The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy

Abstract

The healthy term, and particularly the premature infant, is born with a very low glomerular filtration rate (GFR), controlled by a delicate balance of intrarenal vasoconstrictor and vasodilator forces. Vasoactive disturbances can easily further reduce the already low GFR. The newborn infant is thus prone to develop vasomotor nephropathy (VMNP) or acute renal failure (ARF). The main causes for ARF at this young age are prerenal mechanisms, and include hypotension, hypovolemia, hypoxemia perinatal asphyxia, and neonatal septicemia. Other causes include the administration of angiotensin converting enzyme inhibitors, indomethacin and tolazoline. The most-important factors governing the ultimate renal prognosis are the severity of the underlying disorder, the rapidity of an accurate diagnosis, prompt treatment, and avoidance of severe iatrogenic complications. The immediate treatment is of particular importance in VMNP, i.e., prerenal ischemic ARF, and consists of correcting abnormalities in fluid homeostasis and reduction of the complications of the acute azotemic state (uremia, hyperkalemia, acidosis, and hypertension). In severe and prolonged (established) ARF, temporary dialysis therapy may be indicated. Prerenal ARF with oliguria or anuria warrants immediate volume resuscitation. Special attention should be given to infants with congestive heart failure (CHF). The sick neonate with persistent oliguria and CHF should be treated with intravenous dopamine. Furosemide (FM) is the second line of therapy for babies with indomethacin-induced ARF. In most other conditions, the therapeutic effect of FM is limited to a transient increase in urine flow, without improving basic renal function. The special conditions of the maturing kidney have to be appreciated in order to protect babies from undue renal injury. With the increasing knowledge of the mechanisms governing the development of ARF, progress has been made in the development of new treatment modalities. For example theophylline, calcium antagonists, ATP-MgCl2, thyroxine, and a variety of cytokines may in the near future be used to prevent or ameliorate VMNP and/or recently established ARF. With a combination of time-honored and new therapeutic strategies, there may well be a brighter future for neonates with vasomotor, prerenal, ischemic ARF.

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

“…These results are consistent with the observations reported for hypoxemia alone. They strengthen the notion of a vasomotor origin of the hypoxemia-induced insult on the immature kidney previously reported by our group [2][3][4][5][6] and suggest a role for IGF-1 deficiency in this complex phenomenon. In anesthetized adult rats given IGF-1, Baumann et al reported an increase in GFR, renal plasma flow and diuresis by 35%, 100% and 300%, respectively, whilst RVR decreased by 50%.…”

“…These results confirm that the renal microvasculature in the neonatal period is sensitive to exogenous IGF-1, even in pathogenic circumstances. Combined with the high survival rate seen with IGF-1, these results could be of clinical importance, as neonatal mortality and morbidity rates due to ARF remain very high [2].…”

“…Acute renal failure (ARF) related to perinatal asphyxia accounts for the majority of ARF cases in newborns, along with hypovolemia and hypotension [1,2]. In clinical observations and preclinical animal models, acute normocapnic hypoxemia can induce functional renal insufficiency by increasing the renal vascular resistance (RVR), thus leading to renal hypoperfusion and decreased glomerular filtration rate (GFR).…”

Factors affecting postnatal changes in serum creatinine in preterm infants with gestational age <32 weeks

“…8 Moreover, in sick preterm infants, many clinical conditions inducing hypotension, hypovolemia and hypoxemia and the use of nephrotoxic drugs may lead to further reduction of GFR. 9 In particular, nonsteroidal anti-inflammatory drugs (NSAID) that are given for treatment of patent ductus arteriosus (PDA) have been reported to impair renal perfusion 10 and the immature kidney is regarded as especially sensitive to NSAID renal effects. However, hemodynamically significant PDA (hsPDA) itself can be associated with poor renal perfusion and we could speculate that the NSAID renal effects may be exacerbated by a low GFR preceding NSAID administration.…”

Renal Immaturity Mimicking Chronic Renal Failure in an Infant Born at 22 Weeks Gestational Age

“…[1][2][3] Glomerular function shows a progression directly correlated to gestational age (GA) and postnatal age in preterm infants. 4 In infants with very low GA, due to decreased glomerular filtration rate (GFR), normalization of serum creatinine values may be prolonged during recovery from acute renal failure (ARF).…”