This document discusses the prevention and management of acute kidney injury (AKI) in critically ill patients. It defines AKI and describes its causes and complications. Novel biomarkers for earlier AKI diagnosis are discussed. Prevention focuses on optimizing hemodynamics, fluid balance, and avoiding nephrotoxins. Treatment involves supporting organ functions and addressing complications like electrolyte abnormalities and malnutrition. Dialysis is indicated for fluid overload, hyperkalemia, acidosis or uremic complications. Careful attention to medication dosing and nutrition is important for AKI patients.

1. PREVENTION AND
MANAGEMENT OF AKI IN
CRITICALLY ILL
MODERATOR: DR.PRATHAP M.D
PRESENTOR: DR.ATHIRA

2. ACUTE KIDNEY INJURY:
 It is defined by the impairment of kidney filtration and excretory function over days to
weeks (generally known or expected to have occurred within 7 days), resulting in the
retention of nitrogenous and other waste products normally cleared by the kidneys.
 AKI is not a single disease but rather a designation for a heterogeneous group of
conditions that share common diagnostic features: specifically, an increase in
serum creatinine (SCr).
 Nonoliguric – U.O >400ml/day
 Oliguric – U.O <400ml/day
 Anuric – U.O <100ml/day

5. NOVEL BIOMARKERS
• BUN and creatinine are functional biomarkers of glomerular filtration rather
than tissue injury biomarkers and, therefore, may be suboptimal for the
diagnosis of actual parenchymal kidney damage.
• BUN and creatinine are also relatively slow to rise after kidney injury.
• Several urine and blood biomarkers have been investigated and show
promise for earlier and accurate diagnosis of AKI and for predicting AKI
prognosis.

6. • Kidney injury molecule-1 (KIM-1) is a type 1 transmembrane protein that is
abundantly expressed in proximal tubular cells injured by ischemia or multiple,
distinct nephrotoxins, such as cisplatin.
• KIM-1 is not expressed in appreciable quantities in the absence of tubular
injury or in extrarenal tissues.
• KIM-1 can be detected after ischemic or nephrotoxic injury in the urine and
plasma. Neutrophil gelatinase associated lipocalin (NGAL, also known as
lipocalin-2 or siderocalin) is another biomarker of AKI.

7.  NGAL is highly upregulated after inflammation and kidney injury and can be
detected in the plasma and urine within 2 h of cardiopulmonary bypass–
associated AKI.
 Soluble urokinase plasminogen activator receptor (suPAR) is a signaling
glycoprotein expressed in multiple cell types and thought to be involved in the
pathogenesis of certain kidney diseases; suPAR has been measured in the
plasma and found to predict the subsequent development of AKI.

9. COMPLICATIONS OF AKI
 The kidney plays a central role in homeostatic control of volume status,
blood pressure, plasma electrolyte composition, and acid-base balance,
and for excretion of nitrogenous and other waste products.
 Complications associated with AKI are, therefore, protean, and depend
on the severity of AKI and other associated conditions.
 Mild to moderate AKI may be entirely asymptomatic, particularly early in
the course.

10. ■■UREMIA
• Buildup of nitrogenous waste products, manifested as an elevated BUN
concentration, is a hallmark of AKI.
• BUN itself poses little direct toxicity at levels <100 mg/dL.
• At higher concentrations, mental status changes and bleeding
complications can arise.
• Other toxins normally cleared by the kidney may be responsible for the
symptom complex known as uremia.

11. ■■HYPERVOLEMIA AND HYPOVOLEMIA
 Expansion of extracellular fluid volume is a major complication of oliguric and
anuric AKI, due to impaired salt and water excretion.
 The result can be weight gain, dependent edema, increased jugular venous
pressure, and pulmonary edema; the latter can be life threatening.
 Pulmonary edema can also occur from volume overload and hemorrhage in
pulmonary renal syndromes.
 AKI may also induce or exacerbate acute lung injury characterized by
increased vascular permeability and inflammatory cell infiltration in lung
parenchyma.
 Recovery from AKI is often heralded by an increase in urine output.
 This “polyuric” phase of recovery may be due to an osmotic diuresis from
retained urea and other waste products as well as delayed recovery of tubular

12. ■■HYPONATREMIA
 Abnormalities in plasma electrolyte composition can be mild or life
threatening.
 The dysfunctional kidney has limited ability to regulate electrolyte
balance.
 Administration of excessive hypotonic crystalloid or isotonic
dextrose solutions can result in hypoosmolality and hyponatremia,
which, if severe, can cause neurologic abnormalities, including
seizures.

13. • ■■HYPERKALEMIA
• An important complication of AKI is hyperkalemia.
• Marked hyperkalemia is particularly common in rhabdomyolysis,
hemolysis, and tumor lysis syndrome due to release of
intracellular potassium from damaged cells.
• Muscle weakness may be a symptom of hyperkalemia.
• Potassium affects the cellular membrane potential of cardiac and
neuromuscular tissues.
• The more serious complication of hyperkalemia is due to effects
on cardiac conduction, leading to potentially fatal arrhythmias.

14. ■■ACIDOSIS
Metabolic acidosis, usually accompanied by an elevation in the anion gap, is
common in AKI, and can further complicate acid-base and potassium balance
in individuals with other causes of acidosis, including sepsis, diabetic
ketoacidosis, or respiratory acidosis.

15. ■■HYPERPHOSPHATEMIA AND HYPOCALCEMIA
 AKI can lead to hyperphosphatemia, particularly in highly catabolic patients
or those with AKI from rhabdomyolysis, hemolysis, and tumor lysis
syndrome.
 Metastatic deposition of calcium phosphate can lead to hypocalcemia.
 AKI-associated hypocalcemia may also arise from derangements in the
vitamin D–parathyroid hormone–fibroblast growth factor-23 axis.
 Hypocalcemia is often asymptomatic but can lead to perioral paresthesias,
muscle cramps, seizures, carpopedal spasms, and prolongation of the QT
interval on electrocardiography.
 Calcium levels should be corrected for the degree of hypoalbuminemia, if
present, or ionized calcium levels should be followed.

16.  ■BLEEDING
 Hematologic complications of AKI include anemia and bleeding, both of which
are exacerbated by coexisting disease processes such as sepsis, liver disease,
and disseminated intravascular coagulation.
 Direct hematologic effects from AKI-related uremia include decreased
erythropoiesis and platelet dysfunction.
 ■MALNUTRITION
 AKI is often a severely hypercatabolic state, and therefore malnutrition is a
major complication

17. PREVENTION AND TREATMENT OF AKI
The management of individuals with and at risk for AKI varies according to the
underlying cause.
Common to all are several principles:
 Optimization of hemodynamics,
 correction of fluid and electrolyte imbalances,
 discontinuation of nephrotoxic medications,
 and dose adjustment of administered medications are all critical.
 Common causes of AKI such as sepsis and ischemic ATN do not yet have specific
therapies once injury is established, but meticulous clinical attention is needed to
support the patient until (if) AKI resolves

18. Prerenal Azotemia
 Prevention and treatment of prerenal azotemia require optimization of renal
perfusion.
 The composition of replacement fluids should be targeted to the type of fluid lost.
 Severe acute blood loss should be treated with packed red blood cells.
 In AKI, oliguria alone is not an indication for fluid administration.
 Intravascular hypovolemia should be the only indication.
 Optimal fluid composition is not well defined.
 Crystalloid solutions are less expensive than albumin-containing solutions, and
albumin does not provide a survival benefit compared to crystalloid.

19.  Albumin may decrease fluid requirements but does not reduce the need for renal
replacement therapy.
 Buffered crystalloid solutions (e.g., Ringer’s Lactate, Hartmann’s solution,
Plasma-Lyte) are recommended for patients with AKI who are not
hypochloremic; 0.9% saline is recommended for hypovolemic hypochloremic
patients if the serum chloride concentration is closely monitored.
 Excessive chloride administration from 0.9% saline may lead to hyperchloremic
metabolic acidosis and may impair GFR.
 Hydroxyethyl starch solutions increase the risk of severe AKI and are
contraindicated.
 Bicarbonate-containing solutions (e.g., dextrose water with 150 mEq sodium
bicarbonate) can be used if metabolic acidosis is a concern.

20.  AKI due to acute glomerulonephritis or vasculitis may respond to
immunosuppressive agents and/or plasmapheresis .
 Allergic interstitial nephritis due to medications requires
discontinuation of the offending agent.
 AKI due to scleroderma (scleroderma renal crisis) should be
treated with ACE inhibitors.
 Idiopathic TTP is a medical emergency and should be treated
promptly with plasma exchange.
 Pharmacologic blockade of complement activation may be effective
in atypical HUS.

21.  Early and aggressive volume repletion is mandatory in patients with
rhabdomyolysis, who may initially require 10 L of fluid per day.
 Alkaline fluids (e.g., 75 mmol/L sodium bicarbonate added to 0.45% saline)
may be beneficial in preventing tubular injury and cast formation, but carry the
risk of worsening hypocalcemia.
 Diuretics may be used if fluid repletion is adequate but unsuccessful in
achieving urinary flow rates of 200–300 mL/h.
 There is no specific therapy for established AKI in rhabdomyolysis, other than
dialysis in severe cases or general supportive care to maintain fluid and
electrolyte balance and tissue perfusion.
 Careful attention must be focused on calcium and phosphate status because
of precipitation in damaged tissue and release when the tissue heals.

22. Postrenal AKI
 Prompt recognition and relief of urinary tract obstruction can forestall the
development of permanent structural damage induced by urinary stasis.
 The site of obstruction defines the treatment approach.
 Transurethral or suprapubic bladder catheterization may be all that is
needed initially for urethral strictures or functional bladder impairment.
 Ureteric obstruction may be treated by percutaneous nephrostomy tube
placement or ureteral stent placement.
 Relief of obstruction is usually followed by an appropriate diuresis for
several days.
 In rare cases, severe polyuria persists due to tubular dysfunction and may
require continued administration of intravenous fluids and electrolytes for a

23. SPECIFIC ISSUES
1. Nephrotoxin-specific
a. Rhabdomyolysis: aggressive intravenous fluids; consider forced alkaline
diuresis
b. Tumor lysis syndrome: aggressive intravenous fluids and allopurinol or
rasburicase
2. Volume overload
a. Salt and water restriction
b. Diuretics
c. Ultrafiltration
3. Hyponatremia
a. Restriction of enteral free water intake, minimization of hypotonic
intravenous solutions including those containing dextrose
b. Hypertonic saline is rarely necessary in AKI. Vasopressin antagonists are
generally not needed.

24. 4. 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
5. Metabolic acidosis
a. Sodium bicarbonate (if pH <7.2 to keep serum bicarbonate >15 mmol/L)
b. Administration of other bases, e.g., THAM
c. Renal replacement therapy

25. 6. Hyperphosphatemia
a. Restriction of dietary phosphate intake
b. Phosphate binding agents (calcium acetate, sevelamer
hydrochloride,
aluminum hydroxide—taken with meals)
7. Hypocalcemia
a. Calcium carbonate or calcium gluconate if symptomatic
8. Hypermagnesemia
a. Discontinue Mg2+ containing antacids

26. 9. Hyperuricemia
a. Acute treatment is usually not required except in the setting of tumor lysis
syndrome (see above)
10. Nutrition
a. Sufficient protein and calorie intake (20–30 kcal/kg per day) to avoid
negative nitrogen balance. Nutrition should be provided via the enteral
route if possible.
11. Drug dosing
a. Careful attention to dosages and frequency of administration of drugs,
adjustment for degree of renal failure
b. Note that serum creatinine concentration may overestimate renal function
in the non–steady state characteristic of patients with AKI.

27. Dialysis Indications and Modalities :
Dialysis is indicated when medical management fails to control volume
overload, hyperkalemia, or acidosis; in some toxic ingestions;
and when there are severe complications of uremia:
 asterixis,
 pericardial rub or effusion,
 encephalopathy,
 uremic bleeding.
Late initiation of dialysis carries the risk of avoidable volume, electrolyte, and
metabolic complications of AKI.

28. Electrolyte and Acid-Base Abnormalities.
 Metabolic acidosis is generally not treated unless severe (pH <7.20 and serum bicarbonate
<15 mmol/L).
 Acidosis can be treated with oral or intravenous sodium bicarbonate , but overcorrection
should be avoided because of the possibility of metabolic alkalosis, hypocalcemia,
hypokalemia, and volume overload.
 Hyperphosphatemia is common in AKI and can usually be treated by limiting intestinal
absorption of phosphate using phosphate binders (calcium carbonate, calcium acetate,
lanthanum, sevelamer, or aluminum hydroxide).
 Symptomatic hypocalcemia should be treated with calcium gluconate or calcium chloride.
 Ionized calcium should be monitored rather than total calcium when hypoalbuminemia is
present.

29. Malnutrition
 Increased catabolism with protein energy wasting is common in severe AKI, particularly in the
setting of multisystem organ failure.
 Inadequate nutrition may lead to starvation ketoacidosis and protein catabolism.
 Excessive nutrition may increase the generation of nitrogenous waste and lead to worsening
azotemia.
 Total parenteral nutrition requires large volumes of fluid administration and may complicate
efforts at volume control.
 According to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, patients
with AKI
 should achieve a total energy intake of 20–30 kcal/kg per day.
 Protein intake should vary depending on the severity of AKI: 0.8–1.0 g/kg per day in
noncatabolic AKI without the need for dialysis; 1.0–1.5 g/kg per day in patients on dialysis;
and up to a maximum of 1.7 g/kg per day
 if hypercatabolic and receiving continuous renal replacement therapy.

30.  Anemia
 The anemia seen in AKI is usually multifactorial and is not improved by
erythropoiesis-stimulating agents, due to their delayed onset of action and the
presence of bone marrow resistance in critically ill patients.
 Uremic bleeding may respond to desmopressin or estrogens, but may require
dialysis for treatment in the case of longstanding or severe uremia.
 Gastrointestinal prophylaxis with proton pump inhibitors or histamine (H2)
receptor blockers is required.
 It is important to recognize, however, that proton pump inhibitors have been
associated with AKI from interstitial nephritis, a relationship that is increasingly
being recognized.
 Venous thromboembolism prophylaxis is important and should be tailored to the
clinical setting; lowmolecular- weight heparins and factor Xa inhibitors have
unpredictable pharmacokinetics in severe AKI and should generally be avoided if

31. DOPAMINE FOR THE PREVENTION OR TREATMENT OF AKI
Low-dose dopamine administration (1–3 mg/kg/min) to healthy individuals causes:
 renal vasodilation,
 natriuresis,
 and increased GFR;
 because of these effects,
it has been given as prophylaxis for AKI associated with :
 radiocontrast administration,
 repair of aortic aneurysms,
 orthotopic liver transplantation,
 unilateral nephrectomy,
 renal transplantation, and chemotherapy with interferon

32. NATRIURETIC PEPTIDES FOR THE PREVENTION OR TREATMENT OF AKI
 Several natriuretic peptides are in clinical use or in development for treatment of
congestive heart failure (CHF) or renal dysfunction, and could potentially be useful to
prevent or treat AKI.
 Atrial natriuretic peptide (ANP) is a 28-amino-acid peptide with diuretic, natriuretic, and
vasodilatory activity.
 ANP is mainly produced in atrial myocytes, and the rate of release from the atrium
increases in response to atrial stretch.
 Early animal studies showed that ANP decreases preglomerular vascular resistance and
increases postglomerular vascular resistance, leading to increased GFR.
 It also inhibits renal tubular sodium reabsorption.

33.  Increases in GFR and diuresis have also been confirmed in clinical studies.
 It could thus be expected that ANP might be useful for treatment of AKI, and several
RCTs have been conducted to test this hypothesis
Urodilatin is a natriuretic peptide that is produced by renal tubular cells, and was found
to have the same renal hemodynamic effect as ANP without systemic hypotensive
effects.
Nesiritide (brain natriuretic peptide) is the latest natriuretic peptide introduced for
clinical use, and is approved by the Food and Drug Administration (FDA) only for the
therapy of acute, decompensated CHF.

34. GROWTH FACTOR INTERVENTION
• Recovery from AKI involves increased expression of various growth factors acting
via autocrine, paracrine, and endocrine mechanisms.
• The advent of recombinant growth factors has stimulated research exploring their
therapeutic potential in AKI.
• Experimental studies have yielded promising results with individual growth factors
including insulin-like growth factor-1 (IGF-1), hepatic growth factor, and, more
recently, erythropoietin

35. ADENOSINE RECEPTOR ANTAGONISTS
 The activation of tubuloglomerular feedback in response to elevated luminal chloride
concentrations in the distal renal tubules is an early event in ischemic AKI.
 Adenosine released as part of the tubuloglomerular feedback loop binds to glomerular
adenosine A1 receptor, causing vasoconstriction of the afferent arteriole, decreased
renal blood flow and GFR, and sodium and water retention.
 This well-known role of adenosine in this phenomenon has stimulated a body of
research seeking to prevent or treat AKI with adenosine receptor antagonists, primarily
in three clinical syndromes with increased risk of AKI: perinatal asphyxia, radiocontrast
exposure, and cardiorenal syndrome.
 Theophylline is a nonselective adenosine receptor antagonist.

36. SOME CT STRATEGIES IN PATIENTS AT RISK OF CI-AKI
 Perform CT, when possible, without contrast media; scrutinize the examination and discuss with the
referral physician-surgeon before deciding on the need for contrast media.
 Dosing per kilogram body weight to reduce the amount of contrast media is needed in thin patients.
 Adapt injection duration to scan duration when performing CT-angiography, so that the injection is not
still running when the scan is finished.
 Use a saline chaser to decrease the amount of contrast media, by using the contrast medium that
otherwise would remain in the dead space of the arm veins; this may save 10–20 ml of contrast media.
 Use 80 kVp; contrast-medium dose may be reduced by a factor of 1.5–1.7 compared to the dose used
at 120 kVp since iodine attenuation increases, and combine with increased tube loading (mAs) to
maintain signal-to-noise ratio.
 Further reduction of contrast media may be instituted in patients with known decreased cardiac
output (not unusual in patients with renal impairment) undergoing CT-angiographic studies.

37. Prevention of AKI (KDIGO GUIDELINES)
• In the absence of hemorrhagic shock, they suggest using isotonic crystalloids
rather than colloids (albumin or starches) as initial management for expansion of
intravascular volume in patients at risk for AKI or with AKI.
• they recommend the use of vasopressors in conjunction with fluids in patients
with vasomotor shock with, or at risk for, AKI.

38.  In critically ill patients, they suggest insulin therapy targeting plasma glucose 110–149 mg/dl (6.1–
8.3 mmol/l).
 They suggest achieving a total energy intake of 20–30 kcal/kg/d in patients with any stage of AKI.
 They suggest to avoid restriction of protein intake with the aim of preventing or delaying initiation of
RRT.
 They suggest administering 0.8–1.0 g/kg/d of protein in noncatabolic AKI patients without need for
dialysis (2D), 1.0–1.5 g/kg/d in patients with AKI on RRT (2D), and up to a maximum of 1.7 g/kg/d in
patients on continuous renal replacement therapy (CRRT) and in hypercatabolic patients.
 they suggest providing nutrition preferentially via the enteral route in patients with AKI.
 they recommend not using diuretics to prevent AKI.
 they suggest not using diuretics to treat AKI, except in the management of volume overload.

39. • they suggest not using aminoglycosides for the treatment of infections unless
no suitable, less nephrotoxic, therapeutic alternatives are available.
• they suggest that, in patients with normal kidney function in steady state,
aminoglycosides are administered as a single dose daily rather than multiple-
dose daily treatment regimens.
• they recommend monitoring aminoglycoside drug levels when treatment with
multiple daily dosing is used for more than 24 hours.

40. • they suggest using topical or local applications of aminoglycosides (e.g.,
respiratory aerosols, instilled antibiotic beads), rather than i.v.
application, when feasible and suitable.
• they suggest using lipid formulations of amphotericin B rather than
conventional formulations of amphotericin B.
• they suggest not using NAC to prevent AKI in critically ill patients with
hypotension.
• they recommend not using oral or i.v. NAC for prevention of postsurgical
AKI.

41. • Initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acid-
base balance exist.
• Discontinue RRT when it is no longer required, either because intrinsic kidney
function has recovered to the point that it is adequate to meet patient needs, or
because RRT is no longer consistent with the goals of care.
• They suggest not using diuretics to enhance kidney function recovery, or to reduce
the duration or frequency of RRT.
• In a patient with AKI requiring RRT, base the decision to use anticoagulation for RRT
on assessment of the patient’s potential risks and benefits from anticoagulation.
• We recommend using anticoagulation during RRT in AKI if a patient does not have an
increased bleeding risk or impaired coagulation and is not already receiving systemic
anticoagulation.

42. • For patients without an increased bleeding risk or impaired coagulation and not
already receiving effective systemic anticoagulation, they suggest the following:
• For anticoagulation in intermittent RRT, we recommend using either
unfractionated or low-molecularweight heparin, rather than other anticoagulants.
• For anticoagulation in CRRT, we suggest using regional citrate anticoagulation
rather than heparin in patients who do not have contraindications for citrate.
• For anticoagulation during CRRT in patients who have contraindications for citrate,
we suggest using either unfractionated or low-molecular-weight heparin, rather
than other anticoagulants.

43. • In a patient with heparin-induced thrombocytopenia (HIT), all heparin must be stopped
and we recommend using direct thrombin inhibitors (such as argatroban) or Factor Xa
inhibitors (such as danaparoid or fondaparinux) rather than other or no anticoagulation
during RRT.
• In a patient with HIT who does not have severe liver failure, they suggest using
argatroban rather than other thrombin or Factor Xa inhibitors during RRT.

44. • they suggest initiating RRT in patients with AKI via an uncuffed nontunneled dialysis
catheter, rather than a tunneled catheter.
• When choosing a vein for insertion of a dialysis catheter in patients with AKI,
consider these preferences
• First choice: right jugular vein;
• Second choice: femoral vein;
• Third choice: left jugular vein;
• Last choice: subclavian vein with preference for the dominant side.
• they recommend using ultrasound guidance for dialysis catheter insertion

45. • they recommend obtaining a chest radiograph promptly after placement and before first use of an
internal jugular or subclavian dialysis catheter.
• they suggest not using topical antibiotics over the skin insertion site of a nontunneled dialysis catheter in
ICU patients with AKI requiring RRT.
• they suggest not using antibiotic locks for prevention of catheter-related infections of nontunneled
dialysis catheters in AKI requiring RRT.
• they suggest to use dialyzers with a biocompatible membrane for IHD and CRRT in patients with AKI.
• Use continuous and intermittent RRT as complementary therapies in AKI patients.
• they suggest using CRRT, rather than standard intermittent RRT, for hemodynamically unstable patients.
• they suggest using CRRT, rather than intermittent RRT, for AKI patients with acute brain injury or other
causes of increased intracranial pressure or generalized brain edema

46. • they suggest using bicarbonate, rather than lactate, as a buffer in dialysate and
replacement fluid for RRT in patients with AKI.
• they recommend using bicarbonate, rather than lactate, as a buffer in dialysate and
replacement fluid for RRT in patients with AKI and circulatory shock.
• they suggest using bicarbonate, rather than lactate, as a buffer in dialysate and
replacement fluid for RRT in patients with AKI and liver failure and/or lactic acidemia.
• The dose of RRT to be delivered should be prescribed before starting each session of
RRT.
• they recommend frequent assessment of the actual delivered dose in order to adjust
the prescription

47. • Provide RRT to achieve the goals of electrolyte, acid-base, solute, and fluid balance
that will meet the patient’s needs.
.

48. THANK YOU