This document provides an overview of acute kidney injury (AKI), formerly known as acute renal failure. It discusses the definition and epidemiology of AKI and describes the main causes as pre-renal, intrinsic renal, and post-renal. Pre-renal AKI is the most common type and is caused by reduced renal blood flow. The document outlines the diagnostic evaluation, complications, treatment approaches including dialysis indications, and outcomes of AKI. It emphasizes the importance of identifying and eliminating nephrotoxic agents to optimize management of this condition.

1. Dr. Ratan Jha (consultant nephrologist)
Dr. Mohd Viquas Uddin Saim (DNB medicine
resident)
Medwin hospital

2. introduction
 Previously known as acute renal failure
 Sudden impairment of kidney function
 Retention of nitrogenous waste products
 Not a single disease
 Designation for conditions sharing common
diagnostic features
 Increase in blood urea and serum creatinine
 Severity ranges from asymptomatic to fatal

3. Why term AKI preferred over ARF ?
 failure reflects only part of the spectrum of damage to the
kidney
 In most cases damage is modest
 Modest damage is not nearly as omnious as frank kidney
failure
 Frank kidney failure often requires acute dialysis therapies
 term renal is not well understood in the general population
 Hence kidney has replaced renal

4. epidemiology
 5–7% of acute care hospital admissions
 30% of admissions to the intensive care unit
 Major complication of diarrheal illnesses, malaria and
leptospirosis
 markedly increased risk of death in hospitalized
individuals
 mortality rates may exceed 50% in ICU patients

5. Etiology

6. Pre renal azotemia
 "azo," meaning nitrogen, and "-emia“
 most common form of AKI
 rise in SCr or BUN concentration due to inadequate renal
plasma flow and intraglomerular hydrostatic pressure to
support normal glomerular filtration
 may coexist with other forms of intrinsic AKI
 When prolonged may lead to ischemic injury called Acute
tubular necrosis
 prerenal azotemia involves no parenchymal damage to the
kidney
 rapidly reversible once intraglomerular hemodynamics are
restored.

7. Pathophysiology of prerenal AKI

8. Renal autoregulation
 Normal GFR is maintained by the relative resistances of the
afferent and efferent renal arterioles
 Renal blood flow accounts for 20% of cardiac output
 renal vasoconstriction and salt and water reabsorption
occur as a homeostatic response to decreased effective
circulating volume or cardiac output
 to maintain blood pressure and increase intravascular
volume to sustain perfusion to the cerebral and coronary
vessels
 Mediators of this response include angiotensin II,
norepinephrine, and vasopressin

9. Renal autoregulation
 Glomerular filtration can be maintained despite
reduced renal blood flow by angiotensin II–mediated
renal efferent vasoconstriction
 Intrarenal biosynthesis of vasodilator prostaglandins
(prostacyclin, prostaglandin E2 also increase in
response to low renal perfusion pressure
 also accomplished by tubuloglomerular feedback
 decreases in solute delivery to the macula densa
(specialized cells within the proximal tubule) elicit
dilation of the juxtaposed afferent arteriole

10. Failure of autoregulation
 There is a limit to autoregulation
 in healthy adults, renal autoregulation usually fails once
the systolic blood pressure falls below 80 mmHg
 Atherosclerosis, long-standing hypertension, and older age
cause impaired capacity for renal afferent vasodilation
 NSAIDs inhibit renal prostaglandin production, limiting
renal afferent vasodilation
 ACE inhibitors and angiotensin receptor blockers (ARBs)
limit renal efferent vasoconstriction
 NSAID’s and ARBs should not be given together.

11. Intrinsic AKI
 most common causes of intrinsic AKI are sepsis,
ischemia, and nephrotoxins
 In many cases, prerenal azotemia advances to tubular
injury
 classically termed "acute tubular necrosis
 Other causes of intrinsic AKI are less common

12. Intrinsic AKI - Glomerular causes
 Post-infectious
 SLE
 ANCA associated
 Henoch schnolen purpura
 Cryoglobulinaemia
 TTP
 HUS
 Accounts for 5 % of cases

13. Intrinsic AKI - tubular causes (ATN)
 Ischemic (50%)
 kidneys are the site of one of the most hypoxic regions in the
body, the renal medulla
 outer medulla is particularly vulnerable to ischemic damage
 AKI more commonly develops when ischemia occurs in the
context of limited renal reserve or coexisting insults such as
sepsis,
 Toxins (35%)
 kidney has very high susceptibility to nephrotoxins due to
extremely high blood perfusion
 Endogenous nephrotoxins : hemoglobin, myoglobin
 Exogenous nephrotoxins : contrast agents, antibiotics, etc,.

14. Intrinsic AKI – interstitial & vascular
causes
 Acute interstitial nephritis
 Drugs : NSAID’s, allopurinol, methicillin
 Granulomatous : tuberculosis, sarcoidosis
 Infective : legionnaire’s disease, pyelonephritis
 Monosodium urate crystals
 Vascular causes
 Renal artery occlusion
 Renal vein thrombosis
 Cholesterol emboli

15. Post renal AKI
 occurs when the unidirectional flow of urine is acutely
blocked either partially or totally
 leads to increased retrograde hydrostatic pressure and
interference with glomerular filtration
 For AKI to occur in healthy individuals, obstruction must
affect both kidneys unless
 Unilateral obstruction may cause AKI in the setting of
significant underlying CKD
 Bladder neck obstruction is a common cause of postrenal
AKI and can be due to prostate disease ,neurogenic
bladder, or therapy with anticholinergic drugs
 Other causes of lower tract obstruction are blood clots,
calculi, and urethral strictures

16. Post renal AKI- ureteric obstruction
 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)
 pathophysiology of postrenal AKI involves
hemodynamic alterations triggered by an abrupt
increase in intratubular pressures
 Reduced GFR is due to underperfusion of glomeruli

17. Diagnostic evaluation
 presence of AKI is usually inferred by an elevation in
the SCr concentration
 AKI is currently defined by a rise of at least 0.3 mg/dL
or 50% higher than baseline within a 24–48-hours
period or a reduction in urine output to 0.5 mL/kg per
hour for longer than 6 hours
 The distinction between AKI and chronic kidney
disease is important for proper diagnosis and
treatment

18. Diagnostic evaluation
 Features suggestive of CKD than AKI
 from radiologic studies (e.g., small, shrunken kidneys
with cortical thinning on renal ultrasound, or evidence
of renal osteodystrophy)
 laboratory tests such as normocytic anemia or
secondary hyperparathyroidism with
hyperphosphatemia and hypocalcemia, consistent
with CKD
 distinction is straightforward when a recent baseline
SCr concentration is available

19. Diagnostic evaluation : history &
physical evaluation
 Prerenal azotemia : in the setting of vomiting,
diarrhea, glycosuria causing polyuria, and several
medications including diuretics, NSAIDs, ACE
inhibitors, and ARBs
 Postrenal AKI : history of prostatic disease,
nephrolithiasis, or pelvic or paraaortic malignancy .
Abdominal fullness and suprapubic pain can
accompany massive bladder enlargement
 A careful review of all medications is imperative in the
evaluation of an individual with AKI

20. Diagnostic evaluation : Urine
findings
 Anuria is seen in complete urinary tract obstruction, renal
artery occlusion, overwhelming septic shock, severe
ischemia, or severe proliferative glomerulonephritis or
vasculitis
 oliguria, defined as <400 mL/24 husually denotes more
significant AKI than when urine output is preserved
 Preserved urine output can be seen in longstanding urinary
tract obstruction, tubulointerstitial disease, or
nephrotoxicity from cisplatin or aminoglycosides
 In the absence of preexisting proteinuria from CKD, AKI
from ischemia or nephrotoxins leads to mild proteinuria
(<1 g/d)

22. Diagnostic evaluation : blood lab
findings
 Certain forms of AKI are associated with characteristic
patterns in the rise and fall of SCr
 Prerenal azotemia typically leads to modest rises in
SCr that return to baseline with improvement in
hemodynamic status
 Contrast nephropathy leads to a rise in SCr within 24–
48 hours, peak within 3–5 days, and resolution within
5–7 days
 With aminoglycoside antibiotics and cisplatin ,the rise
in SCr is characteristically delayed for 4–5 days to 2
weeks after initial exposure.

23. Diagnostic evaluation : blood lab
findings
 Severe anemia in the absence of bleeding may reflect
hemolysis, multiple myeloma, or thrombotic
microangiopathy
 Peripheral eosinophilia can accompany interstitial
nephritis, atheroembolic disease, polyarteritis nodosa,
and Churg-Strauss vasculitis
 AKI often leads to hyperkalemia, hyperphosphatemia,
and hypocalcemia
 The anion gap may be increased with any cause of
uremia due to retention of anions such as phosphate,
hippurate, sulfate, and urate

24. Diagnostic evaluation : renal failure
indices

25. Diagnostic evaluation : renal failure
indices
The fractional excretion of sodium (FeNa) is the fraction of the filtered sodium load that
is reabsorbed by the tubules and is a measure of both the kidney's ability to reabsorb
sodium

26. Diagnostic evaluation : novel
biomarkers
 BUN and creatinine are functional biomarkers of
glomerular filtration and not tissue injury biomarkers
 suboptimal for the diagnosis of actual parenchymal
kidney damage
 Kidney injury molecule-1 (KIM-1) : for ischemic /
nephrotoxic ATN
 Neutrophil gelatinase associated lipocalin (NGAL), also
known as lipocalin-2 or siderocalin

27. complications
 Uremia
 Hypervolemia/hypovolemia
 Hyponatremia
 Hyperkalemia
 Acidosis
 Hyperphosphatemia/hypocalcemia
 Bleeding
 Cardiac : arrhythmias, pericarditis, and pericardial
effusion

28. treatment
 General issues
 Optimization of systemic and renal hemodynamics
through volume resuscitation and judicious use of
vasopressors
 Elimination of nephrotoxic agents (e.g., ACE
inhibitors, ARBs, NSAIDs, aminoglycosides)
 Initiation of renal replacement therapy when
indicated

29. Treatment : specific issues
 Nephrotoxin-specific
 a. Rhabdomyolysis: consider forced alkaline diuresis
 b. Tumor lysis syndrome: allopurinol or rasburicase
 Volume overload
 a. Salt and water restriction
 b. Diuretics
 c. Ultrafiltration
 Hyperkalemia
 a. Restriction of dietary potassium intake
 b. Discontinuation of potassium-sparing diuretics, ACE inhibitors, ARBs, NSAIDs
 c. Loop diuretics to promote urinary potassium loss
 d. Potassium binding ion-exchange resin (sodium polystyrene sulfonate)
 e. Insulin (10 units regular) and glucose (50 mL of 50% dextrose) to promote entry
of potassium intracellularly
 f. Inhaled beta-agonist therapy to promote entry of potassium intracellularly
 g. Calcium gluconate or calcium chloride (1 g) to stabilize the myocardium

30. Treatment : specific issues
 Metabolic acidosis
 a. Sodium bicarbonate (if pH <7.2 to keep serum
bicarbonate >15 mmol/L)
 b. Administration of other bases e.g., THAM
(tromeThamine injection)
 c. Renal replacement therapy
 Hyperphosphatemia
 a. Restriction of dietary phosphate intake
 b. Phosphate binding agents (calcium acetate, sevelamer
hydrochloride, aluminum hydroxide—taken with meals)
 Hypocalcemia
 a. Calcium carbonate or calcium gluconate if symptomatic

31. Indications of dialysis
 indicated when medical management fails to
control
 volume overload
 hyperkalemia
 Acidosis
 in some toxic ingestions
 severe complications of uremia
 Many nephrologists initiate dialysis for AKI empirically when the
BUN exceeds 100 mg/dL

32. Outcome and prognosis
 associated with a significantly increased risk of in-
hospital and long-term mortality
 Prerenal azotemia and postrenal azotemia carry a
better prognosis than most cases of intrinsic AKI
 kidneys may recover even after severe, dialysis-
requiring AKI
 up to 10% may develop end-stage renal disease
 Postdischarge care under the supervision of a
nephrologist for aggressive secondary prevention of
kidney disease is prudent

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The end
Thank you 