SYMPOSIUM

Niger J Paed 2013; 40 (3): 314 –320

Katibi OS

Adedoyin OT

Anoba S

Current trends in the management

of acute kidney injury in children

Sowunmi FO

Olorunsola BO

Ibrahim OR

Oyeleye AE

DOI:http://dx.doi.org/10.4314/njp.v40i3,25

Accepted: 6th February 2013

Abstract Acute Kidney Injury

AKI) previously known as acute

fraught with its own limitations.

This has led to discovery of vari-

ous urinary and serum biomarkers

like the cystatin C and neutrophil

gelatinase associated lipocalin

(NGAL) which appear to have

very promising advantages over

the well known creatinine meas-

urements.

Management of AKI continues to

be anticipatory with appropriate

fluid therapy and adequate treat-

ment of infections. The benefits of

furosemide and dopamine in man-

agement are still a constant source

of debate. Treatment of life threat-

ening complications like hyper-

kalaemia and hypertension as well

as maintaining the kidney through

the period of non-function can lead

to remarkable recovery of renal

homeostatic function.

(

Katibi OS

(

)

renal failure (ARF) is a common

problem in the paediatric emer-

gency wards with infections like

sepsis and malaria being the com-

monest causes in Nigeria.

Adedoyin OT, Anoba S

Sowunmi FO, Olorunsola BO

Ibrahim OR, Oyeleye AE

Department of Paediatrics & Child

Health, University of Ilorin,

PMB 1515, Ilorin,

Kwara state, Nigeria.

E-mail: sherikatibi@yahoo.com.

Tel: +2348033797816

It has been known by various no-

menclatures with a lack of stan-

dardised definition. This has made

comparison of data very difficult.

In the last decade, attempts have

been made to standardize the defi-

nition by developing a classifica-

tion criterion termed “RIFLE”.

This is in turn undergoing various

modifications with the most re-

cent classification system devel-

oped by the Kidney Disease: Im-

proving Global Outcomes

(

KDIGO).

Despite these interesting develop-

ments, the basis of these classifi-

cations which is the use of serum

creatinine measurements is

Keywords: acute kidney injury,

paediatrics, management

Introduction

Epidemiology

Acute kidney injury (AKI) formerly known as acute

renal failure (ARF) is a clinical syndrome that has been

known by about twenty-five different nomenclature over

the years. It evolved from the 18th century when it was

first known as “ischuria renalis” (“ischuria” meaning

suppression of urinary output) to the current terminol-

ogy “acute kidney injury” in the 21st century.

As a result of the deficiency of a standardized definition,

epidemiological data have been widely varying and dif-

ficult to compare. AKI or ARF is said to be encountered

in about 3% to 10% of all admissions to neonatal inten-

sive care units with approximately 1% of ill children in

the developed world having AKI at the time of admis-

sion.

Acute kidney injury has also been defined in over thirty-

five different ways in the last few centuries.It is widely

defined as a clinical syndrome characterised by a sudden

deterioration in renal function resulting in an inability of

the kidneys to maintain fluid and electrolyte homeosta-

sis. It has also been defined as onset of reduced kidney

function manifested by increased serum creatinine or a

reduction in urine output.

In Nigeria, incidence rates have been stated as 6.6% in

Zaria, 4.7% in Portharcourt, 7.1% in Enugu and 3.13%

in Ife. Esezebor et al, in Lagos found a prevalence of

17.4 cases per 1000 children Mortality in acute kidney

injury has been found to be high. Adedoyin et al re-

ported 57.9% in Ilorin, Esezebor et al found 28.4%

while Olowu et al reported 46.2% in Ife.

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15

Anatomy and physiology of the Kidney

of the cardiac output and the highly vascularised cortex

takes over 90% of the renal supply.The kidney’s control

over homeostasis allows it to regulate extracellular fluid

(ECF) volume, osmolality, and acid-base balance. The

physiologic functions of the kidney are summarised in

Fig 2.

The kidney is a paired, retroperitoneal organ located

between the transverse processes of T12- L3 vertebrae.

Fig 1 shows the gross anatomy of the kidney with the

microanatomy of the nephron. The kidneys receive 25%

Fig 1: a. Cross section of the kidney b. The nephron (functional unit of the kidney)

A

B

Fig 2: Summary of the physiologic functions of the skin

Causes and pathophysiology of acute kidney injury

(GFR). The kidneys are intrinsically normal with no

evidence of renal parenchyma damage and prerenal

injury is reversible once the blood volume and haemo-

dynamic conditonns have been restored to normal. The

pathophysiology has been summarised in Fig 3.

The causes of acute kidney injury can be divided into

three based on their pathophysiologic mechanisms.

These are highlighted in Table 1

Prerenal injury

Intrinsic renal disease

Prerenal injury occurs when there is diminished effec-

tive circulating arterial volume resulting in inadequate

renal perfusion and a decreased glomerular filtration rate

Renal injury results in damage to the renal parenchyma

and it could result from prolonged renal hypoperfusion

or from nephrotoxic renal insults. This form of AKI

3

16

could complicate diverse diseases of the renal paren-

chyma including diseases of the glomeruli, tubules, vas-

cular and renal interstitial injury. The 3 phases of

ischemic ARF can be seen in fig 3.

Table 1: Common causes of Acute Kidney Injury in children

Intrisic renal Postrenal

Glomerulonephritis

Posterior urethral valves

Prerenal

Hypovolaemia

Acute diarrheoa disease

Excessive vomiting

Poststreptococcal GN

Rapidly progressive glomeruonephritis

Ureteropelvic junction obstruction

Ureterovesicular junction

Diabetes ketoacidosis

Severe hemorrhage

Henoch-scholein purpura

HUS

Ureterocele

Tumor

Burns

Toxic epidermal necrolysis

Staphylococcal scalded skin syndrome (SSSS)

Acute tubular necrosis

Ischaemia (prolonged hypovolaemia

Drugs (aminoglycosisdes,NSAIDS)

Urolithiasis

Hemorrhagic cystitis

Neurogenic bladder

Hypotension

Sepsis

Haemoglobinuria (excessive hemolysis)

Myoglobinuria

Congestive cardiac failure

severe anaphylaxis

Drugs

Ethylene glycol

Heavy metals

Contrast nephropathy

Interstitial nephritis

Penicllins,

sulphonamide

ciprofloxacin

NSAIDS

Infections

Acute pyelonephritis

HBV, EBV,HIV infections

Fig 3: Pathophysiology of Prerenal

and intrinsic renal failure

(ischaemic ARF)

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Post-renal causes

Table 2: Urine chemistries and osmolality in Acute Kidney

Injury

Includes a variety of disorders characterized by obstruc-

tion of various parts of the urinary tract. An increase in

fluid pressure proximal to the obstruction leads to renal

damage with decreased renal function from back pres-

sure effect.

Urinary indices

Prerenal

0) >500

Intrinsic

Renal

<350

<l.020

>20

Urine osmolality (mosmol/kg H

Urine SG

Urinary Na

Fractional excretion of filtered Na

(%) FENa

2

>1.020

< 20

< 1

>1

Epidemiologic variation in aetiology of AKI

FENa= Una x Pcr/ Ucr x Pna

Causes of AKI in industrialised countries have been

found to be majorly due to intrinsic renal disease,

postoperative septic shock (especially after open heart

surgery) and organ/bone marrow transplantation. This is

quite different from what obtains in developing nations

like Nigeria.

Secondary causes of acute renal failure like severe ma-

laria and sepsis were found to be the commonest aetiol-

ogy in Ife. Anochie et al, in Port-Harcourt found gastro-

enteritis and malaria as the most common cause of ARF

in older children while severe birth asphyxia and septi-

caemia were the prominent causes among neonates. Sep-

sis, acute diarrhoeal disease and haemoglobinuria were

the leading causes of ARF in Ilorin.

Novel approaches to diagnosis

The varying definitions of AKI made comparisons be-

tween studies very difficult. In 2004, the Acute Dialysis

Quality Initiative group (ADQI) standardised the defini-

tion of AKI using the RIFLE criteria which was based

on GFR, serum creatinine values and urine output. The

term ARF was also replaced with AKI as defined by this

criteria such that it encompasses the entire spectrum of

the syndrome and not just the aspect of failure. In 2007,

the Acute Kidney Injury Network (AKIN) proposed

some modifications to this criterion that was based on

time in relation to the creatinine values or documented

oliguria. Recently in 2012, Kidney Disease: Improving

Global Outcomes (KDIGO) proposed another classifica-

tion system which combines the RIFLE and AKIN

criteria

Definitions of terminology

Oliguria: Reduction in urine output to less than 300ml/

m² per day or <1ml/kg/hr

Anuria: Defined as urine <75ml/day in an adult or

RIFLE is a mnemonic for level of severity & outcome.

There are 3 levels of severity; Risk, Injury and Failure

and 2 outcomes measures; Loss of renal fuction and End

<

1ml/kg/day in children

Polyuria: Urine output >4ml/kg/hr

Azotaemia: High nitrogenous waste as indicated by

high urea.

Uraemia: Uraemia is the symptom complex reflecting

organ dysfunction that occurs when kidneys

fail to regulate body composition.

-stage renal disease (ESRD). The pRIFLE a modified

form for paediatric use can be seen in Table 3.

Table 3: The modified RIFLE criteria for paediatric patients

(pRIFLE)

CLASS

Change in eCCl

(by Schwartz)

Urine Output

Clinical manifestations

A good history will aid identification of the cause of

AKI. Vomiting, diarrhoea and fever suggest pre-renal

azotemia from hypovolaemia or a septicaemic illness.

Antecedent skin or throat infection suggests intrinsic

AKI from PSAGN. Drug history such as use of NSAIDS

and aminoglycosides could be a pointer to acute tubular

necrosis while flank masses may suggest obstruction as

a cause of post renal AKI.

Risk

Injury

Failure

Decrease by 25 %

Decrease by 50 %

Decrease by 75 %, or

<0.5 ml/kg/hr X 8 hrs

<0.5 ml/kg/hr X 16 hrs

<0.3 ml/kg/hr X 24 hrs

or ANURIA > 12 hrs

<

35ml/min/1.73m²

Loss

Failure > 4 weeks

Failure > 3 months

End Stage Renal

Disease

Schwartz equation -K* Height (cm)/ SCr (mg/dl) where K is constant

Common manifestations due to failure of kidney

function include oliguria or anuria, polyuria, anaemia,

oedema and hypertension.

The RIFLE and AKIN classifications use changes in

serum creatinine to estimate loss in GFR. However, se-

rum creatinine has many limitations. It differs with age,

sex, dietary intake and muscle mass and doesn’t reflect

dynamic changes but only increases when there is sub-

stantial loss of renal function. It cannot be used as a

monitoring tool after dialysis as it is easily dialysed and

its secretion can be impaired by drugs like trimethoprim.

This led to the discovery of newer biomarkers that can

aid earlier detection of kidney injury (Table 4).

Investigations

All suspected cases of AKI should at least have urine

analysis, urine specimen for microscopy and culture and

urinary biochemistry (Table 2). Serum electrolytes may

show hyperkalemia, hyponatraemia and raised urea and

creatinine levels. Full blood count, Chest X-ray, ab-

dominal utrasonography and roentgenograms, autoim-

mune screen, renal biopsy can be done to investigate the

cause of the AKI.

Neutrophil Gelatinase Associated Lipocalin (NGAL) is

secreted by renal tubular epithelium and serum levels

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18

rise markedly after epithelial damage following is

chaemic or nephrotoxic injury. There is increase in urine

levels of NGAL before rise in serum creatinine and has

both diagnostic and prognostic value for AKI.

fluid overload. If anuria persists after 3 fluid boluses, the

possibility of an intrinsic or post renal failure should be

entertained.

Fluid input and output records, daily weights, physical

examination, and serum sodium concentration guide

ongoing therapy. During the recovery phase, children

develop significant polyuria and natriuresis and may

become dehydrated if appropriate adjustments in fluid

requirements are not made.

Table 4: Protein biomarkers for early detection of acute

kidney injury

Oliguria in the presence of volume overload requires

fluid restriction (previous day’s output plus insensible

2

water loss (300ml/m /day) and possibly intravenous

administration of furosemide, mannitol or both. Ration-

ale for the use of loop diuretics in ARF is due to the

inhibition of the Na+/K+/2Cl pump in the thick ascend-

ing limb of the loop of Henle with subsequent decrease

in Na+/K+2ATPase activity, which reduces the oxygen

requirements of these cells and thus their susceptibility

to ischaemic damage. However, recent studies have not

demonstrated any differences in outcome of patients

with or without furosemide.

Dopamine

The use of low dose (1–3 µg/kg/min) dopamine had

been long advocated to increase renal perfusion by caus-

ing vasodilatation in critically ill patients. However,

recently there has been a lot of debate in the literature

about its benefit.

Cystatin C is a protein secreted by all nucleated cells. It

is minimally influenced by weight, sex, race, age, mus-

cle mass but mostly reflects a reduction in GFR rather

than acting as a marker of renal tubular damage. It rises

earlier than serum creatinine

Electrolytes and acid-base balance

Kidney Injury Molecule – 1 (KIM-1) is an epithelial

cell adhesion molecule that is expressed at a low level in

normal kidneys. It is highly up regulated in the proximal

tubules after ischaemic or toxic AKI. Urinary KIM-1 is

used to distinguish ischaemic AKI from pre-renal dis-

ease and chronic renal disease and can be used as a pre-

dictor of graft loss in kidney transplant patients.

Hyperkalaemia (>5.5mEq/L) can be managed by the use

of diuretics, sodium bicarbonate therapy, insulin glucose

infusions and dialysis. The primary treatment of hypona-

tremia is free water restriction and use of hypertonic

saline (3%). Oral phosphate binders (eg calcium carbon-

ate) can be used to treat both hyperphosphataemia and

hypocalcemia. Moderate acidosis to severe acidosis

should be treated with oral or intravenous sodium

bicarbonate.

Treatment of Acute Kidney Injury

Hypertension resulting from hyperreninemia can be

managed with salt and water restriction and diuretic

administration; calcium channel blockers (amlodipine )

or β blockers (propranolol; labetalol) can be used.

Hypertensive urgency/emergency should be treated with

continuous infusions of sodium nitroprusside, labetalol

or esmolol

The anaemia of ARF is usually mild and may require

transfusion of packed red blood cells if the hemoglobin

level falls below seven g/dL. Avoidance of nephrotoxic

drugs like aminoglycosides and dose adaptations should

be taken for medications that are largely eliminated by

the kidney.

Management is generally directed at treating any life

threatening features, attempting to halt or reverse the

decline in renal function and if unsuccessful providing

support by renal replacement anticipating renal

recovery. Provided the patient can be maintained

through the period of non-function and no further insults

accrue, the kidney is remarkable in its ability to recover

its normal homoeostatic role.

Fluid management

The major goal is to restore and maintain intravascular

volume. AKI may manifest with hypovolemia, eu-

volemia or volume overload and an estimation of fluid

status is a prerequisite for initial and ongoing therapy.

Children with intravascular volume depletion require

prompt and vigorous fluid resuscitation. Initial therapy

includes normal saline or lactated Ringer’s solution at

Renal replacement therapy

Dialysis: This aims at removing endogenous and exoge-

nous toxins and to maintain fluid, electrolyte and

acid-base balance until renal function returns. It uses the

principles of diffusion of molecules in solution across a

2

0 ml/kg over 30 minutes and may be repeated twice if

necessary, after careful monitoring to avoid possible

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semi-permeable membrane along an electrochemical

concentration gradient.

Dialysis can be in form of peritoneal dialysis

inducible nitric oxide synthetase, all designed to reduce

renal damage occurring in the context of sepsis.

Infusions of atrial natriuretic peptide (ANP) or a syn-

thetic analogue anaritide may improve renal perfusion.

Recombinant erythropoietin can reduce ischaemic renal

injury. Therapeutic strategies in the more distant future

may include bioartificial kidneys as a renal replacement

modality and possible stem cell therapy to improve na-

tive kidney recovery.

(

continuous or intermittent), haemodialysis, haemofiltra-

tion and haemodiafiltration.

Indications for dialysis include volume overload with

evidence of hypertension and/or pulmonary oedema

refractory to diuretic therapy; persistent hyperkalaemia;

severe metabolic acidosis unresponsive to medical man-

agement; neurologic symptoms (altered mental status,

seizures), blood urea nitrogen greater than 100–150 mg/

dL (or lower if rapidly rising); calcium/phosphorus im-

balance with hypocalcaemic tetany; poor nutrition lead-

ing to progressive loss of weight.

Complications of AKI

Infections develop in 30-70% of patients with AKI due

to impaired defenses from uraemia and excessive use of

antibiotics. Other complications may be cardiovascular

(hypertension, congestive heart failure and pulmonary

oedema); gastrointestinal (anorexia, nausea, vomiting,

ileus, bleeding); haematologic (anaemia, platelet dys-

function); neurologic (confusion, somnolence, seizures)

The choice between haemodialysis and peritoneal dialy-

sis depends on the overall clinical condition, availability

of technique, aetiology of the AKI, institutional prefer-

ences and specific indications or contraindications. In

general, peritoneal dialysis is the preferred method in

infants and younger children. Specific contraindications

include abdominal wall defects, bowel distention, perfo-

ration or adhesions, and communications between the

abdominal and chest cavities. Haemodialysis has the

distinct advantage of rapid correction of fluid, electro-

lyte and acid-base imbalances and may be the treatment

of choice in haemodynamically stable patients, espe-

cially older children. Disadvantages include the require-

ment for vascular access, large extracorporeal blood

volume, heparinization, and skilled personnel.

Prognosis

Recovery of renal function is likely after AKI resulting

from prerenal causes, HUS, ATN, acute interstitial ne-

phritis, 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.

Diet: Aggressive nutritional support is important. Ade-

quate calories to account for maintenance requirements

and supplements to combat excessive catabolism must

be provided. Oral feeding is the preferred route of ad-

ministration.

Conclusion

AKI is a significant cause of morbidity and mortality in

children. The main focus of physicians should be to pre-

vent its occurrence (by adequate rehydration of ill chil-

dren) and when it does occur to intervene promptly and

adequately.

Surgical Care: Patients with AKI secondary to obstruc-

tion frequently require urologic care.

Renal treatment modalities for the future

Conflict of interest: None

Funding: None

Experimental treatments include anti-endothelin anti-

bodies; oxygen free radical scavengers, inhibitors of

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