University of Anbar - College of Pharmacy

Applied Therapeutics I – Acute Kidney Injury 1

Kidney Injury
Kidney injury is the condition which results when the kidneys cannot remove the
body’s metabolic wastes or perform their regulatory functions. This result in
disruption in endocrine and metabolic functions, fluid, electrolyte, and acid-base
disturbances.

The main kidney functions are:

1- Detoxify blood
2- Increase calcium absorption
3- Stimulate RBC production
4- Regulate blood pressure and electrolyte balance

Urine Volume Normal daily urine output

Non-Oliguric >500-400 CC/ 24 Hrs
Oliguric <500-400 CC/24 Hrs
Anuric <50 CC/24 Hrs

Acute Renal failure vs. Chronic Renal failure

Acute Renal failure Chronic Renal failure
Onset sudden onset Progressive
UOP rapid reduction in urine output Variable
Injury Usually reversible Not reversible
Complications Tubular cell death and regeneration Nephron loss

Acute Kidney Injury (AKI)

Acute kidney injury (AKI) or acute renal failure (ARF) is a reversible clinical
syndrome generally defined by an abrupt reduction in kidney function as
evidenced by changes in serum creatinine (S.cr), blood urea nitrogen (BUN), and
urine output.
‫اﻛﺜﺮ اﺛﻨﻴﻦ ﻧﺴﺘﺨﺪﻣﻬﻢ ﻟﺘﺸﺨﻴﺺ‬
Acute kidney injury is a reversible clinical syndrome where there is a: AKI‫ال‬
• sudden and almost complete loss of kidney function (decreased GFR) over a
period of hours to days
• failure to excrete nitrogenous waste products
• failure to maintain fluid and electrolyte homeostasis.
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Applied Therapeutics I – Acute Kidney Injury 2
Classification Schemes for AKI (FYI)

RIFLE S.cr and GFR Criteria Urine Output Criteria

Criteria
Risk S.cr increase to 1.5-fold or GFR decrease >25% <0.5 mL/kg/hr for ≥6 hr
from baseline
Injury S.cr increase to 2-fold or GFR decrease >50% <0.5 mL/kg/hr for ≥12 hr
from baseline
Failure S.cr increase to 3-fold or GFR decrease >75% Anuria for ≥12 hr
from baseline, or S.cr ≥4 mg/dL (354 μmol/L)
with an acute increase of at least 0.5 mg/dL (44
μmol/L)
Loss Complete loss of function (RRT) for >4 weeks
ESKD RRT >3 months

AKIN S.cr Criteria Urine Output Criteria

Criteria
Stage 1 S.cr increase ≥0.3 mg/dL (27 μmol/L) or 1.5- to <0.5 mL/kg/hr for ≥6 hr
2-fold from baseline
Stage 2 S.cr increase >2- to 3-fold from baseline <0.5 mL/kg/hr for ≥12 hr.
Stage 3 Scr increase >3-fold from baseline, or Scr ≥4 <0.3 mL/kg/hr for ≥24 hr or
mg/dL (354 μmol/L) with an acute increase of anuria for ≥12 hr
at least 0.5 mg/dL (44 μmol/L), or need for RRT

KDIGO S.cr Criteria Urine Output Criteria

Criteria
Stage 1 S.cr increase ≥0.3 mg/dL (27 μmol/L) or 1.5- <0.5 mL/kg/hr for 6–12 hr
to 1.9-fold from baseline
Stage 2 S.cr increase 2- to 2.9-fold from baseline <0.5 mL/kg/hr for ≥12 hr.
Stage 3 Scr increase three times from baseline, or Scr Anuria for ≥12 hr
≥4 mg/dL (354 μmol/L), or need for RRT, or
eGFRc <35 mL/min/1.73 m2 (0.34
mL/sec/m2) in patients <18 years
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Applied Therapeutics I – Acute Kidney Injury 3
Causes of Acute Renal Failure (FYI)

A. Prerenal

Volume depletion • hemorrhage

• renal losses (diuretics)
• GI losses (vomiting, diarrhea, NG suctioning)
Impaired cardiac • MI
efficiency • Heart failure
• Dysrhythmias
• Cardiogenic shock
Vasodilation • sepsis
• anaphylaxis
• antihypertensive medications
• other medications that cause vasodilation

B. Intrarenal

Prolonged renal • pigment nephropathy (associated with the breakdown of blood cells
ischemia containing pigments that in turn occlude kidney structures)
• Myoglobinuria (trauma, crush injury, burns)
• Hemoglobinuria (transfusion reaction, hemolytic anemia)
Nephrotoxic • Aminoglycosides antibiotics (gentamicin, tobramycin)
agents • Radiopaque contrast media
• Heavy metals (lead, mercury)
• Solvents and chemicals (carbon tetrachloride, arsenic)
• NSAIDs
• ACE inhibitors
Infectious • Acute pyelonephritis
processes • Acute gastroenteritis

C. Postrenal

Urinary tract • Renal calculi (stones)

obstruction • Strictures and tumors
• BPH
• Blood clots
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Applied Therapeutics I – Acute Kidney Injury 4
Phases of ARF

Initiation It begins with the initial insult and ends when oliguria develops.
Oliguria The oliguria period is accompanied by an increase in the serum
concentration of substances usually excreted by the kidneys (uric
acid, urea, creatinine).
In this phase uremic symptoms first appear and life-threatening
conditions such as hyperkalemia develop.
Diuresis The diuresis period is marked by a gradual increase in urine output,
period which signals that glomerular filtration has started to recover.
Recovery The recovery period signals the improvement of renal function and
period may take 3-12 months. Lab values return to normal level. Although
a permanent 1%-3% reduction in the GFR is common.

Symptoms of ARF
• Decrease urine output (70%) • Pruritus
• Edema, especially lower extremity • Anemia
• Mental changes • Tachypenic
• Heart failure • Cool, pale and moist skin
• Nausea and vomiting

Diagnosis
• Medical and medication histories, physical examination, assessment of
laboratory values, and, if needed, imaging studies are important in the diagnosis
of ARF.
• Urine:
o Urine electrolytes and creatinine urine to calculate fractional excretion of
sodium (FeNa)
o Urine eosinophils
o Urine sediment: casts, cells, protein
o Urine osmolality

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U = Urine S = serum or plasma
University of Anbar - College of Pharmacy
Applied Therapeutics I – Acute Kidney Injury 5
• Serum creatinine (S.Cr.) cannot be used alone to diagnose ARF because it is
insensitive to rapid changes in glomerular filtration rate (GFR) and therefore
may not reflect current renal function.
• The use of blood urea nitrogen (BUN) in ARF is very limited because urea’s
production and renal clearance are heavily influenced by extrarenal factors
such as: critical illness, volume status, protein intake, and medications.

Preventing ARF
• Provide adequate hydration to patients at risk of dehydration:
o surgical patients before, during and after surgery.
o Patients undergoing intensive diagnostic studies requiring fluid restrictions
and contrast agents
o Patients with neoplastic disorders of metabolism and those receiving
chemotherapy
• Prevent and treat shock promptly with blood and fluid replacement.
• Monitor CV and arterial pressures and hourly urine output of critically ill
patients to detect the onset of renal failure as early as possible.
• Treat hypotension promptly.
• Continually assess renal function when appropriate.
• Take precautions to ensure that the appropriate blood is administered to the
correct patient in order to avoid severe transfusion reactions, which can
precipitate renal failure.
• Prevent and treat infections promptly. Infections can produce progressive renal
damage.
• Pay special attention to wounds, burns and other precursors of sepsis
• To prevent infections from ascending in the urinary tract, give meticulous care
to patients with indwelling catheters. Remove catheter ASAP.
• To prevent toxic drug effects, closely monitor dosage, duration of use, and blood
levels of all medications metabolized or excreted by the kidneys.
• Inadequate evidence exists to support use of N-acetylcysteine and ascorbic
acid as antioxidants for prevention of contrast-induced nephropathy or
contrast-induced acute kidney injury (CI-AKI). Study with these two agents
demonstrated no benefit.
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Applied Therapeutics I – Acute Kidney Injury 6
Medical Management:

Goals of Treatment:
Short-term goals include
• minimizing the degree of insult to the kidney.
• Reducing extrarenal complications, and expediting recovery of renal function.
• Restoration of renal function to preARF baseline is the ultimate goal.

Pharmacologic therapy

Management of fluid overload

• Loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid) are
often administered to control fluid volume, but they have not been shown to
hasten the recovery from ARF. Ethacrynic acid is reserved for sulfa-allergic
patients.
• Continuous infusions of loop diuretics appear to overcome diuretic resistance
and to have fewer adverse effects than intermittent boluses.
• Administration of agents from different pharmacologic classes, such as
thiazides or potassium sparing diuretics (amiloride, triamterene and
spironolactone), may be synergistic when combined with loop diuretics.
• Metolazone is commonly used because, unlike other thiazides, it produces
effective diuresis at GFR less than 20 mL/min (0.33 mL/s).

Management of hyperkalemia
• Hyperkalemia is the most life-threatening of changes that occur in renal failure,
the elevated K levels may be reduced by administering cation-exchange resins
(sodium polystyrene sulfonate) orally or by retention enema. It works by
exchanging sodium ions for potassium ions in the intestinal tract.
• Sorbitol may be administered in combination with sodium polystyrene
sulfonate to induce diarrhea type effect (induce water loss in the GIT)
• If hemodynamically unstable, IV dextrose 50%, insulin and calcium
replacement may be administered to shift potassium back into the cells.
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Applied Therapeutics I – Acute Kidney Injury 7
Vasodilators
The vasodilator therapy may improve renal perfusion and reduce renal damage.
However, strong evidence in support of this approach is lacking.

Dopamine in small doses causes selective dilatation of the renal vasculature,

enhancing renal perfusion. Dopamine also reduces sodium absorption, thereby
decreasing the energy requirement of the damaged tubules. This enhances urine
flow, which, in turn, helps to prevent tubular cast obstruction.

Fenoldopam is a selective dopamine-receptor agonist that acts as a rapid-acting

vasodilator. Fenoldopam decreases systemic vascular resistance and increases
renal blood flow to the cortex and medullary regions in the kidney.

The effects of calcium channel blockers are believed to be mediated through

vasodilation, and they are increasingly used to enhance the function of
transplanted kidneys. For example, nifedipine relaxes smooth muscle and
produces vasodilation, which, in turn, improves blood flow and oxygen delivery.

Nutritional Therapy
• Dietary proteins are individualized to provide the maximum benefit. Caloric
requirements are met with high-carbohydrate meals, because carbohydrates
have a protein sparing effect.
• Foods and fluids containing potassium or phosphorous such as banana, citrus
fruits and juices, coffee are restricted.

Renal Replacement Therapy (RRT)

In severe AKI, renal replacement therapy (RRT), such as hemodialysis and
peritoneal dialysis, is used to treat fluid overload, electrolyte disturbances (e.g.,
hyperkalemia), acid–base imbalances, uremic complications, and pulmonary
edema. Intermittent and continuous renal replacement therapy (CRRT) options
have different advantages and disadvantages.
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Applied Therapeutics I – Acute Kidney Injury 8
Common Indications for Renal Replacement Therapy (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)