Acute Kidney Injury

Acute Kidney Injury (AKI):

• Previously known as acute renal failure (ARF).
• Common problem in pediatric emergency wards.
• Characterized by sudden onset of reduced kidney function.
• Manifested by increased serum creatinine (a marker of kidney excretory function) or a reduction in urine output (a quantitative marker of urine production).
• Limited to a duration of seven days.

Historical Review of Nomenclature

AKI has been known by various names over the years, making data comparison difficult. Some historical names include:

• Ischuria renalis: Coined by William Heberden in 1802.
• Acute Bright’s disease: Termed by William Osler in 1909.
• Acute Renal Failure: Coined by Homer W. Smith in 1951.

The term "Acute Kidney Injury" emerged as the first attempt at a unified definition:

• Initiated by the Acute Dialysis Quality Initiative group (ADQI) in 2004.
• Further refined by AKIN (Acute Kidney Injury Network) in 2007.
• Officially defined by KDIGO (Kidney Disease: Improving Global Outcomes) in 2012.

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 <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.

Definition of Acute Kidney Injury

The International Acute Dialysis Quality Initiative (ADQI) provided the first consensus definitions of ARF/AKI with the aim of:

• Standardizing the reporting of ARF/AKI.
• Enhancing the understanding of both its treatment and prevention.

The ADQI proposed the RIFLE classification, a mnemonic for levels of severity and outcomes:

• Three levels of severity: Risk, Injury, and Failure.
• Two outcome measures: Loss of renal function and End-stage renal disease (ESRD).

The modification for Pediatrics is referred to as pRIFLE.

ADQI RIFLE CRITERIA

AKIN CRITERIA

In 2007, the Acute Kidney Injury Network (AKIN) proposed some modifications to the criterion that were based on time in relation to the creatinine values or documented oliguria.

KDIGO

Kidney Disease: Improving Global Outcomes (KDIGO) - 2012

Classification system which combines the RIFLE and AKIN criteria

KDIGO-AKI Definition

AKI is defined as any of the following:

• Increase in SCr by ≥ 0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or
• Increase in SCr to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
• Urine volume <0.5 ml/kg/h for 6 hours

AKI is staged for severity according to the following criteria:

• Prior to adoption of unified and standard definition, epidemiological data vary globally and difficult to compare
• AKI or ARF occurs in about 3% to 10% of all admissions to neonatal intensive care units
• Approximately 1% of ill children in the developed world have AKI at the time of admission.
• In Nigeria, incidence rates include:

• 6.6% in Zaria
• 4.7% in Portharcourt
• 7.1% in Enugu
• 3.13% in Ife

Mortality in AKI tends to be high:

• Adedoyin et al reported 57.9% in Ilorin
• Esezebor et al found 28.4%
• Olowu et al reported 46.2% in Ife

Epidemiologic Variation in Aetiology of AKI

Causes of AKI in high-income countries-majorly:

• Intrinsic renal disease
• Postoperative septic shock (especially after open heart surgery)
• Organ/bone marrow transplantation

Causes of AKI in middle-low-income countries-majorly:

• Secondary causes of acute renal failure like severe malaria, sepsis, severe birth asphyxia, acute diarrhoea disease, and haemoglobinuria

Causes of AKI in the Neonates

• Perinatal asphyxia
• Renal dysgenesis
• Obstructive uropathy
• Renovascular accidents
• Congenital heart disease
• Dehydration/shock
• Hemorrhage
• Sepsis
• Necrotizing enterocolitis

AKI: A Theoretical Model

• AKI due to a reduction of RBF
• Maladaptive molecular responses
• These responses lead to endothelial & epithelial cell injury following the onset of reperfusion
• In some cases is thought to lead to distant organ dysfunction syndrome
• Leading to fatality in such patients

Prerenal Injury

Prerenal injury occurs when there is diminished effective circulating arterial volume resulting in inadequate renal perfusion and a decreased glomerular filtration rate (GFR). The kidneys are intrinsically normal with no evidence of renal parenchyma damage. Prerenal injury is reversible once the blood volume and haemodynamic conditions have been restored to normal.

Intrinsic Injury

Damage to the renal parenchyma can result from prolonged renal hypoperfusion or from nephrotoxic direct renal insults. This form of AKI could complicate diverse diseases of the renal parenchyma including diseases of the glomeruli, tubules, vascular, and renal interstitial injury.

Post-renal

Post-renal AKI includes a variety of disorders characterized by obstruction 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 pressure effect.

Non-oliguric AKI

• Aminoglycoside toxicity
• Resolving acute tubular necrosis
• Partial/intermittent urethral obstruction

A good history will aid in the identification of the cause of AKI:

• Vomiting, diarrhea, and fever suggest pre-renal AKI from hypovolemia or a septicemic illness.
• Antecedent skin or throat infection suggests intrinsic AKI from post-streptococcal glomerulonephritis (PSAGN).
• Drug history, such as the use of NSAIDs and aminoglycosides, could be a pointer to acute tubular necrosis.
• Flank masses may suggest obstruction as a cause of post-renal AKI.

Common manifestations due to failure of kidney function include:

• Oliguria or anuria
• Polyuria
• Anemia
• Edema
• Hypertension

All suspected cases of AKI should at least have:

• Urine analysis
• Urine specimen for microscopy and culture
• Urinary biochemistry
• Serum electrolytes may show hyperkalemia, hyponatremia, and raised urea and creatinine levels.

Additional investigations that may be performed include:

• Full blood count
• Abdominal ultrasonography and roentgenograms
• Autoimmune screen
• Renal biopsy can be done to investigate the cause of the AKI.

Goals of AKI management include:

• Preserve renal function
• Prevent complications of AKI
• Prevent the need for renal replacement therapy (RRT)
• Minimize adverse outcomes
• Prevent death

The management strategy relies on the implementation of:

• Non-pharmacological strategies
• Pharmacological intervention
• Renal supportive/replacement therapies

Fluids Management

The major goal of fluid management in AKI includes:

• Restoring and maintaining intravascular volume
• Estimating fluid status as AKI may manifest with different volume statuses
• Prompt and vigorous fluid resuscitation in children with intravascular volume depletion
• Initial therapy with normal saline or lactated Ringer’s solution at 20 ml/kg over 30 minutes, possibly repeated
• Close monitoring to avoid fluid overload
• Considering intrinsic or post renal failure if anuria persists after fluid boluses
• Recording fluid input and output, daily weights
• Adjusting fluid requirements during the recovery phase to prevent dehydration
• Applying fluid restriction and loop diuretics for oliguria with volume overload
• Use of dopamine/dobutamine for vasodilation and increased renal perfusion

Electrolytes and Acid-Base Balance

Management of electrolytes and acid-base balance includes:

• Handling hyperkalaemia (>5.5mEq/L) with diuretics, sodium bicarbonate therapy, insulin glucose infusions, and dialysis
• Treating hyponatremia with free water restriction and hypertonic saline (3%)
• Using oral phosphate binders (e.g., calcium carbonate) for hyperphosphataemia and hypocalcemia
• Treating moderate to severe acidosis with oral or intravenous sodium bicarbonate

Hyperkalemia

Hypertension

Hypertension resulting from hyperreninemia can be managed with:

• Salt and water restriction
• Diuretic administration
• Using calcium channel blockers (amlodipine) or β blockers (propranolol; labetalol)

Hypertensive urgency/emergency should be treated with continuous infusions of:

• Sodium nitroprusside
• Labetalol
• Esmolol

Other Supportive Care

Other aspects of supportive care include:

• Managing mild anaemia with transfusion of packed red blood cells if hemoglobin level falls below seven g/dL
• Avoiding nephrotoxic drugs like aminoglycosides and making dose adaptations for medications primarily eliminated by the kidney

Renal Replacement Therapy

Renal replacement therapy involves:

• Dialysis, which aims to remove toxins and maintain fluid, electrolyte, and acid-base balance
• Using principles of diffusion across a semi-permeable membrane along an electrochemical concentration gradient
• Peritoneal dialysis (continuous or intermittent)
• Haemodialysis

Indications for dialysis include:

• Volume overload with evidence of hypertension and/or pulmonary edema refractory to diuretic therapy
• Persistent hyperkalemia
• Severe metabolic acidosis unresponsive to medical management
• Neurologic symptoms (altered mental status, seizures)
• Blood urea nitrogen greater than 100–150 mg/dL (or lower if rapidly rising)
• Serum creatinine above 500 umol/L
• Calcium/phosphorus imbalance with hypocalcemic tetany

The choice between haemodialysis and peritoneal dialysis depends on various factors including clinical condition, technique availability, aetiology of AKI, institutional preferences, and specific indications or contraindications.

In general, peritoneal dialysis is preferred in infants and younger children, while haemodialysis is advantageous for rapid correction of imbalances in older, hemodynamically stable patients.

Diet

When managing AKI, consider the following dietary aspects:

• Provide adequate calories to account for maintenance requirements and supplements to combat excessive catabolism.
• Oral feeding is the preferred route of administration.

Surgical Care

Patients with AKI secondary to obstruction often require urologic care:

• Urologic intervention may be necessary to address the underlying obstruction.

AKI can lead to various complications:

• Infections: Develop in 30-70% of patients with AKI due to impaired defenses from uraemia.
• Cardiovascular Complications: These may include hypertension, congestive heart failure, and pulmonary edema.
• Gastrointestinal Complications: Anorexia, nausea, vomiting, ileus, and bleeding can occur.
• Hematologic Complications: AKI can lead to anemia and platelet dysfunction.
• Neurologic Complications: Symptoms like confusion, somnolence, and seizures can arise.

The prognosis of AKI depends on its underlying cause:

• The mortality rate can range from 10% to 60%.
• Recovery of renal function is likely after AKI resulting from prerenal causes, hemolytic-uremic syndrome (HUS), acute tubular necrosis (ATN), acute interstitial nephritis, or tumor lysis syndrome.
• However, recovery of renal function is unusual when AKI results from most types of rapidly progressive glomerulonephritis, bilateral renal vein thrombosis, or bilateral cortical necrosis.

The traditional RIFLE and AKIN classifications rely on changes in serum creatinine to estimate the loss in glomerular filtration rate (GFR). However, serum creatinine has several limitations:

• It can vary with age, sex, dietary intake, and muscle mass, making it less accurate.
• It doesn't always reflect dynamic changes in kidney function.
• It only increases significantly when there is a substantial loss of renal function, usually more than 50% of total renal function.

Neutrophil Gelatinase Associated Lipocalin (NGAL)

NGAL is a protein secreted by renal tubular epithelium and has been found to have diagnostic and prognostic value for AKI:

• It can be detected in both serum and urine.
• NGAL levels in urine can increase before there's a noticeable rise in serum creatinine.
• It serves as a biomarker for both pre-renal and intrinsic renal injuries.

Cystatin C

Cystatin C is a protein secreted by all nucleated cells and is used as a marker for estimating GFR:

• It is minimally influenced by weight, sex, race, and age, making it a more reliable indicator of GFR.
• Cystatin C levels rise earlier than serum creatinine in response to kidney dysfunction.

Kidney Injury Molecule – 1 (KIM-1)

KIM-1 is an epithelial cell adhesion molecule that is highly upregulated in the proximal tubules after ischaemic or toxic AKI:

• It is normally expressed at low levels in healthy kidneys.
• Urinary levels of KIM-1 can help distinguish ischaemic AKI from pre-renal disease and chronic renal disease.
• KIM-1 can also predict graft loss in kidney transplant patients.

Conclusion

Acute Kidney Injury (AKI) is a significant contributor to morbidity and mortality in children. In our environment, infectious diseases such as malaria and sepsis are common causes of AKI. Early diagnosis and prompt management are crucial for improving outcomes in children with AKI. The primary focus of physicians should be on preventing its occurrence through adequate rehydration of ill children. When AKI does occur, timely and effective interventions are essential.

Further Reading

For more information on this topic, you can refer to the following resource:

Current Trends in the Management of Acute Kidney Injury in Children