Issue 25, November 2008 Early Health and Neonatal Care

Acute renal failure in the newborn (I): Classification and causes

Correspondence: Alexander Rakow, MD, Division of Neonatology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. (E-mail and other contact info can be obtained from CWWJ’s Editor-in-Chief).

Key Words: Renal failure, newborn, neonatal intensive care
Running title: Acute renal failure in the newborn (Part I)

Clinical Window Web Journal #25: Acute renal failure in the newborn (Part I): Classification and causes (November 2008). ISSN 1795-6269.

Introduction

Introduction Acute renal failure (ARF) in the newborn, and especially in the preterm newborn, is more common than probably diagnosed. As the term implies, it is a clinical syndrome with an abrupt onset as measured by the decreased glomerular filtration rate (GFR). A significant increase in plasma creatinine above 130 µmol/l (1.5mg/dl) corresponds to a fall in GFR to less than 50% of normal and defines ARF regardless of urine output [1]. ARF should also be suspected when creatinine rises to 26.5 µmol/l (0.3mg/dl) or more per day or fails to decline over time below maternal levels [2,3].

Plasma creatinine is difficult to interpret in newborns, especially the premature, because it is always physiologically high post partum. For smaller infants, the levels are higher and remain high longer [4]. These initial high levels represent the mother’s creatinine value and not the baby’s. Plasma creatinine at birth can be around 70-90 µmol/l and then fall to about 30 µmol/l (15-40 µmol/l) within the first week of life [4].

Oliguria, one of the clinical hallmarks of renal failure, is defined as urine output per hour that is less than 1 ml/kg in infants and less than 0.5 ml/kg in children. The definition is still unclear for preterm infants, especially since they do not begin to concentrate their urine until they are significantly more dehydrated than term infants [5]. In fact, it has been suggested that oliguria in preterm infants may exist already below a urine output less than 1.5 ml/kg/h (Guignard J-P, personal communication, 2005). At onset, oliguria is frequently acute, it is often the earliest sign of impaired renal function, and it poses a diagnostic and management challenge to the clinician. However, it should be remembered that healthy newborns can have their first urine delayed up to 24 hours after birth. Nevertheless, oliguria is not necessary to the diagnosis of ARF. Non-oliguric ARF is definitely more frequent but is infrequently diagnosed. In summary, the definition of acute renal failure (ARF) is a sudden severe derangement of glomerular function indicated by significant elevation of plasma creatinine with or without oliguria.


Causes of ARF

The incidence of ARF is reported to be between 8% and 23% of all newborns admitted to a neonatal intensive care unit, with about 1% of newborn infants in neonatal care needing dialysis [2,6]. The pathogenesis of ARF can be differentiated into prerenal/functional, renal/intrinsic and post renal/obstructive ARF (Table 1).

Prerenal (functional) failure

Prerenal or functional ARF is the most common form in the newborn infant and accounts for approximately 85% of all cases [7]. Renal function depends on sufficient perfusion of the kidney at sufficient pressure to provide filtration. The renal (glomerular) function is more vulnerable in premature and very young infants, therefore it is necessary to preserve the delicate balance between intrarenal vasoconstrictive and vasodilatator forces to assure that the low precarious effective filtration pressure is maintained under most pathophysiological circumstances. If this balance is severely disturbed it can lead to renal dysfunction, with or without parenchymal damage.

The main causes for this dysfunction are hypovolemia, normovolaemic hypotension caused by sepsis, asphyxia, and hypoxia as well as factors increasing renal vascular resistance such as polycytemia, medications like indomethacin or adrenergic drugs (e.g., tolazolin) and, very effectively, hypothermia [8].

Renal (intrinsic) failure

Renal or intrinsic failure is much rarer than prerenal failure (11%). It is direct damage to the kidneys from an insult or congenital anomaly and can be a consequence of persistent prerenal failure (for example, as occurring from sustained hypoperfusion leading to acute tubular necrosis (ATN)). The course of intrinsic ARF can be subdivided into three phases, an initiation phase, a maintenance phase, and a recovery phase [12].

The initiation phase includes the insult and associated events that produce tubular cell injury. This phase corresponds to the period of exposure to ischemia or nephrotoxins. Renal tubular cell damage is initiated during this phase. GFR starts to fall, and urine output decreases.

The maintenance phase consists of sustained low GFR, tubular dysfunction and azotemia, with duration depending in part on the severity and duration of the initial insult. During this phase, renal tubule injury is established, the GFR stabilizes at a level well below normal, and urine output will be low or absent.

The recovery phase of ATN is characterized by polyuria and gradual normalization of GFR; however, when ARF occurs (as it often does) in the context of multiorgan dysfunction, regeneration of renal tissue may be severely impaired and renal function may not return. Morbidity and mortality in such situations remains dismally high, in spite of significant scientific and technological advances.

Perinatal asphyxia is a most common cause of intrinsic acute renal failure in the newborn and the degree of hypoxic- ischemic insult determines the spectrum of renal damage. This can extend from mild tubular dysfunction to acute tubular necrosis to renal infarction with corticomedullary necrosis.
Other causes for intrinsic ARF are congenital malformations, infections, renal vascular causes like renal artery or vein thrombosis and nephrotoxins (aminoglycosides, indomethacin, amphotericin B, methicillin). ARF due to nephrotoxins is typically nonoliguric.

Obstructive (post-renal) failure

Obstructive or post renal failure is a consequence of mechanical or functional obstruction to urine flow and can be caused by a variety of congenital malformations. The obstruction has to be bilateral and can be extrinsic, intrinsic or neurogenic (Table 1). Although some obstructive malformations are considered to be reversible causes of renal failure, a large percentage of neonates with obstructive lesions also have renal dysplasia.

Investigations and monitoring

The major goal in the initial evaluation of neonatal ARF is to promptly diagnose pre-renal and obstructive renal failure, to prevent their transmission into intrinsic renal failure.

The clinical history here is important, as there may be a family history of renal malformations. Oligohydramnios may indicate decreased fetal renal function, or prenatal ultrasound may have already detected urinary tract anomalies.
Monitoring laboratory values

Acute renal failure should be suspected when creatinine has risen to 0.3 mg/dl (26.5 µmol/l) or more per day or fails to decline over time below maternal values, or if serum creatinine is over 1.5 mg/dl (132.5 µmol/l), whether or not oliguria is present [9]. Systemic monitoring of serum creatinine in newborns in danger of developing acute renal failure is vital.

The plasma urea concentration is influenced by dietary protein intake, gastrointestinal bleeding, hypercatabolic state and other factors. Therefore this is not a reliable index for glomerular filtration, although high levels indicate that the infant’s excretory output is insufficient and that dialysis may be needed [9].

Electrolytes may be abnormal in ARF. Hyperkalemia is a severe and potentially lethal medical emergency since it can cause cardiac arrhythmias. Hypocalcemia and hypomagnesaemia, both of which frequently occur in ARF, can bring about hyperkalemia.

Ultrasound and other investigations

As mentioned before, it is essential to detect early prerenal and obstructive renal failure, in order to prevent transition to intrinsic acute renal failure. Ultrasonography of the kidneys and urinary tract should be performed early if acute renal failure is suspected.

If postrenal failure can be excluded, a fluid challenge should be given, to differentiate pre-renal from intrinsic renal failure [10]. The fluid challenge should include enough isotonic solutions to return intravascular volume status to normal; this consists of e.g. weight adjusted amount of 0.9% saline given intravenously over 2 hours. If oliguria continues, then intravenous furosemide should be given.

If there is no diuresis with urine output better than 1 ml/kg/h within 2 hours, and the patient is clinically euvolemic, then intrinsic renal failure should be suspected and fluids restricted.

Continues in part II

Care and outcome

Click here to move to the second part of the article.

References

List of references is incuded in the second part of the article.

Clinical Window Web Journal #25: Acute renal failure in the newborn (Part I): Classification and causes (November 2008). ISSN 1795-6269.

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Last updated: 30 November 2008
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