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Open Access Journal of Urology & Nephrology Research Article 14 min read

Functional Development of Kidneys in Human Ontogenesis

Aizman Roman I*
* Corresponding author
ISSN: 2578-4676  10.23880/oajun-16000266  Received: November 04, 2024  Published: December 04, 2024
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Keywords
Kidneys Structure and Function Age Children Critical Periods of Development Ontogenesis
Abstract

Based on our own and literary results, the process of kidney functions formation in human ontogenesis from the stage of newborn to adulthood is considered. It has been shown that in conditions of relative rest of the body in the morning on an empty stomach, all the main manifestations of kidney functions correspond to the level of adults by 4-5 years old, and only the glomerular filtration rate and tubular reabsorption of fluid increase to 10-11 years of age. A complex analysis of the morphological and functional characteristics of the kidneys as an integral organ reveals their rapid growth up to 4-5 years, the second period of active growth is noted at 10-11 years and the completion of the process formation occurs by the age of 21-22. During periods of intensive growth of the whole organism – 7-8 and 13-15 years, a decrease in the rate of development of the kidneys structure and functions is manifested, which allows us to call these age periods as critical stages of kidney development. The presented results can be used as normative indicators of kidney function in healthy children of different ages.

Introduction

The kidney is not only the main organ of excretion, but also the main organ of regulation of water-mineral homeostasis. Therefore, the study of kidney function in human ontogenesis is of great theoretical and practical importance [1, 2, 3]. However, information on the development of homeostatic kidney functions in children relates mainly to the period of early childhood and very little work has been done on their functioning in juvenile and adolescence [4, 5, 6].

In this work, the aim is set on the basis of literature data and own materials to give a comprehensive assessment of age-related transformations of human kidney functions.

The kidneys begin to function as early as the 9-th week of embryonic development [7]. Ultrasound determination of their function in the fetus showed that from the 22nd to the 41st week of pregnancy, urine production progressively increases from 2.2 to 26.7 ml/h, glomerular filtration rate (GFR) increases to 2.66 ml/min and fluid reabsorption from 72.5 to 78.2% [8, 9].

The regulation of homeostasis in the embryo is carried out mainly through the placenta. Urine, which is released into the amniotic fluid, is exchanged with the maternal extracellular space [2]. Therefore, children with underdeveloped kidneys are born clinically healthy.

Partial kidney functions develop at different time depending on the morphological maturation of the organ. They have been studied in most detail in newborns and children of the first year of life [10, 11, 12, 13, 14, 15, 16, 17]. The glomerular filtration rate in children in the first weeks after birth is 3-4 times lower than in adults [18, 19, 20], depends on the degree of maturity of newborns [21], and at the turn of the first to second year of life it reaches a level corresponding to an adult organism [10, 18, 22, 23]. However, there are no enough convincing facts about an increase in GFR during the entire period of ontogenesis until adolescence [24, 25, 26, 27, 28]. These differences are probably due to the method of determining GFR and the test substances used (creatinine, inulin, urea, radioisotopes 51Cr-EDTA, iohexol, etc.) [22, 29]. It is believed that the assessment of clearance against the background of preliminary hydration of the body gives overestimated values, especially in young children [1, 58]. This is due to either the inclusion of “reserve” nephrons, or an increase in the filtration level in functioning nephrons, as well as possibly both reasons [30, 31].

In parallel, GFR increases the effective renal plasma flow and blood flow up to 13-15 years, and the volume of tubular fluid reabsorption increases to a lesser extent — from 96- 97% to 99% [32, 33, 34, 35].

Another important indicator of the functional development of nephrons is the ability of the proximal tubules to reabsorption and secretion of substances. Comparison of glucose reabsorption intensity (TmGl) in fetuses and young children, compared with adults, it was shown that TmGl increases in ontogenesis up to 5-6.5 years, but these indicators remain below adult values [36, 37]. However, when calculating the maximum glucose reabsorption per 1 ml of glomerular filtrate, it turned out that this ratio is equal to or even slightly higher than in adults [33, 36, 37].

Thus, by the time of birth, children already have an effective glucose reabsorption system corresponding to the level of development of their filtration processes. At the same time, the reabsorption of amino acids is reduced, which leads to aminoaciduria [23, 38]. The loss of proline, oxyproline, and glycine is especially pronounced during the first months of life. This is associated with the insufficient development of the system of regulation of amino acid transport in cells [33]. It is only by the age of 11-14 that the level of amino acid excretion approaches the level of adults [38].

The maturation time of the secretory ability of the kidneys is estimated in different ways. Some authors believe that the level of this function reaches adult values by 2.5 years of life [39], others believe that this function becomes mature by 7 years [27], others note that only by 8.3 years it reaches 50% of the adult norm [39], and its maturation is completed by 14 years [33, 40].

The water and ion excretion function of the kidneys has been studied in sufficient detail. It has been shown that already in the period of newborn and the first year of life, children are able to excrete fluid efficiently enough after optimal water loads and diuretics, which is due to inhibition of its reabsorption in the distal segment of the nephron [10, 11, 12, 13, 28, 30, 41, 42, 43, 44, 45].

The excretion of sodium, potassium and chlorides in the first year of life is reduced [17, 41, 46]. This is due to both lower filtrations loading of the nephron and, mainly, increased ion reabsorption in the tubules of the nephron under the influence of high activity of the renin-angiotensin- aldosterone system (RAAS) [1, 47, 48]. Therefore, sodium purification, for example, is only 1/5 of the adult norm [11], which requires reducing sodium intake from food in children.

After salt loads, electrolyte excretion is significantly reduced compared to adults. Many authors believe that this is due to insufficient inhibition of RAAS [47, 48, 49], however, the role of other intra- and extrarenal factors (insufficient number of functioning nephrons [7, 8, 31], underdevelopment of transport processes in them [4], low secretion of neurohypophysial hormones [50], etc. cannot be excluded.

Evidence of the leading role of endocrine factors in the restructuring of ionuretic function can be provided by data from studies of transport processes in the kidneys. When studying the effect of various diuretics on the renal transport of water and salts, it was found that the main systems of ion reabsorption and secretion reach maturity by the end of the first year of life [3, 33, 51, 52]. This allows us to conclude that the main renal processes already in the first years of life reach a level of development that is necessary to perform homeostatic kidney function in optimal conditions of vital activity of the body and corresponds to the degree of security of these processes from other functional systems.

A comparison of the main parameters of kidney function in children of different ages and adults (all subjects were male) under conditions of spontaneous urination in the morning on an empty stomach showed the absence of pronounced age differences, and only in the process of ontogenesis the volume of filtration and reabsorption processes increased (Table 1).

Parameters of
renal function		Age, years
Newborn
(n=15)		2 - 3
(n=37)		4 - 5
(n=73)		7 - 8
(n=118)		10 - 11
(n=113)		13 - 15
(n=129)		18 - 25
(n=80)
V, ml/min.m20,7±0,150,6±0,080,5±0,040,7±0,07*0,5±0,040,5±0,030,5±0,04
F, ml/min.m222±6*37±3*39±1*50±2*56±3*60±2*73±3
%RH O
2		97,5±0,40*98,4±0,08*98,6±0,0798,4±0,08*99,1±0,0699,0±0,08*99,3±0,04
U ·V,
Na
mcmol
min·m2		9,7±2,4*83,4±12,272,6±11,8105,0±9,386,2±5,579,4±3,682,6±6,4
U ·V,
K
mcmol
min·m2		5,6±1,5*53,3±7,6*43,7±1,8*47,7±3,3*37,1±2,935,5±1,433,7±2,4
EF
Na, %		0,4±0,06*1,6±0,18*2,0±0,14*1,7±0,12*1,2±0,08*1,1±0,070,9±0,10
EF , %
K		7,3±0,90*38,0±6,61*29,7±1,17*21,1±0,74*16,4±0,59*19,6±1,00*11,0±0,67
C , ml/
Na
min.1m2		0,1±0,02*0,6±0,090,6±0,090,8±0,08*0,6±0,040,6±0,030,6±0,04
U ,
osm
mosm/l		146±13*788±38*810±18*883±21890±27798±25*894±23
U /P
osm osm		0,5±0,05*2,8±0,09*2,8±0,05*3,2±0,083,2±0,072,7±0,06*3,2±0,08

Notes: *significant differences compare to adults. The number of examined persons is given in brackets. All subjects were male. Legend: V – diuresis; F – glomerular filtration rate; %RH2O – relative fluid reabsorption; V and V – renal excretion of sodium and potassium; EFNa и EFK – fractional excretion of sodium and potassium; СNa – sodium clearance; Uosm – urine osmolality; Uosm/Posm – osmotic concentration index Тable 1: Background parameters of renal function in children of different ages and adults (M±m).

At the same time, the kidneys as a whole, as the main effector in the system of regulation of water-salt metabolism, under the control of the neuro-hormonal system, continue to develop until adolescence [24, 32, 53, 54]. This is confirmed by the integral morphofunctional characteristic of the kidney at each stage of ontogenesis.

For an integral assessment of the degree of kidney development in ontogenesis, numerical indicators characterizing the structure and functions of the organ based on the method of morpho-kinetic synthesis were combined [55]. When calculating the structural characteristics, the following parameters were taken into account: the diameter of the lumens and the thickness of the walls of the renal artery and vein; the specific volume of tubules and renal bodies; the diameter of peripheral and juxtamedullary renal bodies; the specific volume and diameter of the lumen of the arc and interlobular arteries; the specific volume of capillaries [40, 56]. Kidney function was assessed in practically healthy children in conditions of relative rest, by collecting a morning sample of urine in 1-2 hours with spontaneous urination with straining (Table 1). During the same time period, a blood sample was taken to determine the main parameters of water-electrolyte homeostasis. All partial renal functions were calculated by conventional methods on 1m2 of the body surface [11, 57, 58]. This indicator for children correlates well with the extracellular space, where the main homeostatic reactions are carried out, and therefore can serve as a benchmark for comparing the functional capabilities of the kidneys [13, 28]. The integral morpho-functional characteristic of the organ expressed as a coefficient of correlation of parameters (CCP) in %, revealed the age dynamics of maturation (Figure 1).

Figure 1: Integral morpho-functional characteristics of kidneys in human ontogenesis (calculated by method of morpho-kinetic synthesis and expressed as a coefficient of correlation of parameters (CCP). Solid line - functional correlations; dotted line - morpho-functional correlations.
Click to enlarge
Figure 1: Integral morpho-functional characteristics of kidneys in human ontogenesis (calculated by method of morpho-kinetic synthesis and expressed as a coefficient of correlation of parameters (CCP). Solid line - functional correlations; dotted line - morpho-functional correlations.

As can be seen from Figure, the greatest intensity of the development of renal functions is observed from the first days of a child’s life to 4-5 years (the coefficient of correlation of parameters reflecting the change in the integral renal functions increases from -70% to +35%). The next development leap manifests itself at the age of 10-11, and the final stabilization of renal functions occurs in adolescence. In the periods of 7-8 and 13-15 years, there is a decrease in the rate of functional development, which probably reflects critical stages in the maturation of the kidneys and the mechanisms of regulation of its activity. In general, in terms of the sum of morphological and functional parameters, the kidneys in conditions of relative rest of the body approach the level of adults by the age of 10-11. In adolescence, there is a decrease in the rate of development and disintegration between different parameters of structure and function.

One of the main criteria determining the maturity of the kidneys as a homeostatic organ is the characteristic of its response to water-salt loads, when the reserve and adaptive capabilities of kidney functions and extrarenal mechanisms of its regulation are evaluated [1, 4, 59, 60, 61, 62, 63, 64]. It demands the special study for the future issue.

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@article{aizman2024,
  title   = {Functional Development of Kidneys in Human Ontogenesis},
  author  = {Aizman Roman I},
  journal = {Open Access Journal of Urology & Nephrology},
  year    = {2024},
  volume  = {9},
  number  = {4},
  doi     = {10.23880/oajun-16000266}
}
Aizman Roman I (2024). Functional Development of Kidneys in Human Ontogenesis. Open Access Journal of Urology & Nephrology, 9(4). https://doi.org/10.23880/oajun-16000266
TY  - JOUR
TI  - Functional Development of Kidneys in Human Ontogenesis
AU  - Aizman Roman I
JO  - Open Access Journal of Urology & Nephrology
PY  - 2024
VL  - 9
IS  - 4
DO  - 10.23880/oajun-16000266
ER  -