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At least 217 records · Page 12

Patterning of sympathetic nerve activity in response to vestibular stimulation

Growing evidence suggests a role for the vestibular system in regulation of autonomic outflow during postural adjustments. In the present paper we review evidence for the patterning of sympathetic nerve activity elicited by vestibular stimulation. In response to electrical activation of vestibular afferents, firing of sympathetic nerves located throughout the body is altered. However, activity of the renal nerve is most sensitive to vestibular inputs. In contrast, high-intensity simultaneous activation of cutaneous and muscle inputs elicits equivalent changes in firing of the renal, superior mesenteric and lumbar colonic nerves. Responses of muscle vasoconstrictor (MVC) efferents to vestibular stimulation are either inhibitory (Type I) or are comprised of a combination of excitation and inhibition (Type II). Interestingly, single MVC units located in the hindlimb exhibited predominantly Type I responses while those located in the forelimb and face exhibited Type II responses. Furthermore, brachial and femoral arterial blood flows were dissociated in response to vestibular stimulation, such that brachial vascular resistance increased while femoral resistance decreased. These studies demonstrate that vestibulosympathetic reflexes are patterned according to both the anatomical location and innervation target of a particular sympathetic nerve, and can lead to distinct changes in local blood flow.

NASA Discipline Neuroscience↗

Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.

Hypertension, Renovascular/etiology/pathology/phys↗

Peptides and neurotransmitters that affect renin secretion

Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the pathway by which psychosocial stimuli increase renin secretion.

Review↗

Vestibular stimulation leads to distinct hemodynamic patterning

Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 +/- 2 mmHg (mean +/- SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 +/- 4% decrease in vascular resistance or 36 +/- 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 +/- 6% and conductance decrease of 11 +/- 4%). Relatively small changes (<5%) in renal vascular tone were observed. In contrast, electrical stimulation of muscle and cutaneous afferents produced pressor responses (20 +/- 6 mmHg) that were accompanied by vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.

NASA Discipline Neuroscience↗

Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

NASA Discipline Cardiopulmonary↗

Patterning of somatosympathetic reflexes

In a previous study, we reported that vestibular nerve stimulation in the cat elicits a specific pattern of sympathetic nerve activation, such that responses are particularly large in the renal nerve. This patterning of vestibulosympathetic reflexes was the same in anesthetized and decerebrate preparations. In the present study, we report that inputs from skin and muscle also elicit a specific patterning of sympathetic outflow, which is distinct from that produced by vestibular stimulation. Renal, superior mesenteric, and lumbar colonic nerves respond most strongly to forelimb and hindlimb nerve stimulation (approximately 60% of maximal nerve activation), whereas external carotid and hypogastric nerves were least sensitive to these inputs (approximately 20% of maximal nerve activation). In contrast to vestibulosympathetic reflexes, the expression of responses to skin and muscle afferent activation differs in decerebrate and anesthetized animals. In baroreceptor-intact animals, somatosympathetic responses were strongly attenuated (to <20% of control in every nerve) by increasing blood pressure levels to >150 mmHg. These findings demonstrate that different types of somatic inputs elicit specific patterns of sympathetic nerve activation, presumably generated through distinct neural circuits.

Non-NASA Center↗

Contrasting effects of vasodilators on blood pressure and sodium balance in the hypertension of autonomic failure

Supine hypertension, which is very common in patients with autonomic failure, limits the use of pressor agents and induces nighttime natriuresis. In 13 patients with severe orthostatic hypotension due to autonomic failure (7 women, 6 men, 72 +/- 3 yr) and supine hypertension, the effect of 30 mg nifedipine (n = 10) and 0.025 to 0.2 mg/h nitroglycerin patch (n = 11) on supine BP, renal sodium handling, and orthostatic tolerance was determined. Medications were given at 8 p.m.; patients stood up at 8 a.m. Nitroglycerin was removed at 6 a.m. Compared with placebo, nifedipine and nitroglycerin decreased systolic BP during the night by a maximum of 37 +/- 9 and 36 +/- 10 mmHg, respectively (P < 0.01). At 8 a.m., supine systolic BP was 23 +/- 7 mmHg lower with nifedipine than with placebo (P < 0.05), but was similar with nitroglycerin and placebo. Sodium excretion during the night was not reduced with nitroglycerin (0.13 +/- 0.02 mmol/mg creatinine [Cr] versus 0.15 +/- 0.03 mmol/mg Cr with placebo), but it was increased with nifedipine (0.35 +/- 0.06 mmol/mg Cr versus 0.13 +/- 0.02 mmol/mg Cr with placebo, P < 0.05). Nifedipine but not nitroglycerin worsened orthostatic hypotension in the morning. It is concluded that nifedipine and transdermal nitroglycerin are effective in controlling supine hypertension in patients with autonomic failure. However, nifedipine has a prolonged depressor effect and worsens orthostatic hypotension in the morning. The decrease in pressure natriuresis that would be expected with the substantial decrease in BP obtained with nitroglycerin and nifedipine may be offset by a direct effect of both drugs on renal sodium handling.

Clinical Trial↗

Nutrition and human physiological adaptations to space flight

Space flight provides a model for the study of healthy individuals undergoing unique stresses. This review focuses on how physiological adaptations to weightlessness may affect nutrient and food requirements in space. These adaptations include reductions in body water and plasma volume, which affect the renal and cardiovascular systems and thereby fluid and electrolyte requirements. Changes in muscle mass and function may affect requirements for energy, protein and amino acids. Changes in bone mass lead to increased urinary calcium concentrations, which may increase the risk of forming renal stones. Space motion sickness may influence putative changes in gastro-intestinal-hepatic function; neurosensory alterations may affect smell and taste. Some or all of these effects may be ameliorated through the use of specially designed dietary countermeasures.

Review↗

Amino acid supplementation alters bone metabolism during simulated weightlessness

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Randomized Controlled Trial↗

Medullary Sponge Kidney and Urinary Calculi Aeromedical Concerns

Medullary Sponge Kidney (MSK) is a benign disorder associated with renal stones in 60% of patients. Patients frequently have episodic painless hematuria but are otherwise asymptomatic unless renal calculi or infections complicate the disease. Nephrolithiasis is a relative, but frequently enforced, contraindication to space or other high performance flight. Two case reports of asymptomatic NASA flight crew with MSK and three cases of military aviators diagnosed with MSK are reviewed, all cases resulted in waiver and return to flight status after treatment and a vigorous follow up and prophylaxis protocol. MSK in aviation and space flight necessitates a highly case-by-case dependent evaluation and treatment process to rule out other potential confounding factors that might also contribute to stone formation and in order to re-qualify the aviator for flight duties.

Jones, Jeffrey A.↗

DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

Hester, Robert L.↗

Antiresorptive Treatment for Spaceflight Induced Bone Atrophy - Preliminary Results

Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from critical skeletal sub-regions. The most important BMD losses are from the femoral hip, averaging about -1.6%/mo integral to -2.3%/mo trabecular. Importantly these studies have documented the wide range in individual BMD loss from -0.5 to -5%/mo. Associated elevated urinary Ca increases the risk of renal stone formation during flight, a serious impact to mission success. To date, countermeasures have not been satisfactory. The purpose of this study is to determine if the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss (mass and strength) and reducing renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the spine, femur neck and total hip were significantly improved from -0.8 +/- 0.5%/mo to 1.0 +/- 1.1%/mo, -1.1 +/- 0.5%/mo to -0.2 +/- 0.3%/mo, -1.1 +/- 0.5%/mo to 0.04 +/- 0.3%/mo respectively. QCT-determined trabecular BMD of the femur neck, trochanter and total hip were significantly improved from -2.7 +/- 1.9%/mo to -0.2 +/- 0.8%/mo, -2.2 +/- 0.9%/mo to -0.3 +/- 1.9%/mo and -2.3 +/- 1.0%/mo to -0.2 +/- 1.8%/mo respectively. Significance was calculated from a one-tailed t test. Resorption markers were unchanged, in contrast to measurements from previous ISS crewmembers that showed typical increases of 50-100% above baseline. Urinary Ca showed no increase compared to baseline levels, also distinct from the elevated levels of 50% or greater in previous crews. While these results are encouraging, the current n (4) is small, and the large SDs indicate that, while the means are improved, there is still high variability in individual response. Three additional crewmembers have been recruited to participate in this experiment, with expected completion in late 2011.

LeBlanc, Adrian↗

Men and Women in Space: Bone Loss and Kidney Stone Risk after Long-Duration Space Flight

Bone loss on Earth is more prevalent in women than men, leading to the assumption that women may be at greater risk from bone loss during flight. Until recently, the number of women having flown long-duration missions was too small to allow any type of statistical analysis. We report here data from 42 astronauts on long-duration missions to the International Space Station, 33 men and 9 women. Bone mineral density (dual-energy X-ray absorptiometry), bone biochemistry (from blood and urine samples), and renal stone risk factors were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. The response of bone mineral density to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an Advanced Resistive Exercise Device. Bone biochemistry, specifically markers of formation and resorption, generally responded similarly in male and female astronauts. The response of urinary supersaturation risk to space flight was not significantly different between men and women, although risks were typically increased after flight in both groups and risks were generally greater in men than in women before and after flight. Overall, the bone and renal stone responses of men and women to space flight were not different.

Smith, Scott M.↗

Fibroblast Growth Factor-23 in Bed Rest and Spaceflight

Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight. Presented with an imbalanced dietary phosphorus to calcium ratio, increased secretion of FGF23 will inhibit renal phosphorus reabsorption, resulting in increased excretion and reduced circulating phosphorus. Increased intake and excretion of phosphorus is associated with increased kidney stone risk in both the terrestrial and microgravity environments. Highly processed foods and carbonated beverages are associated with higher phosphorus content. Ideally, the dietary calcium to phosphorus ratio should be at minimum 1:1. Nutritional requirements for spaceflight suggest that this ratio not be less than 0.67 (3), while the International Space Station (ISS) menu provides 1020 mg Ca and 1856 mg P, for a ratio of 0.55 (3). Subjects in NASA's bed rest studies, by design, have consumed intake ratios much closer to 1.0 (4). FGF23 also has an inhibitory influence on PTH secretion and 1(alpha)-hydroxylase, both of which are required for activating vitamin D with the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Decreased 1,25-dihydroxyvitamin D will result in decreased intestinal phosphorus absorption, and increased urinary phosphorus excretion (via decreased renal reabsorption). Should a decrease in 1,25- dihydroxyvitamin D be necessary to reduce intestinal phosphorus absorption, calcium absorption will also proportionally be reduced, potentially leading to skeletal demineralization. Demineralization of bone can increase kidney stone risk, a medical issue that could prove detrimental to mission success. Given the interrelationships described above, we sought to determine circulating FGF23 concentrations in spaceflight and ground analog studies to better understand the potential effects of dietary phosphorus on bone and calcium metabolism. We analyzed serum from ISS astronauts participating in studies of bone biochemistry, including the Nutrition SMO and Pro K experiments, and we also evaluated FGF23 during extended-duration bed rest. Serum intact FGF23 levels were determined using an ELISA kit from Kainos laboratories in Japan. While initial evaluation of the data showed no changes over time during flight or bed rest, evaluation continues of FGF23 data in light of dietary factors, PTH, vitamin D status, and other biochemical and endocrine factors.

Bokhari, R.↗

2014 Bone and Muscle Risks Standing Review Panel

The 2014 Bone and Muscle Risks Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on December 17 - 18, 2014. The SRP reviewed the updated research plans for the Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance (Muscle Risk) and the Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity (Aerobic Risk). The SRP also received a status update on the Risk of Bone Fracture (Bone Risk), the Risk of Early Onset Osteoporosis Due To Spaceflight (Osteo Risk), the Risk of Intervertebral Disc Damage (IVD Risk), and the Risk of Renal Stone Formation (Renal Risk).

Steinberg, Susan↗

Overlapping Conditions in IMPACT

Introduction The IMPACT 1.0 model assumes independence of 119 different medical conditions. That is, it is assumed that one medical event maps to a single medical condition. However, it is often the case that a single medical event may lead to several different concurrent conditions (e.g., a single accident resulting in multiple fractures, chest/abdominal trauma, and sepsis). There is a significant overlap between many of the conditions in ICL 1.0. For example, depression and anxiety are two separate conditions but often co-exist. This overlap may lead to an overestimation in the incidence calculation. In future iterations of the model, we plan to address progression of medical conditions. Methods There are two possible methods to approach progression of a medical condition. The first is to take any medical condition in ICL, calculate its incidence and determine its outcomes no matter what sequelae occur. For example, calculate the incidence of prostatitis and determine its metrics (e.g., loss of crew life, risk of medical evacuation or task time affected) no matter what the sequelae might be (sepsis, hydronephrosis, renal failure, etc.). The second approach is to take any medical condition in the ICL and calculate the outcomes based on transitions to any other condition. For example, calculate the incidence of nephrolithiasis and determine the incidence of each possible transition (e.g., hydronephrosis, renal failure, UTI, pyelonephritis, sepsis) and then determine its metrics. With perfectly informative evidence, the answers should be the same using either method. The question is which approach best reduces the opportunity for overlapping. Results The team identified 31 conditions that were the most likely to transition to a secondary condition such as sepsis and respiratory failure. It was felt that the first approach, as described above, would be the easiest to implement and would have the greatest reduction in overlapping conditions. The identified conditions were primarily infectious conditions, like UTI and pneumonia (which could lead to both respiratory failure and sepsis), toxic inhalations, cardiac arrest, seizures, and trauma. Once these conditions were identified, the conditions were divided between the four clinicians on the team to identify those that were not consistent with the others in way they were approached. There were 13 conditions that were found to be problematic. Some condition definitions needed to be changed to eliminate references to transitions or to update them in cases where the definitions were out of date. Some conditions required new evidence to correct the loss of crew life, and one condition was felt to have so much overlap that it was recommended for elimination. A second effort required modification of the sepsis incidence calculation to prevent double counting of the conditions, such as prostatitis, that could progress to sepsis. Conclusion The team made significant progress in clarifying the method for dealing with transitions from one medical condition to another. In addition, errors were found and corrected in definitions, incidence, and loss of crew life as well as a condition in which reference was made to a CLiFF that was no longer included. These modifications will provide greater fidelity in the IMPACT model and reduce overlap.

Arian Anderson↗

The safety of magnetic resonance imaging contrast agents

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.

59 BASIC BIOLOGICAL SCIENCES↗

A Simplified Model of Adenine-Induced Chronic Kidney Disease Using SKH1 Mice

Commonly used adenine-induced chronic kidney disease (CKD) murine models often employ C57BL/6 mice; however, this strain has inherent limitations due to its natural resistance to developing key pathological features of CKD, such as tubulointerstitial fibrosis and inflammation. There have been attempts to overcome these barriers by using multiple concentrations of adenine-supplemented diets or by performing prolonged experiments up to 20 weeks. Here, we demonstrate that SKH1 Elite mice develop clinically relevant CKD phenotypes (e.g., polyuria, proteinuria, inflammation, and renal fibrosis) over the course of only 6 weeks of low-dose (0.15%) adenine supplementation. As a docile, immunocompetent, and hairless strain, SKH1 Elite mice offer several logistical advantages over C57BL/6 mice, including ease of handling and the ability to study dermal conditions, which are often secondary to CKD.

60 APPLIED LIFE SCIENCES↗