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Acute Kidney Injury


Abrupt deterioration in parenchymal renal function,

which is usually, but not invariably, reversible over a
period of days or weeks
Feature :
Oliguria the low output of urine
Campbell 10th ed : <200 cc/12hr
< 1 cc/kg/hr in infants
< 0.5 cc/kg/hr in children
< 0.5 cc/kg/hr or < 500 cc/24 hr in adults
Anuria absence of urine
Campbell 10th ed : < 50 cc/12 hr
Kumar & Clarks : < 50 cc/24 hr

RIFLE Classification for AKI

Grade GFR criteria UO criteria

Risk SCr x 1.5 UO < 0.5 cc/kg/h x 6 h

Injury SCr x 2 UO < 0.5 cc/kg/h x 12 h

Failure SCr x 3 or UO < 0.3 cc/kg/h x 24 h

> 350 mol/L with acute
rise > 40 mol/L

Loss Persistent ARF > 4 weeks

ESKD Persistent renal failure >

3 months
Reduced excretion of nitrogenous waste products urea


Other causes of altered serum urea and creatinine concentration :

Prerenal Uraemia

Impaired perfusion of the kidneys with blood

Impaired cardiac pump efficiency
Vascular disease limiting renal blood flow
Autoregulation of kidney
Ability of the kidney to maintain glomerular filtration close to normal despite wide
variations in renal perfusion pressure and volume status
Further depression of renal perfusion
drop in glomerular filtration prerenal uraemia
Drugs which impair renal autoregulation :
ACE inhibitors
Prerenal Uraemia

All causes of prerenal uraemia

parenchymal kidney damage
acute renal failure
Excretory function in prerenal uraemia improves
once normal renal perfusion has been restored
Prerenal Uraemia

Criteria to differentiate between prerenal and

intrinsic renal causes of uraemia :
Urine specific gravity and urine osmolality
Urine sodium
Fractional excretion of sodium (FENa)
Postrenal Uraemia

Results from obstruction of the urinary tract at any

point from the calyces to the external urethral orifice
Screening renal ultrasonography
Acute fashion
Obstruction of a single functioning kidney
Insidious onset
Anti Androgen

Hormone Regulation
Testosterone secretion is regulated by the
hypothalamic-pituitary-gonadal axis

The hypothalamic luteinising hormone-releasing

hormone (LHRH) Stimulates the anterior
pituitary gland
Secretes LH and FSH

Luteinising hormone stimulates the Leydig cells

secrete testosterone
1. Testosterone within the prostate cells
testosterone + enzyme 5--reductase
5- dihydrotestosterone (DHT)

2. Circulating testosterone

Oestrogens + circulating androgens

negative feedback control

Hypothalamic LH secretion
If prostate cells are deprived of androgenic
apoptosis (programmed cell death)

Any treatment that results ultimately in

suppression of androgen activity is referred
to as androgen deprivation therapy (ADT)
Anti Androgen

Works at the receptor level in the prostate cell

Compete with testosterone and DHT
promote apoptosis & inhibiting PCa growth
Chemical structure
e.g. cyproterone acetate (CPA), megestrol acetate and
medroxyprogesterone acetate,
e.g. nilutamide, flutamide and bicalutamide.
Steroidal Anti Androgen

Synthetic derivatives of hydroxyprogesterone

peripherally blocking androgen receptors
inhibit the release of gonadotrophins (LH and FSH)
suppress adrenal activity

Since steroidal anti-androgens lower testosterone levels,

the main pharmacological side-effects are
loss of libido
erectile dysfunction
gynaecomastia is quite rare
cardiovascular toxicity (4-40% for CPA)
Non-Steroidal Anti Androgen

Blocking the testosterone feedback centrally

LH and testosterone levels to increase
As monotherapy improved quality of life (QoL) and compliance
Do not suppress testosterone secretion
Libido& overall physical performance
Bone mineral density (BMD)

Pharmacological side-effects :
Breast pain
Hot flashes
Bicalutamide more favourable safety and tolerability profile than
nilutamide and flutamide
All three agents share a common liver toxicity and liver enzymes must
monitored regularly