Copyright by Dr. Thuzar Win Department of Medicine University of Medicine - 2, Yangon Feel free to request to take it down this slide if you are copyright owner.

1. Acute Kidney Injury
Dr Thuzar Win
Lecturer
Department of Medicine
University of Medicine (2) Yangon

2. Definition
Refers to a sudden and usually reversible
loss of renal function, which develops
over a period of days or weeks.

3. Working Definition
 Serum creatinine rises by 26 µmol/L within 48 hours;
or
 Serum creatinine rises by 1.5-fold from the baseline
value, either known or thought to have occurred
within one week; or
 Urine output is less than 0.5 mL/kg/hour for more
than six consecutive hours.

4. Causes
Are divided into
I. Pre-renal (usually reversible and
commonest) -55-60%
II. Intrinsic renal -35-40%
III. Post-renal - < 5 %

5. I. Pre-renal causes
(a) systemic
i – Intravascular volume deplesion
 haemorrhage,
 GI loss,
 renal loss by excessive diuresis,
 increased insensible loss
 third space losses (pancretitis, crush
Syndrome)

6. continuation from pre-renal
cause-1
• ii - Decreased cardiac output
a) cardiac failure,
b) systemic vasodilatation
c) drug induced
d) sepsis, liver failure, anaphylaxis

7. continuation from pre-renal
cause-2
(b) local
i - renal artery occlusion or stenosis
ii - disease affecting renal arterioles
iii - renal vasoconstrition(norepinephrine,
ergotamine,liver disease, sepsis, hypercalcemia).
iv - pharmacological agents that acutely
impair the autoregulation and GFR( ACEI, NSAIDs )

8. II. Intrinsic renal disease
(a) Acute tubular necrosis 85%
Toxic / Septic renal failure
(b) Glomerular disease
- Primary
- Component of systemic disease 5%
(vasculitis, accelerated hypertension, DIC)
(c) Interstitial disease 10%
(acute allergic interstitial nephritis due to drugs)

9. III. Post-renal
(a) Stones
(b) Inflammation if it is bilateral
(c) Tumor.

11. Pathogenesis
I. Pre-renal
Kidney can regulate its own blood flow and GFR over a wide range of
perfusion pressures
Compensatory mechanism
(a) VD of afferent arterioles (b) VC of efferent arterioles
- mechanical
- neurohumoral
-PGs which is
inhibited by
NSAIDs.
-Renin
-Ag II which is
inhibited by
ACEI

12. When compensatory mechanism fails, intact renal
tubules become hyperfunctional and lead to increase
absorption of Na and H2O.
Physical factors
Angiotensin, Aldosterone,
Vasopressin
low urine volume.(Hyperosmolar)
low urinary Na.

13. II. Intrinsic renal
(a) Acute tubular necrosis (ATN)
(b) Sepsis
(c) Rapidly progressive glomerulonephritis (RPGN)
(a) Acute Tubular Necrosis (ATN)
(i) ischaemic ATN
(ii) nephrotoxic ATN

14. (a) (i) ischaemic ATN
- follows after shock and renal blood flow remains 20% of normal
- reduced O2 delivery to tubular cells.
- peroxidation of cell membrane lipids, influx of Ca and cell swelling.
- mitochondrial function impaired
- anaerobic glycolysis and intracellular acidosis
- lysosomal disruption, denaturing of protein and DNA
tubular cell death

15. (a) (ii) Nephrotoxic ATN
- Direct toxicity to tubular cells
- Production of reactive O2 species and peroxidation of membrane
lipids
- interfere with cellular respiration and inhibition of cell protein
synthesis
tubular cell death

16. Tubular cell death
- loss of adhesion between tubular cell and basement membrane
- shedding of cell -focal break in tubular
into tubular lumen basement membrane
tubular obstruction - tubular content leak into
interstitial tissue
interstitial oedema

17. (b) Sepsis (many mechanisms causing ATN)
- Generated arterial vasodilatation.
- Activation of sympathetic nervous system.
- Activation of RAA axis (vascular resistance)
- Non-osmotic release of vasopressin.
- Increase in cardiac output.
- Development of DIC.
- Deficiency of stress hormones, cortisol.
- Metabolic changes like hyperglycemia.
- Fortunately, tubular cells can regenerate and reform the basement
membrane.
- Need to support during regeneration phase.

18. (c) Rapidly Progressive Glomerulonephritis (RPGN)
Recognition
- Rapid loss of renal function over days to weeks
- Urine contains blood and protein
- Normal or large unobstructed kidneys on ultrasound
- Possible evidence of systemic illness or of disease affecting other
organs (but not always)
Defining the cause
- Blood tests: antineutrophil cytoplasmatic antibodies (ANCA),
antinuclear antibodies (ANA), anti-GBM antibodies, complement
immunoglobulins
- Renal biopsy

19. Common causes
- Systemic vasculitis (focal necrotising golmerulonephritis)
- SLE
- Goodpasture's (anti-GBM) disease
- Aggressive phase of other inflammatory nephritis e.g. IgA
nephropathy, post-infectious (post-streptococcal)
glomerulonephritis
Management
- Immunosuppressive treatment, e.g. cyclophosphamide and
prednisolone for most causes.
- Supportive treatment, e.g. dialysis when indicated

20. Clinical Features
I. Pre-renal
- hypotension and signs of poor peripheral perfusion.
- postural hypotension ≥ 20/10mmHg.
- metabolic acidosis, Hyperkalaemia.

21. II. Intrinsic renal
- Oliguria ( Urine output < 500ml/day)
- ↑ Urea, Creatinine (sometimes rate of rise is
>5mmol/day)
- ↑ K+, ↓ Na+, ↓ Ca++
- Metabolic acidosis
- Signs and symptoms of uraemia (anorexia, nausea,
vomiting, apathy, muscle twitching, hiccoughs, fits,
coma)
- tachypnoea (metabolic acidosis), pulmonary oedema
- Anaemia, bleeding tendency, prone to infection

22. Investigations
The following investigation should do
- urea & electrolyte, creatinine, CP, CRP and glucose
- Urine stick test, microscopy, biochemistry and
culture & sensitivity
- Arterial blood gases and pH
- Chest X-ray, USG ( abdomen)
- ECG
- Culture and sensitivity of appropriate fluids in case
of sepsis.

23. continuation from
investigation
Prerenal azotemia Intrinsic ARF
FENa < 1% > 1%
UNa < 10 > 20
Uosm > 500 < 250
BUN/ Cr > 20 < 10- 15

24. Management
I. Emergency resuscitation
II. Determination of the cause of ARF and specific
treatment of the underlying cause.
III. General management of established ARF
IV. Recovery state (diuretics phase)

25. I. Emergency resuscitation
(a) Especially K+
> 6mmol/l with ECG changes.
1. IV Ca gluconate 10ml over 5 mins, repeated every 2-3 minutes till
the ECG changes resolved. ( ideal is Ca cholride, Ca contents of CaCl2 is
3-4 times higher than CaCO3 )
2. IV 1.26% NaHCO3 50cc over 5 mins, repeated every 6 hrs.
3. IV soluble insulin 10 units with 50 ml of 50% dextrose over 5
mins, repeated every 6 hrs.
4. Nebulised 15- 20 ml of salbutamol, repeated every 6 hrs.
5. IV Normal saline with IV Frusemide.

26. (b) Restore the circulatory volume by transfusion with appropriate
fluids. (Monitored by CVP pressure)
(c) Dialysis when there is pulmonary oedema.

27. II. Determination of the cause of ARF and
specific treatment of the underlying
cause.
(a) Investigation to find out the cause. e.g. USG
(abdomen)
(b) Specific treatment of the underlying cause.
e.g. obstruction should be relieved urgently
Corticosteriod and immunosuppressive drugs in
RPGN.

28. III. General management of established ARF
Aims. (a) To control fluid and electrolyte balance.
(b) To maintain nutrition.
(c) To control of biochemical abnormality.
(d) To protect the patient from infection.
(e) To consider for RRT (Renal Replacement Therapy)

29. (a) / (c)
- Daily fluid intake - Urine output + 500 ml.
- Restrict the Na+, K+ intake
- Replace additional fluid and electrolyte
- Daily body weight.
(b)
- Restrict protein intake to 40 g/day (without dialysis) vs 70 g/day
(with dialysis)
- Increase Calorie intake in the form of fat and CHO to suppress
endogenous protein catabolism.
(d) To protect the patient from infection

30. (e) RRT
- HD (haemodialysis)
- PD (peritoneal dialysis)
- HF (haemofiltration)
- CRRT (continuous renal replacement
therapy) (UF 45ml/ kg/ hr)

31. IV. Recovery state (diuretics phase)
In case of ATN and obstruction, develop a diuretic phase when
ARF recover.
Need - Appropriate fluid replacement.
- Suppliments of NaCl , NaHCO3, KCl, Ca, PO4, Mg.
Special situation
(A) ARF with sepsis
Cause high mortality of 50-70%
- DIC - recombinent human activated protein ( Drotrecogin alfa)
- PRP,FFP,Cryoprecipitate

32. - Stress hormone deficiency - IV hydrocortisone 50 mg 6 hrly
- oral fludrocortisone 50 mg/day
for 7 days
- Tight glycemic control with insulin aim the blood glucose level
between 80 - 110mg/ dl.
- IV antibiotics as soon as blood culture was taken.

33. - Volume replacement in 1st 6 hours of sepsis
(i) crystalloid or colloid
(ii) red cell transfusion to keep Hct to ≥ 30%
(iii) Arginine vasopressin to keep mean arterial pressure > 6.5 mmHg.
If above measures are failed, add dobutamine.

34. Prognosis
- Mortality is low in uncomplicated ARF even need RRT.
- 50 - 70% in ARF due to serious infection and multiorgan failure.
Poor prognostic features include
- Age > 50 yrs
- Infection (esp. septicaemia)
- Burns ( > 70% surface area)
- Rising urea ( > 16 mmol/ 24hr)
- Oliguric for > 2 wks
- Multi- organ failure ( > 3)
- Jaundice