Nephrology Dr.

Karrar Alibek
Lec.1 Monday 28/6/2021

(( Acute Kidney Injury ))

Acute Kidney Injury (AKI) :
Formerly called acute renal failure, is a clinical syndrome in which a sudden
deterioration in renal function results in the inability of the kidneys to maintain fluid
and electrolyte homeostasis.

Modified RIFLE criteria (pRIFLE) :

It was developed to characterize the pattern of AKI in critically ill children :

Criteria Estimated CCL (creatinine clearance) Urine output

Risk eCCL decrease by 25% <0.5 mL/kg/hr for 8 hr

Injury eCCL decrease by 50% <0.5 mL/kg/hr for 16 hr
Failure eCCL decrease by 75% or <0.3 mL/kg/hr for 24 hr
eCCL < 35 ml/min/1.73 m² or anuric for 12 hr
Loss Persistent failure >4 wk
End-stage End-stage renal disease
(persistent failure >3 mo)

Because RIFLE focuses on the glomerular filtration rate (GFR), a modification (Acute
Kidney Injury Network) categorizes severity by rise in serum creatinine:

Stage 1 >150%, Stage II >200%, Stage III >300%.

Epidemiology :
AKI occurs in 2-3% of children admitted to pediatric tertiary care centers and in as
many as 8% of infants in neonatal intensive care units.

The co-existence of AKI with critical illness occurs at a rate of 10% and it has 50%
mortality in children requiring dialysis.
Etiology :
AKI has been conventionally classified into 3 categories:

1. Prerenal : It is also called prerenal azotemia, is characterized by :

Diminished effective circulating arterial volume, which leads to inadequate
renal perfusion and a decreased GFR.
Absence of evidence of kidney damage.
The renal function returns to normal if the underlying cause of the renal
hypoperfusion is reversed promptly.
Intrinsic renal parenchymal damage can develop if hypoperfusion is
sustained.
Causes :
A. Dehydration due to diarrhea, malnutrition, DKA
B. Hemorrhage due to aortic or renal vessel injury or trauma
C. Sepsis
D. Shock
E. Hypovolemia associated with capillary leak or nephrotic syndrome
F. Heart failure
G. Burns

2. Intrinsic renal : It is characterized by renal parenchymal damage, including

sustained hypoperfusion and ischemia.
Causes :
A. Glomerulonephritis : including ; Postinfectious/poststreptococcal, Lupus
erythematosus, Henoch-Schönlein purpura, Membranoproliferative, Anti–
glomerular basement membrane nephritides.
B. Hemolytic-uremic syndrome
C. Acute tubular necrosis
D. Nephrotoxins (medications, contrast, myoglobin)
E. Renal vein thrombosis
F. Rhabdomyolysis
G. Acute interstitial nephritis
H. Tumor infiltration
I. Tumor lysis syndrome
Acute tubular necrosis (ATN) :

 It is seen most often in critically ill infants and children.

 It is usually resulted from severe and prolonged ischemic/hypoxic injury and
nephrotoxic insult.

Mechanisms :

 Hypotension/intravascular volume depletion (hemorrhage, third-space fluid

losses, diarrhea).
 Decreased effective intravascular volume (heart failure, cirrhosis, hepatorenal
syndrome, peritonitis).
 Vasodilation/vasoconstriction (sepsis, hepatorenal syndrome).
 Renal artery obstruction (thrombosis, embolization, stenosis).
 Intrarenal artery disease (vasculitis, hemolytic-uremic syndrome, sickle cell
anemia, transplant rejection).
 Impaired renal blood flow (cyclosporine, , angiotensin-converting enzyme [ACE]
inhibitors, angiotensin-receptor blocking agents, radiocontrast agents).

3. Post renal : It includes a variety of disorders characterized by obstruction of

the urinary tract.
 In a patient with 2 functioning kidneys, obstruction must be bilateral to result
in AKI.
 Relief of the obstruction usually results in recovery of renal function, except
in patients with associated renal dysplasia or prolonged urinary tract
obstruction.

Causes :
A. Posterior urethral valve
B. Ureteropelvic junction obstruction
C. Ureterovesicular junction obstruction
D. Ureterocele
E. Tumor
F. Urolithiasis
G. Hemorrhagic cystitis
H. Neurogenic bladder
Clinical Manifestations :
Clinical features range from asymptomatic with mild to moderate elevation in blood
urea and S. Creatinine to anuric renal failure, so there may be :
- Decrease or no urine output
- Fluid overload
- Hypertension -
- Uremia
- Electrolyte disturbances

Diagnosis :

A. History :
A carefully taken history is critical in defining the cause of AKI;
History of acute vomiting and diarrhea most likely has prerenal AKI.
History of diarrhea with pallor and petechiae suggests HUS.
History of a recent pharyngitis who presents with periorbital edema,
hypertension, and gross hematuria most likely has intrinsic AKI related to
acute postinfectious glomerulonephritis.
History of protracted hypotension in critically ill child or with exposure to
nephrotoxic medications most likely to have ATN.
History of neonatal hydronephrosis on prenatal ultrasound and a palpable
bladder most likely has congenital urinary tract obstruction, probably
related to posterior urethral valves.

B. Physical Examination :
It must be thorough, with careful attention to volume status;
Signs of severe dehydration suggest an inadequate circulating volume and
the possibility of prerenal AKI.
Hypertension, peripheral edema, rales, and a cardiac gallop suggest volume
overload and the possibility of intrinsic AKI from glomerulonephritis or ATN.
The presence of a rash and arthritis might indicate SLE or Henoch-Schönlein
purpura nephritis.
Palpable flank masses may be seen with renal vein thrombosis, tumors,
cystic disease, or urinary tract obstruction.
C. Laboratory Investigations :
Anemia; dilutional or hemolytic.
Leukopenia and thrombocytopenia.
Hyponatremia; dilutional.
Metabolic acidosis.
Elevated levels of B. urea, S. creatinine, uric acid, K⁺, PO4ˉ³ & hypocalcemia.
Low level of C3 in Postinfectious GN, SLE, or membranoproliferative GN.
ASO titer in PSGN and ANA in SLE.
Urinalysis; hematuria, proteinuria and RBCs or granular casts suggests
intrinsic renal AKI, in particular glomerular disease and ATN.
Urinary indices to differentiate between prerenal and renal AKI in oliguric
states :
Prerenal Renal
Urine Osmolality >500 mOsm/kg < 350 mOsm/kg
Urine Na⁺ < 20 mEq/L >40 mEq/L
Ratio of urine creatinine to >40:1 < 40:1
plasma creatinine
Fractional excretion of Na⁺ <1% >2%
Urine Specific Gravity >1.020 <1.010

Renal ultrasonography can reveal hydronephrosis and/or hydroureter, which

suggest urinary tract obstruction, or nephromegaly, consistent with intrinsic
renal disease.
Chest radiography may reveal cardiomegaly, pulmonary congestion (fluid
overload), or pleural effusions.

Renal biopsy can ultimately be required to determine the precise cause of AKI in
patients who do not have clearly defined prerenal or postrenal AKI.

Promising AKI biomarkers include changes in plasma neutrophil gelatinase–

associated lipocalin (NGAL), cystatin C levels, urinary changes in neutrophil
gelatinase-associated lipocalin, interleukin 18, and kidney injury molecule-1(
KIM-1).
Treatment :
A. Medical treatment :

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

Principles :
 Prerenal and/or post renal factors should be excluded or corrected.
 Volume repletion in dehydration, stopping an offending nephrotoxic
medication, and relieving urinary tract obstruction.
 In all cases, efforts should be made to limit additional renal injury (e.g.,
ensuring adequate renal perfusion and avoiding nephrotoxic medications).
 Medication dosages should be adjusted for decreased renal function as
appropriate.

Fluid management :

 Determination of the volume status is of critical importance when initially

evaluating a patient with AKI.
 Strict measurement of input and output must be maintained, with input
adjusted as reduction in output dictates.
 If there is hypovolemia, or there is no evidence of volume overload or cardiac
failure, intravascular volume should be expanded by intravenous administration
of isotonic saline, 20 mL/kg over 30 min.
 Severe hypovolemia may require additional fluid boluses.
 Hypovolemic patients generally void within 2 hr; failure to do so suggests
intrinsic or postrenal AKI.
 Hypotension caused by sepsis requires vigorous fluid resuscitation followed by a
continuous infusion of norepinephrine.
 Diuretic therapy should be considered only after the adequacy of the circulating
blood volume has been established.
 Furosemide (2-4 mg/kg) and mannitol (0.5 g/kg) may be administered as a
single IV dose.
 If urine output is not improved, then a continuous diuretic infusion may be
considered.
 If there is no response to a diuretic challenge, diuretics should be discontinued
and fluid restriction is essential.
 Maintenance fluid of euvolemic patients should be limited to 400 mL/ m2/24 hr
(insensible losses) plus an amount of fluid equal to the urine output for that day.

Electrolyte Disturbances :

Hyperkalemia should be treated if serum K⁺ value rises to >6.0 mEq/L.

Hypocalcemia is primarily treated by lowering the serum phosphorus level.
Calcium should not be given intravenously, except in cases of tetany, to avoid
deposition of calcium salts into tissues.
Hyponatremia is most commonly a dilutional disturbance that must be
corrected by fluid restriction rather than sodium chloride administration.
Metabolic acidosis should be treated if it is severe (arterial pH < 7.15; serum
HCO3ˉ < 8 mEq/L) or contributes to significant hyperkalemia.

 GI bleeding is commonly prevented by oral or Intravenous H2 blockers such as

ranitidine.
 Hypertension should be treated by salt and water restriction, diuretic
administration, Longer-acting agents such as calcium channel blockers or β
blockers.
 Neurologic symptoms may be treated by benzodiazepams which are the
most effective agents in acutely controlling seizures, and subsequent therapy
should be directed toward the precipitating cause.
 Anemia of AKI is generally mild (hemoglobin 9-10 g/dL),but children with HUS,
SLE, active bleeding, or prolonged AKI can require transfusion of packed red
blood cells if their hemoglobin level falls below 7 g/dL.

 Nutrition is of critical importance in children who develop AKI :

 In most cases, Na⁺, k⁺, and phosphorus should be restricted.
 Protein intake should be moderately restricted.
  Caloric intake should be maximized to minimize the accumulation of
nitrogenous wastes.
 In critically ill patients, parenteral hyperalimentation with essential amino
acids should be considered.

B. Dialysis :

Is the process of removing excess water, solutes, and toxins from the blood in
patients whose kidneys can no longer perform these functions naturally. This is
referred to as renal replacement therapy.

Indications :

1. Anuria/oliguria
2. Volume overload with evidence of hypertension and/or pulmonary edema
refractory to diuretic therapy.
3. Persistent hyperkalemia
4. Severe metabolic acidosis unresponsive to medical management.
5. Uremia (encephalopathy, pericarditis, neuropathy)
6. Blood urea nitrogen >100-150 mg/dL (or lower if rapidly rising)
7. Calcium:phosphorus imbalance, with hypocalcemic tetany that cannot be
controlled by other measures.
8. Inability to provide adequate nutritional intake because of the need for severe
fluid restriction.

Types of dialysis :

A. Intermittent Hemodialysis :
 Preferred in patients with relatively stable hemodynamic state.
 Highly efficient, 1 session completes in 3-4 hrs .
 It can be done 3-7 times/week.
 Complication : hypotension, bleeding, thrombosis.

B. Peritoneal Dialysis :
 Most commonly used in infants & neonates.
 For 1 session→1 cycle of 45-60 min needs to be repeated for 2-4 times/day.
 The infused volume of the diasylate is 800- 1100ml/m2.
  No need for anticoagulation , so ↓ risk of bleeding .
 It may cause abdominal pain & peritonitis.
 Contraindicated in patients with significant abdominal pathology.

C. Continuous renal replacement therapy (CRRT) :

 Useful in patients with unstable hemodynamic status, concomitant sepsis, or
multiorgan failure in the intensive care setting.
 CRRT is an extracorporeal therapy in which fluid, electrolytes, and small- and
medium-size solutes are continuously removed from the blood (24 hr/day)
using a specialized pump-driven machine.
 Either heparin or citrate may be used for anticoagulation, with the choice
based upon which is more suitable for the situation.

Prognosis :
 Recovery from AKI depends on the etiology, severity, availability of specific
treatments, and other aspects of the patient’s course.

 Children with AKI caused by a renal-limited condition such as postinfectious

glomerulonephritis have a very low mortality rate (<1%).

 AKI related to multiorgan failure has a very high mortality rate (>90%).

 Recovery is likely after AKI resulting from prerenal causes, ATN, acute interstitial
nephritis, or tumor lysis syndrome.

 Recovery of renal function is unusual when AKI results from most types of
rapidly progressive glomerulonephritis, bilateral renal vein thrombosis, or
bilateral cortical necrosis.

 Medical management may be necessary for a prolonged period to treat the

sequelae of AKI, including chronic renal insufficiency, hypertension, renal tubular
acidosis, and urinary concentrating defect.
 Hemolytic Uremic Syndrome

 HUS is the most common glomerular vascular cause of AKI in childhood.

 It is characterized by the triad of microangiopathic hemolytic anemia,
thrombocytopenia, and renal injury.
 It is typically occurs in children < 5 years of age but can occur in older children.
 There are 2 types of HUS :
A. D+HUS :
 The most common type, it is associated with a prodromal diarrheal illness.
 It is the result of contamination of meat, fruit, vegetables, or water with
verotoxin (VT)-producing Escherichia coli (most commonly E. coli O157:H7).
 It may be caused by other E. coli strains and other bacteria such as Shigella.
 VT causes hemorrhagic enterocolitis of variable severity and results in HUS in
5% -15% of affected children.

B. Atypical HUS (D-HUS) :

 It occurs without a prodrome of diarrhea, it may occur at any age.
 It can be secondary to infection (Streptococcus pneumonia, HIV).
 It can be secondary to genetic and acquired defects in complement
regulation, medications (cyclosporine), malignancy, SLE, and pregnancy.

Pathophysiology :

 Circulating verotoxin causes endothelial damage, which leads to platelet

deposition, microvascular occlusion with subsequent hemolysis, and
thrombocytopenia.
 Glomeruli become clogged with platelets and damaged red blood cells.

Clinical manifestations :

 HUS due to E. coli or Shigella begins with a prodrome of abdominal pain,

diarrhea, and vomiting with dehydration is often present.
 Oliguria/ anuria, pallor, and bleeding manifestations, principally gastrointestinal,
or petechiae occur next (7-10 days).
 Hypertension develop in some children especially those who develop severe
renal failure and fluid overload.
 CNS involvement, including seizures, occurs in up to 25% of cases.
 Other potential organ involvement includes pancreatitis, cardiac dysfunction,
and colonic perforation.

Investigations :

 CBC : Profound anemia, thrombocytopenia, leukocytosis

 Peripheral blood smear reveals evidence of microangiopathic hemolysis
(Presence of schistocytes, helmet cells, and burr cells)
 High reticulocyte count with negative Coombs test
 Increased LDH, indirect bilirubin and AST
 Elevated creatinine
 Presence of hematuria, proteinuria, pyuria, casts on urinalysis
 Positive stool culture for E. coli O157:H7 or positive stool test for shiga-toxin
 Elevated amylase/lipase

Treatment :

Volume repletion, electrolyte correction and adequate nutrition support.

Antibiotics and antidiarrheal agents may increase the risk of developing HUS.
Control of hypertension.
Managing complications of renal insufficiency, including dialysis when indicated.
Red blood cell transfusions are provided as needed.
Platelet transfusions should be avoided because they may add to the
thrombotic microangiopathy and are indicated only by active hemorrhage.

Prognosis :

 Most children recover from the acute episode within 2–3 weeks.
 Residual renal disease (including hypertension) occurs in about 30%, and end-
stage renal failure occurs in about 15%.
 Follow-up should include serial determinations of renal function for 1–2 years
and monitoring of blood pressure for 5 years.
 Mortality (3%–5%) is most likely in the early phase, primarily resulting from CNS
or cardiac complications.