1. Acute Renal failure (Acute Kidney Injury) DR. BHUMIKA SAMBYAL

2. To function properly kidneys require:
Normal renal blood flow
Functioning glomeruli and tubules
Clear urinary outflow tract
for drainage and elimination of formed urine from the body.

3. Renal Autoregulation
Autoregulation is the maintenance of a near normal intrarenal hemodynamic environment (RBF, RPF, FF and GFR) despite large changes in the systemic blood pressure

4. Renal autoregulation
RBF - blood perfusing the kidneys each minute (1200 ml/min)
Renal Plasma Flow (RPF) - plasma flowing to kidneys each minute (670 ml/min or 55-60% of RBF)
GFR - amount of plasma filtered each minute by the glomeruli. (Normal GFR -125 ml /min for men and 100 ml/min for women)
Filtration Fraction (FF) - the ratio of GFR to RPF (Normal )

5. Renal blood flow (RBF)
Major sites of renal vascular resistance -Glomerular afferent (Raff ) and efferent (Reff) arterioles
Changes in Raff and Reff affect RBF.

6. Intrarenal autoregulation
Vasoconstrictors
Renin
Angiotensin II
Endothelin
ADH
Vasodilators
PGs
Kinins NO
ANP
RBF
GFR
Figure : RBF / GFR is maintained by a balance between vasodilators and
vasoconstrictors of Afferent and Efferent arterioles

7. Intrarenal Mechanisms for Autoregulation
Afferent Arteriole
PGC
GFR.
Glomerulus
Efferent Arteriole
Tubule
RBF
Reff / Raff ratio =N
N Engl J Med 357;8 August 23, 2007
Figure - shows normal conditions normal renal perfusion pressure and a normal GFR.

8. Intrarenal Mechanisms for Autoregulation under decreased Perfusion Pressure
MAP
Afferent Arteriole
RBF
PGC
Efferent Arteriole
Ang II
PGE
Reff / Raff ratio =
Panel B shows reduced perfusion pressure within the autoregulatory range. Normal glomerular capillary pressure is maintained by afferent vasodilatation and efferent vasoconstriction.
GFR.
N Engl J Med 357;8 August 23, 2007
Figure: shows reduced perfusion pressure within the autoregulatory range. Normal glomerular capillary pressure is maintained by afferent vasodilatation and efferent vasoconstriction.

9. Renal autoregulation failure
Renal autoregulation breaks down as MAP falls below 80 mm Hg,
Further adjustments in intra-renal hemodynamics are unable to maintain RBF and GFR
Hallmark of ARF
After age 30, RBF/ GFR decreases progressively with age; at 80 years it is nearly half of that at 20 years

10. Acute renal failure (ARF) or acute kidney injury (AKI)
Deterioration of renal function over a period of hours to days, resulting in
the failure of the kidney to excrete nitrogenous waste products and
to maintain fluid and electrolyte homeostasis
ARF Rapid deterioration of renal function
(increase of creatinine of >0.5 mg/dl in <72hrs.)
“azotemia” (accumulation of nitrogenous wastes)
elevated BUN and Creatinine levels
decreased urine output (usually but not always)
Oliguria: <400 ml urine output in 24 hours
Anuria: <100 ml urine output in 24 hours

11. The ARF Paradigm
1. Pre-renal
2. Intrinsic Renal
3. Post-renal

12. RIFLE CLASSIFICATION CATEGORY RISK GFR&S.CREATININE CRITERIA
URINE OUTPUT
RISK
GFR decrease >25% or
creatinine up 1.5 times baseline
<0.5 ml/kg/hr for 6 hrs
INJURY
GFR decrease>50% or
Creatinine up 2 times baseline
<0.5 ml/kg/hr for 12 hrs
FAILURE
GFR decrease>75% or
Creatinine up 3 times baseline or
Creatinine>4 mg/dl or
Acute rise0.5 mg/dl
<0.3 ml/kg/hr for 24 hrs
Or anuria for 12 hrs
END STAGE
End stage kidney disease(>3 months)

13. Pre-renal ARF  Renal Perfusion
2. Intrinsic Renal
3. Post-renal
Pre-renal ARF
 Renal Perfusion
Volume Depletion
 Arterial Volume
Renal Vasoconstricn
Renal losses: diuretics, osmotic diuresis, etc
Extra-renal losses: vomiting, diarrhea, skin
Cardiogenic (CHF, ACS, arrhythmias, shock)
Septic shock
Hepatorenal syndrome
Adrenal insufficiency
Radiocontrast
Prostaglandin inhibition
Calcinurin inhibitors
ACE inhibitors
Amphotericin B
When autoregulatory mechanisms are maximized, any small renal insult will subsequently precipitate acute renal failure.

14. PRE-RENAL (Hemodynamic) AKI
Generalized or localized
reduction in RBF
Hypovolaemia
Haemorrhage
Volume depletion
( vomiting,
diarrhoea,
inappropriate diuresis, burns)
Hypotension
Cardiogenicshock
Distributive shock (sepsis, anaphylaxis)
Oedema states
Cardiac failure
Hepatic cirrhosis
Nephrotic syndrome
Renal Hypoperfusion
NSAIDs
ACEI / ARBs
AAA
RAS /occlusion
Hepatorenal
syndrome
Reduced GFR
PRERENAL AKI

15. Ac. Interstitial nephritis
Renal / Intrinsic AKI
Glomerular
Tubular
Interstitial
Vascular
Ac. Interstitial nephritis
Drug induced - NSAIDs,
antibiotics
Infiltrative -lymphoma
Granulomatous- sarcoidosis, tuberculosis
Infection related - post-infective, pyelonephritis
Ac.GN
post-infectious,
SLE,
ANCA associated,
anti-GBM disease
Henoch-Schönlein purpura
Cryoglobulinaemia,
Thrombotic microangiopathy
TTP
HUS
ATN
Ischemia (50%)
Toxins (30%)
Vascular occlusions
- Renal artery occlusion
- Renal vein thrombosis
- Cholesterol emboli
85%
< 2% 5%
8 -12%
N Engl J Med 1996;334 (22):

16. Retroperitoneal fibrosis
Post-renal Urinary outflow tract obstruction
Intrinsic
Extrinsic
Intra-luminal
Stone,
Blood clots,
Papillary necrosis
Intra-mural
Urethral stricture,
BPH,
Carcinoma prostate,
Bladder tumour,
Radiation fibrosis
Pelvic malignancies
Prolapsed uterus
Retroperitoneal fibrosis
Principal POST-RENAL causes of AKI

17. ACUTE RENAL FAILURE
Acute renal failure (ARF) has four well-defined stages/phases: onset, oliguric or anuric, diuretic, and convalescent. Treatment depends on stage and severity of renal compromise.

18. Phases of ARF: Onset – initial phase of insult or injury
Oliguric – less than 400cc/24 hr
- for older (600 – 700 cc/24 hr)
- lasts 8-14 days or 1-2 weeks
-↓K+, ↑Na, ↑Mg
Diuretic – Lasts 10 days
- diuresis of 3-5L/day
- ↑BUN & Creatinine level
- dangers: hyponatremia, hypotension, shock
Recovery – lasts from 6-12 months
- avoid nephrotoxic drugs

19. Relationship between GFR and serum creatinine in ARF
S.Cr. poor marker of renal function.
Poor correlation between S.Cr. and level of GFR related to muscle mass.
S.Cr. of 1.0 does not represent the same level of GFR in a cachectic 70-year-old as in a highly muscular 25-year-old.

20. How do we diagnose it?

21. History & Physical Will Guide DDx
Primer on Kidney Diseases 3rd Ed. pg 248.

22. Acute Renal Failure Diagnosis
Blood urea nitrogen and serum creatinine
CBC, peripheral smear, and serology
Urinalysis
Urine electrolytes
U/S kidneys
Serology: ANA,ANCA, Anti DNA, HBV, HCV, Anti GBM, cryoglobulin, CK, urinary Myoglobulin

23. Acute Renal Failure Diagnosis
Urinalysis
Unremarkable in pre and post renal causes
Differentiates ATN vs. AIN. vs. AGN
Muddy brown casts in ATN
WBC casts in AIN
RBC casts in AGN
Hansel stain for Eosinophils

24. Acute Renal Failure Diagnosis
Laboratory Evaluation:
Scr, More reliable marker of GFR
Falsely elevated with Septra, Cimetidine
small change reflects large change in GFR
BUN, generally follows Scr increase
Elevation may be independent of GFR
Steroids, Catabolic state, hypovolemia
BUN/Cr helpful in classifying cause of ARF
ratio> 20:1 suggests prerenal cause

25. The Value of Urinalysis
Pre-renal
Intrinsic renal
Glomerular
ATN
AIN
Post-renal
High specific gravity, normal or hyaline casts
Proteinuria, hematuria, RBC casts
Low specific gravity, muddy brown casts, tubular epithelial cells
Mild proteinuria, hematuria, WBC, WBC casts, eosinophils
Normal or hematuria, WBC, occasional granular casts

26. Normal or hyaline casts Tubular cells & “muddy brown” granular casts
Pre-renal vs. ATN
Favours
Pre-renal
Favours
ATN
Creatinine:Urea ratio
UNa
Uosm
FENa
U specific gravity
Urinalysis
> 20:1
< 20
> 500 mO/kg
< 1 %
> 1.018
Normal or hyaline casts
<10-15:1
> 40
~ isotonic
> 2 %
< 1.010
Tubular cells & “muddy brown” granular casts

27. Acute Tubular Necrosis
Most common cause of intrinsic cause of ARF
Often multifactorial
Ischemic ATN:
Hypotension, sepsis, prolonged pre-renal state
Nephrotoxic ATN:
Iodinated contrast
Rhabdomyolysis
Hemoglobinuria
Cast nephropathy(myeloma &Tamm horsfall prteins)
Antibiotics-Aminoglycosides,Amphotricin B,I/V acyclovir
Other drugs-Cisplatin,ethylene glycol/methanol
Tumor lysis syndrome

28. Acute Tubular Necrosis
Diagnose by history,  FENa (>2%)
sediment with coarse granular casts, RTE cells
Treatment is supportive care.
Maintenance of euvolemia (with judicious use of diuretics, IVF, as necessary)
Avoidance of hypotension
Avoidance of nephrotoxic medications (including NSAIDs and ACE-I) when possible
Dialysis, if necessary
80% will recover, if initial insult can be reversed

29. Contrast nephropathy 12-24 hours post exposure, peaks in 3-5 days
Non-oliguric, FE Na <1% !!
RX/Prevention: 1/2 NS 1 cc/kg/hr 12 hours pre/post
Mucomyst 600 BID pre/post (4 doses)
Risk Factors: CKD, Hypovolemia ,DM,CHF

30. Acute Glomerulonephritis
Rare in the hospitalized patient
Diagnose by history, hematuria, RBC casts, proteinuria (usually non-nephrotic range), low serum complement in post-infectious GN), RPGN often associated with anti-GBM or ANCA
Usually will need to perform renal biopsy

31. Atheroembolic ARF
Associated with emboli of fragments of atherosclerotic plaque from aorta and other large arteries
Diagnose by history, physical findings (evidence of other embolic phenomena--CVA, ischemic digits, “blue toe” syndrome, etc), low serum C3 and C4, peripheral eosinophilia, eosinophiluria, rarely WBC casts
Commonly occur after intravascular procedures or cannulation (cardiac cath, CABG, AAA repair, etc.)

32. Acute Interstitial Nephritis
Usually drug induced
methicillin, rifampin, NSAIDS
Develops 3-7 days after exposure
Fever, Rash , and eosinophilia common
U/A reveals WBC, WBC casts, + Hansel stain
Often resolves spontaneously
Steroids may be beneficial ( if Scr>2.5 mg/dl)

33. How do we assess a patient with AKI?
Is this acute or chronic renal failure?
History and examination
Previous Serum creatinine measurements
Small kidneys on ultrasound (except for in -Diabetes, PCKD, Urinary Tract Obstruction)
Hilton et al, BMJ 2006;333;

34. Distinguishing ARF from CRF
Helpful clues…
Previous creatinine values
Hb – anemia suggests chronic problem
Renal ultrasound – small, echogenic kidneys suggest a chronic problem
X-rays – renal osteodystrophy suggests chronic problem
Renal biopsy
Exceptions to the “small kidneys = CRF” rule:
early DM, amyloid, HIV nephropathy, PCKD

35. RBCs
Dysmorphic red blood cells suggest glomerular injury.

36. Red blood cell cast
Granular cast
Marker of glomerular injury

37. Pigmented granular (“muddy brown”) casts
Marker of acute tubular necrosis

38. May- Grünwald - Giemsa staining
Marker of acute interstitial nephritis.

39. Biochemistry
Serial blood urea, creatinine, electrolytes, Blood gas analysis, serum bicarbonate –
Important metabolic consequences of ARF include hyperkalaemia, metabolic acidosis, hypocalcaemia, hyperphosphataemia

40. Biochem…. Creatine kinase, myoglobinuria –
Markedly elevated CK and myoglobinuria suggests rhabdomyolysis
Serum immunoglobulins, serum protein electrophoresis, Bence Jones proteinuria –
Immune paresis, monoclonal band on serum protein electrophoresis, and Bence Jones proteinuria suggest multiple myeloma

41. Haematology Full blood count, blood film:
Eosinophilia may be present in acute interstitial nephritis, cholesterol embolization, or vasculitis (CSS)
Thrombocytopenia and red cell fragments suggest thrombotic microangiopathy –TTP, HUS

42. Haem…. Coagulation studies
Disseminated intravascular coagulation associated with sepsis

43. Immunology
Antinuclear antibody (ANA) , Anti-double stranded (ds) antibody -
ANA positive in SLE and other autoimmune disorders;DNA antibodies anti-ds DNA antibodies more specific for SLE
C3 & C4 complement concentrations-
Low in SLE, acute post infectious glomerulonephritis, Cryoglobulinemia
ASO and anti-DNAse B titres
High after streptococcal infection
Hilton et al, BMJ 2006;333;

44. Immunology ANCA AntiGBM antibodies p-ANCA - Anti PR3 antibodies
c-ANCA - Anti MPO antibodies
Associated with systemic vasculitis - Wegener’s granulomatosis; CSS, Microscopic polyangiitis.
AntiGBM antibodies
Present in Goodpasture’s disease

45. serology Hepatitis B and C, HIV serology– Radiology
Important implications for infection control within dialysis area
Radiology
Renal ultrasonography
For renal size, symmetry, evidence of obstruction

46. Management principles in ARF
Identify and correct pre-renal and post-renal factors
Optimise cardiac output and RBF-
Review drugs:
Stop ACEI, ARBs, NSAIDs
Adjust doses / monitor drug concentrations (where appropriate)

47. Avoid Aminoglycosides Amphotericin Radiocontrast media -
33 % of nephrotoxicity “therapeutic levels”
Amphotericin
hydration,
Liposomal formulation
Radiocontrast media -
Hydration
N-acetyl cysteine

48. Management principles..
Accurately monitor fluid balance and daily body weight
Identify and treat acute complications
Hyperkalaemia,
Acidosis,
Pulmonary oedema

49. Optimise nutritional support
Maintaining calories enhances patient survival
Maintaining protein intake MAY enhance recovery & outcome
protein intakes of > g/kg/ day can dramatically increase urea production WITHOUT evidence of outcome benefit

50. Management principles…
Identify and aggressively treat infection;
Minimise indwelling lines
Remove bladder catheter if anuric.
Identify and treat bleeding tendency:
Prophylaxis - proton pump inhibitor or H2 antagonist, avoid aspirin
transfuse if required

51. Initiate dialysis before uraemic complications set in.

52. Radiocontrast induced nephropathy (RCIN)
Less than 1% in patients with normal renal function
Increases significantly with renal insufficiency
Dialysis - rarely needed

53. Prophylactic Strategies
Use I.V. contrast only when necessary
Hydration with normal saline (1-1.5 mL/Kg/ h) h before and after the procedure.
Use Low/ iso osmolar (nonionic) contrast media
Minimize contrast volume
N-acetylcysteine mg BID for two doses before and 2 doses after the procedure

54. Indications for Dialysis (dialyzable drug intoxication)
HYPERKALEMIA not amenable to medical therapy
ACIDOSIS not amenable to medical therapy
UREMIA resulting in pericarditis, neuropathy or encephalopathy
Critical VOLUME OVERLOAD not responsive to diuresis
(dialyzable drug intoxication)

55. Conclusions. ARF is common worldwide
Occurs in all clinical & community settings
It carries a high morbidity and mortality risks.
Involves high cost of management.

56. Conclusions.. ARF is often preventable.
Rapid recognition of incipient ARF and early treatment of established ARF may prevent irreversible loss of nephrons.

57. Conclusions..
No drug treatment has been shown to limit the progression of, or speed up recovery from, ARF.
Advice from a nephrologist should be sought for all cases of ARF.

58. THANK YOU