Anatomical exploration of the kidney
The kidneys serve essential functions, such as filtration and excretion of metabolic waste products from the bloodstream, regulation of necessary electrolytes and stimulation of red blood cell production. They also serve to regulate blood pressure by the use of a renin-angiotensin-aldosterone system, controlling reabsorption of water, maintaining the correct pH level as well as chemical balance and intravascular fluid status of the body. The kidneys also reabsorb glucose and amino acids which may have involved in regulation of hormonal functions via erythropoietin, calcitriol, and vitamin D activation.
The glomerular corpuscle is a spherical structure in the renal cortex. Human glomeruli are all similar in size, but in rat juxtamedullary glomeruli are larger than glomeruli of the superficial cortex. The glomerular corpuscle generates an ultra-filtrate of plasma composed of water, electrolytes and small proteins.
Pigs are mammals. Consequently, all of the major structures found in humans are present in the fetal pig. With proper directions, they can all be readily found, especially with large, full term fetal pig specimens. There are a some differences in structural details, mostly relatively minor in nature. Some examples are given below.
In almost every case, fetal pigs have the same muscles as humans, with some small variations in the size and location of some muscles related to the fact that pigs are quadrupedal and humans are bipedal. For example, the major chest and abdominal muscles found in humans are present in the pig. There are some differences in the location of chest muscles that attach to the shoulder girdle. In the hind limb, the pig has the same muscles as humans in the major thigh muscle groups: quadriceps femoris and the hamstrings; In the hip, however, there are some differences in the gluteal muscles.
Quiz: How are the gluteal muscles of the pig different than the gluteal muscles of the human?
Pigs have all of the same thoracic and abdominal organs as humans. There are small differences in a few organs.
Liver – the human liver has four lobes: right, left, caudate and quadrate. The fetal pig liver has five lobes: right lateral, right central, left central, left lateral, and caudate.
Intestines – there is a significant difference in the structure of the fetal pig colon compared to the human colon. The pig colon is spiral.
Adrenal glands – In the fetal pig, the adrenal glands are found near the aorta towards the cephalic end of the kidneys, instead of on top of the kidneys as is the case in humans.
Quiz: Like humans, the adrenal glands of the fetal pig are retroperitoneal. What other abdominal organs are retroperitoneal?
Stomach, spleen, bile duct system, small intestines, kidneys, bladder, etc. – the remainder of the abdominal organs found in the fetal pig are basically the same as found in humans.
Thymus – the thymus is found in the same areas in pigs as in humans. However, it is much larger than most students1 expect. This is not a difference of pigs from other mammals. All mammals have a large (enormous) thymus gland during the fetal stage. It gradually shrinks, relative to the rest of the body, throughout life.
Lungs – Like humans, pigs have multi-lobed lungs.
Quiz: Humans have three lobes in the right lung, two lobes in the left lung. How many lobes are there in the lungs of the fetal pig?
Pericardium, vena cava, esophagus, phrenic nerve, etc. – these other thoracic organs are basically the same in pigs and humans.
Uterus – The fetal pig uterus is of a type called bicornate, compared to the simplex human uterus. This means that the pig uterus has two large horns in addition to the body. These horns are sometimes confused with the much smaller Fallopian tubes. It is the presence of these horns which allows pigs to have a litter of 8 or 10 pigs.
Urogenital Sinus – Pigs have a relatively long urogenital sinus formed by the fusion of the urethra with the vagina. The urogenital sinus then connects to the external genitalia. While humans have a urogenital sinus during embryological development, it is lost except for the vestibule which is considered to be part of the external genitalia. Consequently, in humans the urethra and vagina have separate external openings.
Urethra, ovaries, uterine tubes, labia, mesenteries, testes, epididymis, vas deferens, inguinal canal, prostate gland, etc. – these structures are basically the same in the fetal pig and human.
Bicarotid trunk – In fetal pigs, the brachiocephalic artery splits into the right subclavian artery and the bicarotid trunk. The bicarotid trunk then splits into the right and left common carotid arteries. Humans do not have a bicarotid trunk; instead, the left common carotid artery branches from directly from the aorta, while only the right common carotid artery originates from the brachiocephalic artery.
Illiac arteries -Humans have a common illiac artery which branches into internal and external illiac arteries. Fetal pigs do not have a common illiac artery. Instead, the internal and external illiac arteries branch directly off of the aorta.
Gasthuys et al. demonstrated that the maturation of the GFR, determined as iohexol plasma clearance, was comparable between children and growing pigs, making the growing pig a potential good preclinical model for pediatric drug research and an amenable model to study renal (patho)physiology (Gasthuys et al., 2017a). To date, GFR estimation in pigs is frequently described in literature; however, limited information on the other porcine renal excretion processes is available. Nevertheless, this information could contribute to the evaluation of the suitability of the pigs as animal model.
A single cocktail approach, in which a serie of marker compounds is administered at once followed by repetitive blood and urine sampling, has been validated in humans (Gross et al., 2001; Udy et al., 2014). This cocktail consisted of sinistrin to determine the GFR, PAH to measure the effective renal plasma flow (ERPF) and net tubular anion secretion, pindolol to evaluate the net tubular cation secretion, and fluconazole as an indicator of the passive reabsorption.
Comparison With Human Values
To assess the suitability of the pig as animal model, the porcine clearance values were compared with human adult values in literature. Pigs within the 4–14 week age category correspond with a human age of 2–12 years (Gasthuys et al., 2016). It is postulated that human adult values for GFR, ERPF, and anion secretion are obtained at an age of 2 years (Rubin et al., 1949). In pigs, adult values of GFR and ERPF are reached around an age of 8 weeks. Adults values for the extraction of PAH, a measure for tubular secretion, are obtained at 3 weeks of age (Friis, 1979). Therefore, it seemed permissible to compare the porcine values of the distinct renal clearance processes in this study with human adult values reported by Gross et al. (Rubin et al., 1949; Gross et al., 2001). The cocktail used in the study of Gross et al. was similar to that administered in the presented study. It consisted of sinistrin, PAH, pindolol, and fluconazole. The latter two compounds were, in contrast to this study, administered orally. Gross et al. determined PK parameter values in the humans using non compartmental analysis. Since Gross et al. only reported PK values not corrected for BSA and BW, the values presented in their study were corrected for the mean BW, which was 72 kg (Gross et al., 2001). The mean BSA was estimated using the formula of Dubois, where the mean BW was 72 kg and mean height 178 cm.
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All piglets survived the surgical procedure without any complication. After administration of the cocktail of renal markers no adverse effects were observed. The pigs showed a normal activity and appetite. For two pigs, leakages of the urine bags were observed during the 48 h urine collection period. Therefore, these pigs were excluded in the calculation of the renal clearances. Those PK parameters, which were independent of urine collection, all pigs were included. During the 48 h observation period, the urinary flow rate was 2.03 ± 1.00 ml/kg/h.