Renal maturation

Dose regimens of renally eliminated drugs in neonates are generally based on postconceptional or postmenstrual age as a measure of renal maturation, and postnatal age, to take into account the adaptive changes that occur after birth. However, these should be regarded as initial doses and dose frequency and should be adjusted according to response. 

From a therapeutic point of view, it is essential to confirm the presence of bacteriuria (a condition in which there are bacteria in the urine) since symptoms alone are not a reliable method of documenting infection. This applies particularly to bladder infection where the symptoms of burning micturition (dysuria) and frequency can be associated with a variety of non-bacteriuric conditions. Patients with symptomatic bacteriuria should always be treated. However, the necessity to treat asymptomatic bacteriuric patients varies with age and the presence or absence of underlying urinary tract abnormalities. In the pre-school child it is essential to treat all urinary tract infections and maintain the urine in a sterile state so that normal kidney maturation can proceed. Likewise in pregnancy there is a risk of infection ascending from the bladder to involve the kidney. This is a serious complication and may result in premature labour. Other indications for treating asymptomatic bacteriuria include the presence of underlying renal abnormalities such as stones which may be associated with repeated infections caused by Proteus spp. 

Azacitidine, a cytidine analog, causes hypomethylation of DNA, which normalizes the function of genes that control cell differentiation to promote normal cell maturation. The suspension is administered as a subcutaneous injection daily for 7 days for the treatment of myelodysplastic syndrome, a preleukemia disease. The pharmacokinetics of azacitidine are best described by a two-compartment model, with a terminal half life of 3.4 to 6.2 hours, whereas peak concentrations are achieved 30 minutes after a subcutaneous injection.7 Azacitidine has been shown to be clinically active in the treatment of myelodysplastic syndromes. The side effects include myelosuppression, renal tubular acidosis, renal dysfunction, and injection-site reactions. 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

Mercuric chloride is a potent nephrotoxicant in the adult rat, but has little effect on the newborn [222], There are significant maturational changes in organ, cellular and subcellular distribution of mercury during the first 4 weeks after birth. With increasing age, mercury is redistributed from the renal cytosolic fraction to the nuclear/mitochondrial fraction, where it may be more damaging. 

Adults. 3 g PO q6h x 4 PRN Supl 1-2 g IM or IV repeat PRN Preeclampsia/pre-mature labor 4 g load then g/h IV inf Cardiac arrest 1-2 g IV push (2-4 mL 50% soln) in 10 mL DjW AMI Load 1-2 g in 50-100 mL D5W, over 5-60 min IV then 0.5-1.0 g/h IV up to 24 h (ECC 2005) Feds. 25-50 mg/kg/dose IM or IV q4-6h for 3-4 doses repeat PRN dose w/ low urine output or renal insuff Caution [B, +] Contra Heart block, renal failure Disp Inj 10, 20, 40, 80, 125, 500 mg/mL bulk powder SE CNS depression, D, flushing, heart block Interactions T CNS depression W/ antidepressants, antipsychotics, anxiolytics, barbiturates, hypnotics, narcotics EtOH T neuromuscular blockade Wf aminoglycosides, atracurium, gallamine, pancuronium, tubocurarine, vecuronium EMS Check for absent patellar reflexes this may indicate tox may cause hypokalemia (flattened T waves) and hypocalcemia OD May cause hypotension, resp arrest, T PR, QRS, and QT interval, AV block, and cardiac arrest calcium salts can be given to reverse resp depression... 

Renal function matures to its peak between 5-12 years of age, and glomerular flltration rate may exceed adult values when corrected for body surface area. 

Physiologically, oxygen transport to metabolising tissues is provided by haemoglobin contained within erythrocytes. This pathway starts in the bone marrow with immunohaematopoietic stem cells that differentiate to progenitors which proliferate to yield the recognisable normoblasts. The latter mature to reticulocytes, which are then released into the circulation. Overall regulation is primarily mediated by the renal hormone called erythropoietin. 

The ability to produce a concentrated urine also matures over time. In the rat, this function is not mature until 2-3 weeks after birth. This is due to the lengthening of the loops of Henle and to maturation of ion transport function. Sodium influx from the renal tubular lumen stimulates proximal tubule growth and upregulates the expression of Na+K+-ATPase, the major transporter of sodium in the kidney, in the basolateral membranes of the epithelium. 

Reference values for amino acids in the urine show a rather sharp decrease from the neonatal period to adulthood (Table 2.1.6). This is mainly due to the maturation of the renal tubular reabsorption system, but is also the result of increasing muscle mass with age, giving rise to increasing creatinine production. 

A form of salt loss in infancy was long considered to be due to renal tubules that were refractory to aldosterone. Recent studies have described variant roots of the condition, either mutations in the mineralocorticoid receptor, the genes coding the epithelial sodium channel (ENaC), or other causes [6]. Many infant patients recover spontaneously, probably due to maturation of proximal tubular function. 

Unlike renal function, hepatic maturation is generally believed to be a two-stage process with the major development completed at 4 weeks postpartum and tlie second stage completed by about 10 weeks of age. In sheep, for example, tlie activity of a number of hepatic drug-metabolizing enzymes was found to be relatively low in animals aged up to 6 months compared with adult individuals... 

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