ACUTE KIDNEY

INJURY

DR/ Walaa FarahNeonatologist in

Elnasr nicu

Presented by

DEFINITION

Acute kidney injury, previously called acute renal failure, is characterized by a reversible increase in the blood concentration of creatinineand nitrogenous waste products and by the inability of the kidney to appropriately regulate fluid and electrolyte homeostasis.

In year 2004 the acute dialysis quality initiative (ADQI) proposed RIFLE criteria for defining AKI .

Later, Acute Kidney Injury Network (AKIN) classified AKI based on the RIFLE system.

RIFLE CRITERIA

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

> 3 months

INCIDENCE

Incidence of AKI in hospitalized children appears to be increasing in a pediatric tertiary care center, 227 children received dialysis therapy during an 8-year interval, for an overall incidence of 0.8 per 100,000 total population.

Very low birth weight (<1,500 g), a low Apgar score, a patent ductus arteriosus, and maternal administration of antibiotics and NSAIDS have been associated with the development of AKI. In addition to environmental factors, some children may have genetic risk factors for AKI.

4-6 % case of AKI seen in general ward and up to 40% in PICU .

Affects children who have sepsis and multi-organ failure.

Children undergoing major cardiac surgery and organ transplantation are at considerable risk for developing AKI.

ETIOLOGY

Pre renal

Intrinsic or renal

Post renal

PRE RENAL

Acute gastroenteritis

Blood loss

Shock

Fulminant hepatic failure

Reye syndrome

Congestive cardiac failure

Nephrotic syndrome

Hepatorenal syndrome

INTRINSIC RENAL Renal vessel obstruction:

- renal vein thrombosis , renal arterial obstruction, hemolytic uremic syndrome , HSP , polyarteritis nodosa and other vasculitis

Glomerular :

Acute glomerulonephritis (poststreptococcal ,other infections ), rapidly progressive GN , lupus nephritis.

Acute interstitial nephritis

Acute tubular necrosis Prolongation of pre-renal insult , intravascular hemolysis , sepsis , nephrotoxixc agents , multi-organ failure , rhabdomyolysis , snakebite , other envenomations , falciparum malaria , leptospirosis

Developmental: Polycystic kidney or hypoplasia.

POST RENAL

• Posterior urethral valves.

• Ureteropelvic junction obstruction.

• Ureterovesicular junction obstruction.

• Ureterocele.

• Tumor.

• Urolithiasis.

• Hemorrhagic cystitis.

• Neurogenic bladder.

A renal ultrasound should be performed promptly in a child with AKI to evaluate for obstructive uropathy, which can be treated by relieving the obstruction.

PRE RENAL

Also called prerenal azotemia, is characterized by diminished effective circulating arterial volume, which leads to inadequate renal perfusion and a decreased GFR.

The kidneys are intrinsically normal, and prerenal failure is reversible once the blood volume and hemodynamic conditions are restored to normal.

Several urinary parameters, including Uosm, urine sodium concentration, the fractional excretion of sodium, and the renal failure index, have all been proposed to help differentiate prerenal failure from vasomotor nephropathy.

•During prerenal failure, the tubules are able to respond to

decreased renal perfusion by appropriately conserving sodium

and water such that the Uosm is greater than 400 to 500 mOsm/L,

the urine sodium is less than 10 to 20 mEq/L, and the fractional

excretion of sodium is less than 1%:

FENa+ (%) = [UNa+/SNa+] × [SCr/UCr] × 100

• Because the renal tubules in newborns and premature infants

are relatively immature compared with those in older infants and

children, the corresponding values suggestive of renal

hypoperfusion are Uosm greater than 350 mOsm/L, urine sodium

less than 20 to 30 mEq/L, and a fractional excretion of sodium of

less than 2.5%.

• When the renal tubules have sustained injury, as occurs in ATN,

they cannot conserve sodium and water appropriately, so the

Uosm is less than 350 mOsm/L, the urine sodium is greater than

30 to 40 mEq/L, and the fractional excretion of sodium is greater

than 2.0%. However, the use of these numbers to differentiate

prerenal failure from ATN requires that the patient have normal

tubular function initially.

Renin

Angiotensin II

Aldosterone

Renal Tubular Na

Reabsorption

Vasopressin

Renal Tubular H2O

ReabsorptionUrine Volume

Concentrated Urine

Urine Sodium

Decreased Renal Perfusion

Mechanisms of Sodium and Water

Conservation in Prerenal Azotemia

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.

RENAL CAUSES

It includes a variety of disorders

characterized by renal parenchymal damage,

including sustained hypoperfusion , ischemia

and nephrotoxins.

OBSTRUCTION OF RENAL ARTERIES AND VEINS

Bilateral renal arterial thrombosis may occur after umbilical artery catheterization in neonates.

Renal vein thrombosis may be a complication of infant of diabetic mother especially following dehydration.

In older children renal vein thrombosis may occur with nephrotic syndrome with anasarcaand dehydration.

Gross hematuria, enlargement of kidney and azotemia are typical manifestation.

PATHOLOGICALLY RADIOLOGICALLY

INVOLVEMENT OF RENAL MICROVASCULATURE

Hemolytic uremic syndrome is a common cause in children

developing AKI .

Following dysentery shigela-toxin enters the circulation and

lead to endothelial injury in microvasculature .

Localized coagulation and deposition of platelet thrombi and

fibrin in glomeruli causing decrease in GFR.

Triad of renal impairment, thrombocytopenia and micro-

angiopathic hemolytic anemia.

Need early and aggressive dialysis.

Antibiotic should not be prescribed in cases of enteritis

especially with E.coli as it increase destruction of bacteria

and increase toxins production (controversial).

Shiga toxin inhibitors are under trial.

ACUTE CORTICAL NECROSIS

• More common in young children, particularly in the neonate.

• Associated with hypoxic-ischemic insults resulting from

perinatal anoxia, placenta abruption, and twin-twin or twin-

maternal transfusions with resultant activation of the coagulation

cascade.

• Clinically, child shows gross or microscopic hematuria and

oliguria and may have hypertension.

•Laboratory features of an elevated BUN and creatinine,

thrombocytopenia may also be present as a result of the micro

vascular injury.

• Radiographic features include a normal renal ultrasound in

the early phase, and ultrasound in the later phases may show

that the kidney has undergone atrophy and substantially

decreased in size. A radionuclide renal scan will show decreased

to no perfusion with delayed or no function.

ACUTE INTERSTITIAL NEPHRITIS

Allergic: antibiotics (β-lactams, sulfonamides, quinolones, rifampin), nonsteroidal anti-inflammatorydrugs,diuretics,others

Infection: pyelonephritis (if bilateral)

Infiltration: lymphoma, leukemia, sarcoidosis

Inflammatory, nonvascular: Sjögren’s syndrome, tubulointerstitial nephritis with uveitis

The patient may have fever , arthralgia , rash and eosinophilia , urine often shows eosinophils .

Radiographic studies demonstrate large echogenic kidneys.

Kidney biopsy demonstrates interstitial infiltrate with many eosinophils.

Therapy for AIN includes withdrawal of the drug implicated in causing AIN. In addition, corticosteroids may aid in the resolution of the renal failure.

Etiology of AIN

ACUTE TUBULAR NECROSIS

Occurs most often in critically ill infants and children who have been exposed to nephrotoxic and/or perfusion insults.

Common causes of ATN include renal hypoperfusionfollowing volume contraction , severe renal vasoconstriction , nephrotoxic agents , sepsis , shock and hypotension.

The mechanisms of injury in ATN can include alterations in intrarenal hemodynamics, tubular obstruction, and passive backleak of the glomerularfiltrate across injured tubular cells into the peritubularcapillaries.

LUPUS NEPHRITISSystemic lupus erythematosus is a systemic inflammatory

disease of uncertain etiology that involves many organs, including the

kidney. Children initially may present with renal disease without extra

renal signs of SLE, but they usually rapidly develop other symptoms

and fulfill the diagnostic criteria for SLE.

More common in young adolescent females (F/M, 8:1), but 20%

to 25% of cases occur in childhood and even, rarely, in infancy.

Asian, black, and Hispanic children are more affected than white

children.

Nephritis is more common in childhood lupus, affecting up to 80%

of patients at some point, usually within the first 6 months after

diagnosis. Children often present with fever, malaise, arthritis, and

anemia.Less than half of children have a classic malar rash, but more

than half have hematuria or proteinuria, and a few have edema, NS,

or hypertension. The extent of the renal involvement may not be

clinically apparent and usually requires referral to a pediatric

nephrologist for full evaluation, including a kidney biopsy.

Laboratory evaluation of SLE may reveal anemia,

leucopenia, and thrombocytopenia, as well as severely

decreased concentrations of serum C3 and C4.

Antinuclear antibody and anti–double-stranded DNA

antibody titers are elevated at diagnosis in 95% of

patients with nephritis. Urine abnormalities include

microscopic and gross hematuria, proteinuria, and casts

(red cell, white cell, hyaline, and/or broad-waxy).

Proteinuria may be mild, moderate, or in the nephrotic

range. Heavy proteinuria is usually associated with more

severe disease. One-half of children with SLE nephritis

have elevated serum creatinine levels and decreased

creatinine clearance during the initial course of their

disease.

Lupus nephritis has been divided into 6 classes by

the appearance of the renal biopsy.

Treatment:

Predinsolone, azathroprine, cyclophosphamide and rituximab.

Prognosis:

No complete cure just remission with frequent relapses.

CLINICAL PRESENTATION

Pre renal

There may be history of volume loss from

vomiting, diarrhea, or blood loss and may

present with dehydration , hypotension ,

tachycardia , pallor , and decreased urine

output .

RENAL

Hematuria, edema, and hypertension indicates a glomerular etiology for AKI.

Dysentry, patechie and pallor- HUS

Sudden passage of dark red urine, pallor and jaundice- acute intravascular hemolysis

Presence of rash, arthritis might suggest SLE or HSP.

History of prolong hypotension or with exposure to nephrotoxic medication most likely have ATN.

Allergic interstitial nephritis should be

suspected with fevers, rash, arthralgias, and

exposure to certain medications, including

NSAIDs and antibiotics.

POST RENAL

History of interrupted urinary stream and

palpable bladder or kidney suggest

obstructive uropathy.

Abdominal colic hematuria and dysuria

suggest urinary tract calculi.

DIAGNOSIS

Physical examination

Obtaining a thorough physical examination is extremely important when collecting evidence about the etiology of AKI. Clues may be found in any of the following

Skin

Eyes

Ears

Cardiovascular system

Abdomen

Pulmonary system

Skin :- Palpable purpura - Systemic vasculitis

Maculopapular rash - Allergic interstitial nephritis

Eye :- Evidence of uveitis may indicate interstitial nephritis

and necrotizing vasculitis. Ocular palsy may indicate

ethylene glycol poisoning or necrotizing vasculitis

Ear :- Hearing loss - Alport disease and aminoglycoside

toxicity

Mucosal or cartilaginous ulcerations - Wegener

granulomatosis

Pulmonary system :- Respiratory rate , pattern

On Auscultation of lungs basal crepts

CARDIOVASCULAR EXAMINATION

Pulse rate and blood pressure recordings

Close inspection of the jugulovenous pulse

Careful examination of the heart and lungs

Assessment for peripheral edema

Cardiovascular examination may reveal the following:

Murmurs - Endocarditis

Pericardial friction rub - Uremic pericarditis

Increased jugulovenous distention, rakles, S3 -Heart failure

Abdomen

Abdominal or costo vertebral angle tenderness -

Nephrolithiasis, papillary necrosis, renal artery

thrombosis, renal vein thrombosis

distended bladder – Urinary obstruction

The presence of tense ascites can indicate

elevated intra-abdominal pressure that can retard

renal venous return and result in AKI.

INVESTIGATIONS Urine R/E: hematuria, proteinuria and casts.

CBC with PBF:*Anemia dilutional, microangiopathic hemolytic anemia(MAHA) or blood loss.*Leucopenia SLE * Leucocytosis sepsis*Thrombocytopenia MAHA

24 hour urinary protien

Blood urea and S. creatinine level : elevated

Serum electrolyte : hyperkalemia, hyponatremia, hypocalemia and hyperphosphatemia.

ASO titer : PSGN

C3 level

Anti ds-DNA: SLE.

ABG : Metabolic acidosis with wide anion gap.

INDICES FOR DIFFERENTIATING PRE-RENAL FROM RENAL AKI

PRE-RENAL INTRINSIC

URINARY SODIUM (mEq/l) < 20 > 40

Urinary osmolality (mOsm/kg) > 500 < 300

Blood urea to creatinine ratio >20:1 < 20:1

Urine to plasma osmolality ratio >1.5 < 0.8 – 1.2

Fractional excretion of sodium < 1 > 1

IMAGING

Ultrasound of KUB - evaluates renal size,

able to detect masses, obstruction, stones

Chest x-ray: cardiomegaly or pulmonary

edema.

DTPA

DMSA

RENAL BIOPSY

Indicated in

Patient in whom the etiology is not identified.

Unremitting AKI lasting longer then 2-3 wks

or in accessing the extent of renal damage

and out come.

Suspected drug induced AKI in a patient

receiving therapy with a potentially

nephrotoxic drugs.

ALGORISM FOR DIAGNOSIS OF AKI

MANAGEMENT

The basic principles of management include

Treatment of life-threatening complications

Maintenance of fluid and electrolyte balance

Nutritional support.

Specific management of underlying disorder

LIFE THREATENING COMPLICATIONS

Hyperkalemia

Fluid overload with heart failure

Severe hypertension with encephalopathy

Profound acidosis

Severe anemia

MANAGEMENT OF COMPLICATION

Hyperkalemia :K restriction

Calcium gluconate 0.5-1 ml/kg over 5 to 10 minute to stabilize cardiac muscle.

Salbutamol nebulization: increase K cellular uptake.

Sodium bicarbonate 1-2 ml/kg .

Kayexelate ( Na polystyrene resin) oral or enema 1mg/kg can be repeated every 2 hrs, exchange of Na and K in the GIT.

Glucose 0.5-1 gm/kg with insulin 1 iu/4 gm glucose (last line before dialysis).

Acidosis

Sodium bicarbonate (if PH<7.15 and Hco3<8)

0.3*BW*(12- actual)

Hypocalcemia:

Due to hyperphosphatemia which can be lowered

by Al(OH)3 or CaCo3.

IV Ca gluconate only if tetany occur as it will

increase phosphate.

Hyponatremia:

Fluid restriction, if Na < 120 give hypertonic saline

3%

(125-actual)*0.6*BW.

Anemia

Pack red cell 3-5 ml/kg

Fluid overload :

fluid restriction (insensible loss + POD)

Pulmonary Oedema:

Oxygen

Dopamine (5-10) mcg /kg /min infusion

Frusemide (2-4)mg /kg

GIT bleeding:

Due to platelets dysfunction, stress ulcer or heparin used in haemodialysis.

Treated with antacids , ranitidine or omperazole.

Convulsion:

due to hypocalcemia , hyponatremia, hyepertensive encephalpathy, uremia or cerebral hge.

Treated with Diazepam and treatment of the

Hypertension :

MILD: salt restriction, frusemide, B blocker

and hydralazine.

Severe: (Heart failure or hypertensive

encephalopathy)

Nitroprusside 1-8 mcg/kg/min

Frusemide 2-4 mg/kg

Nifedipine 0.3-0.5 mg/kg

SUPPORTIVE CARE

Fluids: amount given equals insensible loss

plus urine volume

Nutrition: protein intake of 1 gm/kg

Prevent infection and treat with appropriate

antibiotics.

Avoid nephrotoxic drugs

Measure Weight daily, Prevent weight gain

Monitor urine output

DIALYSIS Uremia: altered sensorium abnormal behavior

seizure.

BUN>100mg/dl.

Hyperkalemia: k+ > 6.5 meq/l, k+ 5.5-6.5 meq/l with ECG changes

Hyponatremia: Na+ < 120 meq/l if symptomatic and not respond to treatment.

Fluid overload: resistant to diuretics, CCF,HTN

Metabolic acidosis: PH< 7.2 despite sodium bicarbonate therapy.

Ca/P imbalance with tetany.

Inability to provide nutritional intake due to severe fluid restriction.

Forms of dialysis:

•Intermittent hemodialysis.

• Peritoneal dialysis.

• Continous renal replacement therapy:

Used in sepsis, unstable hemodynamic state

and multi-organ failure.

MANAGEMENT OF COMMON CONDITION

CAUSING AKI

Prerenal AKI: administer crystalloids, stop

diuretics, NSAIDs, ACE inhibitors.

ATN: supportive care, discontinue drugs or

toxin, treat cause of circulatory failure.

Glomerulonephritis: supportive care If post-

infectious, antibiotic for endocarditis, shunt

infection, steroids and immunosuppressive

medication.

HUS: supportive care, early dialysis, plasma exchange

Vasculitis: immunosuppressive medication, plasma

exchange

Interstitial nephritis: discontinue offending drugs,

consider steroid therapy.

Renal artery , vein occlusion: anticoagulation,

thrombolysis or surgery.

Intrarenal obstruction: discontinue offending drugs,

alkaline diuresis for rhabdomyolysis , haemoglobinuria

or urate crystal.

Urinary tract obstruction: bladder catheterization or

nephrostomy, surgical treatment of obstruction.

OUTCOME

Mortality rates from 30-50% have been reported from developing countries. But the results have markedly improved at tertiary centers with proper expertise and modern facilities.

Outcome depend upon underlying cause.

Prognosis is favorable in ATN from volume depletion, intravascular hemolysis, acute intestinal nephritis and drugs or toxin related AKI especially when complicating factor are absent .

In cresentic GN, atypical HUS, and AKI associated with sepsis, multi organ failure the prognosis is less satisfactory .

PREVENTION OF AKI

Important measures includes prompt rehydration therapy in acute diarrhea, avoidance or judicious use of nephrotoxic drugs.

Maintenance of proper hydration for patients undergoing diagnostic procedures with radio contrast media.

Force diuresis along with the use of allopurinol is effective preventing AKI in patient with TLS.