Renal Disorder pharmacotherapy

1. Renal Disorders Pharmacotherapy
By: Tsegaye Melaku
[B.Pharm, MSc, Clinical Pharmacist]
March, 2017
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et
+251913765609
Chapter 2
Acute Kidney Injury [AKI]

2. Lesson Objectives
 Upon completion of the chapter, you will be able to:
Assess a patient’s kidney function based on clinical presentation,
laboratory results, and urinary indices.
Identify pharmacotherapeutic outcomes and endpoints of therapy
in a patient with AKI.
Apply knowledge of the pathophysiology of AKI to the
development of a treatment plan.
Design a diuretic regimen to treat volume overload in AKI.
Develop strategies to minimize the occurrence of drug and
radiocontrast-induced AKI.
Monitor and evaluate the safety and efficacy of the therapeutic
plan.

3. Mini Case
 H.D., a 63-year-old woman from Agaro, presents to JUMC with complaints
of weakness and nausea. She has a past medical history of stage 2
chronic kidney disease with proteinuria (baseline SCr 1.0 mg/dL ), gout,
hypertension, and chronic back pain. Her estimated GFR is 65 mL/min.
She reports having nausea, vomiting, and a low-grade fever last week.
Her fever resolved with naproxen, but she still feels weak and nauseated.
She states that she feels like she is “holding on to water” even though she
takes her “water pill.” Her weight is usually about 65 kg, and today she
weighs 67.6 kg. Upon preliminary examination, she was found to have 2+
pitting edema, BP 160/94, and crackles on auscultation.

4.  Meds: Fexofenadine 180 mg PO QD; Enalapril 5 mg PO QD; furosemide
40 mg Po QD, atorvastatin 10 mg PO QD; metformin 500 mg PO BID;
glyburide 5 mg po QD; metoprolol 25 mg PO BID; allopurinol 300 mg PO
QD; naproxen 220 mg PRN for arthritis pain and fever
a.What signs and symptoms suggest acute kidney injury (AKI)?
b.What risk factors does she have for developing AKI?
c. What additional laboratory information do you need to fully assess
the patient?
d.What questions would you ask her regarding her pharmacotherapy?
Mini Case…

5. Introduction: AKI
AKI Vs ARF
 AKI : encompasses the entire spectrum of acute injury to the kidney,
from mild changes in kidney function to ESKD [requiring RRT].
 AKI defined:
Abrupt reduction in kidney function [evidenced by changes in,
serum creatinine (Scr), blood urea nitrogen (BUN), and U/OP].
 Serious consequences , especially in hospitalized patients.
 No therapy that directly reverses the injury.

6. AKI…
 A state in which the kidneys’ ability to maintain homeostasis has
been declined suddenly
Accumulation of metabolic waste product, including urea and
creatinine
Electrolyte, acid-base and volume disturbance
 Clinicians use some combination of absolute Scr value, change in
Scr value over time, and/or urine output as primary diagnostic
criteria

7. Classification System of AKI
 3 major classification systems
Risk, Injury, Failure, Loss of Kidney Function, & End-Stage Kidney
Disease [RIFLE], 2004
Acute Kidney Injury Network [AKIN], 2007
Kidney Disease Improving Global Outcomes [KDIGO], 2012
While generally similar, there are a few noteworthy differences
All three staging systems depend on Scr and urine output as the
main diagnostic criteria,,,,, they are associated with the same inherent
weaknesses.

8.  Defines AKI: an abrupt (1-7 days) but sustained (more than 24
hours) decrease in renal function from baseline.
RIFLE based classification

9. Risk
 Increase in Cr of 1.5-2.0 X baseline or
 urine output < 0.5 mL/kg/hr for more than 6 hours.
Injury
Failure
Loss of function
End-Stage Renal disease
RIFLE…..

10. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for more than 6 hrs
Injury
– increase in Cr 2-3 X baseline (loss of 50% of GFR) or
– urine output < 0.5 mL/kg/hr for more than 12 hours.
Failure
Loss of function
End-Stage Renal disease
RIFLE…..

11. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
Failure
 increase in Cr rises > 3X baseline Cr (loss of 75% of GFR) or
 an increase in serum creatinine greater than 4 mg/dL, or
 urine output < 0.3 mL/kg/hr for more than 24 hours or anuria for more than 12
hours.
Loss of function
End-Stage Renal disease
RIFLE…..

12. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for
more than 12 hours
Loss of function
 persistent renal failure (i.e. need for dialysis) for more than 4 weeks.
End-Stage Renal disease
RIFLE…..

13. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs
Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs
Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for
more than 12 hours
Loss of function: Need for dialysis for more than 4 weeks
End-Stage Renal disease
 persistent renal failure (i.e. need for dialysis) for more than 3 months.
RIFLE…..

14. AKIN based classification
 AKIN:
A 48-hour period for the decrease to occur.
Removed RIFLE’s last two classification components (LE) from the
staging system
Places all patients receiving RRT automatically into AKIN stage 3.
Removed all estimated GFR (eGFR) criteria from its staging
system

15. KDIGO based classification
 It extended its scope to pediatric patients (<18 years) in KDIGO
Stage 3 for those with an eGFR of <35 mL/min.
 Seem to identify more patients with AKI and slightly more
predictive of in-hospital mortality than either RIFLE or AKIN.
CrCl =
(k * Ht)
Crserum
k
Infant (LBW < 1 year) 0.33
Infant (Term < 1 year) 0.45
Child or Adolescent Girl 0.55
Adolescent Boy 0.70Schwartz formula

16. RIFLE, AKIN, & KDIGO Classification Schemes
for AKIa
RIFLE Category Scr and GFRb Criteria Urine Output Criteria
Risk Scr increase to 1.5-fold or GFR decrease >25% from
baseline
<0.5 mL/kg/h for ≥6 hours
Injury Scr increase to two fold or GFR decrease >50% from
baseline
<0.5 mL/kg/h for ≥12 hours
Failure Scr increase to threefold or GFR decrease >75% from
baseline, or Scr ≥4 mg/dL (≥354 μmol/L) with an acute
increase of at least 0.5 mg/dL (44 μmol/L)
Anuria for ≥12 hours
Loss Complete loss of function (RRT) for >4 weeks
ESKD RRT >3 months
AKIN Criteria Scr Criteria Urine Output Criteria
Stage 1 Scr increase ≥0.3 mg/dL (≥27 μmol/L) or 1.5- to 2-fold
from baseline
<0.5 mL/kg/h for ≥6 hours
Stage 2 Scr increase >2- to 3-fold from baseline <0.5 mL/kg/h for ≥12 hours
Stage 3 Scr increase >3-fold from baseline, or Scr ≥4 mg/dL (≥354
μmol/L) with an acute increase of at least 0.5 mg/dL (≥44
μmol/L), or need for RRT
<0.3 mL/kg/h for ≥24 hours or
anuria for ≥12 hours
KDIGO Criteria Scr Criteria Urine Output Criteria
Stage 1 Scr increase ≥0.3 mg/dL (≥27 μmol/L) or 1.5-1.9 times
from baseline
<0.5 mL/kg/h for 6-12 hours
Stage 2 Scr increase 2-2.9 times from baseline <0.5 mL/kg/h for ≥12 hours
Stage 3 Scr increase three times from baseline, or Scr ≥4 mg/dL
(≥354 μmol/L), or need for RRT, or eGFRc <35
mL/min/1.73 m2 (<0.34 mL/s/m2) in patients <18 years
Anuria for ≥12 hours

17. Urine output (U/O)
 Urine output reduction emerges earlier in AKI unlike Scr (takes 1 to 2
days, after development of AKI)
But is a very nonspecific marker.
 Anuric: U/O <50 mL/day)
 Oliguric: U/O < 500 mL/day), or
 Non-oliguric: U/O >500 mL/day
 If baseline Scr not known…. estimating the baseline Scr value by
using the four variable MDRD equation with an assumed normal
eGFR of 75 mL/min/1.73 m2
Patient may have AKI and still
maintain a normal urine output
eGFR = 186 × (Scr)–1.154 × (age)–0.203 × (0.742 if
patient is female) × (1.210 if patient is black)

18. Key Concept
 AKI: increase in SCr of at least 0.3 mg/dL (27 μmol/L) within 48
hours, a 50% increase in baseline SCr within 7 days, or a urine
output of <0.5 mL/kg/hour for at least 6 hours.
Only one criterion needs to be met for diagnosis of AKI.

19. Epidemiology
 Uncommon condition in healthy population
Annual incidence ~0.02%
Overall survival rate …. 70%–95%
 Patients with preexisting CKD ….Incidence 13%
 Hospitalized patients at high risk of ARF (incidence 7%)
Overall survival rate…. 30%–50%
 Incidence higher in critically ill patients (6% to 23%)
Overall survival rate…. 10%–30%

20. Etiology
 Divided into three categories based on the anatomic location of the injury
associated with the precipitating factor(s).
Pre-renal: From decreased renal perfusion [in the setting of undamaged
parenchymal tissue]
Intrinsic: Structural damage to the kidney (ischemic or toxic insult) [commonly
the tubule]
Post-renal: Obstruction of urine flow downstream from the kidney.

21. 55%
40%
5%
<5%
10%
85%
<5%

23. Pathophysiology
Results from hypoperfusion of the renal parenchyma, with or without systemic
arterial hypotension.
Decline in intravascular volume or the effective circulating blood volume.
Renal hypoperfusion without systemic hypotension: associated with bilateral/
unilateral renal artery occlusion in a patient with a single functioning kidney.
 Pre-renal AKI/Azotemia
Hemorrhage, excessive GI losses (severe
vomiting or diarrhea), dehydration, extensive
burns, and diuretic therapy.
Conditions associated with a
decreased cardiac output and
systemic vasodilation.

24.  Mild effective circulating blood volume or volume depletion  activation
compensatory mxms [SNS, RAAS & release ADH] to maintain GFR  
Maintain BP via vasoconstriction and stimulation of thirst, which in conscious
patients results in increased fluid intake, as well as sodium and water retention.
 Other: GFR may be maintained by afferent arteriole dilation by
prostaglandins, kallikrein, kinins, and nitric oxide) and efferent arteriole
constriction (by angiotensin II).
 If, however, the decreased renal perfusion is severe or prolonged
compensatory mechanisms may be overwhelmed pre-renal AKI
 Medications: ACEIs/ARBs; NSAIDS

25. Pre-renal…
 Sepsis: associated with AKI
Decreased renal hypoperfusion reduced GFR
A complex interplay [augmented vasoconstriction, capillary
occlusion due to endothelial cell swelling, interaction of endothelial
cells with leukocytes, and activation of coagulation].
Simultaneously occurring renal inflammation and microcirculatory
dysfunction.

26. Pathophysiology…
 Intrinsic AKI/Azotemia
Results from direct damage to the kidney.
Can be of vasculature, glomeruli, tubules, and interstitium.
a. Renal Vasculature Damage
Occlusion of the larger renal vessels [bilateral/unilateral renal arteries]
Atheroemboli or thromboemboli
 Untreated hypertension  compromise renal microvascular blood flow 
diffuse renal capillary damage.
Atheroma dislodgement [angioplasty
and aortic manipulations]
Mural thrombus in the left ventricle
severe CHF or from the atria [AF].

27. Intrinsic AKI/Azotemia…
b. Glomerular Damage
Only 5% of the cases
Similar to damage mechanisms in the renal vasculature [ Because the
glomerulus is a capillary system].
More see glomerulonephritis
c. Tubular Damage [ATN]
85% of all cases;
 50% are a result of renal ischemia
 35% toxins, endogenous (myoglobin, hemoglobin, or uric acid) or exogenous (contrast
agents, aminoglycosides, etc.)

28. d. Interstitial Damage: Acute interstitial nephritis (AIN)
Is an idiosyncratic delayed hypersensitivity immune reaction.
Most common cause: drugs and less commonly by infections, autoimmune
diseases, or idiopathic causes.
Intrinsic AKI/Azotemia…

29.  Post-renal AKI/Azotemia
<5% of all cases of AKI.
Result of obstruction at any level within the urinary collection system
Bladder outlet obstruction [most common cause of obstructive nephropathy]
Prostatic process (hypertrophy, cancer, or infection) physical impingement on the
urethra
Improperly placed urinary catheter.
Blockage at ureter level [nephrolithiasis, blood clots, sloughed renal papillae,
or physical compression by an abdominal process].
Pathophysiology…

30. Post-renal AKI/Azotemia…
Extremely elevated uric acid concentrations [chemotherapy-induced
tumor lysis syndrome] obstruction and direct tubular injury
 Obstruction increased pressure upstream  ureters, renal pelvis,
and calyces expand  decline in GFR  AKI

32. Patient assessment & Clinical Pictures
 Thorough review of medical records [chronic conditions, laboratory
studies, procedures, and surgeries].
 Exhaustive review of prescription and nonprescription medicines.
 Thorough physical examination
 Volume and hemodynamic status
 Presumptive signs and symptoms of AKI need to be differentiated
from a potential new diagnosis of CKD.
But, patients with CKD may develop episodes of AKI as well.

33. Patient assessment….
 Acute change in urinary habitus
 Abrupt rise in the patient’s baseline Scr
 Presence of cola-colored urine : acute glomerulonephritis.
 In hospitalized patients, changes in U/O shows cause of AKI:
Acute anuria: complete urinary obstruction or a catastrophic event (eg, shock
or acute cortical necrosis).
Oliguria [develops over several days]: prerenal azotemia
Non-oliguric: acute intrinsic renal failure or incomplete urinary obstruction.
Suggests AKI

34. Clinical Pictures …
 Change in urinary character (e.g, decreased urine output or urine
discoloration), sudden weight gain, or severe abdominal or flank pain.
 Nausea, vomiting, fatigue, malaise
 Flank pain: suggest a urinary stone.
if bilateral suggest swelling of the kidneys 2˚ to acute
glomerulonephritis or AIN.
 Severe headaches: suggest the presence of severe hypertension and
vascular damage.
 Fever, rash, and arthralgia: indicative of drug-induced AIN or lupus
nephritis.

35. Conventional Markers of Kidney Function
 Scr, eCLcr, eGFR
However, affected by age, gender, muscle mass, diet, and
hydration status.
So: check for changes in the value from a patient’s baseline.
 BUN and urine output
 Normal: BUN: Scr <15:1
 Pre-renal: BUN: Scr >20:1
 Blood and urine tests [CBC, electrolytes ( increase K, P)] and urinary
sediment

36. Markers of Kidney Function…
 Proteinuria: hallmark of glomerular damage.
However, tubular damage can also result in proteinuria
 Hematuria: acute intrinsic AKI 2° to glomerular injury/infection/kidney
stone.
 Cells, casts, and crystals
Crystals: nephrolithiasis/post-renal obstruction.
RBCs or RBC casts: physical injury to the glomerulus, renal
parenchyma, or vascular beds.
WBCs or WBC casts: interstitial inflammation (i.e, interstitial
nephritis), [2˚ to allergic, granulomatous, or infectious process].

37.  Fractional excretion of sodium (FENa)
Better diagnostic parameters to differentiate the cause of AKI
Markers of Kidney Function…
Uvol is urine volume;
Ucr is urine creatinine concentration;
UNa is urine sodium;
GFR is glomerular filtration rate;
t is the time period over which the urine is
collected.
Scr is serum creatinine concentration;
SNa is serum sodium concentration

38.  A low UNa (<20 mEq/L [mmol/L]) and low FENa(<1%) in a patient with
oliguria suggest that:
There is stimulation of the sodium-retentive mechanisms in the
kidney and that tubular function is intact.
Which are most characteristic of prerenal azotemia.
 The inability to concentrate urine  high FENa (>2%)   tubular
damage [as 1˚cause of the intrinsic AKI] .
Markers of Kidney Function…

39.  Highly concentrated urine (>500 mOsm/kg [500 mmol/kg]): suggests
stimulation of ADH and intact tubular function.
These findings are consistent with prerenal azotemia.
Markers of Kidney Function…

40. Dxtic Parameters for Causes of AKIa
Laboratory Test Prerenal AKI Intrinsic AKI Postrenal AKI
Urine sediment Hyaline casts,
normal
Granular casts,
cellular debris
Cellular debris
Urinary RBC None 2–4+ Variable
Urinary WBC None 2–4+ 1+
Urine Na (mEq/L or
mmol/L)
<20 >40 >40
FENa (%) <1 >2 Variable
Urine/serum
osmolality
>1.5 <1.3 <1.5
Urine/Scr >40:1 <20:1 <20:1
BUN/Scr (urea/Scr,
SI)
>20 (>100) ~15 (~60) ~15 (~60)
Urine specific gravity >1.018 <1.012 Variable

41. Urinary Findings for Etiology of AKI
Type of Urinary
Evaluation Presence of Suggestive of
Urinalysis Leukocyte
esterases
Pyelonephritis
Nitrites Pyelonephritis
Protein
 Mild (<0.5 g/day) Tubular damage
 Moderate (0.5-3
g/day)
Glomerulonephritis,
pyelonephritis, tubular damage
 Large (>3 g/day) Glomerulonephritis, nephrotic
syndrome
Hemoglobin Glomerulonephritis,
pyelonephritis, renal infarction,
renal tumors, kidney stones
Myoglobin Rhabdomyolysis-associated
tubular necrosis
Urobilinogen Hemolysis-associated tubular
necrosis
Urine sediment Microorganisms Pyelonephritis

42. Cells
Red blood cells Glomerulonephritis, pyelonephritis, renal infarction,
papillary necrosis, renal tumors, kidney stones
White blood cells Pyelonephritis, interstitial nephritis
Eosinophils Drug-induced interstitial nephritis, renal transplant
rejection
Epithelial cells Tubular necrosis
Casts
Granular casts Tubular necrosis
Hyaline casts Prerenal azotemia
White blood cell
casts
Pyelonephritis, interstitial nephritis
Red blood cell casts Glomerulonephritis, renal infarct, lupus nephritis,
vasculitis
Crystals
Urate Post-renal obstruction
Calcium phosphate Post-renal obstruction
Urinary Findings for Etiology of AKI

44. Prevention of AKI
 Desired Outcomes
Screen and identify patients at risk,
Monitor high-risk patients until the risk has subsided
Implement prevention strategies when appropriate.

47.  Choice of preventive strategy depends on the cause of the renal insult.
 Avoid all potential causes , but not always possible;
E.g. Predictable in decreased perfusion 2˚ to coronary bypass
surgery or of a radiocontrast dye.
Potential AKI: cannot be avoided [preventable or minimized with
aggressive hydration and avoidance or removal of any additional
insults].
 Hydration: Optimal daily fluid intake (~2 L/day) to avoid dehydration
[if on potentially nephrotoxic medication].
Isotonic crystalloids over colloids for intravascular volume expansion in patients at
risk for AKI
Prevention of AKI…Non-pharmacologic

48.  The main concerns associated with the use of large amounts of saline are
hyperchloremic acidosis, interstitial edema, and fluid overload.
 CIN[Contrast induced nephropathy]:
Common cause of ATN
Typically x-ed by an increase in Scr starting at 12 hours up to 5
days after the radiologic procedure
Increase mortality in CKD, diabetes, volume depletion, concurrent
nephrotoxic drug therapy, or hemodynamic instability.
…Non-pharmacologic

49.  CIN Prevention:
Hydration: dilute the contrast media, preventing renal vasoconstriction
that contributes to hypoxia and ischemia, and minimizing tubular
obstruction.
 Normal saline infusion 1 mL/kg/h for 12 hours before and 12 hours after the procedure
Sodium bicarbonate: reduce the formation of oxygen-free radicals by
alkalinizing renal tubular fluid.
 154 mEq/L (mmol/L) infused at 3 mL/kg/h for 1 hour before the procedure and at 1
mL/kg/h for 6 hours after the procedure.
KDIGO recommend using either sodium bicarbonate or isotonic saline in
high-risk individuals receiving radiocontrast media.
…Non-pharmacologic

50.  Vasodilators [dopamine and Fenoldopam] are not recommended due to
lack of benefit and risk of hypotension.
 Theophylline: adenosine receptor antagonist properties,
Its modest benefit does not outweigh potential adverse effects such
as tachycardia, tremor, and drug interactions.
 Anti-oxidants (ascorbic acid and N-acetylcysteine [NAC]) and glycemic
control with insulin
Prevention of AKI…Pharmacologic

51. …Pharmacologic
 Ascorbic Acid
3 g orally before the procedure and 2 g orally twice daily for two
doses after the procedure.
Antioxidant [alleviate oxidative stress caused by CIN-associated
ischemia reperfusion injury].
Its excellent safety profile and low cost make it an attractive option.
 N-Acetylcysteine [NAC]: antioxidant
Its therapeutic benefit is thought to be quite modest.
600 to 1,200 mg PO q12 hrs for 2 to 3 days, with the first two
doses administered prior to contrast exposure.
Due to its favorable safety profile and potential benefit, the KIDGO suggest using
NAC in combination with IV isotonic saline in patients at risk for CIN.

52.  Glycemic Control
In critically ill patients it is important as stress hyperglycemia and
insulin resistance are common during critical illness.
Oxidative stress of hyperglycemia increases the risk of AKI.
Hypoglycemia also considered: especially in AKI or preexisting
kidney disease
 Kidneys are the primary metabolic site of insulin
…Pharmacologic
 KDIGO: Insulin therapy to target plasma glucose of 110 to 149 mg/dL
 ADA & American Society of Parenteral and Enteral Nutrition:
glycemic target 140 to 180 mg/dL in critically ill patients.

53. Treatment of AKI
 No specific treatment that can reverse AKI or hasten its recovery.
 Mainstays of therapy:
Supportive measures that focus on hemodynamics,
Fluid balance, acid-base balance, and
Electrolyte homeostasis.
 Desired Outcomes
Minimizing the degree of insult to the kidney
Reducing extrarenal complications
Expediting the patient’s recovery of renal function.

54. General Approach
 Pre-renal sources of AKI should be managed with hemodynamic support
and volume replacement.
 Post-renal therapy focuses on removing the cause of the obstruction.
 Severe AKI : RRT + fluid, electrolyte, and acid-base balance .
 Patient’s comorbidities and baseline renal function should be considered.

55. Hydration
 Maintaining an adequate fluid status is imperative and challenging at
the same time.
 Maintain or restore effective intravascular volume.
 Avoid too liberal fluid administration [risk of interstitial edema,
increased intra-abdominal pressure, renal venous congestion].
 Monitor: Weight changes, fluid intake & U/O [≥0.5 mL/kg/h ],
pulmonary & peripheral edema, BP (target MAP≥65 mm Hg), and serum
electrolytes.

56.  Anuric or oliguric: slower rehydration [250 mL boluses or 100 mL/h
infusions] considered to [risk for pulmonary edema, especially if HF or
pulmonary insufficiency exists].
Hyperchloremic metabolic acidosis, if rapidly hydrated
 AKI from blood loss or is complicated by symptomatic anemia: RBC
transfusion to a hematocrit no higher than 30% (0.30).
 Albumin: severe hypoalbuminemia (eg, liver disease and nephritic
syndrome) who are resistant to crystalloid therapy
 Critically ill patients with vasomotor shock: vasopressors
[norepinephrine, vasopressin, or dopamine] + fluids
Hydration…

57. Electrolyte Management
 Hypernatremia and fluid retention: frequent complications of AKI.
 Monitor total daily sodium intake.
 Check also for Na containing drugs [metronidazole, ampicillin, piperacillin,
and fluconazole].
 Most common electrolyte disorder encountered: hyperkalemia
More than 90% of potassium is renally eliminated.
Life-threatening cardiac arrhythmias occur if K >6 mEq/L

58.  Monitor for phosphorus and magnesium.
Are eliminated by the kidneys and are not removed efficiently by
dialysis.
Hyperphosphatemia more common than hypophosphatemia in early AKI.
Avoid calcium-containing antacids: to prevent precipitation of calcium
phosphate in the soft tissues.
Electrolyte Management…

59. Nutritional Considerations in AKI
 Stress, inflammation, and injury  hypermetabolic/hypercatabolic states
 alter the nutritional requirements.
 severe malnutrition ~~42% of patients with AKI.
 KDIGO: Caloric intake goal of 20 to 30 kcal/kg/day (84-126
kJ/kg/day),,, ENTERL FEEDING.
 Protein: 0.8 to 1 g/kg/day and 1 to 1.5 g/kg/day if patient is receiving
RRT

60. Diuretics
 Loop diuretics: frequently used for fluid overload.
 Theoretical advantages:
Decreased risk of tubular obstruction secondary to an increased
urine flow and flushing out of debris;
Increased urine output, as non-oliguric AKI is associated with
better outcomes than oliguric AKI
 Currently its use ??
Decrease renal blood flow by reducing effective circulating
arterial volume. Not in euvolemic or hypovolemic individuals.
KDIGO: use only in case of fluid overload

61.  Loop diuretics are all equally effective when given in equivalent doses.
 Therefore, selection is based on the side-effect profile, cost, and
pharmacokinetic differences.
 Ototoxicity: furosemide and ethacrynic acid
 Furosemide risk of ototoxicity is greater when administered by the IV
route at a rate exceeding 4 mg/min.
 Ethacrynic acid: used in a sulfa allergy patient; No sulfonamide moiety
 Loop diuretics also have a ceiling effect where maximal natriuresis
occurs.
bumetanide1mg, and torsemide 20 mg
Diuretics…

62. Adaptive mechanisms by the kidney limit effectiveness of loop diuretic
therapy
 As the concentration of diuretic in the loop of Henle decreases, post-
diuretic sodium retention can occur.
 Minimized by decreasing the dosage interval (i.e, dosing more
frequently) or by administering a continuous infusion
Diuretics…

63. Diuretic resistance
 Relatively common problem in patients with AKI.
A. Excessive sodium [Na] intake: override the ability of the diuretics to
eliminate Na.
B. Reduced number of functioning nephrons on which the diuretic may
exert its action.
C. Heavy proteinuria: Intraluminal loop diuretics cannot exert their
effect in the loop of Henle if they are extensively bound to proteins.
D. Reduced bioavailability of oral furosemide because of intestinal
edema, often associated with high preload states, which further
reduces oral furosemide absorption.

64. How to overcome diuretic resistance
 Increase frequency of administration
 Avoid other factors
 Administer through continuous infusion instead of intermittent boluses.
An initial loading dose is recommended
 Combination therapy : loop diuretics + other diuretic
Oral metolazone: used most frequently because, unlike other, it
produces effective diuresis at a CrCl < 20 mL/min
 If Rx: Furosemide 40mg Po QD + Hydrochlorthiazide25mg PO QD;
which one you recommend to take first in AKI patient? Why??

65. …overcome diuretic resistance

66. Algorithm for treatment of extracellular fluid expansion

68. Renal Replacement Therapy
 Used to treat fluid overload, electrolyte and acid-base imbalances
resulting from severe AKI.
 Continuous versus intermittent RRTs.
 Intermittent hemodialysis (IHD):
Most frequently used RRT
Treatments usually last 3 to 4 hours, with blood flow rates to the
dialyzer 200 to 400 mL/min.
Advantage: rapid removal of volume and solutes
Challenge: hypotension [rapid removal of intravascular volume].

70.  Continuous Renal Replacement Therapy [cRRT]
A. Continuous venovenous hemofiltration (CVVH),
B. Continuous venovenous hemodialysis (CVVHD),
C. Continuous venovenous hemodiafiltration (CVVHDF).
Differ in the degree of solute and fluid clearance , as a result of
the use of diffusion, convection, or a combination of both.
Renal Replacement Therapy…
CRRT-related thrombosis is a significant concern, b/c of reduced blood flow rates
relative to IHD;;; Anticoagulation is necessary

71. Common Indications for RRT
Indication for RRT Clinical Setting
A: acid-base abnormalities Metabolic acidosis (especially if pH <7.2)
E: electrolyte imbalance Severe hyperkalemia and/or
hypermagnesemia
I: intoxications Salicylates, lithium, methanol, ethylene glycol,
theophylline, phenobarbital
O: fluid overload Fluid overload (especially pulmonary edema
unresponsive to diuretics)
U: uremia Uremia or associated complications
(neuropathy, encephalopathy, pericarditis)

72. …RRT
 Absolute indications for dialysis usually include:
BUN greater than 100 mg/dL (35.7 mmol/L)
Potassium greater than 6 mEq/L (6 mmol/L)
Magnesium greater than 9.7 mg/dL (4.0 mmol/L)
Metabolic acidosis with a pH less than 7.15
Diuretic-resistant fluid overload

73. KDIGO Recommendations
Drug Indication
Recommended for
Prevention
Recommended for
Treatment
Comments
ANP AKI No (2C) No (2B)
Diuretics AKI No (1B) No (2C) Acceptable if managing
concurrent fluid overload
Dopamine (1-3 μg/kg/min) AKI No (1A) No (1A)
Fenoldopam AKI
CI-AKI
No (2C)
No (1B)
No (2C)
Isotonic saline IV AKI
CI-AKI
Yes (2B)
Yes (1A)
Yes (2B) For AKI: recommended in
the absence of hemorrhagic
shock
NAC AKI
CI-AKI
No (2D)
Yes (2D)
For CI-AKI: give in
combination with isotonic
saline
RRT AKI
CI-AKI
No (2C) Yes (NG)
Sodium bicarbonate IV CI-AKI Yes (1A)
Theophylline CI-AKI No (2C)
Vasopressors AKI Yes (1C) Yes (1C) Recommended in
combination with fluids in
vasomotor shock
Strength of recommendation levels: 1, recommended; 2, suggested; NG, not graded.
Quality of supporting evidence: A, high; B, moderate; C, low; D, very low.

74. Evaluation of Therapeutic Outcomes
 Vigilant monitoring of patients with AKI is essential.
Parameter Frequency
Fluid intake & output Every shift
Patient weight Daily
Hemodynamics (blood pressure, heart rate, mean arterial pressure, etc.) Every shift
Blood chemistries
Sodium, potassium, chloride, bicarbonate, calcium, phosphate,
magnesium
Daily
Blood urea nitrogen/serum creatinine Daily
Drugs and their dosing regimens Daily
Nutritional regimen Daily
Blood glucose Daily (minimum)
Serum concentration data for drugs After regimen changes and after renal replacement
therapy has been instituted
Times of administered doses Daily
Doses relative to administration of renal replacement therapy Daily
Urinalysis
Calculate measured creatinine clearance Every time measured urine collection performed
Calculate fractional excretion of sodium Every time measured urine collection performed
Plans for renal replacement Daily

75. Carry Home Message
Please read in detail:
A. IHD & CRRT, hybrid dialysis therapies/extended-duration IHD or
hybrid IHD
B. Drug Dosing Considerations in Acute Kidney Injury.
C. Drug Dosing Considerations in Renal Replacement Therapy