A comparative morphometric study of the superficial and juxtamedullary nephrons during the postnatal development in spontaneously hypertensive rats

Background: Hypertensive nephrosclerosis is associated with progressive loss of functional nephrons leading to chronic renal failure. In our study, we analysed the changes in the areas of the renal corpuscles and glomerular capillary tufts of superfi cial and juxtamedullary nephrons in 9 male spontaneously hypertensive rats, distributed in the following age groups: 4, 6 and 12-month-old. Results: The initial increase in the areas of the renal corpuscles and glomeruli representing the compensatory glomerular hypertrophy was followed by decrease in the late stages of glomerulosclerosis. Our results show that juxtamedullary nephrons were more affected than superfi cial nephrons. Conclusion: Hypertensive nephrosclerosis is associated with both morphological and morphometric changes in nephrons, which lead to declining renal function. Research Article A comparative morphometric study of the superfi cial and juxtamedullary nephrons during the postnatal development in spontaneously hypertensive rats Stancho Stanchev*, Alexandar Iliev, Georgi Kotov, Lina Malinova and Boycho Landzhov Department of Anatomy, Histology and Embryology, Medical University of Sofi a, Bulgaria Received: 16 January, 2018 Accepted: 23 January, 2018 Published: 24 January, 2018 *Corresponding author: Stancho Stanchev, MD, Department of Anatomy, Histology and Embryology Medical University of Sofi a, Bulgaria, Tel: +35929172609; E-mail:


Introduction
The prolonged and untreated hypertension is an important risk factor for the development of inevitable structural alterations in many organs and systems, which are collectively described by the term "target organ damage" [1]. In addition, the relationship between elevated blood pressure and chronic renal failure is pathologically referred to as hypertensive nephrosclerosis [2]. It is characterized by progressive morphological parenchymal and interstitial changes -hyaline and fi brinoid arteriosclerosis, intimal smooth muscle cell proliferation of the interlobular and small arteries, and duplication of the internal elastic lamina of arcuate arteries, interstitial fi brosis, tubular atrophy and glomerulosclerosis [3]. In the literature, two types of glomerular injury have been described -solidifi cation and obsolescence. The obsolescent form is characterized by collapse of the glomerulus and intracapsular fi brosis, while the solidifi cation is represented by expansion of mesangeal matrix and enlargement of the glomerular tuft [4].
The spontaneously hypertensive rat (SHR) strain was fi rst derived by Okamoto and colleagues during the 1960s and is the most commonly used experimental model of human essential hypertension [5]. The elevation of blood pressure in SHR begins at 4 weeks of age and the renal morphological changes can be observed at 6-12 months of age. In addition, the severity of the glomerular lesions and tubulointerstitial changes under hypertonic conditions appears to be more pronounced in the inner rather than the outer cortex [6].
The aim of the present study was to analyze and compare the areas of the renal corpuscles and glomerular capillary tufts of the superfi cial and juxtamedullary nephrons traced among three age groups (4-month-old, 6-month-old and 12-monthold) male SHR.

Materials and Methods
In the present study, we used histological material from the kidneys of male SHR. The total number of SHR was 9, distributed in three age groups, each containing three animals: four months old; six months old and twelve months old. All

Results
Results were obtained through assessment of randomly selected areas of the kidneys of SHR, aged 4-, 6-and 12-monthold, which were stained with haematoxylin and eosin. The selected areas included either superfi cial (Figures 1-3) or juxtamedullary nephrons (Figures 4-6). The results were organized in the form of tables and diagrams, representative of the obtained quantitative data for the studied morphometric parameters.
In the group of 4-month-old animals, the comparative analysis of the parameter area of the renal corpuscles shows higher values in juxtamedullary nephrons as opposed to superfi cial nephrons. That trend was preserved in the group of 6-month-old SHR, where we noted that the increase of the area of the renal corpuscles of juxtamedullary nephrons was more pronounced than the respective increase in superfi cial nephrons; furthermore, it reached its highest value in this group. In the group of 12-month-old SHR, the area of the renal corpuscles in superfi cial nephrons increased compared to the value in 6-month-old SHR, while in juxtamedullary nephrons, we reported a decrease in the area of the renal corpuscles, which was comparable to the obtained results in 4-monthold animals (Figure 7) (Table 1). In all age groups, the value of the parameter remained higher in juxtamedular nephrons, however in the group of 12-month-old SHR, the values were closer and this difference was less pronounced.     (Table 2). However, this decrease was better pronounced in juxtamedullary nephrons, where the value of the parameter decreased with more than 25%, while in superfi cial nephrons, the decrease in the value was approximately 10%.

Discussion
In the present study, we conducted a detailed comparative There is evidence that various diseases may affect the morphometric parameters of the renal corpuscles such as glomerular capillary tuft's diameter and Bowman's capsule dimension [7]. Glomerulosclerosis can be observed under pathological conditions such as hypertension, as well as during the process of physiological aging. Smith et al. suggest a formula for estimation of the percentage of age-related sclerotic glomeruli in the human population: age/2-10, when the age is above 40 years [8]. Furthermore, the changes in glomerular size correspond to the phase of glomerulosclerosis -the initial process of glomerular hypertrophy is followed by shrinking of glomerular capillary tufts to a smaller size.      However, some authors hypothesise that the functional renal capacity can't be evaluated by the changes in glomerular size and number, because these morphometric parameters depend on the body size and some sclerotic glomeruli can disappear as age advances [9]. Stojanovi´c et al. suggest that glomerular hypertrophy among nonsclerosed glomeruli may be estimated by their connective tissue content [9]. Alterations in kidney morphology may lead to development of renal insuffi ciency and eventually may progress to endstage renal disease (ESRD). ESRD due to hypertension has been reported as the cause of 25% of newly diagnosed ESRD patients every year in the United States [10]. Most often, hypertensive glomerulosclerosis is observed in the African American population due to a higher severity of elevated blood pressure and poorer socioeconomic status [11]. One study in African American populations found that renal biopsies performed in patients with hypertension more often show presence of focal global glomerulosclerosis (FGGS) rather than focal segmental gloemrulosclerosis (FSGS) [12,13]. Segmental glomerulosclerosis correlated with arteriolar and arterial sclerosis, as well as development of interstitial fi brosis and reciprocal of creatinine levels in the blood serum. Global glomerulosclerosis, on the other hand, has been reported to involve 43 +/-26% of glomeruli [12,13]. This type of glomerulosclerosis did not correlate with arteriolar or arterial thickening; however, correlations were established with levels of creatinine and cholesterol in the serum, development of interstitial fi brosis and systolic blood pressure. glomerulosclerosis with advancing age in SHR. These changes are more pronounced in the inner rather than the outer renal cortex.

Conclusion
Hypertensive nephrosclerosis is a leading factor in the onset of declining renal function.