This document provides an overview of acute kidney injury (AKI) including renal anatomy and physiology, epidemiology, definitions, diagnosis, biomarkers, and treatment. It discusses the kidney's role in fluid, electrolyte and waste regulation. AKI is common, affecting 5-30% of hospitalized or ICU patients. New definitions classify AKI severity into Risk, Injury and Failure stages based on creatinine and urine output. Causes include pre-renal, intrinsic renal and post-renal factors. Treatment focuses on fluid management, electrolyte control, nutrition and preventing complications through dialysis if needed. Biomarkers show promise in early AKI detection but management primarily relies on supportive care as no targeted therapies exist

1. Acute Kidney injury
Prepared by:
Dr. Issam Abou Najab
Ped. Nephrology. Subdivision

2. Outline
Renal Anatomy/Physiology
Epidemiology
New AKI Definitions
Diagnosis
New Advancements - Biomarkers
Treatment

3. renal
capsule
renal
cortex
renal
medulla
renal
pelvis
renal
pyramids
ureter
Kidney
Anatomy

4. Kidney
Anatomy
renal artery
renal vein
nephron

5. renal
cortex
renal
medulla
Collecting duct
Loop of Henle
PCT
DCTGlomerulus

6. artery
afferent
arteriole
efferent
arteriole
glomerulus
peritubular
capillaries
Bowman’s
capsule
proximal
convoluted
tubule
distal
convoluted
tubule
loop of
Henle
collecting
duct
Each kidney
contains over 1
million
nephrons
Nephron Unit

8. Kidney function is dependent on
Adequacy of blood supply to the kidney
– Prerenal
Integrity of renal parenchyma
– Renal
Patency of urinary tract
– Post renal

9.  Formerly referred to as acute renal failure (ARF).
 Defined as an “sudden deterioration in kidney function results
in the inability to maintain fluid and electrolyte homeostasis”
Acute Kidney Injury (AKI): Definition

10. Impairment of
nitrogenous waste
product excretion
Loss of water regulation
Loss of electrolytes
regulation
Loss of acid-base [H+]
regulation
Acute Kidney Injury
Disturbance of renal
physiological functions

11. Diagnosis of AKI is Often Delayed
• Serum creatinine alone is a poor indicator of renal function
• Serum creatinine varies widely with age, gender, diet, muscle
mass, medications, and hydration status
• Up to 50% of kidney function may be lost before serum
creatinine even begins to rise
Each doubling of creatinine
kidney function cuts in half

12. Normal Serum Creatinine Per Ages

13. Normal GFR Values for Children
Estimated Creatinine Clearance (ml/min/1.73 m2)
“Schwartz Formula”
eCCL = k × Height / SCR
 K is 0.33 in pre-term and 0.45 for term infants <1 year
 K is 0.55 in children and adolescent girls, and 0.7 in adolescent boys

14. 0
10
20
30
40
50
60
0 5 10 15 20 25
GFR in Infants
GFR [ml/min/1.73
m2]
Age [days]
Guignard, J Pediatr 87:268-72, 1975

15. EPIDEMIOLOGY

16. AKI: A Common, Serious
Problem
• 5% of all hospitalized patients, and up to 30% of patients in PICU
Stickle SH et al: Am J Kid Dis 45:96-101, 2005

17. Pediatric AKI: Recent Epidemiology
Patient Selection
• Reviewed all admissions to Texas Children’s Hospital from
January 1998 through June 2001
• Selected patients <20 years of age with ARF
• GFR by Schwartz < 75 ml/min/1.73m2 (n=254)
Stickle SH et al: Am J Kid Dis 45:96-101, 2005

18. Pediatric AKI: Recent Epidemiology
Pediatric ARF: Age Distribution
22%
15%
13%
34%
16%
0 to 30 d
1 to 12 mo
1 to 5 yr
6 to 14 yr
15 to 20 yr
Stickle SH et al: Am J Kid Dis 45:96-101, 2005

19. Pediatric AKI: Recent Epidemiology
Most Common ARF Causes
• ATN-Dehydration (21%)
• Nephrotoxic drugs (16%)
• Sepsis (11%)
• Unknown (14%)
• Primary Renal Disease (7%)
Patient Survival
• 176/254 patients (70%)
• 110/185 patients with ICU care (60%)
• 43/77 patients receiving renal replacement therapy (56%)
Stickle SH et al: Am J Kid Dis 45:96-101, 2005

20. All AKI are NOT Equal !
Classification System

21. - R = Risk for renal dysfunction
- I = Injury to the kidney
- F = Failure of kidney function
- L = Loss of kidney function
- E = End-stage renal disease
pRIFLE Criteria
Andreoli SP: Acute kidney injury in children. Pediatr Nephrol 2009

22. pRIFLE Criteria Estimated CrCl
(Schwartz)
Urine output
Early R (risk) ↓ 25% < 0.5 ml/kg/hr x 8 h
I (injury) ↓ 50% < 0.5 ml/kg/hr x 16 h
F (failure) ↓ 75% or eCCl <35
ml/min/1.73 m2
< 0.3 ml/kg/hr x 24 h/ anuria
Late L (loss) Renal failure > 4 weeks
E (end stage) Renal failure > 3 months
Pediatric RIFLE criteria

23. AKI Etiologies

24. The AKI Paradigm
1. Pre-renal
2. Intrinsic Renal
3. Post-renal

25. 1- Prerenal azotemia
a) Volume depletion (hypovolemia)
b) ↓ effective arterial pressure (shock)
c) ↓ effective circulating volume (heart failure)

26. 2- Intrinsic renal disease:
a) Glomerular (glomerulonephritis)
b) Tubulointerstitial: ATN, or interstitial pathology
c) Vascular (arterial or venous thrombosis)
1
2
Glomerular
Tubulointerstitial
3 Vascular

27. Examples of intrinsic renal diseases:
 Glomerulonephritis: postinfectious GN, lupus nephritis, HSP
nephritis.
 HUS is the most common cause in the USA.
 Tumor lysis syndrome : spontaneous or chemotherapy-induced
cell lysis of lymphoproliferative malignancies  
obstruction of the tubules by uric acid crystals
 Acute interstitial nephritis due to hypersensitivity reaction to a
therapeutic agent or various infectious agents
 Acute Tubular Necrosis (ATN)

28. Acute Tubular Necrosis
 Ischemic ATN:
 Hypotension, sepsis, prolonged pre-renal state
 Nephrotoxic ATN:
 Contrast, Antibiotics, Heme proteins

29. Histopathology: ATN
(1) Sloughing of the epithelial cells
(2) Occlusion by casts and cellular debris
(3) Backleak of filtrate

30. 3- Postrenal AKI urinary tract obstruction:
a) Ureteral bilateral
b) Or unilateral in a solitary kidney.
c) Or subvesical
PUV
OBSTRUCTION

31. Diagnosis

32. Detailed History, physical examination and Chart review
are most important
Clinical Evaluation of AKI
Laboratory studies
CBC
Electrolytes
CBG (or VBG)
Diagnosis-specific Lab tests

33. Finding Pre-renal AKI Intrinsic AKI
UOsmol(mOsm/kg) >500 <350
USG >1020 <1010
UNa (mmol/d) <20 >40
FENa (%) <1 >2
Plasma BUN/Cr ratio >20 <10-15
Urine sediment Bland and/or nonspecific May show muddy brown
granular casts
FENa = [Urine Na/ Plasma Na] x [Plasma Cr/ Urine Cr] x 100

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

35. Documents the presence of one or two kidneys
Assesses renal size
Assesses renal parenchyma
Detects urinary tract obstruction
Detects occlusion of major renal vessels (Doppler)
Renal ultrasonography
Other imaging studies as indicated

36. Most commonly obtained in patients with:
1. Suspected glomerulonephritis.
2. In those with otherwise unexplained AKI.
Renal Biopsy

37. Acute GN
Normal Glomeruli

38. BIOMARKERS

39. Biomarkers: AMI versus AKI
Period Acute Myocardial Infarction Acute Kidney Injury
1960s LDH
1970s CPK, myoglobin
1980s CK-MB
1990s Troponin T
2000s Troponin I
Multiple Therapies
50% ↓ Mortality

40. Period Acute Myocardial Infarction Acute Kidney Injury
1960s LDH Serum creatinine
1970s CPK, myoglobin Serum creatinine
1980s CK-MB Serum creatinine
1990s Troponin T Serum creatinine
2000s Troponin I Serum creatinine
Multiple Therapies
50% ↓ Mortality
Supportive Care
High Mortality
Needs early biomarkers of AKI to improve understanding, early
treatment and better outcomes
Biomarkers: AMI versus AKI

41. Role of Biomarkers in AKI
• Early prediction and diagnosis of AKI
• Identify the primary location of injury
• Pinpoint the duration and severity
• Identify the etiology of AKI
• Monitor response to intervention and treatment
Devarajan, Semin Nephrol 27:637-651, 2007
Devarajan, Contrib Nephrol 160:1-16 , 2008

42. Promising AKI Biomarkers
– Neutrophil gelatinase-associated lipocalin (NGAL)
– Interleukin 18 (IL-18)
– Kidney injury molecule 1 (KIM-1)
Devarajan, NEJM 358;3:312, 2008

43. Management

44. AKI - Prevention
• Maintenance of blood flow
– Cardiac output, isovolemia, etc
• Avoidance of toxins
– Aminoglycosides, amphoteracin, NSAIDs
Easy on paper….difficult in practice!!

45. – 1) Volume overload, edema, hypertension
(oliguric type)
– 2) Electrolyte Abnormalities:
– - Hyperkalemia
– - Hyponatremia
– - Acidosis
– - Hyper PO4, Hypo Ca
– 3) Uremic Symptoms
45
Presentation of Acute Renal Failure (AKI – F)

46. A. Maintenance of electrolyte and fluid balance.
B. Avoidance of life-threatening complications.
C. Adequate nutritional support.
D. Treatment of the underlying cause.
Management Goals

47. If no evidence of volume overload or cardiac failure  
Fluid challenge of IV NS , 20 mL/kg over 30 min
No void within 2-4 hr points to intrinsic or postrenal ARF
Vigorous fluid resuscitation may be needed in sepsis
? Diuretics if no void with adequate circulation (CVP ?).
? Renal dose of dopamine (2-3 μg / kg / min)
Management: FLUIDS

48. • TFI = insensible loss (400 ml/m2/d) + UOP
• E.g. 10 y/o, BW 30 kg, BSA 1 m2
Management: FLUIDS - 2
600
400
200
400
400
800
400
800
1200
400
1200
1600
Insensible Loss
UOP
TFI

49. 1. Severe hyperkalemia (>7.0 mEq/L):
- electrocardiographic changes or peripheral muscle weakness
- can be life-threatening and requires immediate attention.
2. Acute management includes administration of:
 IV calcium to stabilize the cardiac membrane;
 and/or glucose/insulin infusion,
 sodium bicarbonate, or beta agonists (promotes
extracellular K shift into the cells)
 Kayexalate (an anion exchange resin): removes excess K
from the body.
 Renal replacement therapy: if medical management fails
Hyperkalemia

50. 1. In children with AKI:
• impaired acid excretion
• increased acid production (shock and sepsis)
2. Sodium bicarbonate should only be administered with life-
threatening acidosis or hyperkalemia.
3. HCO3 > 12 mEq/L and/or arterial pH greater than 7.2 do not
require immediate intervention.
Acidosis

51. • Most often a result of hypervolemia.
• The choice of antihypertensive therapy:
 The degree of hypertension and the clinical
presentation.
Hypertension

52.  Adequate calories are needed to promote recovery
 Renal replacement therapy if sufficient calories cannot be
achieved (patient with oliguria or anuria)
 Patients with inappropriate nutrition have poorer prognosis.
Nutrition

53.  Severe fluid overload unresponsive to management
 Persistent hyperkalemia
 Severe met.acidosis unresponsive to management
 Neurologic symptoms (altered mental status, seizures)
 BUN >100-150 mg/dL (or lower if rapidly rising)
 Ca:PO4 imbalance, with hypocalcemic tetany
 Nutritional support in a child with oliguria or anuria
Indications for dialysis in ARF

54. Comparison of PD, Intermittent HD, and CRRT

55.  Depends upon the etiology, age, clinical presentation, and
status of the patient.
 Hypotension and the need for inotropic support are
significant poor predictors for patient survival.
Worse prognosis (pt survival) in the context of multi-organ
failure.
Prognosis of AKI

56. 56
56

57. Take Home Messages
AKI is a common and serious problem
All AKI are Not equal
The diagnosis of AKI is often delayed
Earlier recognition and treatment of AKI sequelae may
improve outcome
Novel biomarkers are providing tools for the early prediction
of AKI and outcomes, and for testing therapies

58. Thank you for your
attention!