3. Introduction
• Both anesthesia and surgical stress can effect the renal performance
• Indirect
• Hemodynamics
• Sympathetic activity
• Humoral regulation
• Direct
• Dose and agent dependent
• Renal auto-regulation
• Tubular transport of Na and Organic acids
• Alteration of effect of ADH
• Indirect effects are more pronounced than direct effects
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4. • Both the kidneys weight about 0.4% of body weight but they receive 20-
25% cardiac output.
• Auto regulation of blood pressure occurs if MAP is below 80mm of Hg or
above 180 mm of Hg.
• Renal plasma flow = clearance of PAH = PAH(U)/PAH(P) x urine flow.
• Renal blood flow = RPF/1-Hematocrit.
• Normal RPF is 660ml/min, RBF is 1200ml/min.
• Glomerular filtration rate- volume of fluid filtered from glomerular
capillaries in to bowman's capsule per unit time.
• Calculated by inulin or creatinine clearance
• Creatinine (U) x urine flow / creatinine (P)
• Males is around 120+/-20 ml/min, females 90 +/- 20ml/min
• Filtration fraction = GFR/RPF, Normal is 20%
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5. Clinical tests for renal function
• Urine output
• Simple traditional intra operative and postoperative tool
• Less than 0.5 ml/kg/hr is considered as oliguria.
• Better threshold for fluid administration
• Creatinine
• Serum creatinine is reasonable approximation of GFR as it is freely filtered by the
glomerulus
• Relationship between creatinine and GFR is inverse and exponential
• Blood urea nitrogen
• Urea formed in the liver during the deamination of amino acids in the argenine cycle
• Urea is not an indicator for GFR as it is reabsorbed
• Ratio of BUN to creatinine is 10-15 to 1.
• That ratio helps to differentiate between pre-renal causes to tubular causes.
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6. E-GFR
• E-GFR = [140-weight/0.814 x creatinine umol/l] x 1 for male, 0.85 for
female
• Average estimated GFR is tabulated below
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Age E-GFR
20-29 116
30-39 107
40-49 99
50-59 93
60-69 85
70 and above 75
7. Interpretation of e-GFR
Kidney damage
stage
description Estimated GFR Other findings
1 Normal or minimal damage
with normal GFR
90 and above Protein or albumin in urine may
be high. Cells or casts are rarely
seen
2 Mild decrease in GFR 60-89 Protein or albumin in urine may
be high. Cells or casts are rarely
seen
3 Moderate decrease in GFR 30-59 High BP, anemia, abnormal
serum calcium, potassium,
phosphate
4 Severe decrease in GFR 15-29 High BP, anemia, bone disease
abnormal serum calcium,
potassium, phosphate, vitmin D
and parathyroid hormone
5 Kidney failure < 15 7
8. Volatile anesthetics
• They decrease GFR due to decrease in renal perfusion pressure
• Decreasing in systemic vascular resistance – Isoflurane, Sevoflurane
• Decreasing in Cardiac output - Halothane
• Decrease in GFR can be exacerbated by
• Hypovolemia
• Release of catecholamines
• ADH
• Painful stimuli of surgical incision
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9. Inhalational Anesthetic Florine content Effect on kidney
Halothane Fluoride levels are less No Nephrotoxicity
isoflurane Fluoride levels are less No Nephrotoxicity
Desflurane Fluoride levels are less, highly
stable, resists degradation by soda
lime
No Nephrotoxicity
Sevoflurane Fluoride levels are less, unstable,
degradation by soda lime forming
compound A,
Compound A is nephrotoxic
Enflurane Prolonged usage for more than 4
hours can cause accumulation of
inorganic fluoride levels
On prolonged usage nephrotoxic
Methoxyflurane Bio transformed into high inorganic
fluride levels
Highly nepfotoxic.
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10. Sevoflurane
• It is degraded in CO2 absorbents such as Barium hydroxide , soda
lime in to a vinyl ether called compound A.
• Compound A has been implicated to cause renal injury through
fluoride toxicity.
• High intrarenal fluoride impair the concentrating ability of kidney lead
to non oliguric renal failure.
• It is considered safe in patients with renal impairment as long as the
prolonged low flow anesthesia is avoided that is minimum flow more
than 2L/min.
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12. Fluoride induced nephrotoxicity
• Metabolism of inhalational anesthetics causes production of fluoride
ions.
• Isoflurane when used 20 MAC hours could lead to increase in serum
fluoride level above 50uM/L, no postoperative renal dysfunction
noted.
• Methoxyflurane and enflurane might cause renal dysfunction
especially associated with hypovolemia, shock, renal vasoconstriction.
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13. Opioids
• Commonly used for pain control in perioperative period.
• They decrease renal blood flow, GFR, Urine output which is minimal and
transient.
• Remifentanil pharmacokinetics are unaffected by renal functions due to
rapid ester hydrolysis.
• Renal toxicity is in context of inappropriate use that is higher than needed
dose or chronic use of opioids, deranged renal functions or with preexisting
dehydration.
• Chronic use of morphine and meperidine causes respiratory depression in
addition to kidney failure.
• Increased levels of meperidine has been associated with seizures.
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14. IV anesthetics
• Minor effects when used alone.
• Ketamine minimally effects and preserves renal functions during
hemorrhagic hypovolemia, tachycardia with increased blood pressure
makes it useful in patients in shock.
• Propofol is usually safe, but long term infusion can cause propofol
infusion syndrome which is associated with renal failure.
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15. Propofol Infusion Syndrome
• Priming factors – acute disease of central nervous system, sepsis, burns, trauma, pancreatitis.
• Triggering factors
• Glucocorticoids increase proteolysis myopathy rhabdomyolysis renal failure
• High dose propofol >4mg/kg/hr for more than 48 hours duration mitochondrial inhibition increased levels of FFA
arrythmia
• Catecholamines myofibrillar degeneration shock renal failure
• Life threatening condition characterized by acute refractory bradycardia progressing to asystole
with
• Metabolic acidosis
• Rhabdomyolysis
• Hyperlipidaemia
• Enlarged fatty liver
• Risk factors
• >4 mg/kg/hr that is >75umg /kg/min for 48 hours ( can occur at lower doses)
• Younger age
• Acute neurologic injury
• Catecholamine or corticosteroid infusion
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17. Muscle relaxants
• Muscle relaxants releasing histamine causes transient fall in blood
pressure, decrease in renal blood flow, and cardiac output.
Mivacurium, Atracurium, Succinylcholine, d-Tubocurarine.
• This hypotension is attributed to histamine release and autonomic
ganglionic blockade.
• Based on the clinical and experimental data muscle relaxants have
modest decrease in renal blood flow and no significant adverse
influence on the post operative renal functions when blood pressure
and cardiac output are adequately maintained.
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18. Colloids
• Albumin gives renoprotection is by maintaining the renal perfusion,
promoting proximal tubular integrity and function, binding of
endogenous toxin and nephrotoxic drugs and preventing oxidative
damage.
• Carbohydrate based artificial colloids like Hydroxy Ethyl Starch HES,
Dextran are frequently associated with acute kidney injury.
• Degradation products HES, Dextran causes direct tubular injury by
plugging of tubules.
• Renal failure fallowing HES and dextran use is often reported when
renal perfusion is reduce with preexisting renal damage is present.
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19. Dopamine and antidopaminergic drugs
• Dopamine dilate afferent and efferent arterioles in turn increase renal
perfusion.
• Metaclopramide, Phenothiazines and Droperidol impair the dopamine
response may precipitate AKI.
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20. NSAIDs
• Renal synthesis of vasodilating prostaglandins PGD2, PGE2, PGI2 are
important protective mechanism during systemic hypotension and
renal ischemia.
• NSAIDs inhibit the prostaglandin synthesis which impairs the renal
autoregulation during hypovolemia.
• They also causes acute interstitial nephritis.
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21. ACE inhibitors
• Angiotensin II causes generalized vasoconstriction secondarily
reduces the RBF.
• Both afferent and efferent glomerular arterioles are constricted, but
efferent arteriole is smaller the resistance is higher hence GFR is
relatively preserved.
• ACE inhibitors block the protective effect of angiotensin II and may
result in reduction of GFR during anesthesia.
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22. Positive pressure ventilation
• Positive pressure ventilation during general anesthesia
• Decrease venous return
• Decrease cardiac output
• Decrease in renal blood flow
• Decrease in GFR
• Decrease in cardiac output release of catecholamine, ADH, renin
and angiotensin II activation of sympathoadrenal system
decrease in renal blood flow.
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23. Regional anesthesia
• Spinal and epidural anesthesia they slightly decrease GFR, RBF in
proportion to that of MAP.
• Preexisting intravascular volume and quantity of intravenous fluids
given strongly influence the renal response to spinal and epidural
anesthesia.
• Decreased diuresis and marked fall in sodium excretion these trends
usually reversed during recovery.
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24. Effects of surgery on renal system
• Surgery influences renal functions by inducing alterations in prerenal
hemodynamics.
• Operative stress leas to an increase in circulating catecholamines and
angiotensin.
• Significant fluid shift, excessive blood loss, redistribution of third
space may lead to a prerenal oliguric state.
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25. Pneumoperitoneum
• It creates like an abdominal compartment syndrome during
laparoscopy.
• Increase in intra-abdominal pressure typically produces oliguria that
is proportional to insufflation pressures.
• Central venous compression renal, vena cava compression renal
parenchyma compression decrease cardiac output increase in
renin, aldosterone, ADH.
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26. Cardio pulmonary bypass
• Initiation of CPB associated with increase in stress hormone and
systemic inflammatory response.
• Elevated levels of catecholamines, cortisol's, vasopressin, angiotensin
are observed.
• Multiple humoral systems are activated such as complement,
coagulation and fibrinolysis.
• Increased amount of oxygen derived free radicles are generated.
• These mediators can cause decreased renal perfusion, direct tubular
injury and renal vasoconstriction.
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27. Cross clamping of aorta
• Cross clamping of aorta is associated with decrease in organ perfusion
distal to occlusion.
• Clamping of abdominal aorta is associated with transient renal
insufficiency.
• Clamping of thoracic aorta is associated with severe decrease in renal
blood flow, GFR, urine output.
• Mediated by catecholamines, Angiotensin II, sympathetic nervous
system.
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28. Renal protective measures
• Inj. Mannitol infusion prior to cross clamping.
• Int Dopamine renal dose infusion.
• Maintenance of intravascular volume and adequate cardiac functions.
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29. • Lithotomy causes the leg drain blood into central circulation acutely
mean BP and increase in cardiac output.
• Conversely rapid lowering of legs from lithotomy/Trendelenburg
acutely decreases the venous return can result in hypotension.
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30. Ischemic reperfusion
• Ischemic reperfusion is leading cause of perioperative acute kidney
injury which complicates major vascular, cardiac transplant and liver
surgeries.
• It occurs due to oxidative stress, inflammation, cellular necrosis,
apoptosis.
• Isoflurane and sevoflurane have preconditioning of reno protective
effects through anti-inflmatory, anti-apoptotic.
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31. • Sodium thiopentone pre treatment reduced renal ischemic reperfusion
injury induced by free radicals.
• Propofol protects from apoptosis by inhibiting the oxidative and
mitochondrial stress.
• Ketamine ameliorates the upregulation of inflammatory pathways.
• Lidocaine in epidural analgesia protect against IR by preventing
miRNA dysregulation.
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