|Protein-Energy Interactions (International Dietary Energy Consultative Group - IDECG, 1991, 437 pages)|
|Effects of protein-energy interactions on growth|
Protein intake is a major determinant of growth in early life under health and disease conditions. Adult patients with chronic renal insufficiency (CRI) may benefit from moderate protein restriction by a decrease in the rate of progression of renal insufficiency (BRENNER et al., 1982). Recent studies in adults suggest that protein intakes 30 to 50% below the RDA are associated with a significant amelioration in the rate of progression of CRI (ROSMAN, 1984). Studies in experimental animals support this contention, yet the few studies performed in growing animals indicate that severe protein restriction has an adverse impact on growth and does not convey additional benefits in slowing progression of CRI beyond those seen using moderate protein restriction.
Dietary protein intake in infants with CRI should serve to sustain normal growth and development, and at the same time preserve remaining renal function over the longest time possible. These two potentially conflicting objectives need consideration in defining an adequate protein intake for children with CRI (JUREIDINI et al., 1990). No specific protein intake recommendations are available for them. Most authors suggest that the existing RDAs for normal children be used, since they are considered safe (HELLERSTEIN, 1987). However, customary protein intakes of 'healthy' children after 6 months of life in the USA greatly exceed the existing national and international recommendations for protein intake.
We have recently completed a study to evaluate if a dietary protein intake given at levels recommended for 'healthy' children (P/E 5.6%) would sustain growth of children with chronic renal insufficiency, as compared to an intake close to that customarily consumed (P/E 10.4%) (UAUY et al., 1992). The primary outcome variable for growth evaluation was linear growth as measured by length-for-age and length gain velocity.
The initial 2 months prior to randomization (baseline period) were considered necessary for clinical stabilization and to standardize treatment including dietary management. All subjects received dietary protein corresponding to 8% of total energy. At 8 months of age, and for the next 10 months, the patients were randomized either to a low-dietary-protein group (P/E 5.6%) receiving an intake similar to that recommended by the USA NAS/NRC and international bodies (WHO/FAO/UNU), or to a control group (P/E 10.4%) receiving an intake close to that customary for American young children. These diets when consumed at 100 kcal/kg/d provided 1.4 and 2.6 g of protein per kg/d.
The calorie prescription for patients in the study was based on the RDA for normal infants of comparable length (RDA for length) rather than on actual weight of the subjects. The recommendation was that children consume 100-120% of the RDA for length. Protein intake of the study groups based on the formula composition and solid foods dropped from close to 2.0 to 1.4 g/kg/d in the low group and increased from 2.0 to 2.4 g/kg/d in the control diet group. The distribution around this mean indicates that during some months children in the low-protein group received as little as 1.0 or up to 1.8 g/kg/d. In the control group, the intakes ranged from 1.7 to 3.0 g/kg/d.
Mean energy intakes expressed per kg body weight oscillated around 100 kcal/kg/d, but expressed as % RDA for length the intakes were close to 90% of that considered ideal for 'healthy' children of equivalent length. Absolute weight, length, and head circumference increased significantly with time in both groups in a similar fashion. Mean weight gain after randomization to 18 months was 2.11 kg with the low-protein and 2.41 kg in the control-protein intake; the difference between diet groups was not significant. Length gain was 8.9 cm in the low-protein and 10.7 cm in the control group.
The repeated measure ANOVA indicated a significant time/diet interaction (p<0.083). The 1.8 cm difference in length gain between groups over the 10-months' diet intervention period was further explored using length gain velocity comparisons. The effects observed with absolute length were also evident in standardized length-for-age according to gender. The change in length SD score for age 8-18 months was -0.52 SD in the low and -0.04 SD in the control, for the 12-18 months' period the change was -0.06 in the low while it was +0.28 in the control diet group; this interaction of diet group and time was significant by repeated measure ANOVA. Length gain velocity over 6-months' periods was also expressed as SD score. The 0-6 months' data were analyzed based on the reported length at birth, while the 6-12 and 12-18 months' data were measured prospectively as part of the study (Figure 5). The interaction of diet, group and time was significant (p<0.04). Further analysis of this relationship was done using as covariates baseline weight, length, energy intake (expressed as kcal/kg/d and as % RDA for length) and change in length from birth. Baseline weight served to strengthen the effect of protein energy within this interaction model; the effect of diet group had a p < 0.036.
The remaining anthropometric measures showed time-related increases which were similar for both groups. The weight SD scores changed significantly over time for both, regardless of diet-protein level. For weight-for-length there was a significant decrease over time in both groups (p<0.016); the significance was given by the decrease observed from 6 to 8 months, that is, prior to being randomized to the dietary protein groups.
The results of this prospective randomized controlled trial of the effect of protein intake on growth and renal function of children with CRI clearly indicate that low protein energy diets within the range considered safe for 'healthy' children may in fact compromise linear growth of children with renal disease. This observation should be considered in light of the confounding effect of energy intake present in this study; namely, the difficulties in achieving the prescribed energy intakes may have determined a lower protein utilization than otherwise would be obtained if energy intake were sufficient.
As observed in this study, the compromise of linear growth in malnutrition is slow but pervasive. The end result is stunting. The problem relates not only to a few lost centimeters in length but, as suggested by multiple studies in malnourished children, poor linear growth due to lack of food or to chronic illness is subsequently associated with poorer intellectual function and lower capacity for physical work. The presently recommended intakes for normal children do not support catch-up growth of children with CRI. The results of this study lend further support to the use of length velocity SD score as a more sensitive indicator of growth failure and of potential nutritional inadequacies. The advantages of a low-protein diet for children with CRI are not clearly established, based on the available evidence. A moderately low dietary P/E ratio as demonstrated in this study may compromise linear growth without other evidence of protein deficiency.