Acute Kidney Injury

1. ACUTE
KIDNEY
INJURY

2. Definition of Acute Kidney Injury
“ACUTE RENAL FAILURE”
• Rapid decline in renal function (GFR) over hours to
days
• Characterized by
– retention of nitrogenous waste
– oliguria
– electrolyte and acid-base abnormalities
• Rise in creatinine and BUN
• Often reversible

3. ARF is usually asymptomatic and diagnosed when biochemical
monitoring of hospitalized patients reveals a new increase in blood urea
and serum creatinine concentrations.
ARF is often considered reversible, although a return to baseline serum
creatinine concentrations postinjury might not be sufficiently sensitive
to detect clinically significant irreversible damage that may ultimately
contribute to chronic kidney disease.
Acute kidney injury (AKI) has now replaced the term acute renal failure
and a universal definition and staging system has been proposed to
allow earlier detection and management of AKI.
• The new terminology enables healthcare professionals to consider the
disease as a spectrum of injury. This spectrum extends from less
severe forms of injury to more advanced injury when acute kidney
failure may require renal replacement therapy
• Encompasses entire spectrum of ARF
• 10% with severe AKI(recovered) will require HD in the future

4. Acute Kidney Injury: KDIGO
KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
Kidney International Supplements (2012) 2, 8–12
AKI is defined as any of the following:
 Increase in Serum Crea by ≥0.3 mg/dl within 48
hours;
 Increase in Serum Crea to X 1.5 times baseline over
7 days or less;
 Urine volume of < 0.5 ml/kg/h for 6 hours.
Kidney disease improving global outcomes
Anuric/bilateral nephrectomy -- speed of creatinine rise 0.5-1mg/dL per day

5. STAGING OF ACUTE KIDNEY INJURY

6. Acute Kidney Injury Network (AKIN).
The AKIN group modified the RIFLE staging system to
reflect the clinical significance of relatively small rises
in serum creatinine
• Uses serum creatinine, urinary output and time
Staging of AKI - with increased stage of AKI, the risk for
death and need for RRT increases.

7. Factors That Predispose To Acute Kidney Injury

8. CLASSIFICATION AND MAJOR CAUSES OF ACUTE KIDNEY
INJURY

9. PRERENAL
 MOST COMMON
 characterized by a diminished renal blood flow,
primarily due to decreased effective arterial blood
flow
 rapidly reversible process if recognized early and
the underlying cause of reduced renal blood flow is
corrected.
The presence of AKI in the setting of severe heart failure has been termed the
cardiorenal syndrome
INTRARENAL VASOCONSTRICTION: Due to systemic arterial vasodilation with
redistribution of cardiac output to extrarenal vascular space
(sepsis/hepatorenal)

11. AF = to , EF = latin for efferens ‘rom”
The glomerulus is the organ that is sandwithed between 2 blood
vessels…. Subjected to many hemodynamic events
Compensation Phase: Autoregulation of RBF
hypotension-decrease concentration of filtrate flow---
sensed by macula densa-- increase reabsorption of ions and
water--1) dilatation of renal affernt art
2) release of PGE
prostaglandins triggers JG to release of renin----constricts the
efferent art-- increase hydrostatic P in glomerulos
Decompensation phase: BP below 80mmHg
CKD: ACE inhibitor = decreases the intraglomerular pressure(highest
contributor to kidney damage)

12. PRERENAL CAUSES
ETIOLOGY MECHANISM EXTRACELLULAR FLUID
VOLUME
Hemorrhage
Burns
Diuretics
Dehydration
Gastrointestinal losses
True intravascular
volume depletion
Reduced
Congestive heart failure
Cardiac tamponade
Aortic stenosis
Cirrhosis with ascities
Nephrotic syndrome
Decreased effective
circulating volume
increased
ACEI
NSAIDs
Renal artery stenosis
Renal vein thrombosis
Impaired renal
blood flow
Normal
Sepsis
Vasodilatory drugs
Anesthetic agent
Systemic
vasodilation
Normal

13. Effective arterial blood flow is the amount of arterial
blood perfusing vital organs = actual arterial volume,
cardiac output, and vascular resistance.
ACEI/ARB - impair afferent art dilatation
NSAIDS – impair efferent art vasoconstr

14. PRE RENAL
• Pre-renal AKI can be corrected if the
extrarenal factors causing the renal
hypoperfusion are rapidly reversed.
• Failure to restore renal blood flow (RBF)
during the functional pre-renal stage will
ultimately lead to ischemic ATN and
tubular cell injury
ATN
The most common cause of Ischemic Acute Kidney Injury is
unresolved severe/sustained pre--‐renal factors

15. INTRA RENAL
• Decrease in GFR due to sustained renal
hypoperfusion (pre-renal factors), nephrotoxin or
to actual parenchymal damage
• Not immediately reversed upon correction of
the insult
• Associated with some structural and tubular
damage

16. INTRARENAL AKI
CAUSES OF INTRINSIC/INTRA RENAL AKI
ACUTE TUBULAR NECROSIS ISCHEMIC:
NEPHROTOXIC:
ACUTE INTERSTITIAL
NEPHRITIS
INFECTION: Leptospirosis, malaria
DRUGS: NSAIDs
INFLAMMATION: TB
VASCULITIS Malignant HPN, SLE
ACUTE
GLOMERULONEPHRITIS
Post Strept GN, RPGN, Good pastures
• The tubular damage is usually caused by a combination of ischemic
injury resulting in depletion of cellular ATP and direct tubular
epithelial cell injury by nephrotoxins
• S3 segment of the proximal tubule and the medullary thick ascending
limb (mTAL) are particularly vulnerable to hypoxic injury

17. ACUTE TUBULAR NECROSIS
• most common cause of intrinsic AKI
• Acute tubular dysfunction resulting from tubular cell injury
- Effacement/ loss of PCT brush borders, patchy loss of
tubule cells, necrosis
• OUTER MEDULLA(s3 of prox tubule and MTAL) is frequently
involved
TYPES OF ATN
ISCHEMIC Cardiogenic shock, sepsis, burns, severe, volume,
depletion
NEPHROTOXIC EXOGENOUS: radiocontrast, aminoglycosides
ENDOGENOUS: heme pigment, massive intravascular
hemolysis

18. MISNOMER minimal tubule damage; include vacuolization and
loss of brush border in proximal tubular cells. Sloughing of tubular
cells into the lumen leads to cast obstruction, manifested by
tubular dilation. Interstitial edema can produce widely spaced
tubules, and a mild leukocyte infiltration may be present
- Single insult rarely sufficient to induce ATN
- S3 and MTAL most affected – less o2 supply and high metabolic
demand

20. initiation phase, which marks the transition from prerenal to
tubular cell injury and dysfunction, is characterized by severe
cellular depletion of adenosine triphosphate. Renal tubular
epithelial cell injury, especially of proximal tubular cells, is a
prominent feature during this phase, but injury to endothelial and
vascular smooth muscle cells also has been documented. During this
phase, extensive signaling between the proximal tubular cells and
adjacent endothelial cells results in endothelial dysfunction and an
inflammatory endothelial response. Leukocytes of all types play a
role in ongoing inflammation and cell injury. Dendritic cells,
macrophages, neutrophils, and lymphocytes have been shown to
play either a detrimental or protective role. The time course of
involvement varies according to the cell type, and changes in
macrophage
phenotype from M1 to M2 mediate conversion from a
proinflammatory form to a repair-mediating form.

21. EXTENSION PHASE - microvascular congestion with continued
hypoxia and inflammation are most pronounced in the
corticomedullary junction of the kidney, where reperfusion is
limited owing to endothelial dysfunction at the capillary and
postcapillary venule levels, with white blood cell adhesion and
rouleaux formation.
maintenance phase - GFR is at its ebb…. as cells undergo repair,
migration, and proliferation and as the kidney attempts to
reestablish cellular and tubular integrity
.
RECOVERY PHASE - the GFR begins to improve as cellular
differentiation continues and normal cellular and organ function
returns. Proximal tubular cells undergo cellular repair, and
terminally differentiated epithelial cells re-express stem cell
markers and divide to repopulate the nephron. This last phase is
often heralded by increasing urine output.

22. PHASES OF ATN

23. Initiation Phase Drop in intraglomerular pressure as renal
blood flow falls
• Obstruction in flow of filtrate due to casts
(comprised of shed epithelial cells and
necrotic debris)
• Backleak
Extension Phase • occurs with persistent ischemia and ongoing hypoxia
• imbalance in vasoactive mediators and persistent
vasoconstriction in the outer medulla
• worsening decrease in GFR.
Maintenance
Phase
• Typically lasts 1- 2 weeks
• GFR remains markedly depressed
• Persistent intrarenal vasoconstriction and
medullary ischemia
Recovery Phase “Diuretic phase”
• Cellular regeneration and repair
• GFR increases to normal or near normal

24. 1.Renal vasoconstriction
2.Filtration Impairment
3. Tubular Obstruction
4. backleak- this is when the waste materials of the
body find their way back into the

25. ACUTE INTERSTITAL NEPHRITIS
 Etiologies
- Infection: Leptospirosis, streptococcus, malaria
Drugs: NSAIDs, Penicillins, anti TB meds, Sulfur,
Inflammation: TB, Sarcoid
PRESENTATION
– progressive rise in creatinine
– Pyuria
– Hyposthenuria (inability of the kidney to concentrate urine)
– Electrolyte derangements

26. AKI – tululointerstitial disease
Drugs- most common cause
- hypersensitivity reaction to drugs such as penicillins,
nonsteroidal anti-inflammatory drugs (NSAIDs), and
sulfa drugs.
- cellular injury caused by infection, viral or bacterial,
often associated with obstruction or reflux.

27. ACUTE INTERSTITAL NEPHRITIS
 fever, rash, peripheral eosinophilia, and oliguric
renal failure occurring after 7–10 days of treatment
with methicillin or another β-lactam antibiotic, is the
exception rather than the rule.
MANAGEMENT
- withdraw offending agent
- corticosteroids
> Urinary eosinophils are neither sensitive nor specific for AIN;
therefore, testing is not recommended.

28. POST RENAL AKI
• Obstructions:
– stones, blood clots, papillary necrotic tissue
• Urethral disease
• Prostate disease
• Bladder disease
• Anatomic: cancer, schistosomiasis, hemorhgic
cystitis
• Functional: neurogenic bladder
• BILATERAL Ureteral disease:
• Retroperitoneal fibrosis
• After the acute onset of obstruction, GFR declines
progressively, but it does not fall into ZERO

29. • Increases the hydrostatic P of the bowmans capsule-----
decreases GFR
• Bladder; both ureters or both kidneys
• Ex cervical cancer ---- MC of death is Renal failure
Normal urine output does not rule out POST RENAL AKI
- missmatch of GFR(6000ml/min) to Urine flow rate
100ml/min

30. Approach to Patients with AKI
• DETERMINE IF ACUTE OR CHRONIC
• History and physical exam:
– Previous creatinine
– Infection? Medications? Herbal meds?
– Volume status: Skin turgor, sweating, urine output
– history of recent trauma with or without overt blood loss or
muscle trauma - rhabdomyolysis
• Fever, rash, and joint pains- lupus nephritis, vasculitides,
endocarditis, drug allergy, and infectious diseases
• Flank pain - renal vein thrombosis;
• upper quadrant pain- acute renal infarction (e.g., renal
artery emboli)

31. Evaluate patients with AKI promptly to determine the cause, with
special attention to reversible causes
ACUTE vs CHRONIC or acute on top of chronic kidney disease(pre
existing CKD)
- less than 3 mos
- kidney size
- anemia, electrolyte abnormalities
- phoshate incr, Calcium dec – Ca:Phos ratio

32. Approach to Patients with AKI
• URINALYSIS:
– ATN: muddy, brown cast
– crystals – calcium oxalate in ethylene glycol ingestion
- uric acid in TUMOR LYSIS SYN
– Renal Imaging: UTZ, CT stonogram
– RENAL BIOPSY: Gold Standard from differentiating AKI from
CKD and other renal diseases
- Acute GN
- Acute KI in transplant patients
- acute tubulointerstial disease
• Determine the prognosis and chance of recovery of renal fxn
in dialysis dependent pts
URINE: calcium oxalate crystals are seen in cases of ethylene glycol ingestion AND and
uric acid crystals are seen in cases of tumor lysis syndrome

33. Other Laboratory Test
serum creatine kinase and
myoglobin
rhabdomyolysis
LDH Thrombotic Thrombocytopenic
Purpura
Fragmentocytes
(schistocytes)
TTP/hemolytic
uremic syndrome (HUS
NT pro BNP Cardiorenal syndrome
Serum/urine
electrophoresis
Multiple myeloma

34. URINE FINDINGS IN AKI

35. Muddy brown granular casts = pathognomonic of ATN
Uric acid
Calcium oxalate

37. PRERENAL: In this setting, tubular function is typically normal, renal
reabsorption of sodium and water is increased, and consequently urine
chemistries reveal a low urine sodium (<20 mmol/l) and a concentrated
urine >500 mOsm/kg(not caused by sodium but by urea, nitrogenous waste
product; normal concntrating ) as long as no loop diuretic has been
administered
SG: indirect measurement of osmolality(not ideal for pts with proteinuria)
ATN decreased concentrating ability
Osmolality <350 - near to serum osmolality(isosthenuria)
Urine sodium concentration is a less sensitive index for distinguishing
prerenal ARF from ischemic and nephrotoxic ARF as values overlap between
groups
The renal failure index, calculated as UNa/(UCr ÷ PCr), provides information
comparable to that of the FENa, because clinical variations in serum Na+
concentration are relatively small.
The fractional excretion of urea (FEurea), calculated as ([Uurea ÷ Purea]/[UCr
÷ PCr] × 100), has been proposed as an alternative to the FENa, with
particular usefulness in patients receiving diuretic therapy

38. The normal BUN/Cr ratio of 10:1
• The ratio is usually elevated (>20:1) in prerenal conditions and in
some patients with obstructive uropathy
Prerenal
•BUN: crea >20:1
•Slow flow to prox tubule - more time for
urea to be absorbed for the same amount of
creatinine filtered
• during states of water conservation, urea is reabsorbed from
the medullary collecting duct, explaining the discrepant rise
in BUN relative to creatinine

39. • BUN/Cr ratio may increase in UGIB
• BUN/Cr ratio may be reduced in liver failure, malnutrition, and
rhabdomyolysis.
The urine-to-plasma creatinine ratio (U:PCR) represents the
proportion of water filtered by the glomerulus that is withdrawn by
the distal tubule. Normally, about 98 percent of water is withdrawn,
and urine creatinine is much greater than plasma creatinine.
- The ratio can increase a hundred-fold in severe prerenal
states.
- When tubular function is lost, the ratio declines to less
than 20:1.

40. Fractional excretion of sodium (FENa)
a measure of the extraction of sodium and water from the
glomerular filtrate. It is the ratio of the sodium filtration rate to
the overall GFR rate (estimated by the renal filtration of
creatinine).
• Patients with prerenal ARF have a FENa of <1.0%
• EXCEPT: patients are receiving diuretics or with
preexisting chronic kidney disease, certain salt-wasting
syndromes, or adrenal insufficiency
• HIGH >1% in ATN;
• EXCEPT: sepsis-induced, pigment-induced, and some
forms of nephrotoxic ATN (e.g., contrast-associated,
Acute GN)

41. • FENa is most accurate for differentiating prerenal from INTRINSIC AKI
when determined in the patient with hypotension and oliguria
• The FeNa is a measure of the extraction of sodium and water from
the glomerular filtrate. It is the ratio of the sodium filtration rate to
the overall GFR rate (estimated by
the renal filtration of creatinine).
• In prerenal azotemia, the FENa is usually less than 1%, while in ATN it
is usually GREATER than 1%;
• exceptions: ATN due to severe burns, radiocontrast nephropathy
or underlying liver disease.
The FENa is typically less than 1%: acute glomerulonephritis, because
tubular function remains intact with increased proximal tubular
sodium reabsorption.
.

42. Novel markers of ACUTE KIDNEY INJURY
NGAL
(neutrophil gelatinase-
associated lipocalin)
• Early marker of AKI following transplantation
• Increases with intrinsic renal failure but not with pre
renal
• BLOOD and URINE
Cystatin C • a cysteine protease inhibitor that is freely filtered at the
glomerulus and normally reabsorbed by proximal
tubule cells
• more sensitive than serum creatinine concentrations at
detecting small reductions in GFR
IL-8 (also IL-6) • Noninvasive markers of vesicoureteral reflux (VUR) and
renal parenchymal scarring (RPS) in children in the
absence of a recent UTI
• BLOOD
KIM 1
Kidney Injury Molecule
1
• Distinguishes ischemic from prerenal and CKD
• BLOOD

43. Serum creatinine - may take 24–36 h to rise after a definite renal
insult; affected by drugs which compete with tubular secretion;
reduced production in sepsis, liver disease
URINE OUTPUT – may persist in severe RF; physiologic response to
fasting; dependent on volume status
- obese patients
New biomarkers in AKI – critically ill patients with fluid overload,
sepsis, muscle wasting
New RIFLE criteria ---- will include markers
Only present in AKI, not CKD

45. MANAGEMENT
ACUTE KIDNEY INJURY

46. MANAGEMENT
• Treatment is mainly SUPPORTIVE
– Fluid management
– Isotonic crystalloids – 1st
– Hypovolemia by hemorrhage - packed red
blood cells; colloids
– Shock – add vasopressors
– Intrinsic – etiology directed
– Post renal – relieve obstruction
– avoid nephrotoxins
– Nutrition and glucose control

47. NUTRITION
20-30Kcal/kg/day
0.8 to 1.0 g/kg/day protein in noncatabolic AKI
patients without need for dialysis
1.0 to 1.5 g/kg/day in patients with AKI on RRT
Glucose control
In critically ill patients, insulin therapy targeting
plasma glucose 110 to 149 mg/dl

48. MANAGEMENT:
– DOPAMINE - low dose dopamine has no effect in the
outcome of renal failure
- fenoldopam – no long term studies
– Diuretics – no effect on long term outcomes
– FUROSEMIDE
– MANNITOL – Induces osmotic diuresis
- O2 radical scavenger (?)
- no long term effect on renal failure
– RRT/DIALYSIS - for severe cases
- in oliguric AKI

49. DOPAMINE – renal vasodilator at 1ug/kg/min --- did not
improve survival, improve AKI outcome or delay HD,
Loop Diuretics –not totally proven
• Induce diuresis
• Vasodilators
• Flush tubular casts
• Converts oliguric to non-oliguric ARF

50. MANAGEMENT OF COMPLICATIONS
FLUID OVERLOAD - highest effect in
mortality
– loop diuretics
– early RRT
HYPERKALEMIA
– Loop diuretics
– K binding resins
– Insulin, D50 glucose, salbutamol
METABOLIC ACIDOSIS
– treat when pH < 7.2 or HCO3 < 15
HYPERPHOSPHATEMIA AND HYPOCALCEMIA
– hyperPO: rhabdomyolysis, hemolysis, and tumor lysis syndrome
HYPERURICEMIA

51. RENAL REPLACEMENT THERAPY
• HEMODIALYSIS, PERITONEAL DIALYSIS
• INDICATIONS
• Electrolytes imbalances: refractory hyperK
• Acid--‐base disturbances: met acidosis
• Uremic complications
• Encephalopathy
• Pericarditis
• Persistent nausea, and food intolerance
• Refractory volume overload
• Removal of toxic agents in overdose: Ethylene Glycol,
Methanol, Salicylates, Lithium, Theophylline, Isopropanol
Dialysis may delay recovery of renal function in AKI
- lead to hypotension and activation of inflammatory mediators

52. CASES

53. Contrast Induced Nephropathy (CIN)
RISK FACTORS:
• Baseline renal insufficiency
• Diabetes mellitus
• Congestive heart failure
• Large volume of contrast
• NSAIDs or ACE inhibitors
• Volume depletion
• rise in serum creatinine beginning 24–48 hours following
CONTRAST exposure, peaking within 3–5 days, and
resolving within 1 week

54. Pathophysiologic Mechanisms
Endothelial dysfunction
Vasoactive mediators
Free radicals and reperfusion damage
Hemorrheological factors
Tubular toxicity and immunological mechanisms

55. Direct cellular injury
and Renal medullary
hypoxia

56. Contrast--‐Induced Nephropathy (CIN)
MANAGEMENT
- best strategy is one of prevention
 Avoidance of volume depletion
- HYDRATION: NaHCO vs PNSS
– avoidance of NSAIDs, nephrotoxic drugs
• Use of low osmolal/nonionic contrast
agents
• Acetylcysteine(fluimucil,exflem) -?
• hemodialysis

57. HEPATORENAL SYNDROME
• defined as the development of renal failure in patients with
advanced liver dse in the ABSENCE of any identifiable causes
of renal pathology
• PRECIPITATING FACTORS
• diuretic therapy, SBP, large volume paracentesis, GI bleeding
• Functional renal failure
• hallmark of HRS is renal hypoperfusion, which is due to a
reduction in the renal perfusion pressure as well as to active
renal vasoconstriction
> Diagnosis of exclusion

58. HEPATORENAL SYNDROME
PORTAL HYPERTENSION

59. HYERDYNAMIC CIRCULATION
Liver dse and PORTAL HPN --- dilatation of the splanchnic
circulation, a result of both increased resistance to portal
flow due to the cirrhosis and to the presence of excess
vasodilators and/or decreased responsiveness of the
vasculature to endogenous vasoconstrictors.
• The severe jaundice can sensitize the renal vasculature to
the vasoconstrictive effects of norepinephrine, resulting
in greater renal vasoconstriction with any given level of
circulating norepinephrine.
• High levels of bile acids observed in cholestasis can cause
arterial vasodilation, thereby exaggerating the
hemodynamic instability.

61. HEPATORENAL SYNDROME
• Management of underlying cause
- liver transplant
• Stop diuretics, Low salt diet and free water
restriction
• Midodrine + Octreotide + Albumin
• Terlipressin + Albumin
• RRT- hemodialysis
• TIPS (Transjugular Intrahepatic portosystemic
Shunt)

62. • Fluids should be administered slowly, because nonresponders
may suffer an increase in ascites formation or pulmonary edema,
or both
• Albumin
• Paracentesis --- spontaneous bact peritonitis
Vasopressin (V1) receptor agonists, either alone or in combination
with the a-agonist midodrine, have shown promise in the reversal
of established HRS
• TIPS is prosthesis that bridges a branch of the portal vein with a
branch of the hepatic vein, effectively functioning as a side-to-
side portal caval shunt. It is very effective
in reducing portal pressure.

63. Heme Pigment Nephropathy
• RHABDOMYOLYSIS and severe Hemolysis
CAUSES OF RHABDOMYOLYSIS
Muscle Injury, Ischemia Trauma, pressure necrosis, burns, electric shock
Myofiber Exhaustion Seizures, excessive exercise, heat exhaustion
Toxins Alcohol, cocaine, amphetamine, ecstasy
Drugs Statin, fibrates, zidovudine, lithium, diuretics
Electrolyte disorders Hypophosphatemia, hypokalemia
Infections Viral(influenzae, HIV), bacterial(legionella, S.
pneumoniae, salmonella, S. aureus
Familial McArdle Disease, malignant hyperthermia
Other Hypothyroidism, polymyositis, dermatomyositis

64. Causes of hemoglobinuric AKI include incompatible
blood transfusion, autoimmune hemolytic anemia,
malaria (blackwater fever), glucose-6-phosphate
dehydrogenase deficiency, paroxysmal nocturnal
hemoglobinuria, march hemoglobinuria, and toxins
(dapsone, venoms)

65. Heme Pigment Nephropathy

66. • Heme pigment nephropathy is a common cause of AKI and usually
secondary to the breakdown of muscle fibers (rhabdomyolysis),
which release potentially nephrotoxic intracellular contents
(particularly myoglobin) into the systemic circulation or massive
hemolysis
• Free Heme ---bioactive and pro oxidant effect
• directly injury to structural components of muscle cells ----
depletion of energy stores, which lowers the normal threshold for
injury.
- poor physical condition or preexistent injury, typified by
alcoholic myopathy, vol depletion, exercise in heat
The renal injury is caused by a combination of factors, including
volume depletion, renal vasoconstriction, direct heme-protein–
mediated cytotoxicity, and intraluminal cast formation

67. Rhabdomyolysis: Treatment
• intravenous hydration: PNSS
– Maintain Urine Output @ 300ml/min
– A solution with 2.7% sodium bicarbonate (50 mmol/l)
should be given every second or third liter to maintain
urinary pH above 6.5 and to prevent intratubular
deposition of myoglobin and uric acid.
– Mannitol: prevent renal tubular cast deposition,
expand extracellular volume, and reduce
intracompartmental pressure, muscle edema, and
pain
• complications: hypocalcemia,

68. intravenous hydration should be initiated with isotonic saline
before the crushed limb is relieved to prevent precipitation of
the pigment in the tubular lumen. A solution with 2.7% sodium
bicarbonate (50 mmol/l) should be given every second or third
liter to maintain urinary pH above 6.5 and to prevent
intratubular deposition of myoglobin and uric acid. The urine
output should be maintained around 300 ml/h, which may
require an infusion of up to 12 liters of fluid per day
Muscle damage induces stretch activated ion channels, allowing
for influx of calcium into cells after reperfusion. The resultant
hypocalcemia is usually asymptomatic but
can lead to cardiac dysrhythmias.
- hypocalcemia should be treated only if symptomatic

69. Aminoglycoside Nephrotoxicity
• GENTAMYCIN
• the drug bind to the brush border of proximal tubule cells
and are then internalized by endocytosis - TUBULAR
NECROSIS--tubular obstruction --- decrease GFR
• Brush border loss -dysfunction of rearbsorption ---
TGFeedback activation----- decrease GFR
• AKI typically manifests after 5–7 days of therapy and can
present even after the drug has been discontinued.
• Hypomagnesemia

70. Acute Kidney Injury in a Patient with Cancer
• caused either by prerenal azotemia: vomiting, often in the
presence of NSAIDs,
• intrinsic renal azotemia:
TUMOR LYSIS SYNDROME(TLS)
- following chemoTx with lymphoma, solid tumors
- caused by uric acid and calciumphosphate
precipitation in the tubules.
- Tx: prophylactic allopurinol
HYPERCALCEMIA
- PTHrP, bone mets or tumor production of calcitriol
CHEMOTHERAPY AGENTS - cisplatin

71. TUMOR LYSIS :
Necrosis of tumor cells, typically following chemotherapy, may
release large amounts of nephrotoxic intracellular contents (uric
acid, phosphate, xanthine) into the circulation. This usually occurs
after treatment of lymphomas (particularly Burkitt) and leukemias
but may occur with solid tumors
Hyperuricemia - intratubular crystal obstruction and interstitial
nephritis, although this is usually prevented by prophylactic use of
allopurinol before chemotherapy
Cisplatin- Nephrotoxic injury affects both the proximal and distal
nephron and clinically may be associated with magnesium wasting,
impaired urinary concentration, and rarely salt wasting with
volume depletion.

72. Acute Kidney Injury in Heart Failure
(CARDIORENAL and RENOCARDIAC
SYNDROMES
Disorders of the heart and kidneys whereby
acute or chronic dysfunction in one organ
may induce acute or chronic dysfunction of
the other

75. (1) Acute Cardio-Renal Syndrome (Type 1): an acute
worsening of cardiac function leading to renal
dysfunction;
(2) Chronic Cardio-Renal Syndrome (Type 2): chronic
abnormalities in cardiac function leading to renal
dysfunction;
(3) Acute Reno-Cardiac Syndrome (Type 3): an acute
worsening of renal function causing cardiac
dysfunction(hyperkalaemic arrhythmias, fluid overload
induced by oliguria or anuria, pericarditis from delayed
treatment of severe AKI)
(4) Chronic Reno-Cardiac Syndrome (Type 4): chronic
abnormalities in renal function leading to cardiac disease;
(5) Secondary Cardio-Renal Syndromes (Type 5): systemic
conditions causing simultaneous dysfunction of the heart
and kidney

76. ACUTE ON CHRONIC KIDNEY FAILURE

77. Of all the risk factors for acquiring AKI, the presence of
preexisting chronic kidney disease is the most
predictive
“acute-on-chronic kidney disease” is used when AKI
occurs in the background of pre-existing CKD. The
presence of CKD greatly increases the risk of
developing renal injury.

78. HERBAL MEDICINE induced AKI
AFRICA - 25% to 35% of all AKI
from medical causes in hospitals
are related to herbal remedies
• aristolochic acid nephropathy
or balkan nephropathy
• Noni juice - hyperK
• star fruit – oxalate crystal
deposition
• Raw bile of the grass carp,
poisonous mushrooms, and
cottonseed oil are directly toxic
to renal tubules

79. After an episode of AKI there are
four potential outcomes
1. Full recovery and return of renal function to
baseline
2. Incomplete recovery of renal function resulting in
CKD
3. Exacerbation of pre-existing CKD accelerating
progression towards ESRD
4. Non-recovery of renal function leading to ESRD

80. SUMMARY
• AKI is defined as abrupt decline in kidney function
– KDIGO criteria
– BUN, creatinine elevation
– Diagnosis: history, urine indices, novel markers
– Life threatening condition
- volume overload
- met acidosis
- uremia
– Volume status should be assed and corrected
– Low dose dopamine no use in AKI

81. AKI in LEPTOSPIROSIS
• Leptospira interrogans
• leptospirae have special tropism for kidneys
• Kidney involvement is almost universal in leptospirosis but
becomes relevant in Weil’s disease
• AKI is typically nonoliguric
• Tubular changes characterized by high urinary fractional
excretion of sodium and hypokalemia
• MUDDY BROWN URINE---ATN
TREATMENT
• antibiotics-PCN, ceftriaxone
• early hemodialysis, mech vent(resp failure)

82. Weil disease is characterized by multiorgan
involvement, with diffuse alveolar hemorrhage,
pulmonary edema, acute respiratory distress
syndrome, or a combination of these features,
accompanied by AKI

83. NON CONVENTIONAL HEMODIALYSIS IN AKI
Continuous Renal Replacement
Therapy (CRRT)
• SLOW, controlled removal of
fluid(24-48Hrs)
• For hemodynamically unstable
patients
• All major studies had failed to
show better survival rates with
CRRT, despite its theoretical
superiority

84. HEPATORENAL SYNDROME
TYPE 1 TYPE 2
• rapid onset of renal failure
with a doubling of serum
creatinine to > 2.5 mg/dL or a
50% reduction in over a 2-wk
period.
• fulminant course with
oliguria, encephalopathy,
marked hyperbilirubinemia
• death usually within 1 month
of presentation
• Indolent course; stable GFR
• common in patients with
cirrhosis and portal
hypertension
• These patients tend to be less
severely jaundiced and
mainly present with
refractory ascites caused by
poor response to diuretics
• Death after 6 mos.

86. Intrarenal AKI is often the result of untreated or
untreatable prerenal azotemia that leads to ischemic AKI
RISK FACTORS :
• elderly patients
• with diabetes mellitus
• hypotensive and patients with a reduced effective
arterial volume