Acute renal failure in the newborn etiology & pathophysiology

Acute renal failure in the newborn
Tej K Mattoo, MD, DCH, FRCP

DEFINITION — Acute renal failure (ARF) is defined as the sudden impairment of kidney function (estimated from the glomerular filtration rate [GFR]) that results in the lack of excretion of waste products. The serum creatinine at birth is equal to the concentration in the mother (usually less than 1.0 mg/dL [88 micromol/L]). It then falls over time to a lower normal value. Newborns are considered to have renal failure if the serum creatinine concentration is >1.5 mg/dL (133 micromol/L) [1,2].

ARF may be oliguric (urine volume less than 1 mL/kg per h) or nonoliguric,
INCIDENCE — the incidence of ARF has ranged from 0.4 percent of live births to 3.5 percent of hospital admissions, to 8 percent of admissions to a neonatal intensive care unit [3,4]. Most newborns with ARF are preterm and/or critically ill.
PATHOPHYSIOLOGY — Renal embryogenesis is completed by the 35th week of gestation, resulting in 0.6 to 1.2 million nephrons in each kidney. However, several factors make newborn infants, especially those born preterm, more susceptible to renal failure than older infants or children. These include: Developmental immaturity that limits the function of the immature kidney. Hemodynamic changes that occur at birth and in the early neonatal period that affect the kidney. An increased risk of hypovolemia because of large insensible water losses.

Several changes in renal function occur in the perinatal period. Renal blood flow (RBF) increases substantially soon after birth because renal vascular resistance decreases and systemic blood pressure increases. As a proportion of cardiac output, RBF increases from 2 to 4 percent in the fetus to approximately 10 percent by one week after birth (the normal adult value is approximately 20 percent). Interference with this transition may lead to diminished renal function.

Autoregulation of RBF, in which small changes in systemic pressure produce parallel changes in renal vascular resistance so that RBF is maintained, is set at a lower range of blood pressure than in adults. This reduces a newborn's ability to compensate for significant hemodynamic changes and may lead to compromised renal function. Impaired autoregulation can predispose to ARF when the blood pressure is reduced [5-7].

Urine concentrating ability is limited in the newborn compared to the older infant. The maximum urine concentration that can be achieved increases from 400 mosmol/kg in the first few days after birth to 1200 mosmol/kg at one year of age. The reasons for poor urine concentrating ability in infants include low corticomedullary solute gradient, decreased formation of cyclic AMP in response to antidiuretic hormone (ADH), a short loop of Henle, and interference by prostaglandins [8-10].
Limited urine concentrating ability increases the risk of volume depletion if intake is reduced and/or fluid loss is increased. There is also an impairment in maximum reabsorption of sodium that may be mediated in part by reduced responsiveness to aldosterone [5-7]. The fraction of the filtered sodium that is excreted (FENa) is as high as 5 percent in preterm infants compared to less than 2 percent in older children.

Another source of fluid loss is insensible water loss through the skin, which may be high in newborns who have a greater body surface area for their mass compared to older children and adults. Insensible losses are increased by radiant warmers or phototherapy.

ETIOLOGY — The causes of ARF in newborns are distributed as follows [11]:
- Prerenal failure, due to inadequate renal perfusion — 85 percent
- Intrinsic renal failure, due to intrarenal pathology — 11 percent
-Postrenal failure, due to obstruction to the flow of urine — 3 percent

Perinatal asphyxia — Perinatal asphyxia is the most common cause of ARF in newborns, which results mostly from impaired renal perfusion. As many as 61 percent of severely asphyxiated infants may develop ARF that is predominantly nonoliguric [4,12-14]. In a report of 33 term infants with severe asphyxia, ARF was classified as nonoliguric, oliguric, and anuric in 60, 25, and 15 percent of cases, respectively [12].

The mechanisms of ARF in perinatal asphyxia include diminished renal blood flow because of hypovolemia and hypotension, which can lead to impaired GFR and tubular function. Pulmonary disorders frequently accompany perinatal asphyxia, which may lead to hypoxemia, hypercapnia, and acidosis. These abnormalities result in increased secretion of catecholamines, adenosine, renin and aldosterone, and antidiuretic hormone (ADH). Increased catecholamines, adenosine, and angiotensin cause preglomerular vasoconstriction and postglomerular dilatation, which decreases GFR. The activated renin-angiotensin system and increased ADH secretion aggravate salt and water retention with oliguria. The use of mechanical ventilation may decrease venous return and cardiac output, which contributes to hypovolemia and hypotension [15-17].

Prerenal disease and acute tubular necrosis — Decreased renal perfusion can cause a direct fall in GFR without any intrinsic renal disease (called prerenal disease or functional oliguria) and can also lead to ARF associated with tubular damage, a disorder called acute tubular necrosis (ATN) or, previously, vasomotor nephropathy [18]. Almost all of the pathophysiology of ATN has been studied in experimental models and adults. As a result, some links will be provided for further information in the adult section.

The most common causes of prerenal disease/ATN are hypovolemia, hypoxemia, and septicemia. Each of these factors can induce hypotension, with secondary renal vasoconstriction due to activation of the renin-angiotensin and sympathetic nervous systems. The net effect is a reduction in RBF, GFR, and renal oxygen delivery that can predispose to tubular injury [18-21].

Additional factors may contribute among septic patients, including the release of cytokines such as tumor necrosis factor, and activation of neutrophils by endotoxin and by FMLP, a three amino acid (fMet-Leu-Phe) chemotactic peptide in the bacterial cell walls [20,21].

Similar changes can be induced by prolonged hypothermia and certain medications [18,22]. These include prostaglandin synthesis inhibitors (eg, indomethacin), angiotensin converting enzyme inhibitors (eg, captopril), neuromuscular blocking agents (eg, pancuronium), and nephrotoxic drugs (eg, gentamicin). Renal vasodilator prostaglandins are most important in settings of decreased renal perfusion in which they help to maintain RBF. Blocking prostaglandin synthesis in such patients can lead to ARF.

Renal vascular thrombosis — Bilateral renal vascular thrombosis can result in intrinsic renal failure. A more common manifestation of less severe renal vascular thrombosis is hypertension.

Renal artery thrombosis — Renal arterial abnormalities often are due to thrombosis associated with umbilical artery catheter (UAC) placement [23-26]. Thrombi that form on the tip or surface of the catheter can partially or completely occlude the abdominal aorta, thereby decreasing renal perfusion. These thrombi may embolize to the renal artery, resulting in areas of infarction and increased renin release [27].

Thrombi are common in newborns with UACs and usually are asymptomatic [24,26]. However, bilateral renal artery thrombosis can cause ARF [28,29].

Renal vein thrombosis — Renal vein thrombosis (RVT) is uncommon, with an incidence estimated as 2.2 per 100,000 live births [30]. Approximately one-half of affected infants are preterm [30]. Bilateral RVT usually is associated with irreversible renal failure.

Predisposing conditions are those associated with hemoconcentration or diminished renal perfusion including diarrhea, sepsis, perinatal asphyxia, polycythemia, administration of contrast media, congenital nephrotic syndrome, homozygous protein C deficiency, homocystinuria, or a diabetic mother [31]. RVT commences in the small renal veins and subsequently propagates via larger interlobar veins to the main renal vein and inferior vena cava [32]. The adrenal glands also may be affected.

RVT typically presents with a palpable flank mass, often accompanied by hypertension and reduced urine output. Affected infants have gross or microscopic hematuria, proteinuria, and diminished renal function. Associated hematologic findings often include thrombocytopenia, anemia, fragmented red blood cells, laboratory findings of disseminated intravascular coagulation, and leucocytosis.

Renal and urinary tract abnormalities — The preceding discussion has emphasized renal failure developing after delivery in presumably normal kidneys. A similar picture can be produced by any severe renal or urinary tract abnormalities, although the renal disease is not really acute. Examples include polycystic kidney disease, multicystic dysplastic kidneys, renal agenesis, and urinary tract obstruction.

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Acute renal failure in the newborn etiology & pathophysiology Dralatwani2gif

thanks doctor off yor add .
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Thank you Dr.salim Alatwani very nice subject which we facing daily best wishes as well regards ....thanks alot for more adds & contributions.

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