ACUTE RENAL FAILURE

INTRODUCTION –
 Decrease in renal function over a period of hours to days , resulting in the
accumulation of nitrogenous waste materials (azotemia)
 It is a reversible process.
 Serum creatinine increase is the base line for aki.
 It is categorised into pre – renal , renal ,post renal .
Epidemiology-
 Aki occurs almost exclusively in hospitalised patients .
 Major factos are older age , higher baseline creatinine ,DM,CVD,resp.
disorders,dehydration,acute infection, nephrotoxins.
 Incidence of community acquired aki is 1%, it can be reversed by
correcting the underlying problems .
 Hospitalised acquired aki is much more common and the incidence and
severity vary based on ICU and non-ICU.
 The most common cause is renal azotemia,nephrotoxins, post operartive
complications which might leads to higher incidence of aki.
PROGNOSIS-
 A mild elevation of serum creatnine level in ICU patients is associated with a twofold
increase in the risk of the death
 50% of mortality rate in critically ill patients .
 10% increase in mortality in organ failure patients .
SIGNS AND SYMPTOMS-
Three phases of AKI
1)oliguria- occurs over the course of 1-2 days and is charecterized by a progressive decrease
in urine output . it is <400 ml/24 hrs.
When the urine production is less than 150-50 ml/24 hrs it is called as anuria.
Strict fluid and electrolyte monitoring and management are required during this phase until
renal function normalizes .
2) diuretic phase –
After the oliguric phase ,increased urine production occurs for several days this is called as
diuretic phase .
in part , return to normal kidney function after the initial repair of the kidney.
In this stage the patient begin to loss electrolyes and volume depletion occurs .so monitoring
should be given by supplying adequate amount of electrolyes and fluids .
3)recovery phase – occurs over the course of week to months depending on severity of
patients Aki.
This phase signals the return to the patients baseline kidney function , normalizes of urine
production and the return of the dilting and concentrating abilities of the kidney.

PATHOGENISIS –
The production and elimination of urine requires 3 major events:
1)blood flow to glomeruli
2)ultra filtrate by the glomeruli and tubular cells
3)excretion of urine through ureters,bladder,urethra.
many conditions can alter the physiological conditions leading to AKI, divided
into
a)pre-renal
b)functonal
c)intrinsic
d)post renal

A)PRE RENAL –
-kidneys receive 25%of cardiac output ,which os greater than 1l/min of blood
flow .if the amount of inflow is reduced / decreased can lead to pre-renal
azotemia.
-factors :-
 -decreased intravascular volume
 -decreased effective circulatory volume(CHF)
 -hypotonic agents (anti hypertensives)
 -renovascular vasoconstriction
-in this condition , no structural damage occurs to the kidney parenchyma,
condition can be revert with prompt and proper treatment .
B) FUNCTIONAL –
-results in medical condition or drugs impair glomerular ultrafiltrate production
or intraglomerluar hydroststic pressure
-blood travels through he afferent arterioles and enters the glomerulus.where it
is filtered ,and exists through the efferent arterioles .
-this process is balanced by hydrostatic gomerular pressure (HGP)
-many medications can alter HGP and gfr by producing afferent
vasoconstriction and efferent vasodilation.
C) INTRINSIC-
-occur at he microvascular level of the nephron,glomeruli, renal ubules or
interstitium.
-ATN is the most common intrinsic AKI
-causes- aminoglycosides, pencillins.

D) POST RENAL :-
-occurs due to outflow obstruction in the upper and lower urinary tract .
-causes:- prostatic hypertrophy, cervical cancer,spincter spasmor renal caliculi.
-resolved rapidly afer the obstruction has been removed.

DIAGNOSIS-
# blood tests:- bun,serum creatinine
#urinalysis- differentiate into different stages of AKI
#urine volume
#osmolality
#proienuria
#heamaturia
#urine volume
(140−age)(wt in kgs)
#gfr = X0.82
scr

#intra vascular monitoring

Pre renal and functional acute kidney injury :
a) ACEI/ARB induced AKI
-Dec. renal perfusion renin secretion from cells into lymph and plasma
angiotensinogen converted to angiotensin 1 ----------angiotensin 2 -----
efferent arteriole vasocons. and syst. Vasocons.
-ACEI/ARB inhibit angiotensin converting enzyme thus restricting
angiotensin 2 production and further prohibition of efferernt arteriole
constriction and systemic vasoconstriction.
Chronic heart failure in AKI-
In CHF patients , cardia output in diminished and results in decreased
effective circulating blood volume and activation of the RAAS which
impairs renal perfusion .

INTRINSIC AKI-
 Intrinsic AKI is general term that connotes damage at the paranchymal
level of the kidney
 This can be divided into vascular , tubular , glomerular disorders.
 Acute renal artery or vein occlusion can be caused by vasculitis,
atherothrombolism,thromboembolism, dissection , clamping of aorta
during surgery.
 Reduced blood flow to kidney vasculature also cause intrinsic AKI
 Nephrotoxic drugs can also cause intrinsic type of kidney damage (drug
induced ATN).
Acute glomerulonephritis caused by post streptococcal infection.

Streptococcal antigens bind with antibodies

↓
Formation of antigen –antibody immune complex (AAIC)
↓
This AAIC deposited on to the walls of glomerulus
↓
Activation of Complementary cascade , infl. Mediators , immune cells
 ↓
Activated inflammatory mediators attack on AAIC causing inflammation
around glomerulus
↓
glomerulonephritis

ACUTE TUBULAR NECROSIS:

Causes due to ischemia or drugs .
Burns, hypotension, trauma,surgery can cause ischemia ATN
Aminoglycoside and some othe drugs can cause drug induced ATN

Pathophysiology of ATN:

Low level of circulating oxygen

↓
Hypoxia of tubular cells
↓
Ischemia of tubular cells
↓
Tubular cells damage - tubular dead cells accumulate into slough
↓
Slough is accumulated into lumen of the tubules
↓
Accumulated slough is converted into CAST (red muddy product)
↓
Cast obstructs lumen of tubules
↓
 This obstruction creates a) inter tubular pressure
b) Back leak of ultrafiltrate
↓
Total GFR rate decrease

Sign and symptoms-

1) Predromal phase
2) Dec. urine output (oliguria,anuria)
3) Incr. urine output(polyuria)
Diagnosis-
 Urine sediment
 Urine osmolality
 BUN
 Creatinine test
 FeNa %
Drug induced ATN-
 *1-3% of cases of total AKI
 Drugs which cause –pencillins,cephalosporins,
quinolones,sulfanamides,rifamopin,nsaids.
 Exact pathosphysiology is not understood
But the pathophysiology has two pathways a) humoral b) cell mediated
immune mechanism.

a) Humoral type
Drug absorbed
↓
Drug converted into metabolite
↓
This metabolite is falsely recognised as HAPTEN (antigen type )
↓
Hapten binds to proteins
↓
Antibodies of immune system binds to hapten
↓
This creates an antigen-antibody complex (AAC)
↓
 AAC Resides and binds onto renal tubules
↓
Production of inflammatory cascade
↓
Inflammation of tubules  ATN
b) Cell mediated auto immune mechanisim
This type is otherwise called as hypersensitivity reaction

POST RENAL
Obstruction of urine output at any level of the urinary tract is termed post renal
aki
Causes – 1) nephrolithiasis
2)calcium stones
3)struvite stone
4)uric acid stone
5) cystiene stone
Nephrolithiasis-
This type effects 13% men and 7 % women.
Risk factors- hyperuricosuria,hypercalciuria,hyperoxaluria.
Causes- obesity , DM , HTN,
Calcium stones –
Apprx. 70-80%of stones are formed b this type
Two types – calcium oxalate ,calcium phosphate.
Struvite stones-
Combination of magnesium ammonium phosphate crystals termed as struvite
stones
Have high morbidity and mortality
Uric acid stones –
Occurs in the patients with abnormal uric acid metabolism
Gout and chemotherapy plays a major role in this type of stone formation