INTERNAL MEDICINE ACUTE KIDNEY INJURY

AY 2021-2022
NICKSON AUSTRIA, M.D.
Renal Module 03/16/2022

2. AKD
TOPIC OUTLINE a. Transition point of varying Crea and UO for <3
I. Definition mos.
3. CKD
II. KDIGO Criteria and Staging for AKI Diagnosis
a. Kidney damage for > 3mos as defined by
III. Epidemiology structural or functional abnormalities
IV. Etiology and Pathophysiology b. with or without decreased GFR irrespective of
a. Prerenal Azotemia cause
b. Intrinsic Renal Parenchymal Disease c. Kidney damaged is ascertained by GFR and
c. Postrenal Obstruction albuminuria
V. History and Physical Examination d. CKD is staged 1-5 by GFR (based on crea or
crystatin and A1 to A3 by albuminuria.
a. Urine Findings
b. Serum Labs KIDNEY BASICS
c. Imaging ● Filters around 1700L of blood per day to produce around
d. Biopsy 1L of concentrated urine
e. Biomarkers ● Maintains homeostasis
VI. Complications ● Chief regulator of fluid balance, pH, electrolytes,
VII. Treatment endocrinologic, hematologic, immunomodulatory
functions.
a. Renal Replacement Therapy
● Structurally complex
● Basic unit: NEPHRON
LEARNING OBJECTIVES ● Best to appreciate it in 4 morphologic components
1. Discuss acute kidney disorders in terms of: ○ glomerulus
a. Epidemiology ○ Tubules
○ interstitium
b. Etiology (causes)
○ vasculature
c. Clinical Presentation
d. Diagnosis MECHANISMS OF KIDNEY INJURY
● Pre renal : hypotension, excessive fluid loss, shock,
LEGEND: volume depletion, CHF, liver cirrhosis
Clinical Guide ● Renal: Glomerular, tubular/ iterstitial, vascular
PPT Lecturer Book ● Post renal: obstruction distal to the kidneys,
Correlation/SGDs Questions
nephrolithiasis, cancers, prostatic enlargement etc.
● ❖
II. KDIGO CRITERIA AND STAGING FOR AKI
I. DEFINITION DIAGNOSIS
● Impairment of kidney filtration and excretory fxn over
days to weeks causing retention of nitrogenous and other
waste products
● Increase in SCr conc. Often associated w/ redxn in urine
vol
● Clinical dx, NOT a structural one

SPECTRUM OF KIDNEY DISEASE

1. AKI
a. Sudden loss of kidney function generally
occurring with in hours to days resulting in the
retention of metabolic waste products,
dysregulation of fluids, electrolytes and
acid-base homeostasis.
Stage 1 Rise in Crea 1.5 - 1.9 fold (7 days or 0.3
mg/dl in 48hrs; OU <0.5ml/kg/hr for 6 hrs
Stage 2 2.0-2.9 fold OU <0.5ml/kg/hr for >12 hrs.
Stage 3 >3x or Crea >4.0mg/dl with an acute
increase of >0.5 mg/dL; UO <0.3 mg/kg/hr
for > 24 hrs or anuria >12hrs
Fig 1. Staging of AKI
*also found in Appendix figure 5
III. EPIDEMIOLOGY
● AKI increases risk for worsening CKD
● Px who survived and recovered from episode of severe
AKI requiring dialysis has increased risk for later
development of dialysis-requiring ESRD
● Common causes of community-acquired AKI: vol
depletion, HF, ADR, UT obstruction, malignancy
 INTERNAL MEDICINE ACUTE KIDNEY INJURY

● Common causes of hospital acquired: sepsis, major ● RBF = 20% of CO

surgical procedure, critical illness following HF or liver
failure, nephrotoxic medication administration
IV. ETIOLOGY AND PATHOPHYSIOLOGY
● 3 categories: prerenal azotemia, intrinsic renal
parenchymal ds., post-renal obstruction
● Mediators of renal vasoconstriction + salt and water
reabsorption in response to decreased circulating vol/
CP: angiotensin II, myogenic reflex, tubuloglomerular
feedback
● Factors inhibiting autoregulatory response: hyalinosis
and myointimal hyperplasia from long-standing HTN/old
age/ atherosclerosis, CKD, NSAIDs, ACE-I, ARBs, advanced
liver ds (hepatorenal syndrome)

b. Intrinsic Renal Parenchymal Disease

INTRINSIC AKI
- Can be classified as damage to any of the 4 regions:
glomerular, tubular, interstitial and vascular.

● MC causes: sepsis, ischemia, nephrotoxins

● Contributors: inflammation, apoptosis, altered regional
perfusion

1. Sepsis-Associated AKI
a. Can complicate as much as 50% of severe sepsis
b. Usually occurs with hypotension
c. Damage mediated by inflammatory cytokines
Fig 2. AKI etiology leading to loss of autoregulation
d. Initially: afferent vasodilation and release of NO
a. Prerenal Azotemia etc.
PRE- RENAL AKI e. Later: severe vasoconstriction and
- Decreased effective circulatory volume (shock, hypoperfusion and reduction in GFR.
hypovolemia) -> norepinephrine, angiotensin, f. Most cases in setting of hemodynamic collapse
vasopressin release -> Salt and water reabsorption -> requiring vasopressor support
blood shunts to critical organs g. Hemodynamic efx of sepsis (generalized
- Afferent artery vasoconstriction -> down regulation in vasodilation) decreases GFR
vasodilatory agents (PG, NO, kallikreins and kinins) h. Efferent arteriole vasodilation, renal
- Reverse: TG feedback via the macula densa can work to vasoconstriction from SNS activation/ RAAS/
preserve GFT i states of hypotension but limited to the vasopressin/ endothelin, endothelial damage
nature of the systemic condition resulting to thrombosis, permeability, and
- Key concept: autoregulation activation of ROS which injure renal tubular
- Kidneys are very altruistic organs. cells

- insults occur before the kidneys and hence is more
related to systemic issues.
- Absence of damage to the kidney structure/ parenchyma
itself
- Results in the retention of nitrogenous wastes (azotemia)
- Seen as reductions in the renal plasma flow and
decreased intraglomerular hydrostatic pressure.
- Should reverse with resumption of renal blood flow.
- May progress to intrinsic renal injury if not managed
properly.
Common causes: hypovolemia, decreases ECV (CHF/ Cirrhosis)
Dysregulation: NSAIDS RAS blockers.
● MC AKI
● Inadequate renal plasma flow and intraglomerular
hydrostatic P to support normal glomerular filtration
● Hypovolemia, dec. CO, NSAIDs, Angiotensin II inhibitors
● Prolonged prerenal azotemia may lead to ischemic injury
(acute tubular necrosis)
● No parenchymal damage
● Rapidly reversible upon normalization of parenchymal
blood and intraglomerular hemodynamics
2. Ischemia-Associated AKI
a. Apart from receiving 10% of resting energy
consumption
b. Outer medulla – most susceptible to ischemic
damage
c. Ischemia alone in healthy kidney is NOT
sufficient to cause severe AKI
d. AKI more common if ischemia is with CKD or
coexisting insults (sepsis, nephrotoxic drugs,
rhabdomyolysis, etc)
e. Prerenal azotemia and ischemia associated AKI
= from renal hypoperfusion
f. Post-op AKI: significant blood loss/ intraop
hypotension; RF being CKD, old age, DM, CHF,
ER procedures
g. Burns/ Acute Pancreatitis: extensive fluid losses
in the extracellular compartment
h. Microvascular diseases leading to ischemia:
thrombotic microangiopathies, scleroderma,
atheroembolic ds.

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 INTERNAL MEDICINE ACUTE KIDNEY INJURY

i. Large vessel ds: renal artery dissection, V. HISTORY AND PHYSICAL EXAMINATION
thromboembolism, thrombosis, renal v.
● Prerenal azotemia: vomiting, diarrhea, glycosuria
compression/ thrombosis causing polyuria, diuretics, NSAIDs, ACE-I, ARBs,
orthostatic hypotension, tachycardia, reduced JVP,
decreased skin turgor, dry mucosa, congestive HD, liver
failure
● Interstitial AKI: extensive vascular ds., asymmetric
kidneys, livedo reticularis, emboli to legs, sepsis,
medications, recent blood transfusion, injuries,
chemotherapy, infection, pruritic rash (AIN = fever, rash,
arthralgias)
● Postrenal AKI: nocturia + urinary hesitancy/frequency
(prostatic ds.), nephrolithiasis, pelvic/paraaortic
malignancy, colicky flank pain radiating to groin (ureteric
obs.)

a. Urine Findings

3. Nephrotoxin-Associated AKI
a. Contrast Agents: iodinated contrast (contrast
nephropathy), high-dose gadolinium for MRI,
oral Na phosphates, bowel purgatives
b. Antibiotics: vancomycin, aminoglycosides,
amphotericin B, Acyclovir, Foscarnet,
Pentamidine, Tenofovir, Cidofovir, Penicillin,
Cephalosporin, Quinolones, Sulfonamides,
Rifampin
c. Chemo-drugs: Cisplatin, carboplatin, ifosfamide,
bevacizumab
d. Toxic agents: ethylene glycol, Melamine, Fig 3. Urine findings in AKI
Aristolochic acids
e. Endogenous Toxins: myoglobin, hemoglobin, ● Complete anuria causes: complete UT obs., RA occlusion,
uric acid, myeloma chains overwhelming septic shock, severe ischemia, severe
f. Other causes of acute tubulointerstitial disease proliferative GN/ vasculitis
leading to AKI: allergic response causing acute ● Oliguria: obs., nephrotoxicity, TIN
tubulointerstitial nephritis ● Anuria (<400mL/day): severe sepsis/ shock
● Heme + w/o RBC: rhabdomyolysis/ hemolysis
4. Glomerulonephritis ● Prerenal AKI: hyaline casts
a. Involves glomerular podocytes, mesangial cells, ● ATN: muddy brown cast w/ tubular epithelial cells
endothelial cells ● GN: >20% RBCs dysmorphic, RBC casts; heavy
b. Compromised filtration barrier and blood flow proteinuria (>1g/day or 3.5 g nephrotic)
w/in renal circulation ● AIN: urine eosinophils
c. Less common cause of AKI ● Ethylene glycol toxicity: Ca oxalate crystalluria
d. Can respond to tx w/ immunosuppressants/ ● TLS: uric acid crystalluria
therapeutic plasma exchange
b. Serum Labs
c. Postrenal Obstruction
● Serial SCr monitoring (prerenal azotemia should return
● Normally unidirectional flow of urine is blocked partially promptly to normal upon correction of hemodynamic
or totally stat)
● Increased retrograde hydrostatic P w/ interference to ● CBC: anemia (multifactorial), elevated WBC (sepsis),
glomerular filtration thrombocytopenia w/ schistocytes (TTP), eosinophilia
● Preservation of urine output may be misleading in hiding (AIN)
postrenal partial obstruction ● Hyperkalemia, hyperphosphatemia, hypocalcemia
● MC: bladder neck obstruction ● TLS: hyperkalemia, hyperphosphatemia, hypocalcemia,
● Hemodynamic alterations triggered by abrupt increase in hyperuricemia
intratubular P (initial hyperemia from afferent arteriolar ● ABG: acidosis + high anion gap
vasodilation followed by intrarenal vasoconstriction from ● Myeloma: low anion gap (high anionic protein released
the generation of angiotensin II, thromboxane A2, from myeloma)
vasopressin, and reduction in NO production) ● Ethylene glycol tox: osmolal gap in serum Osm

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 INTERNAL MEDICINE ACUTE KIDNEY INJURY

● ANA, anti-dsDNA, ANCA, complement levels, o Complicate acid-base and potassium imbalance
cryoglobulins in px’s w/ other causes of acidosis (sepsis,
diabetic ketoacidosis, resp acidosis)
c. Imaging ● Hyperphosphatemia + Hypocalcemia
● Ultrasound o Rhabdomyolysis, TLS, hemolysis
o Useful in postrenal AKI o Hypocalcemia: perioral paresthesia, muscle
o Finding: dilation of collecting system, cramps, seizures, carpopedal spasm, prolonged
hydroureteronephrosis QT-i
o Absence of radiologic abnormalities in vol ● Bleeding
depletion, retroperitoneal fibrosis, encasement o Direct hema efx from uremia
w/ tumor, early obs. o Decreased erythropoiesis and pltlt dysfxn
o Differentiate CKD from AKI (CKD = small kidney ● Infections
usually <8cm o Common precipitant of AKI
o Enlarged CKD kidney: DM, HIV nephropathy, o Dreaded complication of AKI
infiltrative ds., AIN o Impaired host immunity esp in ESRD
o Avoid: MRI w/ Gadolinium contrast ● Cardiac Complications
(nephrogenic systemic fibrosis) o Arrhythmias, pericarditis, effusion
● Malnutrition
d. Biopsy o From severely hypercatabolic state in AKI
● If AKI cause is NOT apparent on Hx, PE labs, imaging
● Diagnostic and prognostic evaluation VII. TREATMENT
● If the ff are unlikely: Prerenal azotemia, postrenal AKI, ● Volume Mgt
ischemic AKI, nephrotoxic AKI o Address hypovolemia (be cautious about pulmo
● If ff are considered: GN, vasculitis interstitial nephritis, edema)
myeloma, TTP/ HUS, allograft dysfxn o Restrict fluids and Na
o Use of diuretics
e. Biomarkers o Low dose dopa : NO BENEFIT
● BUN + Crea = biomarkers of glomerular filtration, NOT ● Electrolytes
tissue injury; suboptimal for dx of actual parenchymal o Acidosis: target pH > 7.2 (HCO3 15 mmol/L)
damage; slow to rise after kidney injury o Avoid overcorrection (metabolic alkalosis,
● Kidney Injury Molecule – 1 (KIM-1) = expressed in prox hypocalcemia, hypokalemia, vol overload)
tubular cells injured by ischemia/ nephrotoxins o Hyperphosphatemia: phosphate binders ( Ca
● Neutrophil Gelatinase Associated Lipocalin (NGAL/ carbonate, alum hydroxide, etc)
lipocalin-2/ siderocalin) = highly upregulated after ● Anemia
inflammation/ kidney injury w/in 2 hrs of cardiopulmo o NOT improved by EPO
bypass assoc. AKI o Replace blood loss
o Uremic bleeding: desmopressin or estrogen
o GI prophylaxis: PPIs / H2 receptor blockers
VI. COMPLICATIONS
● Malnutrition
● Uremia o Inadequate nutrition: starvation ketoacidosis
o Elevated BUN and protein catabolism
o BUN has LITTLE direct toxicity if <100 mg/dL o Excessive nutrition: nitrogenous waste
o At higher levels = mental stat changes, bleeding generation and worsening azotemia
● Hypervolemia o KDIGO Guideline on total energy intake of px w/
o Expansion of extracellular fluid vol AKI: 20-30 kcal/kg/day
o Impaired salt and H20 excretion o Protein intake based on AKI severity
● Hypovolemia ▪ Noncatabolic AKI w/o need for
o Polyuria accompanying AKI recovery (osmotic dialysis: 0.8-1.0g/kg/day
diuresis from retained urea) ▪ Px on dialysis: 1.0-1.5g/kg/day
● Hyponatremia ▪ Hypercatabolic w/ RRT: max
1.7g/kg/day
o From administration of excessive hypotonic
crystalloid/ isotonic dextrose sol’n in pc with
dysfunctional kidneys unable to regulate
electrolyte balance
● Hyperkalemia
o Most feared
o Fatal arrhythmias
● Acidosis
o Metabolic acidosis + elevated anion gap

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a. Renal Replacement Therapy

● Indications: mgt fails to control vol overload,
hyperkalemia, acidosis, toxic ingestions, severe
complications of uremia (asterixis, pericardial
rub/effusion, encephalopathy, uremic bleeding)
● Late initiation: risk of avoidable vol, electrolyte, metabolic
complications of AKI
● Early Initiation: infection, bleeding, hypotension,
procedural complications from IV lines and invasive
procedures
● Diffusive clearance: small solutes removed across
semipermeable membrane down conc gradient
● Convective clearance: solutes removed along w/
movement of plasma

1. Hemodialysis
a. Vascular access: femoral, IJV, Subclavian vein
b. Intermittent, diffusive and convective
c. 3-4 hrs/day, 3-4x/wk
d. Most common form of RRT
e. Complications: hypotension (may perpetuate
AKI)
2. Continuous Renal Replacement Therapy (CRRT)
a. Convective (Continuous Venous Hemofiltration)
b. Diffusive (continuous venous hemodialysis)
3. Slow low efficiency dialysis (SLED)
a. Extended daily dialysis
b. Blood flow and dialysate flow are higher than
CVVHD but tx time reduced to </=12 hrs
4. Peritoneal Dialysis
a. Use temporary intraperitoneal catheter
b. Dialysate sol’n instilled into and removed from
peritoneal cavity at regular intervals in order to
achieve diffusive and convective clearance of
solutes across peritoneal membrane
c. Dextrose dialysate sol’n
d. Continuous, convective and diffusive
e. May NOT be sufficient in hypercatabolic px due
to inherent limitations in dialysis efficacy

Guide Questions

1. How much urine per day to be considered anuric

2. When will you think of interstitial/tubular kidney
disease as opposed to prerenal azotemia
a. 500 mOsm/L urine osmolality
b. 300 mOsm/L urine osmolality
3. Regarding #2, why is that the answer?
4. Why is the S3 segment prone to ischemia?
5. Where do you expect to find ischemia first?
a. Cortex
b. Medulla

Answers: </=400mL/day, B, if the interstitium and tubules are already affected, the
ability of the kidney to concentrate urine will be impaired resulting to a dilute urine, It
is the most metabolically active where most NaCl and H20 are reabsorbed, B

References:
● Dr. Austria’s Slides
● Jameson, J., Kasper, D., Longo, D. … Loscalzo, J. (2018).
Fig 4. Management of AKI Harrison’s principles of internal medicine (20th edition).
New York, New York: McGraw-Hill Education.

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APPENDIX

Fig 5. Staging of AKI

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