we delve deeper into the understanding of acute kidney injury

1. Prepared by
Dr. Mohamed m. abdirahman

2. Definition of AKI
• Acute kidney injury (AKI) is formerly called acute renal
failure (ARF), is commonly defined as an abrupt decline in
renal function, clinically manifesting as a reversible acute
increase in nitrogen was products measured by blood urea
nitrogen (BUN) and serum creatinine level over the course
of hours to days.(ROYAK, GORRIAN C, TREACY C, KAVANAUGH E, ET
AL 2013)
• >30 different definitions have been used in the literature
creating much confusion and making comparisons difficult.
(RINALDO BELLOMO, CLAUDIO RONCO et al 2004)

3. KDIGO Definition of AKI ( 2012
)
Defined by any of the following:
 Increase in Ser Cr by ≥0.3 mg/dL within 48 hours
 Increase in Ser cr by ≥1.5 times baseline (50%↑),
which is known or presumed to have occurred within
the prior seven days
 Urine volume <0.5 ml/kg/h for 6 hours

4. KDIGO Classification of AKI ( 2012 )
KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012
Kidney Disease: Improving Global Outcomes

5. RIFLE CRITERIA FOR AKI

6. Modified RIFLE as proposed by AKIN
r
Acute
Kidney
Injury
Network
(AKIN))

7. Acute
Tubular
Necrosis
Acute
Interstitial
Nephritis
Acute
GN
Acute
Vascular
Syndromes
Intratubular
Obstruction
Classification of the Etiologies of AKI
Prerenal
AKI
Postrenal
AKI
Intrinsic
AKI
Acute
Renal
Injury
7

8. Prerenal AKI
• Is a form of renal insufficiently caused by diminished perfusion
of the kidney on any basis. The kidney it self is normal, if the
kidney could receive adequate perfusion the BUN and
creatinine would normalize.
• Causes of prerenal disease — Prerenal disease may result
from the following:
 True volume depletion – Volume depletion may be caused by
gastrointestinal disease (vomiting, diarrhea, bleeding), renal
losses (diuretics, glucose osmotic diuresis), skin or respiratory
losses (insensible losses, sweat, burns).
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9. Cont….
 Hypotension – Severely decreased blood pressure can result
from shock (hypovolemic, cardiogenic or septic) and post
treatment of severe hypertension.
 Edematous states – Heart failure and cirrhosis can result in
marked reductions in kidney perfusion that parallel the
severity of the underlying disease. The respective mechanisms
are decreased cardiac output in heart failure and splanchnic
venous pooling and systemic vasodilatation in cirrhosis.

10. >>
 Selective renal ischemia – Bilateral renal artery stenosis or
unilateral stenosis in a solitary functioning kidney is frequently
made worse by treatment with angiotensin-converting enzyme
inhibitors, angiotensin II receptor blockers, or direct renal
inhibitors.
 Drugs affecting glomerular hemodynamics – Drugs that
affect glomerular hemodynamics can reduce the glomerular
filtration rate (GFR) by lowering the intraglomerular pressure
that drives this process.

11. Prerenal Azotemia

12. Prerenal Azotemia Tx
• Dx: The firts clue to the diagnosis of prerenal azotemia is a
BUN creatinine ratio of 20:1. there is also low urine sodium
and low fractional excretion of sodium (FeNa <1%)
• In early stages can be rapidly corrected by aggressive
normalization of effective arterial volume.
• Correction of volume deficits
• Optimization of cardiac function
• Discontinuation of antagonizing medications
– NSAIDs/COX-2 inhibitors, Diuretics, RAAS blockers 12

13. INTRINSIC RENAL CAUSES
• Intrinsic renal causes are also important sources of acute
kidney injury and can be categorized by the component of the
kidney that is primarily affected (i.e., tubular, glomerular,
interstitial, or vascular)
• Tubule: ATN (sepsis, ischemic, toxins)
• Interstitium: AIN (Drug, infection, neoplasm)
• Glomerulus: AGN (primary, post-infectious,
rheumatologic, vasculitis, HUS/TTP)
• Vasculature:
– Atheroembolic dz, renal artery thromboembolism, renal artery
dissection, renal vein thrombosis

14. Cont…
• Intratubular Obstruction
– myoglobin, hemoglobin, myeloma light chains,
uric acid, tumor lysis, drugs (bactrim, indinavir,
acyclovir, foscarnet, oxalate in ethylene glycol toxicity)
Acute tubular necrosis is the most common type of intrinsic
acute kidney injury in hospitalized patients. The cause is
usually (sepsis, ischemic, toxins) ischemic (from prolonged
hypotension) or nephrotoxic (from an agent that is toxic to the
tubular cells).

15. Laboratory Findings in Acute Kidney Injury

16. Postrenal AKI: Classification
– Level of obstruction
• Upper tract (ureters)
• Lower tract (bladder outlet or urethra)
– Degree of obstruction
• Partial vs. Complete
– Type
• Anatomic lesion (unilateral vs. bilateral)
• Functional
– Duration (Acute vs Chronic)
– Cause (Congenital vs Acquired)

17. Etiologies: Upper tract obstruction
 Intrinsic:
• Nephrolithiasis
• Blood clot
• Papillary necrosis
• Cancer
Extrinsic:
 Retroperitoneal or pelvic
malignancy
 Endometriosis/Prolapsed
uterus
 Abdominal aortic aneurysm
or Iliac artery aneurysm
 Retroperitoneal fibrosis

18. Etiologies: Lower tract obstruction
– BPH or prostate cancer
– Bladder cancer
– Urethral strictures
– Bladder stones
– Blood clots
– Functional obstruction as a result of
neurogenic bladder

19. Postrenal AKI tx
• Prompt recognition and relief of obstruction can prevent the
development of permanent structural damage.
– Lower tract obstruction (bladder catheter)
– Upper tract obstruction
• ureteral stents
• percutaneous nephrostomies
• Monitor for post-obstructive diuresis
• Recovery of renal function dependent upon duration of obstruction.

20. Clinical Presentation
• Clinical presentation varies with the cause and severity of renal injury, and
associated diseases. Most patients with mild to moderate acute kidney
injury are asymptomatic and are identified on laboratory testing.
Patients with severe cases, however, may be symptomatic and present with
listlessness, confusion, fatigue, anorexia, nausea, vomiting, weight gain, or
edema. Patients can also present with oliguria (urine output less than 400
mL per day), Anuria (urine output less than 100 mL per day), or normal
volumes of urine (nonoliguric acute kidney injury). Other presentations of
acute kidney injury may include development of uremic encephalopathy
(manifested by a decline in mental status, asterixis, or other neurologic
symptoms), anemia, or bleeding caused by uremic platelet dysfunction.

21. How do we assess a pt with AKI?
• Is this acute or chronic renal failure?
– Establish baseline Cr and assess Cr trend
– History and examination
– Small kidneys on ultrasound (except for in -Diabetes,
PCKD, Urinary Tract Obstruction)
Hilton et al, BMJ 2006;333;786-790
Hilton et al, BMJ 2006;333;786-790

27. Patterns of Creatinine Rise
• Contrast induced Nephropathy: Rise in SCr within 24-48
hrs. Peak within 3-5 days and back to baseline in 5-7 days.
• Prerenal azotemia: A rise in creatinine that downtrend when
volume status is corrected.
• Atheroembolic disease: Typically a subacute rise in SCr (Can
be rapid rise and severe in some cases).
• Nephrotoxic agents like aminoglycosides, carboplatins: Rise
in SCr delayed 3-14 days after exposure

28. Diagnostic workup?
 Urine microscopy:
Muddy brown casts in ATN
WBC casts in AIN
RBC casts in AGN

31. Cont…
1. Calculations are as follows: Anion gap = sodium – (chloride + bicarbonate)
2. Calculated serum osmolality = 2(sodium [in mEq per L]) + (blood urea
nitrogen [in mg per dL] ÷ 2.8) + (glucose [in mg per dL] ÷ 18)
3. Osmolar gap = measured serum osmolality – calculated serum osmolality.
Adapted with permission from Agrawal M, Swartz R. Acute renal failure [published correction appears in Am
Fam Physician. 2001;63(3):445]. Am Fam Physician. 2000;61(7):2081.

32. Kidney Biopsy
• A biopsy can give diagnostic information when
prerenal, postrenal, ischemia and nephrotoxic
etiologies are unlikely.
• Useful in diagnosing glomerulonephritis, vasculitis,
interstitial nephritis, myeloma kidney, etc
• This procedure carries a risk of serious bleeding,
especially when patients are coagulopathic.

33. Complications of AKI
• Hypervolemia
• Uremia
– Uremia poses little direct toxicity at levels below 100 mg/dl
– At higher concentrations can cause mental status changes and bleeding
• Electrolyte abnormalities including hyperkalemia,
hyponatremia, hyperuricemia, hyperphosphatemia,
hypocalcemia, and hypomagnesemia
• Metabolic acidosis
• Cardiac complications can include arrhythmias, pericarditis,
and pericardial effusion

34. Management of AKI:
treat complications
• Correct fluid imbalances: strict I/O’s, daily wts.
determine fluid balance goals daily, fluid selection or
diuresis, readjust for UOP recovery, post diuresis or
dialysis
• Electrolyte imbalances (low K/phos diet)
• Metabolic acidosis (Bicarb deficit, mode and rate of
replacement)
• Nutrition: adjust TPN/protein intake
• Medication dosing: adjustment for eGFR to avoid under
or over dosing, timing for dialytic therapy, reassess
dosing for renal recovery or dialysis modality)
• Procedural considerations (prefer non-contrast CT,
appropriate to delay contrast exposure, prophylaxis)
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35. Nephrotoxic Drug Exposure
• Minimizing nephrotoxin
– Avoid Aminoglycosides, Amphotericin,
Bactrim, Vancomycin, NSAIDs, IV contrast,
Fleet’s enemas
• Renal dose medications – especially antibiotics
and monitor level
• Cautious use (metformin, long acting oral
hypoglycemic agents, insulin, gemfibrozil and
statins, neurotin, colchicine/allopurinol,
morphine/codeine, lmwh)
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36. Indications for Emergent Dialysis
• AEIOU mnemonic:
– Acidemia: Persistent academia that is either non-responsive to bicarb
or when giving bicarb would result in volume overload
– Electrolyte abnormalities such as hyperkalemia in setting of EKG
changes
– Intoxications: Salicyclic acid, lithium, isopropanol, magnesium and
ethylene glycol
– Overload
– Uremia causing complications such as pericarditis, encephalopathy,
bleeding

37. Treatment of AKI
• Treatment depends on the etiology and focuses on
treating underlying insult
– For instance, in setting of post-renal obstruction,
relieving the obstruction or in prerenal etiologies such
as hypovolemia, correcting the hypovolemia.
• Patients may need medications renally dose in the
setting of AKI.
– Avoid NSAIDs and consider holding ACEi/ARBs in
the setting of acute AKI

39. Be aware of pts who are at risk for AKI
Volume depletion or Hypotension
Sepsis
Pre-existing renal, hepatic, or cardiac dz
Diabetes mellitus
Elderly
Exposure to nephrotoxins
Aminoglycosides, amphotericin, immunosuppressive agents, chemo.,
NSAIDs,, RAAS blockers, intravenous contrast media
Post cardiac or vascular Surgery pts or ICU pts with multiorgan failure
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40. • AKI is increasingly common.
• It involves high cost of management, carries a high morbidity and
mortality risks.
• The most common cause of in-hospital AKI is ATN that results
from multiple acute insults (sepsis, ischemia, or nephrotoxin).
• No drug treatment has been shown to limit the progression of, or
speed up recovery from AKI.
• Review medications and adjust dose
• Recognize risk factors
• The Best Treatment is PREVENTION and avoid further renal
damage!!!
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41. End
Thank you