Pharmacotherapy of Acute Kidney Disease

1. Acute Kidney Injury
Sreenu Thalla
Associate Professor
Department of Pharmacology

3. Definition
• Acute kidney injury (AKI) is a clinical syndrome
defined by the impairment of kidney filtration and
excretory function over days to weeks resulting in
retention of nitrogenous and other waste products
normally cleared by kidneys.
• Increase in serum creatinine concentration associated
with urine volume reduction is seen.

8. Epidemiology
• AKI affects over 13 million people and results in 1.7
million deaths each year around the world.
• The overall incidence of AKI ranges from 20% to 50%
with lower incidence seen in surgical patients and higher
incidence in sepsis patients.
• In indian population, incidence of AKI was 17.3
cases/1000 persons.

9. Incidence & Outcomes of AKI

16. Prerenal Azotemia
• Prerenal azotemia is the most common form of AKI.
• Prerenal azotemia involoves no parenchymal damage to kidney
and rapidly reversible once parenchymal blood flow and
intraglomerular hemodynamics are restored.
• Due to inadequate renal plasma flow and intraglomerular
hydrostatic pressure there is a rise in SCr and BUN
concentrartion.
• Prolonged periods of prerenal azotemia may lead to ischemic
injury, termed as acute tubular necrosis (ATN).

17. Drugs Causing Prerenal Azotemia
• NSAIDs inhibits renal prostagladin production, limiting
renal afferent vasodilation.
• ACEIs and ARBs limit renal efferent vasoconstriction this
effect is seen in patients with unilateral or bilateral renal
artery stenosis because efferent arteriolar vasoconstriction
is needed to maintain GFR due to low renal perfusion.
• Combined use of NSAIDs with ACEIs and ARBs causes
high risk for developing prerenal azotemia.

18. • Many individuals with advanced liver disease
exhibit hemodynamic profile resemble prerenal
azotemia in total body volume overload.
• AKI is common complication in this setting and it
can be triggered by volume depletion and
spontaneous bacterial peritonitis.
• Hepatorenal syndrome
1. Type-1
2. Type-2

19. Intrinsic AKI
• The most common causes of intrinsic AKI are
 Sepsis
 Ischemia
 Nephrotoxins

20. Types of Intrinsic AKI
• Ischemia associated AKI.
• Postoperative AKI.
• Burns and Acute Pancreatitis.
• Diseases of the microvasculature leading to ischemia.
• Nephrotoxin associated AKI.
• Glomerulonephritis.

21. Postrenal AKI
• Occurs when normally unidirectional flow of urine is blocked partially
or totally leading to increased retrograde hydrostatic pressure and
interfere with glomerular filtration.
• For AKI to occur in individuals with two healthy functional kidneys,
obstruction must affect both kidneys in order to observe large increase
in SCr.
• Unilateral Obstruction may cause AKI in reflex vasospasm of
contralateral kidney.
• Bladder neck obstruction is common cause of postrenal AKI impacts
both kidneys

22. Diagnostic Evaluation
• Presence of AKI is defined by an elevation in SCr concentration
or reduction in urine output.
• AKI is currently defined by a rise from baseline of at least
0.3mg/dL within 48h or atleast 50% higher than baseline within
1 week, or reduction in urine output to <0.5mL / kg per h for
longer than 6 h.
• The distinction between AKI and CKD is important for proper
diagnosis and treatment.
• No set of tests, can rule out AKI superimposed on CKD because
AKI is frequent complication of CKD patients.
• Serial blood tests showing continuous rise of SCr represents
clear evidence of AKI.

23. Biomarkers
• BUN and creatinine are functional biomarkers.
• Kidney injury molecule-1 (KIM-1): abundantly expressed in
proximal tubular cells injured by ischemia, detected shortly after
injury in urine.
• Neutrophil gelatinase associated lipocalcin (NGAL): upregulated
after inflammation and injury, detected in plasma and urine.
• Cystatin C:
 Functional marker in blood.
 Tubular marker in urine.

24. Others
 IL-18
 Vimentin
 Alanine aminopeptidase
 Alkaline phosphatase
 Gamma glutamyl transpeptidase

31. TREATMENT OF AKD