume resuscitation
→ Use loop diuretics instead for clearance of potassium → Severe: Isotonic crystalloid/colloid (0.9% saline)
→ Use potassium binding ion-exchange resin (sodium → Less severe: Hypotonic crystalloid, also used for
polystyrene sulfonate) hypernatremia
→ Promotion of intracellular potassium intake • Acidosis
▪ Insulin (10 units) + Glucose (50mL of 50% dextrose) → Bicarbonate containing solutions.
▪ Inhaled beta-agonists • Do not give hydroxyethyl starch solutions, they increase the risk
→ Calcium gluconate/calcium chloride 1g for stabilization of of severe AKI
myocardium • Optimization of cardiac function in AKI may require use of
• Metabolic Acidosis inotropic agents, preload- and afterload-reducing agents,
→ Sodium Bicarbonate (Keep bicarbonate levels >15mmol/L if antiarrhythmic drugs, and mechanical aids such as ventricular
pH is <7.2) assist devices. Invasive hemodynamic monitoring to guide
→ No need to treat if above 7.2pH therapy may be necessary.
→ Tromethamine [Transers note: discontinued na po siya] Postrenal AKI
→ Renal replacement therapy
• Relief of obstruction
→ Overcorrection should be avoided because of the possibility of
• Fluid replacement
metabolic alkalosis, hypocalcemia, hypokalemia, and volume
• For strictures – transurethral/suprapubic catheterization
overload
• Ureteric Obstruction- percutaneous nephrostomy tube
replacement or ureteral stent
MED 2 Nephrology | Acute Kidney Injury 11 of 16
 Intrinsic AKI → Likely to suffer from cardiac issues
• Usually supportive treatment, alongside observation → “Walking bomb”
• Glomerulonephritis/Vasculitis – treat with immunosuppressive → Can progress to CKD, or another AKI case
agents and/or plasmapheresis
• Allergic interstitial nephritis – discontinue the agent that
caused the hypersensitivity
• AKI due to scleroderma – give ACEi
• Idiopathic TTC-HUS – Plasma exchange
• Rhabdomyolysis – aggressive and early volume replacement,
dialysis, supportive care
Cirrhosis and Hepatorenal Syndrome
• Fluid management is challenging because of the frequent
difficulty in ascertaining intravascular volume status
• Administration of IV fluids as a volume challenge may be required
diagnostically as well as therapeutically
→ Excessive volume administration may, however, result in
worsening ascites and pulmonary compromise in the setting
of hepatorenal syndrome or AKI due to superimposed
spontaneous bacterial peritonitis
• Definitive treatment of hepatorenal syndrome: orthotopic liver
transplantation
• Bridge therapies that have shown promise include terlipressin,
combination therapy with octreotide and midodrine, and
norepinephrine, in combination with IV albumin
A. DIALYSIS
Indications for Dialysis
• Intractable acidosis
→ When pH remains below 7.2 despite repeated bicarbonate
administration
• Intractable electrolyte imbalance
• Intoxication
→ Large drug intake (like lithium)
• Intractable fluid overload
• Uremia symptoms (>100mg/dL)
→ Vomiting → Seizures
→ Altered sensorium → Bleeding
→ Altered sleep/wake cycle → Asterixis
→ (2021 trans) if BUN >100mg/dL, even with the absence of
clinical symptoms
Options for Dialysis
• Peritoneal dialysis – requires access to the peritoneal cavity
• Hemodialysis – require vascular access (femoral, internal
jugular, or subclavian)
→ Conventional
→ Slow low-efficiency hemodialysis – blood flow, and faster
treatment time, <12h
→ Forms of clearance
▪ Convective, removal of solutes through movement of
plasma
▪ Diffusive- removal via concentration gradient
▪ Combination of the two
• Continuous Renal Replacement Therapy – good for patients
who are hemodynamically unstable, as they don’t induce rapid
shifts of volume. Osmolality or electrolytes
→ Forms of clearance
▪ Convective (continuous venovenous hemofiltration or
CVCH) similar to the dialysis one, but solutes are removed
through hydrostatic pressure and replaced by crystalloid
▪ Diffuse (continuous venovenous hemodialysis or
CVVHD) -Similar to hemodialysis but slower
B. PROGNOSIS
• High risk of long inpatient hospital stays and increased costs
→ Due to waiting for recovery and drug dose adjustment
• Pre/Postrenal azotemia patients fare better than most cases of
AKI, except for patients with Cardiorenal and Hepatorenal
Syndrome
• Post-discharge care to prevent secondary issues
• AKI patients are more likely to die prematurely despite full
recovery
MED 2 Nephrology | Acute Kidney Injury 12 of 16
 VI. REFERENCES
Jameson, J. L., Kasper, D. L., Longo, D. L., Fauci, A. S., Hauser, S. L., & Loscalzo, J. (2018). Harrison’s principles of internal medicine. (20th ed.). New York: McGraw Hill
Education Medical
Dr. Alsun S. Cabarles’ lecture
2022 Trans
-END OF TRANSCRIPTION-
VII. APPENDIX
Table A. Specific Risk Factors for the Development of AKI in Common Clinical Situations
SPECIFIC RISK FACTORS FOR THE DEVELOPMENT OF AKI IN COMMON CLINICAL SITUATIONS [Doc’s PPT]
Post-Operative Cardiac Surgery Critically Ill Sepsis Contrast Nephrotoxic Agents
Nephropathy
Hemodynamic • Pre-operative • Active cancer • Serum bilirubin >1.5 • SBP <80 mmHg for Amphotericin
• Multiorgan failure SCr >2.1 mg/dL • Low serum albumin mg/dL >1 hr & need for • Volume depletion
• Aortic cross- • Pre-op IABP • High A-a gradient • Age inotropic support • Concurrent other
clamping • Heart Failure • High intra- • SCr >1.3 mg/dL • IABP 24 hrs after nephropathy
• CHF • LVEF <35% abdominal pressure • Elevated CVP (>8 procedure
• Sepsis • Combination CABG cm) • Use of IABP
• Infection + valve surgery • Hemodynamic • Heart Failure
• Hypertension • Emergency surgery instability (NYHA 3 or 4)
• Cardiac instability • Valve surgery only • Hx of pulmonary
• Major vascular • Previous cardiac edema
surgery surgery • SCr >1.5 mg/dL or
GI & Endocrine • Other cardiac eGFR <60 mL/min Aminoglycosides
• Liver cirrhosis surgery per m2 • Pre-existing renal
• Biliary surgery • Insulin-dependent • Volume of contrast dysfunction
• Obstructive DM >100 mL • Duration of therapy
jaundice • COPD • Age >75 yrs >7 days
• DM • ACEi therapy • DM • Sepsis
Renal • Female gender • Anemia, blood loss • Volume depletion
Transplantation (Hct <39% for men; • Divided-dose
• SCr >2 mg/dL <36% for women) regimens
• Oliguria (<400 • Intra-arterial • Liver disease
mL/day) injection • Old age
Miscellaneous
• Massive blood
transfusion
• Trauma
• Age >70 y/o
IABP: Intra-Arterial Balloon Pump
Table B. Nephrotoxic Agents Leading to AKI
NEPHROTOXIC AGENTS LEADING TO AKI
Pre-Renal Azotemia Glomerular Disease Acute Interstitial Nephritis
• Antihypertensive agents Rapidly Progressive Glomerulonephritis • Antibiotics (penicillins, cephalosporins,
• Diuretics • D-Penicillamine rifampicin, sulfamethoxazole, ciprofloxacin)
• Hydralazine • NSAIDs
• Propylthiouracil • Loop & thiazide diuretics
• Organic solvents • Allopurinol
• Cimetidine
• Mesalazine
• Omeprazole
• Phenytoin

Small Vessel Disease Acute Tubular Necrosis Nephrotoxic Agents

Renal Vasoconstriction • Amphotericin • Acyclovir
• NSAIDs • Aminoglycosides • Indinavir
• ACEi or ARB • Foscarnet • Ethylene glycol
• Radiocontrast agents • Tenofovir, cidofovir, adefovir • Methotrexate
• Cyclosporine • Cisplatin • Triamterene
• Tacrolimus • Ifosfamide • Sulfonamides
• Norepinephrine • Acetaminophen
• Cocaine • Heavy metals Postrenal Obstruction
• Herbal remedies Papillary Necrosis
Thrombotic Microangiopathy • Radiocontrast agents • NSAIDs
• Cyclosporine • Pentamidine • Compound analgesics
• Tacrolimus • Organic solvents
• Mitomycin C • Herbicides Urinary Retention
• Clopidogrel • IV Ig • Anticholinergics
• Quinine • TCAs
• OCP

MED 2 Nephrology | Acute Kidney Injury 13 of 16

 Figure A. Evaluation of Azotemia

Figure B. Interpretation of Urinary Sediment Findings in AKI

MED 2 Nephrology | Acute Kidney Injury 14 of 16

 Figure C. Major Causes of Intrinsic AKI

Figure D. Causes of AKI

MED 2 Nephrology | Acute Kidney Injury 15 of 16

 Figure E. Approach to Diagnosis

Figure F. Pathophysiology of Ischemic Acute Renal Failure

MED 2 Nephrology | Acute Kidney Injury 16 of 16