- Email: [email protected]
Feasibility of prenatal diagnosis of nonketotic hyperglycinemia: Existence of the glycine cleavage system in placenta
124
Clinical and laboratory observations
similar to those previously reported? The 17-OHP levels in this study were lower than those previously described by Forest et al? The most likely explanation for this discrepancy is that our infants were healthy and asymptomatic, whereas those studied by Forest were initially suspected of having pituitary, gonadal, or adrenal dysfunction, but because of normal urinary 17-ketostei'oids no endocrinologic disease was diagnosed. Even if the infants studied by Forest had no adrenal disorder, they were not healthy, and acute illness or stress may elevate 17-OHP levels. Another possible explanation for our lower 17-OHP values is that none of our patients was of Jewish background. Laron et al. 7 reported an increased incidence of 21-hydroxylase deficiency in the Jewish population. A higher percentage of the infants studied by Forest may have been Jewish. The low basal morning cortisol levels were not unexpected; newborn infants typically have not yet developed a diurnal pattern. Our results confirm that a single basal morning cortisol level in a neonate is not useful as a means of diagnosing cortisol deficiency. We thank Darrel M. Mayes, M.D., and Endocrine Sciences for the determination of the adrenal steroid values; and Charlene Deuber, R.N., for help in obtaining the blood samples.
The Journal of Pediatrics January 1987
2.
3.
4.
5.
6.
7.
3-beta-hydroxysteroid dehydrogenase deficiency. N Engl J Med 1985;313:618. de Peretti E, Forrest MG. Pitfalls in the etiological diagnosis of congenital adrenal hyperplasia in the early neonatal period. Horm Res 1982;16:10. Forest MG, de Peretti E, Bertrand J. Developmental pattel"ns of the plasma levels of testosterone, A4-androstenedione, 17~-hydroxyprogesterone, dehydroepiandrosterone and its sulfate in normal infants and prepubertal children. In: James, VH, Serio M, Giusti G , Martini L, eds. The endocrine function of the human adrenal cortex. Orlando, Fla.: Academic Press, 1978:561-82. Rosier A, Leiberman E, Rosenmann A, Ben-Uzilio R, Weidenfeld J. Prenatal diagnosis of I 1-/~-hydroxylase deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab 1979;49:546. Holler W, Scholz S, Knorr D, Bidlingmaier F, Keller E, Albert E. Genetic differences between the salt-wasting, simple virilizing, and nonclassical types of congenital adrenal hyperplasia. J Clin Endocrinol Metab 1985;60:757. Honour JW, Anderson JM, Shackleton CHL. Difficulties in the diagnosis of congenital adrenal hyperplasia in early infancy: the 11-~-hydroxylase defect. Acta Endocrinol 1983; 103:101. Laron Z, Pollack MS, Zamir R, et al. Late onset 21hydroxylase deficiency and HLA in the Ashkenazi population: a new allele at the 21-hydroxylase locus. Human Immunol 1980;1:55.
REFERENCES
1. Cara JF, Moshang T, Bongiovanni AM, Marx BS. Elevated 17-hydroxyprogesterone and testosterone in a newborn with
Feasibility of prenatal diagnosis of nonketotic hyperglycinemia: Existence of the glycine cleavage system in placenta Kiyoshi Hayasaka, M.D., Keiya Tada, M.D., Noboru Fueki, M.D., Iku Takahashi, M.D., Akira Igarashi, M.D., Toshifumi T a k a b a y a s h , M.D., and Regula Baumgartner, M.D. From the Departments of Pediatrics, and Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan, and the Metabolic Unit, UniversityChildren's Hospital, Basel, Switzerland
Nonketotic hyperglycinemia is an autosomal recessive disorder of glycine metabolism characterized by markedly Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, and by grants from the Ministry of Public Welfare, Japan. Submitted for publication July 21, 1986; accepted Sept. 15, 1986. Reprints requests: Keiya Tada, M.D., Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980 Japan.
elevated levels of glycine in body fluids. 1 The fundamental defect is in the main pathway of glycine catabolism, that is, the glycine cleavage system. 2,3 The enzyme system, which NKH
Nonketotic hyperglycinemia
[
is confined to the mitochondria, is composed of four protein components: P-protein (a pyridoxal phosphatedependent glycine decarboxylase), H-protein (a lipoic acid-containing protein), T-protein (a tetrahydrofolate-
Volume 110 Number 1
requiring enzyme), and L-protein (a lipoamide dehydrogenase). 4,5 The two clinical types of N K H are typical (neonatal) and atypical (late onset)i 1 Typical N K H is characterized by rapid development of neurologic symptoms, including lethargy, hypotonia, apnea, and seizures, in the neonatal period? The majority of patients died within a few weeks of life; the survivors have severe psychomotor retardation. Several therapeutic approaches have been attempted, including exchange transfusion, dietary restriction of glycine intake, and administration of agents such as methionine, sodium benzoate, leukovorin, pyridoxine, strychnine, and benzodiazepam.6,7 However, no effective treatment is known to alter the neurologic consequences. Therefore, there is a special need for prenatal diagnosis of NKH. It has been reported that the glycine/serine ratio in amniotic fluid at weeks 17 and 19 of gestation correctly predicted the presence of N K H in a fetus who was delivered at term and shown to have the disease) However, Wendt et al. 9 reported that there was overlapping of individual values in the glycine/serine ratio between amniotic fluid specimens from normal pregnancies and those from affected fetuses at weeks 38 tO 40 of gestation. Mesvage et al? ~showed that the glycine/serine ratio is not a reliable indicator for the prenatal diagnosis of NKH. We investigated the possibility of prenatal diagnosis by enzymatic analysis of the chorionic villi and of fetal tissues.
Clinical and laboratory observations
125
T a b l e I. Activities of glycine cleavage system in liver
and brain of fetus at risk for nonketotic hyperglycinemia and in control fetuses
Activity (~mol product/g protein/hr) Liver Fetus at risk for NKH Control fetus (12 wk) Control fetus (12 wk) Control fetus (16 wk) Control adults Brain Fetus at risk for NKH Control fetus (12 wk) Control fetus (12 wk) Control adults
1.7 28.6 27.4 22.3 3.9-5.2 0.2 3.2 2.7 0.7-1.2
The placenta at week 12 of gestation had about five times the activity of the cleavage system than that at term, whereas the placenta of the fetus at risk for N K H had significantly lower activity (Table II). There was no detectable activity of T-protein, but other components of the glycine cleavage system were not decreased. From these findings it was confirmed that the aborted fetus was a homozygote for NKH, with a defect in T-protein. DISCUSSION
METHODS The fourth pregnancy of a woman was monitored. The family has one healthy child (14 years of age) and an 11-year-old severely retarded daughter with NKH. Their first-born child died of N K H at the age of 3 weeks in 1970, after a typical clinical course.11 An abortion was performed in week 12 of gestation, according to the parents' desire. The glycerine/serine ratio of the amniotic fluid was found to be 4.9. This value seems not to be significantly higher than average (3.28) of the ratio for normal gestation between weeks 7 and 18, reported by Reid et al. ~2 Specimens of the fetal liver, brain, and placenta were immediately frozen at - 6 0 ~ C. Control specimens of fetal liver, brain, and placenta at week 12 of gestation were obtained from other legal abortions. The enzymatic analyses were performed according to methods reported previously? RESULTS The overall activity of the glycine cleavage system in the liver and brain of control fetuses was higher than that in the liver and brain of control adults, and the activity in both tissues of the fetus at risk for N K H was extremely low (Table I). These specimens were insufficient to allow analysis of the components of the glycine cleavage system.
Our study showed the existence of the glycine cleavage system in the placenta of fetuses at week 12 of gestation and at term. Our findings indicate that similar studies in chorionic villi should provide a reliable method for the prenatal diagnosis of N K H . About 30 to 50 mg wet weight chorionic villi may be needed for measurement Of the glycine cleavage system. However, the specimens must be subjected to analysis immediately after biopsy, or frozen immediately at - 8 0 ~ C until analysis, because the enzyme activity is labile in room temperature. REFERENCES
1. Nyhan WK. Nonketotic hyperglycinemia. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS, eds. The metabolic basis of inherited disease. New York: McGraw-Hill, 1983:561-9. 2. Tada K, Corbeel LM, Eeckels R, Eggermont E. A block in glycine cleavage reaction as a common mechanism in ketotic and nonketotic hyperglycinemia. Pediatr Res 1974;8:721. 3. Hayasaka K, Tada K, Kikuchi G, Winter S, Nyhan WL. Nonketotic hyperglycinemia: two patients with primary defects of P-protein and T-protein, respectivel3~-inthe glycine cleavage system. Pediatr Res 1983;17:967. 4. Kochi H, Kikuchi G. Mechanism of reversible glycine cleavage reaction in Arthrobacter globiformis: function of lipoic acid in the cleavage and synthesis of glycine. Arch Biochem Biophys 1976;173:71.
12 6
Clinical and laboratory observations
The Journal of Pediatrics January 1987
T a b l e II. Activities of glycine cleavage system and individual enzyme components in placenta of fetus at risk for nonketotic hyperglycinemia, control fetuses at week 12 of gestation, and full-term ~ormal babies
Activity (/~mol product/g protein/hr) Source of placenta
Glycine cleavage
P-protein
H-protein
T-protein
Llpoarnide dehydrogenase
Fetus at risk for NKH Control fetus (12 wk) Control fetus (12 wk) Control fetus (12 wk) Control infant (38 wk) Control infant (39 wk)
0.2 4.8 2.5 4.1 0.8 0.8
4.4 6.6 4.5 . . .
6.7 10.4 5.1
0 2.8 2.6
865.5 1582.4 734.5
5. Motokawa T, Kikuchi G. Glycine metabolism by rat liver mitochondria: reconstitution of the reversible glycine cleavage system with partially purified protein components. Arch Biochem Biophys 1974;164:624. 6. Gitzelmann R, Steimann B. Clinical and therapeutic aspects of non-ketotic hyperglycinemia. J Inher Metab Dis 1982; 5:113. 7. Matalon R, Naidu S, Hughes JR, Michals K. Nonketotie hyperglycinemia: treatment with diazepam, a competitor for glycine receptors. Pediatrics 1983;71:581. 8. Garcia-Castro J, Isales-Forsyth I, Levy H, et al. Prenatal diagnosis of nonketotic hyperglycinemia. N Engl J Med 1982;306:79.
. . .
. . .
. . .
9. Wendt LV, Simil/i S, Ruokonen A, Hartikainen-Sorri AL. Problems of prenatal diagnosis of nonketotie hyperglycinemia. J Inher Metab Dis 1983;6:112. 10. Mesvage C, Nanee CS, Flannery DB, Weiner DL, Suehy SF, Wolf B. Glycine/serine ratios in amniotic fluid: an unreliable indicator for the prenatal diagnosis of nonketotic hyperglycinemia. Clin Genet 1983;23:354. 11. Bachmann C, Mihatsch M J, Baumgartner R, et al. Nichtketotische hyperglyziniimie: perakuter Verlauf im Neugeborenenalter. Helv Paediatr Aeta 1971;26:228. 12. Reid DW, Gampbell D J, Yakymuyshyn LY. Quantitative amino acids in amniotic fluid and maternal plasma in early and late pregnancy. Am J Obstet Gynecol 1971;111:251.
Acute peritoneal dialysis in infants weighing <1500 g B. T. Steele, M.D., A. Vigneux, R.N., S. Blatz, R.N., M.Ed., M. Flavin, M.D., a n d B. Paes, M.D. From the Departments of Pediatrics and Nursing, McMaster University, Hamilton, Ontario, Canada
Acute renal failure is not uncommon in neonatal intensive care units. Some infants have a transient, mild impairment of renal function, whereas others have progressive anuric renal failure, sometimes accompanied by multiple organ failure. Apart from occasional case reports, 1-3there is little published information on dialysis techniques or results in very low birth weight neonates. W e describe the results of a simple dialysis procedure used in 13 infants weighing <1500 g.
Submitted for publication May 28, 1986; accepted Aug. 18, 1986. Reprint requests: B. T. Steele, M.D., Department of Pediatrics, McMaster University Medical Centre, 1200 Main St., W., Hamilton, Ontario, Canada L8N 3Z5.
METHODS Between July 1983 and July 1985, 13 infants weighing between 380 and 1400 g (mean 894 g) required acute peritoneal dialysis. In 12 infants dialysis was required for acute, anuric renal failure (Table). Severe hyaline membrane disease with persistent pulmonary hypertension, associated with hypotensive episodes, was the most common explanation for acute renal failure. Five infants had hyperkalemia associated with arrhythmias, and 10 had severe fluid retention with generalized edema. The degree of fluid retention had, in all cases, increased ventilation requirements and severely limited fluid intake. As a result, all had required at least one dose of 20% dextrose to correct hypoglycemia. One infant did not have renal failure but required dialysis to correct arrhythmias second-
Clinical and laboratory observations
similar to those previously reported? The 17-OHP levels in this study were lower than those previously described by Forest et al? The most likely explanation for this discrepancy is that our infants were healthy and asymptomatic, whereas those studied by Forest were initially suspected of having pituitary, gonadal, or adrenal dysfunction, but because of normal urinary 17-ketostei'oids no endocrinologic disease was diagnosed. Even if the infants studied by Forest had no adrenal disorder, they were not healthy, and acute illness or stress may elevate 17-OHP levels. Another possible explanation for our lower 17-OHP values is that none of our patients was of Jewish background. Laron et al. 7 reported an increased incidence of 21-hydroxylase deficiency in the Jewish population. A higher percentage of the infants studied by Forest may have been Jewish. The low basal morning cortisol levels were not unexpected; newborn infants typically have not yet developed a diurnal pattern. Our results confirm that a single basal morning cortisol level in a neonate is not useful as a means of diagnosing cortisol deficiency. We thank Darrel M. Mayes, M.D., and Endocrine Sciences for the determination of the adrenal steroid values; and Charlene Deuber, R.N., for help in obtaining the blood samples.
The Journal of Pediatrics January 1987
2.
3.
4.
5.
6.
7.
3-beta-hydroxysteroid dehydrogenase deficiency. N Engl J Med 1985;313:618. de Peretti E, Forrest MG. Pitfalls in the etiological diagnosis of congenital adrenal hyperplasia in the early neonatal period. Horm Res 1982;16:10. Forest MG, de Peretti E, Bertrand J. Developmental pattel"ns of the plasma levels of testosterone, A4-androstenedione, 17~-hydroxyprogesterone, dehydroepiandrosterone and its sulfate in normal infants and prepubertal children. In: James, VH, Serio M, Giusti G , Martini L, eds. The endocrine function of the human adrenal cortex. Orlando, Fla.: Academic Press, 1978:561-82. Rosier A, Leiberman E, Rosenmann A, Ben-Uzilio R, Weidenfeld J. Prenatal diagnosis of I 1-/~-hydroxylase deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab 1979;49:546. Holler W, Scholz S, Knorr D, Bidlingmaier F, Keller E, Albert E. Genetic differences between the salt-wasting, simple virilizing, and nonclassical types of congenital adrenal hyperplasia. J Clin Endocrinol Metab 1985;60:757. Honour JW, Anderson JM, Shackleton CHL. Difficulties in the diagnosis of congenital adrenal hyperplasia in early infancy: the 11-~-hydroxylase defect. Acta Endocrinol 1983; 103:101. Laron Z, Pollack MS, Zamir R, et al. Late onset 21hydroxylase deficiency and HLA in the Ashkenazi population: a new allele at the 21-hydroxylase locus. Human Immunol 1980;1:55.
REFERENCES
1. Cara JF, Moshang T, Bongiovanni AM, Marx BS. Elevated 17-hydroxyprogesterone and testosterone in a newborn with
Feasibility of prenatal diagnosis of nonketotic hyperglycinemia: Existence of the glycine cleavage system in placenta Kiyoshi Hayasaka, M.D., Keiya Tada, M.D., Noboru Fueki, M.D., Iku Takahashi, M.D., Akira Igarashi, M.D., Toshifumi T a k a b a y a s h , M.D., and Regula Baumgartner, M.D. From the Departments of Pediatrics, and Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan, and the Metabolic Unit, UniversityChildren's Hospital, Basel, Switzerland
Nonketotic hyperglycinemia is an autosomal recessive disorder of glycine metabolism characterized by markedly Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, and by grants from the Ministry of Public Welfare, Japan. Submitted for publication July 21, 1986; accepted Sept. 15, 1986. Reprints requests: Keiya Tada, M.D., Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai, 980 Japan.
elevated levels of glycine in body fluids. 1 The fundamental defect is in the main pathway of glycine catabolism, that is, the glycine cleavage system. 2,3 The enzyme system, which NKH
Nonketotic hyperglycinemia
[
is confined to the mitochondria, is composed of four protein components: P-protein (a pyridoxal phosphatedependent glycine decarboxylase), H-protein (a lipoic acid-containing protein), T-protein (a tetrahydrofolate-
Volume 110 Number 1
requiring enzyme), and L-protein (a lipoamide dehydrogenase). 4,5 The two clinical types of N K H are typical (neonatal) and atypical (late onset)i 1 Typical N K H is characterized by rapid development of neurologic symptoms, including lethargy, hypotonia, apnea, and seizures, in the neonatal period? The majority of patients died within a few weeks of life; the survivors have severe psychomotor retardation. Several therapeutic approaches have been attempted, including exchange transfusion, dietary restriction of glycine intake, and administration of agents such as methionine, sodium benzoate, leukovorin, pyridoxine, strychnine, and benzodiazepam.6,7 However, no effective treatment is known to alter the neurologic consequences. Therefore, there is a special need for prenatal diagnosis of NKH. It has been reported that the glycine/serine ratio in amniotic fluid at weeks 17 and 19 of gestation correctly predicted the presence of N K H in a fetus who was delivered at term and shown to have the disease) However, Wendt et al. 9 reported that there was overlapping of individual values in the glycine/serine ratio between amniotic fluid specimens from normal pregnancies and those from affected fetuses at weeks 38 tO 40 of gestation. Mesvage et al? ~showed that the glycine/serine ratio is not a reliable indicator for the prenatal diagnosis of NKH. We investigated the possibility of prenatal diagnosis by enzymatic analysis of the chorionic villi and of fetal tissues.
Clinical and laboratory observations
125
T a b l e I. Activities of glycine cleavage system in liver
and brain of fetus at risk for nonketotic hyperglycinemia and in control fetuses
Activity (~mol product/g protein/hr) Liver Fetus at risk for NKH Control fetus (12 wk) Control fetus (12 wk) Control fetus (16 wk) Control adults Brain Fetus at risk for NKH Control fetus (12 wk) Control fetus (12 wk) Control adults
1.7 28.6 27.4 22.3 3.9-5.2 0.2 3.2 2.7 0.7-1.2
The placenta at week 12 of gestation had about five times the activity of the cleavage system than that at term, whereas the placenta of the fetus at risk for N K H had significantly lower activity (Table II). There was no detectable activity of T-protein, but other components of the glycine cleavage system were not decreased. From these findings it was confirmed that the aborted fetus was a homozygote for NKH, with a defect in T-protein. DISCUSSION
METHODS The fourth pregnancy of a woman was monitored. The family has one healthy child (14 years of age) and an 11-year-old severely retarded daughter with NKH. Their first-born child died of N K H at the age of 3 weeks in 1970, after a typical clinical course.11 An abortion was performed in week 12 of gestation, according to the parents' desire. The glycerine/serine ratio of the amniotic fluid was found to be 4.9. This value seems not to be significantly higher than average (3.28) of the ratio for normal gestation between weeks 7 and 18, reported by Reid et al. ~2 Specimens of the fetal liver, brain, and placenta were immediately frozen at - 6 0 ~ C. Control specimens of fetal liver, brain, and placenta at week 12 of gestation were obtained from other legal abortions. The enzymatic analyses were performed according to methods reported previously? RESULTS The overall activity of the glycine cleavage system in the liver and brain of control fetuses was higher than that in the liver and brain of control adults, and the activity in both tissues of the fetus at risk for N K H was extremely low (Table I). These specimens were insufficient to allow analysis of the components of the glycine cleavage system.
Our study showed the existence of the glycine cleavage system in the placenta of fetuses at week 12 of gestation and at term. Our findings indicate that similar studies in chorionic villi should provide a reliable method for the prenatal diagnosis of N K H . About 30 to 50 mg wet weight chorionic villi may be needed for measurement Of the glycine cleavage system. However, the specimens must be subjected to analysis immediately after biopsy, or frozen immediately at - 8 0 ~ C until analysis, because the enzyme activity is labile in room temperature. REFERENCES
1. Nyhan WK. Nonketotic hyperglycinemia. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS, eds. The metabolic basis of inherited disease. New York: McGraw-Hill, 1983:561-9. 2. Tada K, Corbeel LM, Eeckels R, Eggermont E. A block in glycine cleavage reaction as a common mechanism in ketotic and nonketotic hyperglycinemia. Pediatr Res 1974;8:721. 3. Hayasaka K, Tada K, Kikuchi G, Winter S, Nyhan WL. Nonketotic hyperglycinemia: two patients with primary defects of P-protein and T-protein, respectivel3~-inthe glycine cleavage system. Pediatr Res 1983;17:967. 4. Kochi H, Kikuchi G. Mechanism of reversible glycine cleavage reaction in Arthrobacter globiformis: function of lipoic acid in the cleavage and synthesis of glycine. Arch Biochem Biophys 1976;173:71.
12 6
Clinical and laboratory observations
The Journal of Pediatrics January 1987
T a b l e II. Activities of glycine cleavage system and individual enzyme components in placenta of fetus at risk for nonketotic hyperglycinemia, control fetuses at week 12 of gestation, and full-term ~ormal babies
Activity (/~mol product/g protein/hr) Source of placenta
Glycine cleavage
P-protein
H-protein
T-protein
Llpoarnide dehydrogenase
Fetus at risk for NKH Control fetus (12 wk) Control fetus (12 wk) Control fetus (12 wk) Control infant (38 wk) Control infant (39 wk)
0.2 4.8 2.5 4.1 0.8 0.8
4.4 6.6 4.5 . . .
6.7 10.4 5.1
0 2.8 2.6
865.5 1582.4 734.5
5. Motokawa T, Kikuchi G. Glycine metabolism by rat liver mitochondria: reconstitution of the reversible glycine cleavage system with partially purified protein components. Arch Biochem Biophys 1974;164:624. 6. Gitzelmann R, Steimann B. Clinical and therapeutic aspects of non-ketotic hyperglycinemia. J Inher Metab Dis 1982; 5:113. 7. Matalon R, Naidu S, Hughes JR, Michals K. Nonketotie hyperglycinemia: treatment with diazepam, a competitor for glycine receptors. Pediatrics 1983;71:581. 8. Garcia-Castro J, Isales-Forsyth I, Levy H, et al. Prenatal diagnosis of nonketotic hyperglycinemia. N Engl J Med 1982;306:79.
. . .
. . .
. . .
9. Wendt LV, Simil/i S, Ruokonen A, Hartikainen-Sorri AL. Problems of prenatal diagnosis of nonketotie hyperglycinemia. J Inher Metab Dis 1983;6:112. 10. Mesvage C, Nanee CS, Flannery DB, Weiner DL, Suehy SF, Wolf B. Glycine/serine ratios in amniotic fluid: an unreliable indicator for the prenatal diagnosis of nonketotic hyperglycinemia. Clin Genet 1983;23:354. 11. Bachmann C, Mihatsch M J, Baumgartner R, et al. Nichtketotische hyperglyziniimie: perakuter Verlauf im Neugeborenenalter. Helv Paediatr Aeta 1971;26:228. 12. Reid DW, Gampbell D J, Yakymuyshyn LY. Quantitative amino acids in amniotic fluid and maternal plasma in early and late pregnancy. Am J Obstet Gynecol 1971;111:251.
Acute peritoneal dialysis in infants weighing <1500 g B. T. Steele, M.D., A. Vigneux, R.N., S. Blatz, R.N., M.Ed., M. Flavin, M.D., a n d B. Paes, M.D. From the Departments of Pediatrics and Nursing, McMaster University, Hamilton, Ontario, Canada
Acute renal failure is not uncommon in neonatal intensive care units. Some infants have a transient, mild impairment of renal function, whereas others have progressive anuric renal failure, sometimes accompanied by multiple organ failure. Apart from occasional case reports, 1-3there is little published information on dialysis techniques or results in very low birth weight neonates. W e describe the results of a simple dialysis procedure used in 13 infants weighing <1500 g.
Submitted for publication May 28, 1986; accepted Aug. 18, 1986. Reprint requests: B. T. Steele, M.D., Department of Pediatrics, McMaster University Medical Centre, 1200 Main St., W., Hamilton, Ontario, Canada L8N 3Z5.
METHODS Between July 1983 and July 1985, 13 infants weighing between 380 and 1400 g (mean 894 g) required acute peritoneal dialysis. In 12 infants dialysis was required for acute, anuric renal failure (Table). Severe hyaline membrane disease with persistent pulmonary hypertension, associated with hypotensive episodes, was the most common explanation for acute renal failure. Five infants had hyperkalemia associated with arrhythmias, and 10 had severe fluid retention with generalized edema. The degree of fluid retention had, in all cases, increased ventilation requirements and severely limited fluid intake. As a result, all had required at least one dose of 20% dextrose to correct hypoglycemia. One infant did not have renal failure but required dialysis to correct arrhythmias second-