|Year : 2019 | Volume
| Issue : 6 | Page : 842-848
Glomerular hyperfiltration in excess weight adolescents
NJ Iduoriyekemwen1, MO Ibadin1, HA Aikhionbare1, SE Idogun2, MT Abiodun1
1 Department of Child Health, University of Benin/University of Benin Teaching Hospital, P.M.B. 1111, Benin City, Nigeria
2 Department of Chemical Pathology, University of Benin/University of Benin Teaching Hospital, P.M.B. 1111, Benin City, Nigeria
|Date of Acceptance||19-Feb-2019|
|Date of Web Publication||12-Jun-2019|
Dr. N J Iduoriyekemwen
Department of Child Health, University of Benin Teaching Hospital, P.M.B. 1111, Benin City
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Childhood overweight/obesity burden is on the rise worldwide. Obesity affects virtually all organs. In the kidney, glomerular hyperfiltration that manifests as elevated glomerular filtration rate is a frequent manifestation in obesity. This adaptive renal manifestation to excess metabolic demand on the kidney, in children, has been studied mainly in the severely obese and is uncertain if it is present in less severe forms of excessive weight. In addition, glomerular hyperfiltration has been reported to be associated with high levels of the indicators of cardiometabolic risk, and these latter finding are solely from adult studies. Objective: To ascertain if glomerular hyperfiltration occurs in overweight and less severely obese children and to determine any significant relevance of some indicators of cardiometabolic risk associated with hyperfiltration. Subjects and Methods: This cross-sectional study involved 49 adolescents (28 overweight, 21 obese) and 49 normal weight adolescents. The participants were subjected to clinical examination, anthropometric measurement, laboratory investigation using standard techniques. Estimated glomerular filtration rates (eGFR) were calculated using the modified Schwartz equation. Hyperfiltration was defined as eGFR ≥140 ml/min/1.73 m2. Results: Hyperfiltration was observed in 20 (40.8%) of the overweight/obese adolescents. The prevalence of hyperfiltration among the overweight and the obese adolescent was 24.5% and 16.3%, respectively. The mean estimated glomerular filtration rate of the overweight/obese adolescents was 141.0 ± 46.2 ml/min/1.73 m2, whereas that of the normal weight adolescents was 99.2 ± 17.1 ml/min/1.73 m2 (P = 0.0001). A higher prevalence of hypertension was observed among the overweight/obese adolescent with glomerular hyperfiltration. Conclusion: Glomerular hyperfiltration is not limited to morbidly obese children as the burden is also high in overweight and less severely obese adolescents.
Keywords: Adolescents, hyperfiltration, kidney, obesity, overweight
|How to cite this article:|
Iduoriyekemwen N J, Ibadin M O, Aikhionbare H A, Idogun S E, Abiodun M T. Glomerular hyperfiltration in excess weight adolescents. Niger J Clin Pract 2019;22:842-8
|How to cite this URL:|
Iduoriyekemwen N J, Ibadin M O, Aikhionbare H A, Idogun S E, Abiodun M T. Glomerular hyperfiltration in excess weight adolescents. Niger J Clin Pract [serial online] 2019 [cited 2020 Jul 7];22:842-8. Available from: http://www.njcponline.com/text.asp?2019/22/6/842/260028
| Introduction|| |
Childhood overweight/obesity is a pandemic with burden reported to be on the increase. Obesity via several mechanisms promotes the development of cardiometabolic risk factors such as dyslipidaemia, hyperinsulinaemia, and hypertension., These factors independently and collectively increase renal disease risk in obesity. In the kidney, glomerular hyperfiltration, which is a frequent finding from several studies on evaluation of the renal function of obese adults,,, and children,,, is a functional abnormality that manifest as elevated GFR. Glomerular hyperfiltration in the obese has been postulated by some authors to result from an increased metabolic/excretory demand on the kidney because of the excessive weight, which independent of obesity-induced cardiometabolic risk factors leads to the development of glomerulosclerosis and thus CKD., Recently however, other authors view this elevated GFR in obese individual as a nonpathogenic adaptive response to increased metabolic/excretory demand on the kidney because of the excessive weight, similar to what occurs in the pregnant state. This notion stems from the observation that although the prevalence of obesity is high and rising, the prevalence of Chronic kidney disease (CKD) and End stage renal disease (ESRD) among obese individual is very low (even when they are morbidly obese) especially in the absence of; the obesity-induced cardiometabolic risk factors, pre-existing renal disease, and/or pre-existing congenital or acquired low nephron numbers, implying that in the obese, glomerular hyperfiltration alone cannot cause CKD. In addition, studies have shown that elevated GFR in morbidly obese adults reversed to normal levels after substantial weight reduction.,
In the literature, there is no consensus for defining glomerular hyperfiltration in children as well as in adults., The glomerular hyperfiltration range for most of the available studies reported in a systematic review on glomerular hyperfiltration assessment was 130--140 ml/min/1.73 m. Furthermore, glomerular hyperfiltration is poorly studied in childhood, with the available studies mainly focusing on the severely obese children.,, Of note, there are two studies on less severely obese children. Although they are large population studies, one predominantly studied normal weight adolescents and the definition of glomerular hyperfiltration used in the study was within the pediatric reference range for normal glomerular filtration, whereas in the other study, the overweight/obese children were not separated as a subset. They were not compared with the normal weight children, and in addition, no definition for glomerular hyperfiltration was stated. These reasons make it uncertain whether glomerular hyperfiltration is also present in the less severe forms of childhood obesity and even in healthy normal weight adolescents as some studies in adult population suggest.
The presence of glomerular hyperfiltration has been postulated by some authors as a marker of metabolic risk. This view is supported by observations of higher values of some indicators of cardiometabolic risk (such as blood pressure, blood glucose, and serum lipids levels) among obese adult with glomerular hyperfiltration compared with normal weight individuals. In children, similar studies evaluating the relationship between hyperfiltration and cardiovascular and metabolic risk exclusively in obese children are lacking. A related available study was on normal weight adolescent where the definition for hyperfiltration given was within the normal pediatric reference range of glomerular filtration, thus raising the question whether the children actually had hyperfiltration. Hence, this study was carried out to ascertain if glomerular hyperfiltration occurs in overweight and less severe obese children, and to determine the association of some indicators of cardiometabolic risk (systolic blood pressure, diastolic blood pressure, blood glucose, and lipid profile levels) with hyperfiltration.
| Subjects and Methods|| |
Study setting and subject selection
This cross-sectional study was carried out in a private secondary school in Egor Local Government Area (LGA) of Edo State, from May to June 2016. The school was selected by simple random method (balloting) from the list of private secondary schools which was obtained from the State Ministry of Education. Egor Local Government area has 20 private schools. The preference for private schools was based on previously published work from the same locale by Sadoh et al. who reported higher prevalence of obesity in private schools than public school.
The total school population was 460 students. A convenience sample size of 49 subjects were recruited from the arms of class one to class six. The subjects were recruited consecutively until the required number of subjects was met. In addition, each subject was matched to a control for age and gender.
Subjects wereapparently healthy adolescents aged 10-17 years with body mass index (BMI) ≥85th percentile on the Centre for Disease Control (CDC) BMI growth chart. Controls were apparently healthy normal weight adolescents with a with BMI between the 5th to ≤85th percentile on the CDC BMI growth chart who were aged and sex marched with subjects Any student with a positive history or obvious clinical evidence of renal disease, endocrine disease, fever, and complaints suggestive of symptomatic urinary tract infection (UTI) (such as dysuria, loin pain, suprapubic pain, frequency, urgency) was not recruited.
Ethical approval was obtained from the University of Benin Ethics Committee. Permission was sought from the administrative heads of the school and the Ministry of Education. Written informed consent was obtained from the parent(s) of the study subjects and verbal assent from each of the adolescents.
Data collection and evaluation
A proforma was used to obtain information concerning each child's age, gender, parental occupation, and educational status. The father's occupation and mother's educational status were used in deriving the socioeconomic class of the family by the method developed by Olusanya et al. Thereafter, physical examination of each child was carried out, parameters measured were their blood pressure (BP), weight, height, waist circumference (WC), and hip circumference (HC).
The BP was determined using mercury sphygmomanometer with the adolescent seated comfortably after 5 min of rest using an appropriately sized cuff covering two-thirds of the right upper arm; three blood pressure readings were taken and the average determined.
Each child was weighed using a Seca® weighing scale (Seca gmbh & co, Germany) with a sensitivity of 0.1 kg. Weighing was undertaken after heavy clothing and accessories such as school cardigans or blazers, belt, wrist watches, and shoes had been removed and the pockets of their school uniform emptied. The heights of the adolescents were taken using a stadiometer. Each child stood erect on the stadiometer looking straight ahead with hands on the side, feet (without shoes) placed together and his/her occiput and buttock resting on the stadiometer, the lever was then lowered to the vertex and the height read off the calibrated scale.
The waist circumference of the adolescents was measured using a non-distensible tape snugly wrapped around the subject, midpoint between the top of the iliac crest, and the lower margin of the last palpable rib in the mid axillary line. The adolescent stood upright, with arms relaxed at the side, feet evenly spread apart, and body weight evenly distributed during the measurement.
The hip circumference was also measured using a non-distensible tape at the largest circumference of the buttocks. During the measurement, the adolescent stood upright, with arms relaxed at the side and feet joined together. All measurements were in centimeters (cm) to the nearest 0.1 cm. All anthropometric measurements were performed by one of the authors with a chaperone in attendance.
Six milliliters (ml) of blood was obtained from each child by venepuncture using aseptic technique, 1 ml was emptied into anti-coagulant bottle containing fluoride oxalate for fasting blood sugar determination. The remaining was emptied into a sterile bottle containing no anti-coagulant which was then centrifuged. The obtained serum was used for determination of serum lipid profile (total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride) as well as serum creatinine levels determination.
The serum creatinine concentration was determined by the modified Jaffe kinetic method. Then, the end product was read at a wavelength of 500 nm using a spectrophotometer (Unico 1200 spectrophotometer). The concentration of creatinine in the tested sample was derived by the formula concentration of creatinine = (absorbance of test × concentration of standard)/absorbance of standard. The serum creatinine obtained was used in the calculation of eGFR using the modified Schwartz equation (eGFR in mL/min/1.73 m2 = k x (height in cm/Scr mg/dl) where k = 0.413).
BMI was determined using the formula weight (Kg)/Height 2 (m2). Overweight was defined as a BMI ≥85th but ≤95th percentile on the CDC BMI chart, whereas obesity was defined as a BMI >95th percentile. There are no criteria for classifying severity of obesity in children, thus, in this study, less severe obesity was taken as a BMI less than 34 kg/m2, whereas severe obesity was ≥34 kg/m2 according to the BMI grading used in the study by Freedman et al. who studied a large population of normal weight and obese children. Hypertension was defined as Systolic Blood pressure (SBP) and/or Diastolic Blood pressure (DBP) greater than or equal to the 95th percentile for sex, age, and height. Hyperfiltration was defined as eGFR ≥140 ml/min/1.73 m2.
The data was analysed using IBM SPSS version 20 (SPSS for Window Inc; Chicago, LL, USA) Statistical software. Continuous data such as child's age and all measurements obtained including the glomerular filtration rates were summarized as mean ± standard deviation (SD). The categorical data such as age group, gender, and socioeconomic class were represented as proportions. The student's t-test was used to compare two means, whereas the one-way analysis of variance (ANOVA) was used to compare multiple means. The Pearson's Chi-square or Fisher's exact tests were used to compare categorical data, i.e., the age group, gender, and socioeconomic class. The level of significance of each test was set at P < 0.05.
| Results|| |
General characteristic of study population
A total of 49 subjects were recruited for this study, 28 (57.1%) were overweight and 21 (42.9%) obese. In addition, 49 normal weight adolescents were recruited as controls.
Demographic characteristic of the study population
The mean age of the adolescent subjects studied was 12.3 ± 1.4 years. Most of the children 44 (89.8%) were in the early adolescent's stage (10--14 years). There were 29 (59.2%) females and 20 (40.8%) males with a female to male ratio of 1.5:1. These parameters of age and gender of the subjects were used in the recruitment of well-matched normal weight adolescents that served as controls. [Table 1]. Although most of the overweight/obese adolescents were from upper socioeconomic class families (32, constituting 65.3%), the normal weight adolescents were mostly from the middle socioeconomic class families (28, constituting 57.1%). The number of overweight/obese adolescents from upper socioeconomic class families was significantly higher than the number of normal weight adolescents from upper socioeconomic class P = 0.004 [Table 1].
|Table 1: Demographic characteristics of the overweight/obese and the normal weight adolescents|
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The mean GFR values and prevalence of Hyperfiltration of the overweight/obese and the normal weight adolescents
The mean GFR of the overweight/obese adolescents (141.0 ± 46.2 ml/min/1.73 m2) was significantly higher than that of the normal weight adolescents (99.2 ± 17.1 ml/min/1.73 m2, P = 0.0001. Hyperfiltration was observed in 40.8% (20) of the overweight/obese adolescents and in none of the normal weight adolescents. The prevalence of hyperfiltration of the overweight adolescents was 24.5% (12), whereas among the obese adolescents it was 16.3% (8). The proportion of the overweight adolescent with hyperfiltration was not significantly higher than the obese adolescents with hyperfiltration (P = 0.777).
Demographic and anthropometric characteristics of the Overweight/obese adolescents with hyperfiltration, those without hyperfiltration and the normal weight adolescents
The overweight/obese adolescents with hyperfiltration were not significantly different from those without hyperfiltration or the normal weight adolescents in terms of their age, age group, and gender [Table 2]. The overweight/obese adolescents with hyperfiltration were significantly more from upper socioeconomic class families compared with the normal weight adolescent (P = 0.0I2). However, the overweight/obese adolescents with hyperfiltration were similar to the overweight/obese adolescents without hyperfiltration with regard to socioeconomic class status. The mean BMI, mean waist circumference, and mean hip circumference were significantly higher in the overweight/obese adolescents with hyperfiltration (24.8 ± 3.4 kg/m2, 85.5 ± 10.1 cm and 101.7 ± 9.8 cm, respectively) compared with the normal weight adolescents (17.0 ± 2.0 kgm2, 70.9 ± 5.5 cm and 82.7 ± 6.9 cm, respectively) P = <0.0001 for each [Table 2]. The mean BMI and anthropometric measurements of the overweight/obese adolescents with hyperfiltration were similar to the overweight/obese adolescents without hyperfiltration.
|Table 2: Demographic and anthropometric characteristics of the overweight/obese adolescents with and without hyperfiltration and the normal weight adolescents|
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Cardiometabolic indicators of the Overweight/obese adolescents with hyperfiltration, those without hyperfiltration and the normal weight adolescents
The overweight/obese adolescents with hyperfiltration had significantly higher systolic and diastolic blood pressure values than the normal weight adolescents (P = 0.0002 and P = 0.018 respectively). The overweight/obese adolescents with hyperfiltration, however, had similar systolic and diastolic blood pressure values compared with those without hyperfiltration [Table 3]. Of note, hypertension was observed in 15% (3) of the overweight/obese adolescents with hyperfiltration, 3.4% (1) of the overweight/obese adolescents without hyperfiltration, and 2.0% of the normal weight adolescent. However, there was no significant difference between the groups P = 0.076. The overweight/obese adolescents with hyperfiltration did not differ from the other groups with regard to their blood glucose and blood lipid prolife levels, i.e. mean total cholesterol, mean HDL-cholesterol, mean LDL-cholesterol, and mean triglyceride.
|Table 3: Cardiometabolic indicators of the overweight/obese adolescents with Hyperfiltration, those without hyperfiltration and the normal weight adolescents|
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| Discussion|| |
In this study, we report that glomerular hyperfiltration is present even as early as the preobese state of excess weight. This suggests, perhaps that, the onset of glomerular hyperfiltration occurs as soon as excessive body fat begins to accumulate. Similar to reports from other studies,,, data from the present study also show that eGFR in overweight/obese adolescents was significantly higher than the normal weight adolescents. This finding supports the postulation by other authors that increased excretory demand driven by the excess body weight is responsible for the eGFR. The finding is however in contrast with the findings of Duzova et al. that reported that their overweight/obese children had significantly decreased GFR compared with their normal weight children. The exclusion of adolescents with pre-existing renal disease in this present study may explain the reason for the dissimilarity. Of note, in the population-based study by Duzova et al., there was no exclusion criteria; thus, children with pre-existing renal disease who already had reduced glomerular filtration may have been unduly captured.
This study revealed a high prevalence of hyperfiltration in the overweight and the less severely obese adolescents. However, absence of similar studies on the overweight/obese pediatric population precludes comparison. The only available pediatric study that provided a prevalence of glomerular hyperfiltration was carried out on normal weight adolescents and the definition of glomerular hyperfiltration was GFR ≥120 ml/min/1.73 m2, a value that is within the normal reference range for GFR in children. The finding in this study that the prevalence of hyperfiltration among the overweight adolescents was higher than the obese adolescent is in contrast with that of Wuerzner et al. who reported a prevalence of hyperfiltration of 14.8% and 27.1% among their studied overweight and obese adults, respectively. The reason for this difference may be our small sample size in addition to the overpowering higher number of the overweight adolescents in this study.
The only indicator of cardiovascular and metabolic risk revealed in this study was BP. Significantly higher blood pressure levels were observed among the overweight/obese adolescents with and without hyperfiltration than the normal weight adolescents. This finding support reports from several studies,, which shows that a direct relationship exists between BP and overweight/obesity. It is postulated that the excessive adipose tissue activates the sympathetic nervous system and the renin angiotensin aldosterone system, which result in increased sodium reabsorption and water retention that alters the renal pressure-natriuresis and ultimately increasing blood pressure. Although the above finding does not prove that glomerular hyperfiltration is driven by the higher blood pressure levels, as it was elevated in both the overweight/obese adolescent with and those without hyperfiltration. This study also revealed higher prevalence of hypertension among the overweight/obese adolescent with hyperfiltration compared with those without hyperfiltration and the normal weight adolescents. However, this was not statistical significant, which is in contrast to other studies; Tomaszewski et al. in adult reported that hypertension was a significant determinant of glomerular hyperfiltration with an odds ratio of 2.3 and even after adjusting for other demographic and metabolic variables, the odds ratio remained as high as 1.9. The small sample size of this current study may be responsible for the absence of association between hypertension and glomerular hyperfiltration.
Surprisingly, the three groups of adolescents studied had similar mean levels of the indicators of metabolic risk (i.e., the blood glucose levels, total cholesterol, HDL-cholesterol, LDL- cholesterol, and triglyceride levels). This finding is similar to that of Tomaszewski et al. whose study revealed that the blood glucose levels, total cholesterol, and LDL-cholesterol levels were not different in the obese subjects with hyperfiltration compared with their normal weight adults who had normal filtration. However, they found higher levels of triglyceride and lower levels of HDL-cholesterol among their obese subjects with hyperfiltration. A possible reason for the difference is that the overweight/obese adolescents in this study were not extremely obese.
The limitation of this study is the use of eGFR based on serum creatinine measurement. The standard method for GFR determination is the inulin clearance, the application of this method is cumbersome in children and difficult to perform in a school setting. Other methods such as timed creatinine clearance is also cumbersome and may be difficult to administer to secondary school students. Renal scintigraphy for estimation of the GFR on the other hand is very expensive and not readily available.
| Conclusion|| |
This study reveals that glomerular hyperfiltration is not limited to morbidly obese children, providing evidence that the development of this renal functional abnormality occurs early in the obesity disease process. Even though from the literature it is unclear if glomerular hyperfiltration alone in obese individuals can cause CKD, some evidence are however available that in the presence of obesity, induced cardiometabolic factors do potentiate risk for the development of CKD. Therefore, as one is not certain as to when obesity induced cardiometabolic risk factors begin to take adverse effect, and in the light of the significant proportion of adolescents with excessive weight revealed in this study who had glomerular hyperfiltration, it is recommended that such children should be identified early and placed on weight reduction programme immediately. This is important especially as weight loss at the overweight and less severe stage of obesity can reverse this renal abnormality. In addition, achieving considerable weight loss is easier in the less severe stages of obesity than in extremely obese state. Early identification of these children can be achieved via effective school health screening programme.
The authors thank Miss Itohan Ibhawa for data entry and the management of Baptist High School, Benin City for providing the enabling environment for the study
Financial support and sponsorship
We declare that funds used for this study were from the authors' personal finance.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]