Acute Kidney Disease (AKD), Acute Renal Disease, Acute Renal Failure (ARF) - Definition, epidemiology, risk factors, classification, etio-pathogenesis, clinical presentation, physical examination, diagnosis, treatment and management

1. ARF

2. DEFINITIONS
• Acute renal failure (ARF) is broadly defined as a
decrease in glomerular filtration rate (GFR)
occurring over hours to weeks that is associated
with an accumulation of waste products,
including urea and creatinine
• Clinicians use a combination of the serum
creatinine (Scr) value with change in either Scr or
urine output (UOP) as the primary criteria for
diagnosing ARF

4. Epidemiology
• ARF is an uncommon condition in the
community-dwelling, generally healthy
population, with an annual incidence of
approximately 0.02%
• The hospitalized individual is at high risk of
developing ARF; the reported incidence is 7%
• The incidence of ARF is markedly higher in
critically ill patients, ranging from 6% to 23%

5. Epidemiology
• The high mortality rate related to ARF, which is
reported to range from 35% to 80%, is a
significant clinical concern that has been
relatively unresponsive to therapeutic
intervention over the last four decades

6. Risk factors
Clinical Setting Frequency (%)
Severe Burns 20-60
Rhabdomyolysis 20-30
Aminoglycoside use 10-30
Chemotherapy 15-25
Open heart surgery 5-20
ICU 5-25
General medicine 3-5

7. ETIOLOGY
• The etiology of ARF can be divided into broad
categories based on the anatomic location of
the injury associated with the precipitating
factor(s)

8. ETIOLOGY
• Traditionally, the causes of ARF have been categorized as
(a) Prerenal, which results from decreased renal perfusion in
the setting of undamaged parenchymal tissue
(b) Intrinsic, the result of structural damage to the kidney,
most commonly the tubule from a ischemic or toxic insult
(c) Postrenal, caused by obstruction of urine flow
downstream from the kidney

9. ETIOLOGY
• The most common cause of hospital-acquired
ARF is prerenal ischemia as the result of
reduced renal perfusion secondary to sepsis,
reduced cardiac output, and/or surgery
• Drug-induced ARF may account for 18% to
33% of in-hospital occurrences

10. ETIOLOGY
Other risk factors for developing ARF while
hospitalized include
• Advanced age (>60 years of age)
• Male gender
• Acute infection
• Preexisting chronic diseases of the respiratory
or cardiovascular systems

11. Clinical Presentation
• Community-dwelling patients often are not in
acute distress
• Hospitalized patients may develop ARF after
either a notable reduction in blood pressure or
intravascular volume, significant insult to the
kidney, or sudden obstruction after
catheterization
• Generally, an acute reduction in urine output
coinciding with a rise in BUN and Scr is observed

12. Clinical Presentation
• Symptoms in the outpatient setting include
change in urinary habits, weight gain, or flank
pain
• Signs include edema, colored or foamy urine,
and, in volume-depleted patients, orthostatic
hypotension

13. Specific clinical correlations !
• A decrease in the force of the urinary stream:
obstruction
• Presence of cola-colored urine: Hematuria,
Rhabdomyolysis
• The onset of flank pain: urinary stone
• Headache: HTN

14. Specific clinical correlations !
• Acute anuria is typically caused by either
complete urinary obstruction or a catastrophic
event
• Oliguria (<500 mL/day of urine output), which
often develops over several days, suggests
prerenal azotemia
• Nonoliguric (>500 mL/day of urine output) renal
failure usually results from acute intrinsic renal
failure or incomplete urinary obstruction

15. Laboratory Tests
• Elevations in the serum potassium, BUN,
creatinine, and phosphorous, or a reduction in
calcium and the pH (acidosis), may be present
• An increased serum white blood cell count
may be present in those with sepsis-
associated ARF, and eosinophilia suggests
acute interstitial nephritis.

16. Laboratory Tests
• Urine microscopy can reveal cells, casts, or
crystals that help distinguish among the
possible etiologies and/or severities of ARF.
• Urine chemistry also indicates the presence of
protein, which suggests glomerular injury, and
blood, which can result from damage to
virtually any kidney structure.

17. Other tests
• Renal ultrasonography may be needed to rule
out obstruction; renal biopsy is rarely used,
and is reserved for difficult diagnoses

18. Diagnosis
• Monitoring changes in UOP can help diagnose the
cause of ARF. Acute anuria (less than 50 mL
urine/day) is secondary to complete urinary
obstruction or a catastrophic event (e.g., shock).
Oliguria (400 to 500 mL urine/day) suggests
prerenal azotemia
• Nonoliguric renal failure (more than 400 to 500
mL urine/day) usually results from acute intrinsic
renal failure or incomplete urinary obstruction.

19. PREVENTION OF ACUTE RENAL
FAILURE
• Nephrotoxin administration (e.g., radiocontrast dye)
should be avoided whenever possible. When patients
require contrast dye and are at risk of contrast dye–
induced nephropathy, renal perfusion should be
maximized through strategies
• Such as assuring adequate hydration with normal
saline or sodium bicarbonate solutions and
administration of oral acetylcysteine 600 mg every 12
hours for four doses. Strict glycemic control with
insulin in diabetics has also reduced the development
of ARF

20. PREVENTION OF ACUTE RENAL
FAILURE
• Amphotericin B nephrotoxicity can be
reduced by slowing the infusion rate to in at-
risk patients, substituting liposomal
amphotericin B
• Many other strategies are popular but lack
supportive evidence, including mannitol, loop
diuretics, dopamine an fenoldopam

21. Pharmacotherapy

22. Pharmacotherapy
• Low dose Dopamine (≤2 mcg/kg/min)
• Not so beneficial

23. Pharmacotherapy
• The use of diuretics to prevent nephrotoxicity
may actually result in intravascular volume
depletion
• May increase the risk of ARF

24. Pharmacotherapy
• Fenoldopam: Fenoldopam mesylate is a
selective dopamine A-1 receptor agonist
• Fenoldopam had salutary properties for the
prevention of drug-induced nephrotoxicity

25. Pharmacotherapy
• Acetylcysteine: may effectively reduce the risk
of developing CIN in patients with pre-existing
kidney disease, although a therapeutic benefit
has not been consistently demonstrated
• The recommended N-acetylcysteine dosing
regimen for prevention of CIN is 600 mg orally
every 12 hours for 4 doses with the first dose
administered prior to contrast exposure

26. Pharmacotherapy
• Theophylline may reduce the incidence of CIN
with an efficacy that is perhaps comparable to
that reported in studies of Nacetylcysteine

29. Pharmacotherapy
• Glycemic Control
• Tight blood glucose resulted in significant
improvements in mortality and a 41% reduction
in the development of ARF
• Intensive insulin therapy may now also become
the standard of care for all critically ill patients to
prevent ARF and improve mortality