Glomerular filtration rate in children

Schwartz GJ, Haydock GB, Edelman CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics, 51 875-878. 

B22. Bokenkamp, A., Domanetzki, M., Zinck, R., Schumann, G., Byrd, D., and Brodehl, J., Cystatin C—A new marker of glomerular filtration rate in children independent of age and... 

H7. Helin, I., Axenram M., and Grubb, A., Serum cystatin C as a determinant of glomerular filtration rate in children. Clin. Nephrol. 49(4), 221—225 (1998). 

Al-Harbi N, Lireman D. Comparison of three different methods of estimating the glomerular filtration rate in children after renal transplantation. Am J Nephrol 1997 17 68-71. 

Schwartz Gj, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents. Pediatr Clin North Am 1987 34 571-590. 

Schwartz GJ, Feld LG, Langford DJ (1984) A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr 104 849-854 Seikaly MG, Ho PL, Emmett L et al (2003) Chronic renal insufficiency in children The 2001 annual report on the NAPRTCS. Pediatr Nephrol 18 796-804 Smith JM, Ho PL, McDonald RA (2002) Renal transplant outcomes in adolescents A report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 6 493-499... 

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],... 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

NRC 1993 Vieira et al. 1996). Whether differences in xenobiotic metabolism make the child more or less suseeptible also depends on whether the relevant enzymes are involved in activation of the parent compound to its toxic form or in detoxification. There may also be differences in excretion, particularly in the newborn who has a low glomerular filtration rate and has not developed efficient tubular secretion and resorption capacities (Altman and Dittmer 1974 NRC 1993 West et al. 1948). Children and adults may differ in their capacity to repair damage Irom chemical insults. Children also have a longer lifetime in which to express damage Irom chemicals this potential is particularly relevant to cancer. 

By 1 year of age, glomerular filtration rate and renal tubular mechanisms for secretion have reached adult levels however, fluid intake may be greater in children. Thus, lithium has a shorter half-life and more rapid renal clearance in children as compared with adults (40). 

Metabolism and elimination rates are generally lower in neonates than in adults. The elimination half-lives of substances used as indicators of liver function (e.g. bromosulfthalein, bilirubin), for example, are longer in newborns than in adults. Renal clearance has been shown to be lower in neonates than in older children and adults, for all chemical classes lipophilic, hydrophilic, and organic ions (Clewell et al., 2002). Glomerular filtration rate at normal-term birth is about one third of the adult value when expressed on the basis of body surface area and matures in about six months. On the other hand, the tubular reabsorption process reaches adult levels within a few days after birth. 

Age-related alteration of renal function is a very important factor in selecting the dose regimen. Renal function in newborns is incompletely developed. Neonatal renal plasma flow and glomerular filtration rates (normalized for body surface) are only 30-40% of those of adults. The half-life of penicillin G is 3.2 h in newborns (up to 6 days of age) and 1.4 h in infants (14 days of age or older), whereas in older children and adults, it is about 0.5 h. The mean half-life of gentamicin is about 5h in newborns under 1 week of age and about 3 h in infants 1-4 weeks of age. The half-life of gentamicin in older infants and adults is approximately 2 h. Thus, drugs that depend on renal excretion as the principal mode of elimination would be expected to have a longer residence time in infants. 

Renal function in 14 children born to women with transplants treated throughout pregnancy with a ciclosporin-based regimen has been extensively investigated at a mean of 2.6 years after delivery (205). No renal function abnormahties were found. In particular, glomerular filtration rate was within the reference range. Renal function was found to be normal in 22 children evaluated after a mean of 39 months after birth (206), and no adverse effects on the immune function were identified in the few infants examined in this respect (203). 

Counahan R, Chantler C, Ghazali S, Kirkwood B, Rose F, Barratt TM. Estimation of glomerular filtration rate from plasma creatinine concentration in children. Arch Dis Child 1976 51 875-8. 

Hyperphosphatemia is usually secondary to the inability of the kidneys to excrete phosphate. In acute or chronic renal failure, a decrease in glomerular filtration rate (GFR) reduces the renal excretion of phosphate, resulting in hyperphosphatemia. Moderate increases of serum phosphate occur in individuals with low PTH (hypoparathyroidism), PTH resistance (pseudohypoparathyroidism), or acromegaly (increased growth hormone) caused by an increased renal phosphate threshold. Growdi hormone is responsible for the increased renal phosphate threshold and higher phosphate concentrations observed in children. EDTA therapy has also been associated with hyperphosphatemia. 

---