acute renal failure

1. AKI
Acute Kidney Injury
By clinical pharmacist
Ahmed Shaltoot
Clinical pharmacy diploma(Ain Shams Univ.)
Pharm D (Beni-suif Univ.)
Healthcare and hospital management diploma(AUC)
Clinical pharmacy Egyptian Fellowship(in progress)

2. objectives
Categorize acute kidney
injury (AKI) as prerenal,
intrinsic, or postrenal, based
on patient history, physical
examination, and laboratory
values.
Identify risk factors for AKI.
Formulate preventive
strategies to decrease the
risk of developing AKI in
specific patient populations
Formulate a therapeutic
plan to manage AKI

3. Definition
• formerly called acute renal failure,
• Reversible, rapid, sudden decrease in glomerular filtration rate (GFR)
and the resultant accumulation of nitrogenous waste products (eg,
creatinine), with or without a decrease in urine output.

4. NORMAL VALUES OF GLOMERULAR FILTRATION
RATEas measured by inulin clearance (gold
standard)
Age GFR (Mean) (mL/min/1.73 m2) Range (mL/min/1.73 m2)
Neonates <34 wk gestational age
2–8 days 11 11–15
4–28 days 20 15-28
30–90 days 50 40-65
Neonates >34 wk gestational age
2–8 days 39 17–60
4–28 days 47 26-68
30–90 days 58 30–86
1–6 mo 77 39–114
6–12 mo 103 49–157
12–19 mo 127 62–191
2 yr–adult 127 89–165

5. Estimation of GFR
• Cockcroft-Gault Formula
• MDRD Study Equation

6. Jelliffe equation
• Ess (males) = IBW x (29.3 -[0.203 x (age)])
Ess (females) = IBW x (25.1 -[0.175 x (age)])
E = Esscorr - [4 x IBW x (Scr2-Scr1)] / (Time difference in days)
Scr2= latest serum creatinine. Scr1= earlier serum
creatinine.
CrCl (ml/min/1.73 m2) = E / (14.4 x Scr)

7. CHILDREN
• Schwartz equation: Traditional equation for eGFR. However, given
changes in the laboratory assays used to determine creatinine,
this equation systemically overestimates GFR and should be
considered when applying clinically:
• eGFR (mL/min/ 173m2) = kL/Pcr ,
• Where k = proportionality constant; L = height (cm); and Pcr= plasma
creatinine (mg/dL)

8. PROPORTIONALITY CONSTANT FOR
CALCULATING GLOMERULAR FILTRATION RATE
Age k Values
Low birth weight during first year of life 0.33
Term AGA during first year of life 0.45
Children and adolescent girls 0.55
Adolescent boys 0.70

9. Definition

10. EPIDEMIOLOGY AND ETIOLOGY
• Approximately 5% to 7% of all hospitalized patients develop AKI.
• AKI is 5 to 10 times more prevalent in the hospital setting than
in the community setting, and 30% to 40% of survivors progress
to chronic kidney disease (CKD).
• Despite improvements in the medical care of individuals with
AKI, mortality generally exceeds 15% for patients in general
wards to 50% for ICU patients.
• AKI occurs in 2-3% of children admitted to pediatric tertiary care
centers and in as many as 8% of infants in neonatal intensive
care units

11. Staging

13. Risk factors for AKI

14. Causes Of AKI
Acute
kidney
injury
Prerenal
Intrinsic
or
Intrarenal
Postrenal

16. Phases of acute kidney injury.

17. Prerenal azotemia
• Intravascular volume depletion(common cause)
• Decreased effective circulating volume
• Hypotension, shock syndromes
• Increased renal vascular occlusion or constriction

18. Functional acute kidney injury
• Afferent arteriole vasoconstrictors
• Efferent arteriole vasodilators

21. Renal:
• a. Parenchymal disease due to vascular or glomerular lesions
• b. ATN: Typically a diagnosis of exclusion when no evidence of
renal parenchymal disease is present and prerenal and postrenal
causes have been eliminated if possible

22. Postrenal
• Ureter obstruction(bilateral or unilateral in solitary kidney):
• Malignancy(prostate or cervical cancer)
• Prostate hypertrophy
• Anticholinergic drugs(affect bladder outlet muscles)
• Renal calculi
• commonly due to inherited anatomic abnormalities in children

23. Drug induced renal injury
• prerenal
diuretics,ACEI,ARBs,NSAIDs,cyclosporine,interferon,interleukin-
2,tacrolimus
• intrinsic
Radiocontrast dye,Aminoglycosides,Foscarnet,Amphotericin
B,Penicillins,Rifampin,Immunoglobulin,Methotrexate,Lithium,Tetracycli
nes,Phenytoin,Cimetidine,Cocaine,mannitol,statins,cidofovir,Pentamidi
ne,Fluroquinolones,Allopurinol8,cisplatin,Cephalosporins,Thiazides,Ifo
sfamide,Indinavir,Gold,Mesalamine
• post renal
Indinavir,acyclovir,Sulfonamide

24. Diagnosis
Clinical
presentati-
on+ physical
examinati-
on,labs,di-
agnostic
procedures
Medication
history
Patient
history

25. Signs and Symptoms of AKI
• Peripheral edema signs
• Weight gain
• Nausea, vomiting, diarrhea, anorexia
• Mental status changes
• Fatigue
• Shortness of breath
• Pruritus
• Volume depletion (prerenal AKI) signs
• Weight loss (prerenal AKI)
• Anuria alternating with polyuria (postrenal AKI)
• Colicky abdominal pain radiating from flank to groin (postrenal AKI)

26. Clinical Presentation in children
• A carefully taken history is critical in defining the cause of AKI.
• An infant with a 3 day history of vomiting and diarrhea most likely
has prerenal AKI caused by volume depletion
• A 6 yr. old child with a recent pharyngitis who presents with
periorbital edema, hypertension, and gross hematuria most likely has
intrinsic AKI related to acute postinfectious glomerulonephritis.
• Pallor, decreased urine output, edema, hypertension, vomiting,
and lethargy. The hallmark of early kidney failure is oftenoliguria.

27. Oliguria
• Urine output <300 mL/m2/24 hr, or <0.5 mL/kg/hr in children
and <1.0 mL/kg/hrin infants. May be a reflection of intrinsic
or obstructive kidney disease. Always interpret urine output in
the context of physical exam, clinical scenario and fluid delivery.
For example, low urine output may be appropriate(physiologic
response to water depletion in a prerenal state) and “normal”
urine output may be inappropriate in a volume-depleted
patient (potentially representing kidney tubular damage or another
pathologic state).

28. LABORATORY DIFFERENTIATION OF OLIGURIA
Test Urine Prerenal Renal
Faena ≤1% >3%
BUN/Cr ratio >20:1 <10:1
specific gravity >1.015 <1.010

29. Physical Examination Findings (Signs)
• Increased blood pressure
• Jugular venous distention (JVD), pulmonary edema, rales(volume status)
• Asterixis
• Pericardial or pleural friction rub
• Hypotension or orthostatic hypotension, tachycardia, dry mucous
membranes, and poor peripheral perfusion (prerenal AKI)
• Rash, arthritis (intrinsic AKI due to acute interstitial nephritis,SLE)
• Bladder distention (postrenal bladder outlet obstruction)
• Palpable flank masses may be seen with renal vein thrombosis, tumors, cystic
disease, or urinary tract obstruction.

30. Laboratory Tests (Signs)
• Elevated SCr (reference range approximately 0.6–1.2 mg/dL)
• Elevated BUN (reference range approximately 8 to 25 mg/dL)
• BUN-to-creatinine ratio greater than 20:1 for units of mg/dL
(prerenal AKI); less than 20:1 for units of mg/dL (intrinsic or
postrenal AKI)
• Hyperkalemia
• Metabolic acidosis

31. Urinalysis
• Scant or bland (prerenal or postrenal AKI)
• Brown, muddy granular casts (intrinsic ATN)
• Proteinuria (glomerulonephritis or allergic interstitial nephritis)
• Eosinophiluria (acute interstitial nephritis)
• Hematuria or red blood cell casts (glomerular disease or
bleeding in urinary tract)
• WBCs or casts (acute interstitial nephritis or severe
pyelonephritis)

34. Common Diagnostic Procedures
• Urinary catheterization (used to rule out urethral obstruction. A catheter is
inserted into the bladder; increased urine output may occur with postrenal
obstruction.)
• Renal ultrasound (uses sound waves to assess size, position, and abnormalities
of the kidney. Can assist in the differentiation between AKI [normal-sized
kidneys] and CKD [small kidneys]. Can also show obstruction of the urinary tract
which is indicative of postrenal AKI.)
• Computed tomography (provides similar information as renal ultrasound but
with greater spatial resolution; assists in the diagnosis of masses, stones, and
pyelonephritis.)

35. Common Diagnostic Procedures(cont.)
• Magnetic resonance imaging (Uses strong magnetic fields and radio waves to
form images of the kidney; used as an alternative to CT.)
• Renal angiography (shows blood flow through the kidney; IV contrast dye is
administered and narrowing of the vasculature can be seen in conditions
such as renal artery stenosis and renal vein thrombosis.)
• Retrograde pyelography (injection of contrast dye into the ureters to localize
the site of urinary tract obstruction.)
• Kidney biopsy (collection of a kidney tissue sample for microscopic
evaluation; may aid in the diagnosis of glomerular and interstitial diseases.)
• CXR may reveal cardiomegaly, pulmonary congestion (fluid overload), or
pleural effusions

36. • Unfortunately, serum creatinine is a delayed and unreliable indicator of acute kidney
injury (AKI), for the following reasons:
• The creatinine level is influenced by multiple non-renal factors, such as age, gender,
muscle mass, muscle metabolism, diet, medications, and hydration status
• In AKI, the serum creatinine level can take several hours or days to reach a new steady
state and thus does not reflect the actual decrease in GFR in the acute setting
• Because of renal reserve, the serum creatinine level may not rise until more than half of
the kidney function has been lost
• Serum creatinine measurement does not allow differentiation between
hemodynamically mediated changes in renal function, such as pre-renal azotemia from
intrinsic renal failure or obstructive uropathy

37. • It must be generated by the damaged cells and exhibit the organ
specificity.
• Its concentration in the body must be proportional to the extent of
damage.
• It should be expressed early after the organ damage, when such
damage is still potentially reversible.
• Its concentration should decrease quickly after the acute injury episode
to enable its use as a therapeutic monitoring tool.
• It should be rapidly and reliably measurable.
• Stable in its matrix
• Inexpensive to measure

38. Novel Biomarkers of Acute Kidney Injury
Neutrophil gelatinase-associated lipocalin (NGAL)
Interleukin-18 (IL-18)
Kidney injury molecule 1 (KIM-1)
Cystatin C
Liver-type fatty acid–binding protein (L-FABP)
N acetyl B D glucosaminadase

39. (NGAL, IL-18)
(NGAL, cystatin C)
(NGAL, IL-18)

40. Treatment
Maintain state of euvolemia with good urine
output(at least 1ml/kg/hr.)
Return Sr.Cr to baseline
Correct electrolyte and acid-base
abnormalities
Appropriate drug dosages based on kidney
functions and avoidance of nephrotoxic drugs
Goals of therapy

42. Treatment Considerations in children
• 1. Placement of indwelling catheter to monitor urine output
• 2. Prerenal and postrenal factors should be excluded,and
intravascular volume maintained with appropriate fluids in
consultation with a pediatric nephrologist.
• 3. Diuretic therapy should be considered only after the adequacy of
the circulating blood volume has been established.
4.
5. If there is no response to a diuretic challenge, diuretics should be
discontinued and fluid restriction is essential.

43. Pharmacologic Therapy
• Loop Diuretics: Most studies evaluating loop diuretics (furosemide,
bumetanide, torsemide, and ethacrynic acid) for prevention or
treatment of AKI demonstrate improved urine output but no effect on
survival or need for dialysis.
• There are some reports that loop diuretics may worsen kidney function
and may be due in part to preload reduction that results in renal
vasoconstriction.
• Thus, loop diuretics should be reserved for the treatment of volume
overload and should not be given to prevent AKI or hasten recovery of
kidney function in euvolemic or hypovolemic individuals.

44. Pharmacologic Therapy(cont.)
• Several adaptive mechanisms by the kidney limit
effectiveness of loop diuretic therapy. As the concentration
of diuretic in the loop of Henle decreases, postdiuretic
sodium retention can occur. This effect can be minimized by
decreasing the dosage interval (ie, dosing more frequently)
or by administering a continuous infusion.

45. Pharmacologic Therapy(cont.)
• Prolonged administration of loop diuretics can lead to a second type of
diuretic resistance. Hypertrophy of distal convoluted tubule cells can occur
secondary to enhanced delivery of sodium to the distal tubule.
• Subsequently, increased sodium chloride absorption occurs in the distal
tubule, which diminishes the effect of the loop diuretic on overall sodium
excretion.
• Addition of a distal convoluted tubule diuretic, such as metolazone or
hydrochlorothiazide, to a loop diuretic can result in a synergistic increase in
urine output.
• It is common practice to administer the distal convoluted tubule diuretic 30
to 60 minutes prior to the loop diuretic in an attempt to inhibit sodium
reabsorption at the distal convoluted tubule.

48. Pharmacologic Therapy(cont.)
• Thiazide diuretics, when used as single agents, are generally not effective for
fluid removal.
• Mannitol is also not recommended for treating volume overload associated
with AKI. In patients with renal dysfunction, mannitol excretion is decreased,
resulting in expanded blood volume and hyperosmolality.
• Potassium sparing diuretics, which inhibit sodium reabsorption in the distal
nephron and collecting duct, are not sufficiently effective in removing fluid.
In addition, they increase the risk of hyperkalemia in patients already at risk.
• Thus loop diuretics are the diuretics of choice for managing volume
overload in AKI.

49. Pharmacologic Therapy(cont.)
• Based on the lack of conclusive evidence, there is no indication for
use of low dose dopamine in treating the AKI.
• Fenoldopam, a selective dopamine-1 receptor agonist approved for
short-term management of severe hypertension, has also been
studied for prevention and treatment of AKI. No data conclusively
support its use, and the risk of hypotension further limits routine
administration.
• Studies are underway to investigate the utility of atrial natriuretic
peptide, a hormone secreted by the heart that generates sodium
loss, in prevention or early treatment of AKI.

50. To sum up

51. Nonpharmacologic Treatment
• Renal Replacement Therapy: dialysis may be necessary in patients with established AKI to treat volume overload
that is unresponsive to diuretics, to minimize accumulation of nitrogenous waste products, and to correct
electrolyte and acid–base abnormalities while renal function recovers. There is wide variation in practice on
indications for RRT, timing of initiation and discontinuation of RRT, intensity of treatment, and optimal type of
RRT.
• Absolute indications for dialysis usually include:
• BUN greater than 150 mg/dL (35.7 mmol/L), uremic pericardial effusion, neurologic symptoms
• Potassium greater than 6.5 mEq/L (6.5 mmol/L) despite restriction of delivery and medical management.Calcium
and phosphorus imbalance (e.g., hypocalcemia with tetany, seizures in the presence of a very high serum
phosphate level).Derangements implicated in neurologic abnormalities.
• Metabolic acidosis with a pH less than 7.15(Intractable metabolic acidosis)
• Diuretic-resistant fluid overload
• Ingestion or accumulation of dialyzable toxins or poisons: Lithium, ammonia, alcohol,
barbiturates,ethylene glycol, isopropanol, methanol, salicylates,theophylline.

52. Comparison of Peritoneal Dialysis, Intermittent
Hemodialysis, and Continual Renal Replacement
Therapy

53. Supportive Therapy
• Supportive therapy in AKI includes adequate nutrition,
correction of electrolyte and acid–base abnormalities
(particularly hyperkalemia and metabolic acidosis), fluid
management, and correction of any hematologic abnormalities.
• Because AKI can be associated with multiorgan failure,
treatment may include the medical management of infections,
cardiovascular and GI conditions, and respiratory failure.

54. Management of complications
Complication Management
Hyperkalemia •Calcium gluconate 1.0 mL/kg IV, over 3-5 min
•Sodium bicarbonate, 1-2 mEq/kg IV, over 5-10 min
•Insulin 0.1 units/kg + G 50% solution 1 mL/kg, over 1
hr
•Beta 2 agonist(salbutamol) 10-20 MG NEUBILIZER
•hemodialysis
Acidosis IV or oral sodium bicarbonate
Hemodialysis if severe acidosis < 7.15
Hypocalcemia  low-phosphorus diet, and phosphate binders
should be orally administered to bind any ingested
phosphate and increase GI phosphate excretion.
Hyponatremia  fluid restriction
 hypertonic (3%) saline with symptomatic
hyponatremia (seizures, lethargy) or with a serum
sodium level <120 mEq/L

55. Management of complications(cont.)
Complication Management
GI bleeding H2 blockers such as ranitidine are commonly
administered to prevent this complication
Hypertension • Salt and water restriction
• Diuretics, amlodipine, propranolol, labetalol
administration
Neurologic symptoms(headache, seizures, lethargy,
and confusion (encephalopathy).
Benzodiazepams and managing precipitating cause
anemia (hemodilution)  packed red blood cells if their hemoglobin level
falls below 7 g/dL(HUS,SLE,Bleeding)
Nutrition o sodium, potassium, and phosphorus should be
restricted
o Protein intake should be moderately restricted
while maximizing caloric intake, parenteral
hyperalimentation with essential amino acids
should be considered.

56. Treatment
1. Prerenal azotemia: Correct primary hemodynamics.
a. Normal saline if volume depleted
b. Pressure management if needed
c. Blood products if needed
2. Intrinsic: No specific therapy universally effective
a. Eliminate the causative hemodynamic abnormality or toxin.
b. Avoid additional insults.
c. Manage fluid and electrolytes to prevent volume depletion or overload and
electrolyte imbalances.
d. Nutrition support is important, but no specific recommendations are widely
accepted.

57. Treatment (Cont.)
e.Medical therapy
i. Loop diuretics: Recommend not using to prevent AKI (Kidney Disease: Improving Global Outcomes
[KDIGO], Grade 1B) and suggest not using to treat AKI, except to manage hypervolemia (KDIGO,
Grade 2C)
ii. Fenoldopam: Suggest not using to prevent or treat AKI (KDIGO, Grade 2C)
iii. Dopamine: Recommend not using low-dose dopamine to prevent or treat AKI (KDIGO, Grade 1A)
iv. Atrial natriuretic peptide: Suggest not using to prevent (KDIGO, Grade 2C) or treat (KDIGO, Grade
2B) AKI
v. Recombinant human insulin-like growth factor-1: Recommend not using to prevent or treat AKI
(KDIGO, Grade 1B)
3. Postrenal AKI: Relieve obstruction. Early identification is important. Consult urology or radiology.

58. Refrences
• American board pharmacotherapy
• Chapter 19, THE HARRIET LANE HANDBOOK TWENTY-FIRST
EDITION,The Harriet Lane Service at The Charlotte R. Bloomberg
Children’s Center of The Johns Hopkins Hospital
• Chapter 535 Renal Failure, Section 5 Acute Kidney Injury and Chronic
Kidney Disease, PartXXIII Nephrology, Nelson TEXTBOOK of
PEDIATRICS, EDITION 20