DR.P.

SANKARANARAYANAN MD

EMERITUS PROFESSOR OF MEDICINE

ACS MEDICAL COLLEGE & HOSPITAL

Thirukkural :

 The act of kindness is bounded,

 Not by its own boundaries,
 But by those
 Of the culture of the recipient.
 Udavi varaithanru udavi, udavi

 Seyappatar salbin varaithu.

 Acute kidney injury
 Acute kidney injury, formerly called acute
renal failure is a complex clinical disorder.
 There is sudden, rapid decline in GFR
resulting in retention of nitrogenous waste
products manifesting as oliguria and
elevation of blood urea and creatinine.
 Majority of patients [80 %] have oliguria
others are nonoliguric.
KDIGO Criteria for AKI
 Increase in serum creatinine >0.3mg/dl
 With in 48 hours. OR

 Increase in serum creatinine 1.5 times the

base line with in preceeding 7 days
 OR
 A urine volume of < 0.5 ml/kg/hr for 6
hours.
staging system for AKI
 Stage serum creatinine criteria
 1. rise in Scr >0.3mg/L or
 >150%-200% from baseline
 2. rise in Scr >200%-300% from
 base line.
 3. rise in Scr >300% from baseline
 or Scr > 4mg/dl with an acute
increase of atleast 0.5 mg/l.
staging system for AKI

 STAGE URINE OUTPUT CRITERTA

 1. <0.5 ml/kg/h for >6 hours.

 2. <0.5 ml/kg/h for > 12 hours.

 3. <0.3 ml/kg/h for >24 hours

 or anuria > 12 hours.
CLASSIFICATION OF AKI

 PRERENAL

 RENAL

 POST RENAL
 PRERENAL CAUSES

 1. Hypovolemia
2. Low cardiac output
3. Altered renal systemic vascular
resistance ratio
4. Renal hypoperfusion with impairment
of renal autoregulatory responses
5.Hyperviscosity syndrome
 Hypovolemia

Haemorrhage ,burns, dehydration

 Gastrointestinal fluid loss: vomiting,
diarrhoea, surgical drainage
 Renal fluid loss: diuresis, osmotic
diuresis,[DM], hypoadrenalism
 Sequestration in extra vascular space:
pancreatitis,peritonitis, trauma, burns.
Severe hypoalbuminemia
 low cardiac output

 Diseases of myocardium, valve,

pericardium, arrhythmias,,tamponade.

 Massive pulmonary embolism,

 Pulmonary hypertension
 Positive pressure mechanical
ventilation
Altered renal systemic
vascular resistance ratio
 Systemic vasodilatation: sepsis,
antihypertensives, afterload reducers,
anaesthesia, anaphylaxis.
 Renal vasoconstriction: hypercalcemia,
norepinephrine, epinephrine,
cyclosporine, tacrolimus, amphotericin B
 Cirrhosis with ascites [hepatorenal
syndrome ]
 Renal hypoperfusion

 Cyclooxygenase inhibitors

 ACE inhibitors.
Hyperviscosity syndrome

 Multiple myeloma

 Macroglobulinemia

 Polycythemia
Khushwant singh joke :

 A man went into a bar and ordered

a drink.
 After he had finished and got up to
leave, the bar tender asked, what
about the bill ?
 “ i have already paid “ he replied and
left.
 Soon after, another man came in.
 He too, ordered a drink, drank it and
left saying that he had already paid.
 The third customer came in.
 As he was drinking, the bartender told
him, ‘before you two men came here,
they ordered drinks and left, telling me
that they had already paid.
 What do you think about that ?
 Stop arguing and “ return my change “

 The man said.

 Intrinsic renal AkI

 Renovascular obstruction
 Disease of the glomeruli or renal
microvasculature
 Acute tubular necrosis
 Interstitial nephritis
 Intra tubular deposition and obstruction
 Renal allograft rejection
Renovascular obstruction

 Renal artery obstruction:

 atherosclerotic plaque, thrombus,
embolism, dissecting aneurism.
Vasculitis

 Renal vein obstruction: thrombus,

compression.
Disease of the glomeruli

 Glomerulonephritis and vasculitis

 HUS, TTP, DIC, SLE
 Toxemia of pregnancy
 Accelerated hypertension
 Radiation nephritis
 scleroderma
Acute tubular necrosis
 Ischemic :
 Almost any of the causes of severe pre
renal disease can lead to ATN,
 Particularly hypotension in the settings of
surgery [ primarily open heart surgery or
abdominal aortic aneurysm repair ] sepsis or
obstetric complications like placenta previa,
abruptio placenta, and post partum hge.
;
 Toxins :
 Exogenous : radiocontrast,
aminoglycosides, acetomenophen,
cyclosporine, cisplatin,ethylene glycol,
illegal abortifacients
 Endogenous : rhabdomyolysis,
haemolysis, uric acid, oxalate, myeloma.

 Interstitial nephritis

 Allergic : antibiotics, NSAID, diuretic,

captopril.
 Infection : bacterial, viral, fungal
 Infiltration: leukemia, lymphoma,
sarcoidosis
 idiopathic
Intratubular deposition
and obstruction
 Myeloma proteins
 Uric acid
 Oxalate
 Sulphonamides
 Acyclovir
 Methotrexate
 Post renal ARF

 Ureteric : Calculai, blood clot, sloughed

papillae,cancer, external compression,
 Bladder neck: neurogenic bladder,
prostatic hypertrophy, cancer, calculi,
blood clot.
 Urethra: stricture, congenital valve,
phimosis.
Pathogenesis-pre renal
ARF
 Both haemodynamic and neurohumoral factors
contribute to decrease in GRF with
hypovolemia.

 Systemic hypotension is initially sensed by

pressure [ or stretch ] receptors in the heart and
in the arterial circulation [ such as those in
the carotid sinus and the afferent glomerular
arteriole.
 .
Teachings of Buddha

 To enjoy good health,

 To bring true happiness to one’s family,
 To bring peace to all,
 One must discipline and control one’s
own mind.
 If a man can control his mind he can
find the way to Enlightenment, and all
wisdom and virtue will come to him.
 PRE RENAL ARF

 The ensuing release of norepinephrine

and angiotensin 2 leads to systemic
and renal vasoconstriction.

 This response is in part appropriate in

that it maintains the BP and
preserves perfusion to the heart and
brain.
 Pre renal ARF

 However ,the renal ischemia ultimately

lowers the GRF, as manifested by a
rise in blood urea nitrogen and
plasma creatinine concentration.
 Physical examination
pre renal ARF
 Decreased skin turgor
 Low jugular venous pressure
 Postural tachycardia
 Hypotension are signs of true volume
depletion that can lead to
 pre renal disease and possibly to post
ischemic ATN. In contrast, peripheral or
pulmonary edema or ascites suggests HF or
hepatic cirrhosis.
 AKI-PRE RENAL
 The gold standard to define pre renal from
ATN is return of baseline renal function
within 48 to 72 hours of increasing the
effective circulating volume, [ by
administering fluids or treating
hypotension ] reflect pre renal disease;
 in comparison, continued renal failure
despite adequate fluid repletion is called
ATN.
 LAB.FINDINGS
 PRERENAL ATN

 BUN/Pcr ratio >20:1 10-15:1

 URINE sodium <20meq/L >40 meq
 FENa <1 % >2%
 Urine osmalality >500mosm/kg <350
 Urine analysis normal muddy brown
 epithelial cell
 casts
 TREATMENT

 Therapy is aimed at fluid repletion

 The tonicity of the administered fluid is
determined by plasma Na concentration
 Hypotonic fluids if the patient is
hypernatremic.
 The proper fluid may vary from dextrose
in water to quarter or half isotonic saline.
 TREATMENT

 This depends on whether there is

pure water loss-[ as with insensible
losses or diabetes insipidus ] or both
sodium and water loss.
 In contrast, isotonic, or if plasma
sodium concentration is below 110-115
meq/L, hypertonic saline is indicated in
hyponatremic patients.
 TREATMENT

 Finally, either half isotonic or isotonic

saline can be used if plasma sodium
concentration is normal.

 In addition, blood replacement may be

required in patients with active
bleeding or marked anemia.
Pathophysiology of
ischemic kidney injury
 Ischemic ATN in many circumstances is a
progression or persistence of the prerenal
condition that leads to damage of the
tubular epithelium.
 Although 25% of the cardiac output flows
in to the renal circulation,
 Most of the blood flow is relegated to the
cortex, and the medulla is maintained in a
relative hypoxic state.
 AKI
 The S3 segment of the proximal tubule is
especially vulnerable in ischemic states
and most of the damage occurs in this
segment.
 Overwhelming levels of Angiotensin 2 ,
endothelin-1, and circulating catechol
amines cause intense intrarenal
vasoconstriction, overcoming protecting
effects of prostaglandins and nitric oxide.
 AKI

 Other factors also come into play.

 The ischemic response stimulates
release of inflammatory cytokines,
which in turn leads to increased
expression of adhesion molecules on
the leukocytes and their ligands on
the endothelium.
 AKI

 This environment results in increased

leukocyte- endothelium adhesion and
endothelial injury.
 Congestion and obstruction of
capillaries in the outer medulla causes
persistent medullary ischemia.
 pathophysiology of
ischemic kidney injury
 There are two major histological changes in
ATN.
 Tubular necrosis with denuding of the
epithelial cells and occlusion of the tubular
lamina by casts and by cellular debris
[including the brush border of the proximal
tubular cells and Tamm-Horsfall
mucoprotein released from damaged cells
in the thick ascending limb of loop of Henle]
 ATN
 These changes are often patchy and seem
relatively mild in relation to the severity of
the renal failure.
 It is important to remember, however, that
many nephrons drain into a single cortical
collective tubule.
 Thus, obstruction of a seemingly small
number of collecting tubules can lead to
marked renal dysfunction.
 ATN
 In addition to tubular obstruction, two other
factors appear to contribute to the
development of renal failure in ATN.
 Backleak of the filtrate across the
damaged tubular epithelia; and a primary
reduction in glomerular filtrate, due both to
arteriolar vasoconstriction and to
mesangial contraction. [ the latter limits the
surface area for filtration]
 ATN

 Capillaries adjacent to the tubules

show ischemic changes and to some
extent of inflammation of interstitium
is seen.
 With the regenerating capacity of
tubules, there is formation of new
tubules and restoration of renal
function back to normal.
 ATN
 The disease can go through the following
stages,namely oliguric phase in which there
is decreased urine volume for 10-14 days.
 This stage is followed by the recovery
phase wherein the urine volume
progressively increases over a period of
15-25 days and which heralds the recovery
of renal function, although GFR has not
yet improved. ,
Teachings of BUDDHA

 Just as treasures are uncovered from

the earth,
 So virtue appears from good deeds,
and wisdom appears from a pure and
peaceful mind.
 To walk safely through the maze of
human life, one needs the light of
wisdom and the guidance of virtue.
 Management

 In the oliguric phase:

 There is the need for restriction of
salt, fluids, and intake of foods rich in
potassium.
 No protein restriction is required.
 Give adequate carbohydrate as a
source of energy, protein for
maintaining anabolism and vitamins.
 ATN

 Finally GFR improves in the last phase

and there is recovery of renal function to
near normal.
 Although there is normalization of serum
creatinine,
 the full function of kidneys takes a long
time to recover with the concentration
capacity of tubules returning last.
 ATN
 In catabolic situation, more than 1g/kg/day
of protein is required.
Increase in azotemia, and developement of
acidosis or hyperkalemia or pulmonary
edema or complications of renal failure
like pericarditis,/ neuropathy,
/encephalopathy/ severe gastrointestinal
symptoms would require dialysis therapy till
GFR improves.
 ATN
 Gastrointestinal symptoms include:
 Nausea, vomiting, anorexia, hiccup, diarrhea,
or GI bleeding.
 Respiratory rate could be high due to
acidosis or fluid excess as in pulmonary
edema.
 Neurological symptoms include drowsiness,
apathy, neuropathy, muscle twitching, fits,
paresthesia, or coma.
 ATN

 Anaemia due to haemolysis, bleeding, or

impaired production of RBC by marrow
due to lack of adequate erythropoitin
from the kidney.

 Bleeding may be due to abnormal

platelet function / or coagulation.
 ATN

Hyperkalemia is the result of ineffective

excretion of this ion or of increased release
from breakdown of cells in haemolysis or
rhabdomyolysis or of associated metabolic
acidosis.

It can produce muscle weakness and cardiac

arrhythmia.
 ATN

 Besides control of potassium rich food,

intravenous calcium to prevent cardiac
arrhythmia, insulin dextrose infusion,
potassium binding resin, beta-2
adrenoceptor agonist inhalation and
bicarbonate therapy, if there is severe
metabolic acidosis, are required to bring
serum potassium level to normal.
 ATN

Metabolic acidosis due to impaired

excretion of hydrogen ions in urine or

excessive cell breakdown, can

produce respiratory distress and
vasoconstriction causing low BP.
 ATN

 Salt and fluid retention during the

phase of oliguria leads to
hypertension.
 Hypertension could be significant
enough to become malignant with its
complications.
 Define success.
 Success is 1 percent inspiration and
 99 percent perspiration.
 PROGNOSIS

 Most patients with AKI without sepsis

when recognized promptly in the early
part of the disease recover to normal
and mortality is low.

 However, in the presence of sepsis

there could be a mortality of about
50%
Pathogenesis–post renal

 In case of post renal failure:

 The intratubular and ureteral pressure
rise with progression of the disease
 And this leads to increase in renal
vascular resistance
 And fall in GFR subsequently.
 Obstruction is manifested as sudden
or progressive reduction in urine
volume, symptoms of acidosis and
uremia.
 Physical examination may reveal
hypertension, either bladder distension
or palpable kidney[s] with or without
tenderness,
 management
 Azotemia , hyperkalemia, and acidosis may
be seen on lab.findings.
 Relief of obstruction leads to resolution of
many of the problems and renal function
improves over a long time and the
completeness of this recovery depends on
the duration of the obstruction and the
concentration defect recovering the last.
Complications of AKI
 METABOLIC:

 Hyperkalemia
 Hypocalcemia
 Hyperphosphatemia
 Hypermagnesemia
 hyperuricemia
 Metabolic acidosis
 cardiovascular

 Cardiac arrhythmias
 Pericarditis
 Pericardial effusion
 Pulmonary edema

 Gastrointestinal :
 GI haemorrhage
 Neurologic :
 Altered sensorium
 Seizures

 Haematologic:
 Anaemia
 Bleeding
 Miscellaneous:
 Infections :
 pneumonia
 urinary tract infections
 septicaemia.
 What is the biggest obstacle standing

 In the way of success ?

 Discouragement .
 investigations
 Complete haemogram
 Urine analysis
 Blood chemistry: BUN,creatinine, electrolytes,
HCO3, Ca, p
 Special tests: urine for eosinophil,
 Bence-jones protein
 Serology : ANA ,ANCA, anti-GBM, compliment,
cryoglobulins, ASO, protein
electrophoresis,
 Imaging:
 plain radiograph of abdomen
 renal ultrasound
 CT urography
 MRI

 Renal biopsy.
 special tests

 ANA, double stranded DNA –

 lupus nephritis
 C-ANCA [often+proteinase 3 ab ]
 wegeners granulomatosis
 P-ANCA [often+myeloperoxidase ab ]
 microscopic polyangitis
 churg-strauss syndrome.
 Rheumatoid arthritis factor:
 vasculitis; cryoglobulinemia
 Cryoglobulins:
 cryoglobulinemia-associated MPGN
 Anti-GBM antibodies:
 good pasture syndrome
 ASO-titre - PSGN
 Compliment levels [low ]
 PSGN, cryoglobulinemic MPGN, LN,
 shunt nephritis, GN with SBE,
 atheroemboli.
 Hepatitis B and C antibodies
 membranous GN, or MPGN
 HIV : collpsing FSGS,
 interstitial nephritis
 Urine and serum protein
electrophoresis and immune fixation
and serum light chains:
 myeloma kidney [cast nephropathy ]
 monoclonal deposition disease
 Amyloidosis.
 CT AND MRI

 To rule out obstruction due to

microcalculi or a fibrotic process in
cases where dilatation of calyces may
not be seen on ultrasound.
 Novel BIOMARKERS
 Serum creatinine slowly identifies renal
injury and does so indirectly, it is derived
from muscle filaments and not kidney
structure.
 An ideal biomarker would instead reflect
actual cellular injury derived from the
kidney [ like treponin for myocardial
infarction ] and detect such injury iwthin
hours of the event.
 BIOMARKERS

 If therapy can be started in the early

stages of AKI [ initiation phase ], then
this can potentially prevent the
continued deterioration of renal
function.
 Promising biomarkers include serum
and urine neutrophil gelatinase
associated lipocalin [NGAL ]
 BIOMARKERS

 NGAL increases as early as 1 hour

after coronary artery bypass grafting in
patients who later develop AKI.

 INTERLEUKIN-18 has also shown

similar results, including in the setting
of delayed graft function after kidney
transplantation.
 BIOMARKERS

 Other molecules of interest include

 cystatin C and kidney injury molecule-1

 Further studies are underway to

determine if any of these markers will
enhance the diagnostic utility of
creatinine in AKI.
Thirukkural :

He, who lives on the earth,


 in the manner he should,

 Will be placed among the Gods

 dwelling in Heaven.