Kidney size in Children of Post-Weaning age: Does Nutrition have an Effect?

significantly


Introduction
Malnutrition is one of the most prevalent health issues, involving hundreds of millions of children all over the world, and particularly in the developing countries. 1 Growth retardation following malnutrition generally affects children of post-weaning age, usually as a result of dietary deficiency of protein or calorie or both. 2 Renal growth is thought to run in parallel to somatic growth, but this is overly simplistic and currently unsubstantiated. But, one of the most important factors identified to be responsible in the growth of the kidneys is the nutritional status of the child. 3 Kidney size is an important parameter used in the evaluation of renal growth in children, and ultrasonography (USG) has evolved as a non-invasive, reliable and relatively inexpensive method for the assessment of renal size. 1 Though kidney size is mostly Copyrights & Licensing © 2022 by author(s). This is an Open Access article distributed under Creative Commons Attribution License (CC BY NC )

Original Article
Effect of nutrition on kidney size described by its length, due to the inherent variability in shape among different individuals, three-dimensional measurements, i.e. total volume of renal tissue, may be a more precise description of kidney size. 4 Previously, studies have been done to compare kidney sizes in low birth weight children 4 and in children with neuropathic bladder due to meningomyelocoele 5 with that of the normal controls. Kidney growth was also evaluated in formula-fed versus breast-fed healthy infants 6 and in healthy 10 year old children, lean body mass was found to be the strongest predictor of renal volume. 7 The effect of malnutrition in diminishing kidney size in children has been shown in a study from Turkey. 1 However, kidney sizes have not been studied sufficiently in Indian children with malnutrition. The present study is therefore intended to measure and compare kidney sizes of children with malnutrition between six months to five years with those of healthy controls of the same age.

Methods
This hospital-based descriptive observational study with a comparison group was carried out in the Department of Paediatric Medicine in a tertiary care hospital, Kolkata, India between June 2016 to May 2017. After getting Institutional Ethical approval and informed consent from the parents, 50 malnourished children and 50 healthy children (Controls) within the age group of six months to five years, attending the OPD or admitted in the hospital were included. Malnourished children were selected randomly when found to be suitable for inclusion. Children in control group were selected after age-matching with the cases. Children having weight for age less than or = 80% of the expected were included in the malnourished group, whereas those with < 80% of the expected weight for age were included in the control group. Malnourished children were further subdivided into Grade I (Weight for age 71 -80% of expected), Grade II (Weight for age 61 -70% of expected), Grade III (Weight for age 51 -60% of expected) and Grade IV (Weight for age < 50% of expected) malnutrition according to the IAP classification of malnutrition. 8 Children, who were born either premature (< 37 wks) or postmature (< 42 wks) and / or small for gestational age (SGA) or large for gestational age (LGA) were excluded from the study. Also the children having congenital anomalies and disorders of the kidney and urinary tract, chronic diseases as tuberculosis, AIDS etc. were excluded.
Proper history and anthropometric measurements were recorded for all the children included in the study as per the pre-designed proforma. Weight was measured by a standard weighing machine, and height (upright; < 2 years) or length (recumbent; < 2 years) by stadiometer or infantometer respectively. BMI was used as a measure of weight for height and was calculated by the formula BMI (Kg / m 2 ) = Weight ( [MAC] was measured in the left arm with the help of a standard measuring tape, at the mid-point between tip of acromion & tip of olecranon. Body fatness was estimated by measuring triceps skinfold thickness using a skinfold caliper at the same point as MAC. 10 All children were subjected to ultrasound examination to determine their kidney sizes. If any congenital or anatomical abnormalities were found during USG examination, they were excluded. All the measurements were taken by the same radiologist (Dr. SD) at the same device (L & T Medical, NEC -Accusync 500), using the 2-5 MHz probe for the older children and 5 -14 MHz probe for the younger ones. The kidneys were identified in the sagittal plane along their longitudinal axis. Measurements of the largest length, width and depth at the hilar level were taken. 11 Kidney volume was calculated in cm 3  All the data were collected, compiled and subjected to statistical analysis with the help of SPSS software (Version 17.0; IBM). Microsoft Word and Excel 2007 were used to generate the tables, graphs etc. Results were expressed as mean ± standard deviation for continuous variables and as number (%) for categorical data. Differences between children of the malnourished group and control group were tested with Chi square test (Categorical variables) and Student's t test (Continuous variables). One way ANOVA test with Post Hoc Analysis was used to study the differences in kidney parameters between different grades of malnutrition. Differences between boys and girls and various parameters of left and right kidney were also determined by Student's t test. Pearson's correlation co-efficient was used to determine correlations between different anthropometric and renal variables. Multiple linear regression analysis was performed, when several parameters correlated with a single dependent variable. Significance was assessed at the level of 0.05 (5%).

Results
Among the 100 children included in the study, the mean age of the malnourished group was 27.56 ± 17.49 months and of the control group was 28.06 ± 16.91 months. Both the groups of children matched according to their age, sex distribution and socioeconomic status (p value < 0.05) [ Table 1]. But, mean PCI (Per capita income) of the control group (1402.54 ± 923.07) was significantly greater than the malnourished group (920.70 ± 569.29) with a p value of 0.002 (t = -3.142, df = 98).
Malnourished children had significantly lower weight, mid arm circumference (MAC), skinfold thickness (SFT), body mass index (BMI) and body surface area (BSA) [p < 0.001], but did not differ significantly with regard to their height / length (p value = 0.074), though mean height was more in children of the control group (85.38 ± 13.66 cm vs 80.36 ± 14.15 cm in malnourished group) [ Table 1].

Original Article
Effect of nutrition on kidney size  The length, width, depth and volume of both left and right kidneys were significantly lower in the malnourished children than that of their healthy counterparts (p < 0.001). RRV was found to be significantly higher in the malnourished group (6.11 ± 1.96 cm 3 / kg vs 5.40 ± 1.11 cm 3 / kg in control group; p value 0.030) [ Table 2].
The majority of the malnourished children in this study were having grade II malnutrition (34%), followed by grade I (28%), grade III (20%) and grade IV (18%) malnutrition. Both right and left kidney lengths decreased significantly with increase in the severity of malnutrition (p value 0.007). But, the same significance has not been found with kidney width, thickness or volume. The change in RRV was also not significant with increasing severity of malnutrition [ Table 3].

Original Article
Effect of nutrition on kidney size There were no significant differences in the kidney sizes between male and female children in either of the groups [Data not shown]. Significant difference had also not been found between the kidney parameters of right and left side in any of the 2 groups. However, mean values of length, width, thickness and volume were more with the left kidney compared to the right one [Data not shown].
Right and left kidney volumes were best correlated with the height of the child (p value < 0.001), followed by their weight and age (p < 0.001) in both the groups [Data not shown]. In the combined group (N = 100), all the anthropometric parameters (i.e. age, weight, height, MAC and SFT) were found to have significant correlation with all the renal parameters. Strongest positive correlation was between RRV and height, followed by renal volumes and weight and renal volumes and age (p < 0.001). RRV was found to have significant negative correlation with MAC (p value 0.016) and SFT (p value 0.003). Skinfold thickness was least correlated with kidney parameters among all others [ Table  4]. But, multiple regression analysis showed that only height and weight significantly affected the kidney lengths and volumes in the combined group (p value < 0.05) [ Table 5].

Original Article
Effect of nutrition on kidney size

Discussion
In the present study, mean PCI of the control group was significantly greater than the malnourished group, which reinforces the effect of economic deprivation as a strong etiologic factor behind the increased prevalence of malnutrition in the developing countries. The malnourished children had significantly lower weight, MAC, SFT, BMI and BSA. But, children of the two groups did not differ significantly with regard to their height / length, though mean height was more in the control group. Insignificant height difference may be due to the fact that we excluded children with chronic diseases and also those born SGA, factors which could affect height significantly. The length, width, depth and volume of both left and right kidneys in the malnourished children were significantly lower than that of the healthy controls (p < 0.001).

Original Article
Effect of nutrition on kidney size The primary cause for the decreased kidney size in malnourished children is the decreased protein intake which hampers the normal growth and development of the renal tubular cells, particularly of the proximal tubules. Malnutrition produces certain changes such as decreased multiplication of cells and decreased cell size (Mostly due to the depletion in the enzyme granules and cellular organelles). 13 It has been established that though the nephron formation is complete by birth, the glomeruli and renal tubular cells continue to grow in the post natal period and if there is inadequate dietary intake, and particularly protein, it decreases the cell size and contributes to the overall decrease in size of the kidneys.
In contrast to all other measurements, the malnourished children had significantly higher RRV than healthy controls. This may be explained partially by increased solute load due to the catabolic state in malnourished children and their relatively high lean body mass as a percentage of total body weight. 7 Body composition in the form of lean body mass has a significant impact on kidney size with leaner child has greater kidney volume. 7 In support with this suggestion, a comparison between kidney weight in lean and obese adults showed decreased relative kidney weight in the obese individuals. 14 The more the degree of malnutrition, the effect on kidney is more pronounced. This statement is well supported in this study, where both right and left kidney lengths have been shown to decrease significantly with increase in the severity of malnutrition. But, the same significance has not been found with kidney width, thickness or volume. In some instances, there was even an increase in the mean value of kidney parameters with increasing grade of malnutrition, probably because of the differences in age distribution among the children with different grades of malnutrition. In the present study, no significant difference was found in the kidney sizes of male and female children in either of the groups. There are differences in opinion regarding the effect of gender on kidney size. Some reports showed larger kidneys in boys than girls, 15,16 while others found no gender differences. [17][18][19][20] Mean values of left kidney parameters were found to be higher than that of the right one in both the groups, but the difference was not statistically significant. Previously published data show controversies concerning differences between left and right kidneys. 7,17,18,21 However, there has been no disagreement about the left kidney being the longest. 11,17,19,22,23 Correlation between different anthropometric and kidney parameters were found to be highly significant in the present study. It is utterly important to know whether the kidney size of a child is appropriate for his age or anthropometric measurements. Kidneys which are reported as "small" in USG usually undergo additional invasive imaging procedures, including renal scan and voiding cysto-urethrography, in order to exclude hypoplastic-dysplastic kidney or atrophic kidney secondary to reflux nephropathy. If prior knowledge about relationship of small kidneys with malnutrition exists, unnecessary imaging procedures can be avoided. Moreover, by regression analysis, we have tried to formulate equations for various renal parameters, which can help us to predict the expected value for a given child, if we can just perform a thorough anthropometric survey of that child.
There is increasing understanding of the importance of organ growth and differentiation early in life as possible predictors of disease in adulthood. 7 Poor renal growth is thought to have some long-term consequences in the form of increased risk of developing hypertension, or tendency to develop chronic kidney disease in the future. 24,25 But, whether the risk of hypertension or kidney disease in later life will be greater in case of malnourished children than for healthy subjects, could not be predicted from this study. This point can be clarified with further longitudinal studies.

Conclusions
Malnourished children had smaller kidneys than the normally nourished children, signifying a mention-worthy role of nutrition in kidney growth. However, RRV of children with malnutrition was higher than the controls. These differences in the kidney size of malnourished children should be kept in mind while assessing their renal ultrasound.