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Comparison of two micronutrient supplements in children with chronic renal failure
Comparison of Two Micronutrient Supplements in Children With Chronic Renal Failure Janet E. Coleman, BSc, SRD,* Alan R. Watson, FRCP,† Shefali Chowdhury, BPharm (Hons), MRPharmS,‡ Deborah Thurlby, RSCN,† and Jean Wardell, PhD, MRCPath§ Objective: To compare a newly formulated renal-specific micronutrient (RSM) supplement (vitamins C, E, K, and B complex, copper, zinc) with Ketovite (Paines & Byrnes, Middlesex, UK) tablets (vitamins C, E, K, and B complex) in children with chronic renal failure (glomerular filtration rate [GFR] ⬍ 25 mL/min/1.73 m2) or on chronic peritoneal dialysis (CPD) and hemodialysis (HD). Design: Children currently prescribed Ketovite tablets were changed to RSM for 3 months. Questionnaires on palatability, acceptability, and ease of administration were assessed while on Ketovite and after 3 months on RSM along with plasma levels of zinc, copper, folate (serum, red cell), vitamin B12, and homocysteine. Setting: Regional pediatric nephrology unit. Patients: Fifteen children (10 male) with a mean age of 10.4 years (range, 1.1 to 16 y) were recruited (11 had GFR ⬍ 25 mL/min/1.73 m2, 2 CPD, 2 HD). Two children received overnight gastrostomy button feeding. Main Outcome Measures: Fourteen children (1 child refused RSM after 1 week) and their families completed questionnaires using a Likert scale: 1 (liked) to 7 (disliked). Plasma levels were analyzed at baseline on Ketovite and after 3 months on RSM. Results: Children disliked the smell of Ketovite compared with RSM (P ⫽ .004). The size of Ketovite was preferable to the size of the RSM (P ⫽ .015) and was believed to be easier to administer (P ⫽ .046). There were no differences in patient/parent rating of appearance, texture, or taste, but 8 of 15 patients (53%) expressed a preference for the RSM if available. Plasma values of copper, zinc, folate, and vitamin B12 were within the normal reference range on Ketovite and showed no significant change on RSM. Mean plasma homocysteine levels were above normal reference ranges in all groups (GFR ⬍ 25 mL/min/1.73 m2, 7.6 [SD, 3.1]; CPD, 11.5 [SD, 1.6]; HD, 12 [SD, 8.7]) on Ketovite and were unchanged after 3 months on RSM. Conclusions: This pilot study confirms the acceptability of the RSM, particularly in relation to its smell and chewability, but the current size may preclude its widespread use. The incorporation of zinc and copper will be beneficial for many children, but reduction in homocysteine levels may necessitate an increase in folic acid content. © 2002 by the National Kidney Foundation, Inc.
A
T PRESENT, THERE IS no approved micronutrient supplement specifically formulated for infants and children with chronic renal
*Department of Dietetics and Nutrition, Nottingham City Hospital NHS Trust, Nottingham, UK. †Children and Young People’s Kidney Unit, Nottingham City Hospital NHS Trust, Nottingham, UK. ‡Department of Pharmacy, Nottingham City Hospital NHS Trust, Nottingham, UK. §Department of Clinical Chemistry, Nottingham City Hospital NHS Trust, Nottingham, UK. Address reprint requests to Janet E. Coleman, BSc, SRD, Department of Dietetics and Nutrition, Nottingham City Hospital NHS Trust, Hucknall Rd, Nottingham, NG5 1PB, UK. © 2002 by the National Kidney Foundation, Inc. 1051-2276/02/1204-0006$35.00/0 doi:10.1053/jren.2002.35317
244
failure (CRF) that is palatable and of a size and format suitable for various methods of administration. Neither is there an approved composition or policy for its prescription.1 Before dialysis, estimated requirements should be based on amounts sufficient to meet the requirements of reference nutrient intakes (RNI) for healthy children in the United Kingdom,2 after individual dietary assessment.3 On chronic dialysis, requirements are less clear, with prescribing practices being based mostly on adult study recommendations that allow for the potential dialysate losses of particular vitamins, and this may be inappropriate for pediatric practice. Micronutrient requirements vary in infants and children of different ages, and the micronutrient intakes obtained from Journal of Renal Nutrition, Vol 12, No 4 (October), 2002: pp 244-247
COMPARISON OF TWO MICRONUTRIENT SUPPLEMENTS IN CHILDREN
infant formulas and from prescribed nutritionally complete supplements must be included.4 Previous pediatric studies have shown that the combination of dietary and supplemented micronutrient intakes have been associated with blood concentrations that meet or exceed normal values.5-7 Recent pediatric nutrition guidelines in the United States recommend that 100% of dietary reference intakes should be achieved for vitamins B1, B2, B6, B12, and folic acid and the recommended dietary allowance for vitamins A, C, E, and K, copper, and zinc.8 A questionnaire survey on the micronutrient supplements and regimens prescribed in pediatric renal units in the United Kingdom and Ireland resulted in a consensus on the development of a suitable micronutrient supplement specifically for infants and children with CRF. This was subsequently produced by Vitaline Pharmaceuticals UK, Ltd, and Vitaline Corporation, USA (Wilsonville, OR), and referred to as the renal-specific micronutrient supplement (RSM).9 A prospective study was then undertaken to compare the palatability, ease of administration, and subsequent plasma levels of micronutrients of the proposed RSM with the currently prescribed vitamin preparation, Ketovite tablets (Paines & Byrnes, Middlesex, UK).
Methods After Research Ethics Committee approval and informed consent, we recruited 15 patients (10 male) who were younger than 18 years and who had been on Ketovite tablets for a minimum of 3 months. The study included 11 patients predialysis with a glomerular filtration rate (GFR) ⬍ 25 mL/min/1.73 m2, 2 on chronic peritoneal (CPD) and 2 on hemodialysis (HD). Patients who had had peritonitis episodes within 1 month were excluded. At baseline, a questionnaire was administered to the patients on Ketovite and their families by a research nurse to assess their opinions about the medication with respect to appearance, smell, texture, ease of administration, taste, size, and acceptability. A Likert scale was used, ranging from 1 (liked) to 7 (disliked). Fasting blood samples were obtained for standard renal function tests, plasma and red cell folate, vitamin B12, zinc, copper, and homocysteine levels. Homocysteine was measured by
245
Table 1. Composition of Ketovite and the RSM
Vitamin B1 (mg) Vitamin B2 (mg) Vitamin B3 (mg) Vitamin B5 (mg) Vitamin B6 (mg) Folate (g) Vitamin B12 (g) Biotin (g) Vitamin C (mg) Vitamin E (mg) Vitamin K (g) Copper (mg) Zinc (mg) Prescription (tablets/d)
Ketovite Tablets (per tablet)
RSM (per tablet)
1 1 3.3 0.4 0.3 250 – 170 17 5
0.4 0.5 6 3 1 200 0.5 10 20 3 10
500 (di-alphatocopherol) – – 1-3
0.4 4 1 (⬍ 5y, proposed) 2 (⬎ 5y, proposed)
high-performance liquid chromatography with fluorescence detection with a mean respective value in healthy children of 6.5 ⫾ 1.2 mol/L. Ketovite was prescribed as 1 to 3 tablets daily as based on individual dietary assessment. The new RSM supplement was then prescribed as 1 tablet for children younger than 5 years and 2 tablets for children older than 5 years. The composition of Ketovite and RSM are shown in Table 1. After a further 3 months, the families were asked to complete the same acceptability questionnaire and fasting blood samples were repeated.
Statistics Analysis of the questionnaire on patient acceptability and palatability of the preparations was by Wilcoxon signed rank sum test.
Results Of the 15 children recruited, 14 completed the study. One child refused to take the RSM after 1 week because of its taste. Eleven children were predialysis, 2 on CPD, and 2 on HD. The mean age was 10.4 years (range, 1.1 to 16 y). The mean intake of folic acid, exclusive of diet, was 433 g (SD, 114) on Ketovite and 373 g (SD, 70) on RSM. Copper and zinc intakes provided by the RSM were 0.75 mg (SD, 0.14) and 7.5 mg (SD, 1.4), respectively. Mean plasma values on Ketovite and the RSM
246
COLEMAN ET AL
Table 2. Mean and SD Serum Values Over Study Period While on Ketovite (Baseline) and the RSM (End) Baseline
End
Table 3. Mean and SD Serum Homocysteine Values Over Study Period While on Ketovite (Baseline) and the RSM (End)
Reference Range
15.6 (4.3) 16.9 (3.4) 13-24 Copper mol/L Zinc mol/L 15.6 (2.6) 17.0 (3.4) 11-20 Serum folate g/L 28.8 (12) 24 (9.5) 2.6-14 Red cell folate g/L 1,435 (526) 1,336 (427) 130-600 Vitamin B12 ng/L 554 (385) 578 (332) 300-1,100
for copper, zinc, folate, red cell folate, and vitamin B12 are shown in Table 2. Mean plasma homocysteine values over the study period while on Ketovite and RSM are shown in Table 3. The results of the questionnaire comparing patient responses to each supplement are shown in Table 4 and were expressed as a median score. Eight of the 15 patients (53%) said they would like to change to the RSM if it were made available.
Discussion Our study would suggest that children preferred the smell of the new RSM compared with Ketovite tablets, and although the taste of the RSM was generally said to be better than that of Ketovite, this was not statistically significant. Ketovite tablets, because of their smaller size, are generally swallowed by children and crushed if added to tube feeds. The RSM was chewed by most children, with some being reluctant to swallow it because of its larger size, and it was also more difficult to crush. Overall, the palatability score was no different between Ketovite and RSM, but 53% of families were in favor of
No. of Patients
Baseline
End
10 2 2
7.6 (3.1) 11.46 (1.6) 12 (8.7)
7.8 (3.5) 10.1 (1.4) 13.52 (8.8)
Predialysis CCPD HD
NOTE. Reference range for healthy children ⫽ 6.5 ⫾ 1.2 mol/L.12 Abbreviation: CCPD, continuous cycling peritoneal dialysis.
changing to the new RSM, especially if its size were reduced. Both zinc and copper levels were within the normal reference range on Ketovite tablets despite no supplementation, and no significant difference was seen after supplementation on the RSM. We have previously reported similar findings to show that although dietary zinc and copper intakes in children on chronic dialysis are below recommended intakes, plasma zinc and copper levels were normal.5 It is well recognized that plasma levels are known to poorly reflect zinc and copper stores. We believe, however, that we should at least be aiming to achieve the recommended nutrient intake/dietary allowance in concurrence with recently published guidelines.8 Plasma vitamin B12 levels were within the normal reference range on Ketovite tablets, despite no supplementation, and remained essentially unchanged on the RSM. Plasma and red cell folate levels were well above the normal reference range on both Ketovite and the RSM, which we and others have previously reported in children receiving folate supplementation.5-7 The
Table 4. Results of Questionnaire (15 Patients)
Appearance Smell Texture Taste Size Ease of administration Acceptability Administration (no. of patients) Swallowed whole Chewed Crushed, swallowed Crushed, administered via gastrostomy button NOTE. Scale: 1 (liked) to 7 (disliked)
Ketovite Tablets Median Score (Range)
RSM Median Score (Range)
P Value
4 (1-7) 7 (2-7) 4 (1-7) 7 (1-7) 3 (1-7) 1 (1-7) 4 (1-7)
3 (1-7) 2 (1-7) 3 (1-7) 3 (1-7) 5 (3-7) 3 (1-7) 3 (1-7)
.4 .004 .06 .06 .015 .046 .9
12 2 – 1
3 10 1 1
COMPARISON OF TWO MICRONUTRIENT SUPPLEMENTS IN CHILDREN
increasing focus on hyperhomocysteinemia and its relation to cardiovascular risk led us to measure baseline plasma folate concentrations in our patient group.10,11 The RSM was formulated before recent studies suggesting that increased folate intakes12 may reduce elevated homocysteine levels, and therefore it did not contain an additionally high folate content. However, all patients had been receiving folic acid supplementation from their prescribed Ketovite tablets, and hence their mean supplementary intakes were greater at the start of the study. This may explain high plasma folate levels when we began the study. Vitamins B6 and B12 also play an important role as cofactors/substrates in metabolism of methionine/homocysteine, and any depletion may be related to hyperhomocysteinemia.13 Vitamins B6 and B12 are contained in the new RSM. Homocysteine levels were elevated above normal age-related reference ranges in 10 of 15 patients on Ketovite tablets, particularly in those children on dialysis, and remained elevated in 8 of 15 patients while on the RSM. One other study of pediatric patients on chronic dialysis reported even higher homocysteine levels (median, 20 mol/L; range, 13.7 to 26) in children who had not received any folate supplementation, with a reduction after 4 weeks of treatment with 2.5 mg of folic acid to a median of 12 mol/L (range, 9.8 to 14.3).12 We conclude that the RSM is a safe and useful addition to the micronutrient preparations currently available, and the incorporation of zinc and copper will be beneficial for many children. Adjustments to its size and shape might result in greater acceptability, ease of prescription, and possibly improvement in compliance. Further study is required to determine the optimum folate
247
concentration needed to reduce homocysteine levels significantly in children with CRF.
References 1. Coleman J: Micronutrient supplements for children. Br J Renal Med 3:21-23, 1998 2. Department of Health: Dietary Reference Values for Food, Energy and Nutrients for the United Kingdom. Department of Health Report on Health and Social Subjects. No. 41. London, HMSO, 1991 3. Coleman JE: The kidney, in Shaw V, Lawson M (eds): Clinical Paediatric Dietetics, ed 2. Boston, Blackwell Science, 2001, pp 158-182 4. Coleman JE, Watson AR: Vitamin, mineral and trace element supplementation of children on chronic peritoneal dialysis. J Hum Nutr Diet 4:13-17, 1991 5. Coleman JE, Watson AR: Micronutrient supplementation in children on continuous cycling peritoneal dialysis, in Khanna R, Nolph KD, Twardowski ZJ (eds): Advances in Peritoneal Dialysis. Toronto, Canada, University of Toronto Press, 1992, pp 396-401 6. Kriley M, Warady BA: Vitamin status of pediatric patients receiving long-term peritoneal dialysis. Am J Clin Nutr 53:14761479, 1991 7. Warady BA, Kriley M, Alon U, et al: Vitamin status in infants receiving long-term peritoneal dialysis. Pediatr Nephrol 8:354-356, 1994 8. K/DOQI Clinical practice guidelines for nutrition in chronic renal failure. Pediatric guidelines. Am J Kidney Dis 35(suppl 2):S105-S136, 2000 9. Coleman JE, Fyfe A, Watson AR: Micronutrient supplements for chronic renal failure: a survey of paediatric practice. J Renal Nutr 5:46-51, 1995 10. Makoff R, Dwyer J, Rocco M: Folic acid, pyridoxine, cobalamin and homocysteine and their relationship to cardiovascular disease in end stage renal disease. J Renal Nutr 6:2-11, 1996 11. Bostom AG, Culleton BF: Hyperhomocysteinaemia in chronic renal disease. J Am Soc Nephrol 10:891-900, 1999 12. Schroder CH, de Booer AW, Giesen AM, et al: Treatment of hyperhomocysteinemia in children on dialysis by folic acid. Pediatr Nephrol 13:583-585, 1999 13. Leblanc M, Pichette V, Geadah D, et al: Folic acid and pyridoxal-5⬘-phosphate losses during high efficiency hemodialysis in patients without hydrosoluble vitamin supplementation. J Renal Nutr 10:196-201, 2000
A
T PRESENT, THERE IS no approved micronutrient supplement specifically formulated for infants and children with chronic renal
*Department of Dietetics and Nutrition, Nottingham City Hospital NHS Trust, Nottingham, UK. †Children and Young People’s Kidney Unit, Nottingham City Hospital NHS Trust, Nottingham, UK. ‡Department of Pharmacy, Nottingham City Hospital NHS Trust, Nottingham, UK. §Department of Clinical Chemistry, Nottingham City Hospital NHS Trust, Nottingham, UK. Address reprint requests to Janet E. Coleman, BSc, SRD, Department of Dietetics and Nutrition, Nottingham City Hospital NHS Trust, Hucknall Rd, Nottingham, NG5 1PB, UK. © 2002 by the National Kidney Foundation, Inc. 1051-2276/02/1204-0006$35.00/0 doi:10.1053/jren.2002.35317
244
failure (CRF) that is palatable and of a size and format suitable for various methods of administration. Neither is there an approved composition or policy for its prescription.1 Before dialysis, estimated requirements should be based on amounts sufficient to meet the requirements of reference nutrient intakes (RNI) for healthy children in the United Kingdom,2 after individual dietary assessment.3 On chronic dialysis, requirements are less clear, with prescribing practices being based mostly on adult study recommendations that allow for the potential dialysate losses of particular vitamins, and this may be inappropriate for pediatric practice. Micronutrient requirements vary in infants and children of different ages, and the micronutrient intakes obtained from Journal of Renal Nutrition, Vol 12, No 4 (October), 2002: pp 244-247
COMPARISON OF TWO MICRONUTRIENT SUPPLEMENTS IN CHILDREN
infant formulas and from prescribed nutritionally complete supplements must be included.4 Previous pediatric studies have shown that the combination of dietary and supplemented micronutrient intakes have been associated with blood concentrations that meet or exceed normal values.5-7 Recent pediatric nutrition guidelines in the United States recommend that 100% of dietary reference intakes should be achieved for vitamins B1, B2, B6, B12, and folic acid and the recommended dietary allowance for vitamins A, C, E, and K, copper, and zinc.8 A questionnaire survey on the micronutrient supplements and regimens prescribed in pediatric renal units in the United Kingdom and Ireland resulted in a consensus on the development of a suitable micronutrient supplement specifically for infants and children with CRF. This was subsequently produced by Vitaline Pharmaceuticals UK, Ltd, and Vitaline Corporation, USA (Wilsonville, OR), and referred to as the renal-specific micronutrient supplement (RSM).9 A prospective study was then undertaken to compare the palatability, ease of administration, and subsequent plasma levels of micronutrients of the proposed RSM with the currently prescribed vitamin preparation, Ketovite tablets (Paines & Byrnes, Middlesex, UK).
Methods After Research Ethics Committee approval and informed consent, we recruited 15 patients (10 male) who were younger than 18 years and who had been on Ketovite tablets for a minimum of 3 months. The study included 11 patients predialysis with a glomerular filtration rate (GFR) ⬍ 25 mL/min/1.73 m2, 2 on chronic peritoneal (CPD) and 2 on hemodialysis (HD). Patients who had had peritonitis episodes within 1 month were excluded. At baseline, a questionnaire was administered to the patients on Ketovite and their families by a research nurse to assess their opinions about the medication with respect to appearance, smell, texture, ease of administration, taste, size, and acceptability. A Likert scale was used, ranging from 1 (liked) to 7 (disliked). Fasting blood samples were obtained for standard renal function tests, plasma and red cell folate, vitamin B12, zinc, copper, and homocysteine levels. Homocysteine was measured by
245
Table 1. Composition of Ketovite and the RSM
Vitamin B1 (mg) Vitamin B2 (mg) Vitamin B3 (mg) Vitamin B5 (mg) Vitamin B6 (mg) Folate (g) Vitamin B12 (g) Biotin (g) Vitamin C (mg) Vitamin E (mg) Vitamin K (g) Copper (mg) Zinc (mg) Prescription (tablets/d)
Ketovite Tablets (per tablet)
RSM (per tablet)
1 1 3.3 0.4 0.3 250 – 170 17 5
0.4 0.5 6 3 1 200 0.5 10 20 3 10
500 (di-alphatocopherol) – – 1-3
0.4 4 1 (⬍ 5y, proposed) 2 (⬎ 5y, proposed)
high-performance liquid chromatography with fluorescence detection with a mean respective value in healthy children of 6.5 ⫾ 1.2 mol/L. Ketovite was prescribed as 1 to 3 tablets daily as based on individual dietary assessment. The new RSM supplement was then prescribed as 1 tablet for children younger than 5 years and 2 tablets for children older than 5 years. The composition of Ketovite and RSM are shown in Table 1. After a further 3 months, the families were asked to complete the same acceptability questionnaire and fasting blood samples were repeated.
Statistics Analysis of the questionnaire on patient acceptability and palatability of the preparations was by Wilcoxon signed rank sum test.
Results Of the 15 children recruited, 14 completed the study. One child refused to take the RSM after 1 week because of its taste. Eleven children were predialysis, 2 on CPD, and 2 on HD. The mean age was 10.4 years (range, 1.1 to 16 y). The mean intake of folic acid, exclusive of diet, was 433 g (SD, 114) on Ketovite and 373 g (SD, 70) on RSM. Copper and zinc intakes provided by the RSM were 0.75 mg (SD, 0.14) and 7.5 mg (SD, 1.4), respectively. Mean plasma values on Ketovite and the RSM
246
COLEMAN ET AL
Table 2. Mean and SD Serum Values Over Study Period While on Ketovite (Baseline) and the RSM (End) Baseline
End
Table 3. Mean and SD Serum Homocysteine Values Over Study Period While on Ketovite (Baseline) and the RSM (End)
Reference Range
15.6 (4.3) 16.9 (3.4) 13-24 Copper mol/L Zinc mol/L 15.6 (2.6) 17.0 (3.4) 11-20 Serum folate g/L 28.8 (12) 24 (9.5) 2.6-14 Red cell folate g/L 1,435 (526) 1,336 (427) 130-600 Vitamin B12 ng/L 554 (385) 578 (332) 300-1,100
for copper, zinc, folate, red cell folate, and vitamin B12 are shown in Table 2. Mean plasma homocysteine values over the study period while on Ketovite and RSM are shown in Table 3. The results of the questionnaire comparing patient responses to each supplement are shown in Table 4 and were expressed as a median score. Eight of the 15 patients (53%) said they would like to change to the RSM if it were made available.
Discussion Our study would suggest that children preferred the smell of the new RSM compared with Ketovite tablets, and although the taste of the RSM was generally said to be better than that of Ketovite, this was not statistically significant. Ketovite tablets, because of their smaller size, are generally swallowed by children and crushed if added to tube feeds. The RSM was chewed by most children, with some being reluctant to swallow it because of its larger size, and it was also more difficult to crush. Overall, the palatability score was no different between Ketovite and RSM, but 53% of families were in favor of
No. of Patients
Baseline
End
10 2 2
7.6 (3.1) 11.46 (1.6) 12 (8.7)
7.8 (3.5) 10.1 (1.4) 13.52 (8.8)
Predialysis CCPD HD
NOTE. Reference range for healthy children ⫽ 6.5 ⫾ 1.2 mol/L.12 Abbreviation: CCPD, continuous cycling peritoneal dialysis.
changing to the new RSM, especially if its size were reduced. Both zinc and copper levels were within the normal reference range on Ketovite tablets despite no supplementation, and no significant difference was seen after supplementation on the RSM. We have previously reported similar findings to show that although dietary zinc and copper intakes in children on chronic dialysis are below recommended intakes, plasma zinc and copper levels were normal.5 It is well recognized that plasma levels are known to poorly reflect zinc and copper stores. We believe, however, that we should at least be aiming to achieve the recommended nutrient intake/dietary allowance in concurrence with recently published guidelines.8 Plasma vitamin B12 levels were within the normal reference range on Ketovite tablets, despite no supplementation, and remained essentially unchanged on the RSM. Plasma and red cell folate levels were well above the normal reference range on both Ketovite and the RSM, which we and others have previously reported in children receiving folate supplementation.5-7 The
Table 4. Results of Questionnaire (15 Patients)
Appearance Smell Texture Taste Size Ease of administration Acceptability Administration (no. of patients) Swallowed whole Chewed Crushed, swallowed Crushed, administered via gastrostomy button NOTE. Scale: 1 (liked) to 7 (disliked)
Ketovite Tablets Median Score (Range)
RSM Median Score (Range)
P Value
4 (1-7) 7 (2-7) 4 (1-7) 7 (1-7) 3 (1-7) 1 (1-7) 4 (1-7)
3 (1-7) 2 (1-7) 3 (1-7) 3 (1-7) 5 (3-7) 3 (1-7) 3 (1-7)
.4 .004 .06 .06 .015 .046 .9
12 2 – 1
3 10 1 1
COMPARISON OF TWO MICRONUTRIENT SUPPLEMENTS IN CHILDREN
increasing focus on hyperhomocysteinemia and its relation to cardiovascular risk led us to measure baseline plasma folate concentrations in our patient group.10,11 The RSM was formulated before recent studies suggesting that increased folate intakes12 may reduce elevated homocysteine levels, and therefore it did not contain an additionally high folate content. However, all patients had been receiving folic acid supplementation from their prescribed Ketovite tablets, and hence their mean supplementary intakes were greater at the start of the study. This may explain high plasma folate levels when we began the study. Vitamins B6 and B12 also play an important role as cofactors/substrates in metabolism of methionine/homocysteine, and any depletion may be related to hyperhomocysteinemia.13 Vitamins B6 and B12 are contained in the new RSM. Homocysteine levels were elevated above normal age-related reference ranges in 10 of 15 patients on Ketovite tablets, particularly in those children on dialysis, and remained elevated in 8 of 15 patients while on the RSM. One other study of pediatric patients on chronic dialysis reported even higher homocysteine levels (median, 20 mol/L; range, 13.7 to 26) in children who had not received any folate supplementation, with a reduction after 4 weeks of treatment with 2.5 mg of folic acid to a median of 12 mol/L (range, 9.8 to 14.3).12 We conclude that the RSM is a safe and useful addition to the micronutrient preparations currently available, and the incorporation of zinc and copper will be beneficial for many children. Adjustments to its size and shape might result in greater acceptability, ease of prescription, and possibly improvement in compliance. Further study is required to determine the optimum folate
247
concentration needed to reduce homocysteine levels significantly in children with CRF.
References 1. Coleman J: Micronutrient supplements for children. Br J Renal Med 3:21-23, 1998 2. Department of Health: Dietary Reference Values for Food, Energy and Nutrients for the United Kingdom. Department of Health Report on Health and Social Subjects. No. 41. London, HMSO, 1991 3. Coleman JE: The kidney, in Shaw V, Lawson M (eds): Clinical Paediatric Dietetics, ed 2. Boston, Blackwell Science, 2001, pp 158-182 4. Coleman JE, Watson AR: Vitamin, mineral and trace element supplementation of children on chronic peritoneal dialysis. J Hum Nutr Diet 4:13-17, 1991 5. Coleman JE, Watson AR: Micronutrient supplementation in children on continuous cycling peritoneal dialysis, in Khanna R, Nolph KD, Twardowski ZJ (eds): Advances in Peritoneal Dialysis. Toronto, Canada, University of Toronto Press, 1992, pp 396-401 6. Kriley M, Warady BA: Vitamin status of pediatric patients receiving long-term peritoneal dialysis. Am J Clin Nutr 53:14761479, 1991 7. Warady BA, Kriley M, Alon U, et al: Vitamin status in infants receiving long-term peritoneal dialysis. Pediatr Nephrol 8:354-356, 1994 8. K/DOQI Clinical practice guidelines for nutrition in chronic renal failure. Pediatric guidelines. Am J Kidney Dis 35(suppl 2):S105-S136, 2000 9. Coleman JE, Fyfe A, Watson AR: Micronutrient supplements for chronic renal failure: a survey of paediatric practice. J Renal Nutr 5:46-51, 1995 10. Makoff R, Dwyer J, Rocco M: Folic acid, pyridoxine, cobalamin and homocysteine and their relationship to cardiovascular disease in end stage renal disease. J Renal Nutr 6:2-11, 1996 11. Bostom AG, Culleton BF: Hyperhomocysteinaemia in chronic renal disease. J Am Soc Nephrol 10:891-900, 1999 12. Schroder CH, de Booer AW, Giesen AM, et al: Treatment of hyperhomocysteinemia in children on dialysis by folic acid. Pediatr Nephrol 13:583-585, 1999 13. Leblanc M, Pichette V, Geadah D, et al: Folic acid and pyridoxal-5⬘-phosphate losses during high efficiency hemodialysis in patients without hydrosoluble vitamin supplementation. J Renal Nutr 10:196-201, 2000