School of Physiology (ETDs)
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Item Effects of dietary supplementation with β-sitosterol on Cobb 500 broiler chicken productivity, health and product quality(University of the Witwatersrand, Johannesburg, 2024) Bopape, Malebogo Audrey; Chivandi, ElitonAntibiotic use as growth promoters in chicken feeds results in antibiotic resistance and environmental pollution. To mitigate these challenges alternatives natural growth promoters are required. Beta-sitosterol is one of several phytosterols with chemical structures similar to that of cholesterol. β-sitosterol has antimicrobial, antioxidant, anti-inflammatory and hypocholesterolaemic activities, thus might replace synthetic antibiotics as a feed supplement in chicken feeds. The current study evaluated β-sitosterol’s potential to replace oxytetracycline in Cobb 500 broiler chicken feeds by determining its effects on growth performance, meat yield and quality and bird health. β-sitosterol replaced oxytetracycline at 0 (control: 50 mg/kg oxytetracycline), 500, 1000 and 1500 mg/kg feed for diet 1 to 4, respectively with doses similar in starter, grower, and finisher diets. Chickens were fed from day 1 to 42 days of age. Body mass and feed intake were measured. Body mass gain, average daily gain and feed conversion ratio were computed. Terminally, broiler chickens were fasted, weighed, humanely slaughtered and dressed. The carcass yield, viscera morphometry and plasma surrogate markers of health were also determined. Meat pH, colour, thawing and cooking loss (TL; CL), water holding capacity (WHC), tenderness and myofibrillar fragmentation length (MFL) and nutrient content were determined. Femora and tibiae mass, length, breaking strength and liver fat content and histology were determined. Dietary β- sitosterol had similar (P > 0.05) effects as oxytetracycline on the chickens’ growth performance and feed intake utilization efficiency, gastrointestinal tract (GIT) and GIT accessory viscera macromorphometry, meat yield, meat colour, pH, TL, CL, WHC, tenderness and MFL. However, breast meat crude protein content of chicken fed diet 4 was higher (P < 0.0001) compared to that of counterparts fed diets 2 and 3. Breast meat fat content of chicken fed diet 2 and diet 4 was higher (P < 0.0001) compared to that of counterparts fed diets 1 and 3. Dietary β-sitosterol had similar (P > 0.05) broiler chickens’ breast meat total saturated fatty acids (TSFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), palmitic, oleic and linoleic content as oxytetracycline. Dietary treatments had no effect on chickens’ tibiae masses and breaking strength (P > 0.05) albeit tibiae from chickens fed diet 4 were shorter (P < 0.01) than those of counterparts fed diet 2. Dietary β-sitosterol at 1000 and 1500 mg/kg feed increased (P < 0.05) liver lipid content but had no effect on hepatic microarchitecture. However, at 1500 mg/kg feed it caused micro- and macro hepatic steatosis and lobular inflammation and higher (P < 0.05) non-alcoholic fatty liver disease activity scores (NAS). Compared to control, dietary β- vii sitosterol decreased (P < 0.0001) the chickens’ malondialdehyde (MDA) concentration but increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities and glutathione S-transferase (GST) and glutathione (GSH) concentration (P < 0.05). Diet 4 increased (P < 0.01) plasma AST and GGT activities compared to diet 1 (control). At 1000 and 1500 mg/kg feed it increased plasma cholesterol concentration compared to control and β-sitosterol at 500 mg/kg feed. β-sitosterol can replace oxytetracycline as growth promoter in Cobb 500 broiler chicken diets without negatively affecting growth performance, meat yield and quality and potentially mitigates oxidative stress by upregulating systemic antioxidant enzymes activities. However, at 1500 mg/kg feed, it can increase the risk of fatty liver disease development and hypercholesterolaemia.Item Myrmecophagous mammals in a changing world: the ecology of aardvarks and temminck’s pangolins in the kalahari(University of the Witwatersrand, Johannesburg, 2024) Phakoago, Makabudi valery; Fuller, A.Little is known about the distribution and ecology of the aardvark (Orycteropus afer) and Temminck’s pangolin (Smutsia temminckii) in southern Africa as they are rarely seen and difficult to study. Both species are myrmecophagous (feed on ants and termites), primarily nocturnal, 2and they tend to be solitary. Climate change, which is resulting in hotter and drier environments in most parts of southern Africa, may affect the aardvark and Temminck’s pangolin through direct impacts on the animals and through impacts on their prey resources. Understanding how climate change may impact these two myrmecophagous mammals requires us to gather further insights on how their environment and food sources are changing, how their diets overlap, how they use the environment and alter their activity to source food and buffer themselves from heat and cold, and how they are distributed across southern Africa. Previous research conducted in the semi-arid Kalahari of southern Africa showed that a decline in ant and termite populations (as indicated by counts in pitfall traps) associated with drought resulted in starvation of aardvarks and pangolins and decreased reproductive output of pangolins. Individuals of both species starved, despite previous work indicating that the diets do not overlap, with aardvark preying predominantly on harvester termites (Hodotermes mossambicus) and pangolins preying predominantly on ants (mainly Crematogaster ants). However, the research on each species was conducted at different times, so the dietary differences may have arisen from various factors that differed between the study periods. As part of a long-term project aimed at assessing the potential impacts of climate change on myrmecophagous mammals in the Kalahari ecosystem, the present study collected faecal samples from aardvark and Temminck’s pangolin at the same time in the Kalahari for one year to compare their diets and assess dietary overlap (Chapter 3). In addition to dietary analysis, the study added to our long-term data (since September 2014) of grass cover and counts of ants and termites in pitfall traps, from September 2019 to August 2022 (Chapter 2). These long-term data revealed substantial fluctuations in grass and insect availability over time, with termite populations apparently less likely to recover after drought years compared to ants (Chapter 2). The study also assessed the abundance xiii and orientation of burrows that are available to the aardvark and Temminck’s pangolin in the duneveld in the Kalahari during winter of 2021 (Chapter 4). Lastly, the study assessed the distribution and ecology of the aardvark and Temminck’s pangolin in southern Africa using freely available images and videos from Facebook and Instagram over 10 years (2010 – 2019) (Chapter 5). During the study, the study site, Tswalu Kalahari Reserve, experienced higher than average rainfall (2020 and 2021), resulting in high grass cover and an increase in the number of ants in pitfall traps, following a very hot and dry period in 2019. In contrast, termite numbers remained low. Despite the apparent low number of termites, as reflected in the pitfall traps, aardvark preferred termites over ants in their diet, and consumed predominantly termites of the genus Trinervitermes (45% of their diet) over the study period. Temminck’s pangolin preferred ants over termites and consumed mainly ants of the genus Crematogaster (42%). Although aardvarks and Temminck’s pangolin had preferences for their specific prey items, it was shown for the first time that there was dietary overlap between the two mammal species, with higher overlap when prey resources were readily available during autumn, and lower dietary overlap when prey resources were scarce during spring. The present study, however, was conducted during an unusually wet period characterized by above-average rainfall, so it is important to determine how competition for dietary items will change in hotter and drier years, when insect populations will likely be lower. Ants and termites rely on grasses for their survival; therefore, one would predict that the abundance of burrows, dug primarily by aardvark, is likely to be related to grass cover. The present study site comprised two distinct areas, differing in grass cover as a result of differences in historical grazing pressure. I therefore investigated the availability and use of burrows in the area with low grass cover and the area with high grass cover, during winter. Burrows serve as a beneficial buffer against climatic conditions for burrowing species, offering heat avoidance during the day and warmth during the night. It was found that burrow numbers were positively associated with grass cover. More burrows also were found on the western side of the dunes than on the eastern side, most likely because the xiv western side receives more direct sunlight in the afternoon, providing a warmer microclimate overnight during the cold winter. Finally, the study explored whether social media could provide supplementary information on the distribution and ecology of the aardvark and Temminck’s pangolin in southern Africa. The data, which were collected through examining photos and videos on Facebook and Instagram, confirmed that the aardvark is found throughout South Africa while Temminck’s pangolin is restricted to the northern regions of South Africa. The images also confirmed recent research that poor body condition is associated with greater diurnal activity for the aardvark, likely a response to high energetic demands of being active on cold nights. Little is known about drinking behaviour by the aardvark and Temminck’s pangolin, with only 7 records previously published for the aardvark. It was found a further 32 records for the aardvark, and 7 for the pangolin, showing that both species do occasionally drink opportunistically. The records also provided information on the predation of both myrmecophagous mammals. Predation was observed at almost all times of the year for both species, with leopard (Panthera pardus) the most common predator for the aardvark, and lion (Panthera leo) the most common predator for Temminck’s pangolin. Even though there were far fewer records of images in other southern African countries, social media appears to be a useful tool for collecting data on the distribution and ecology of the aardvark and Temminck’s pangolin. Understanding the ecology and distribution of the aardvark and Temminck’s pangolin in the Kalahari and other regions in relation to available prey resources and local climate is crucial for improving our conservation efforts of the species through informed management practices.Item Isolated nocturnal hypertension and target organ damage in a population of African descent(University of the Witwatersrand, Johannesburg, 2024) Phukubje, Edgar Matome; Maseko, MuziThe use of ambulatory blood pressure monitoring (ABPM) has revolutionised the approach to hypertension diagnosis and management. The ability to monitor blood pressure over a 24-hour period has enabled researchers to monitor blood pressure profile away from the doctor’s clinic, which has led to the diagnosis of various hypertension phenotypes like masked hypertension, isolated nocturnal hypertension (INH) and isolated daytime hypertension (IDH), and others. Previous studies have shown that night-time blood pressure is more closely related to target organ damage compared to daytime blood pressure. Since more studies indicate that people of African ancestry have elevated night-time blood pressure compared to other population groups, nocturnal blood pressure monitoring in this population group is crucial. However, there are few studies that have investigated the prevalence of INH, and their results are inconclusive. Hence the impact of INH on cardiovascular target organ damage is not well understood in this population group. It has been reported that dietary salt intake (DSI) has more severe cardiovascular outcomes in African populations compared to non-African populations groups because they are said to be salt sensitive. However, there are no studies that have investigated the relationship between 24-hour urinary salt excretion and 24-hour dipping patterns in populations of African ancestry. In addition, the impact of INH on target organ damage has never been compared to that of IDH. Hence, current intervention strategies primarily rely on daytime blood pressure to diagnose and treat hypertension. The relationship between age and blood pressure is well understood, but current studies have mainly focused on daytime blood pressure. The impact of age on nocturnal blood pressure is not well understood in this population group, and it is also unclear whether the age-related changes in nocturnal blood pressure translate to any cardiovascular target organ changes. Therefore, the aim of this study was to determine the relationship between INH and cardiovascular target organ damage in a South African population of African ancestry. A total 1600 participants above 18 years were recruited. These form part of the ongoing South African Hypertension and Diet Study in the Human Nutrition Research Laboratory. Office blood pressure was measured conventionally and through SpaceLabs ambulatory oscillometric monitors for 24-hours. Target organ function was determined through echocardiographic measurements and applanation tonometry using the sphygmocor device. 24-hour urine samples were collected to determine electrolyte excretion rates. Blood was collected when the participants visited the clinic. Only data with complete 24-hour ABPM matched with complete urinary collections were included for data analysis and the final sample was 796 participants. v Findings from the current study showed that 11% of the participants had INH, 13% had 24- hour sustained hypertension and 4% had IDH. The three groups had different dipping patterns. The sustained hypertensive group were non-dippers, IDH group were dippers, and the INH group had two dipping patterns: non-dipping (IND) and reverse dipping (IRD). Urinary electrolyte concentrations were significantly higher in IDH, and lower in INH. The INH group and 24-hour sustained hypertensives were the oldest cohort, while the NT and IDH were youngest. Pulse wave velocity (PWV) was significantly higher in the IND and IRD. The NT and IDH group had the lowest PWV. PWV in the INH was similar but not significantly different to the 24-hour sustained HT group. These findings indicate that the two INH subtypes (IND and IRD) damage large arteries to a similar effect as 24-hour sustained hypertension, while IDH does not cause any damage. The ABPM results were used to show changes in blood pressure with age. Different age group ranges were used, in increments of 10 years. Increased nocturnal blood pressure was associated with being older. Additionally, age-related changes in nocturnal blood pressure were associated with pre-clinical diastolic dysfunction. The current findings further show that blood pressure related cardiovascular target organ damage occurs during night-time in this population group. Urine analysis showed increased excretion in IDH and sodium retention in INH. Aldosterone levels were significantly higher in the INH, compared to 24-hour sustained HT group. Low aldosterone and salt retention increased nocturnal BP in the INH group. This means the current rise in the prevalence of cardiovascular disease in people of African descent despite increased efforts to diagnose and treat hypertension, is driven by INH, which remains undiagnosed because of the over reliance on conventional blood pressure measurementItem Is 24-hour augmentation index a better indicator of arterial stiffness compared to clinic augmentation index?(University of the Witwatersrand, Johannesburg, 2024) Mukhovha, Wantonda Papinah; Maseko, MuziArterial Stiffness is a major independent risk factor that is strongly associated with an increased risk of developing cardiovascular diseases (CVDs), making it an important marker in the assessment of CVD risk. Therefore, in an effort to reduce the rising incidence of cardiovascular diseases in South Africa, it is crucial to determine the best indicator for arterial stiffness. Currently two indices are used to measure arterial stiffness, pulse wave velocity (PWV) and augmentation index (AI). Since arterial stiffness measurement techniques were developed much later than blood pressure (BP) measurement techniques, important lessons can be learned from BP measurement. Studies have indicated that 24-hour BP measurement is a much better tool of measurement compared to a once off conventional BP measurement. This creates a possibility that 24-hour arterial stiffness assessment is a better tool for measuring arterial stiffness compared to a once off clinic arterial stiffness measurement. Therefore, in this study we compared 24-hour AI to in-clinic AI and also assessed gender differences. Previous studies conducted on 24-hour AI were focused on establishing normal 24-hour AI reference values. To date, no studies have been conducted to compare 24-hour AI to in-clinic AI. Moreover, gender differences in the 24-hour arterial stiffness profile have never been studied. We recruited 125 individuals of black African descent and took anthropometric measurements. We measured both conventional BP and 24-hour BP. Pulse wave analysis was performed to obtain both in-clinic and 24-hour AI. In the total population, 24-hour augmentation index (AI24) was significantly higher than in-clinic augmentation index (AIC) (p<0.0001). When participants were stratified according to gender, AI24 was significantly higher than AIC in both men (p<0.0001) and women (p<0.0001). Night-time augmentation index (AIN) in the total population was significantly higher than daytime augmentation index (AID) (p=0.0143). When participants were stratified according to gender, our results show that AIN was only significantly higher in women (p=0.0291) and not in men. Our results show that AIC may grossly be underestimating the prevalence of arterial stiffness and its adverse effects on cardiovascular target organs. Secondly, our results also show that there are gender differences in arterial stiffness fluctuations over the 24-hour period. In men, daytime arterial stiffness does not differ from night-time arterial stiffness. However, in women arteries become stiffer during the night-time compared to the daytime. These findings indicate that special attention must be given to night-time arterial stiffness because it may be more closely related to target organ damage than daytime arterial stiffness.Item The association between poor sleep quality and cardiometabolic risk in HIV+ individuals and the general population living in a rural area of South Africa(University of the Witwatersrand, Johannesburg, 2024) Reddy, Tracy; Scheuermaier, Karine; Karstaedt, AlanStudies show that both poor sleep quality and HIV infection independently increase cardiometabolic risk (CMR). Additionally, poor sleep quality is common with HIV infection. Our study investigated whether HIV infection interacts with poor sleep quality to affect CMR in people living with HIV (PLWH) in a rural area of South Africa. We recruited 200 HIV+ participants and 200 controls from Qwa Qwa in Free State in South Africa and assessed their CMR, sleep quality, daytime sleepiness, risk of obstructive sleep apnoea and degree of depressive symptoms. Sleep quality (p = 0.15), daytime sleepiness (p = 0.31) and the cardiometabolic risk score (MetScore) (p = 0.93) were similar between HIV+ and control participants. Fewer HIV+ participants had a high risk of sleep apnoea (p = 0.019) but more HIV+ participants had symptoms of clinical depression (p = 0.0007). Poorer sleep quality in the HIV+ participants was associated with pain (p = 0.0006), more severe depressive symptoms (p<0.0001) and longer HIV duration (p = 0.011). However, HIV infection was not associated with a higher MetScore (p = 0.18) once age, sex and sleep and depression markers were adjusted for. Additionally, HIV infection increased the risk of hypertension (p = 0.016). HIV status did not interact with sleep quality (p = 0.32) to affect CMR. Our findings indicate that healthcare facilities should consider monitoring CMR factors in HIV+ individuals.Item Comparison of Aortic Haemodynamics in Community Participants and Patients with Systolic Heart Failure and the Impact of Blood Pressure Control(University of the Witwatersrand, Johannesburg, 2024) Lebelo, Ntapo MarcusIn patients with systolic heart failure (HF), both decreases and increases in pulse pressure (PP) are associated with poor prognosis. If aortic PP in systolic HF is decreased due to systolic dysfunction, then improvements in stroke volume (SV) or forward wave pressure (Pf) would be beneficial. Alternatively, if hypertension is the primary cause of systolic HF, aortic PP may be increased as a consequence of high aortic characteristic impedance (Zc) and backward wave pressure (Pb), which would be detrimental. Accordingly, blood pressure (BP) lowering would be advantageous. However, the changes in central hemodynamics that accompany systolic HF are currently unclear. Hence, I aimed to assess central hemodynamics in systolic HF patients compared to community participants. I therefore compared aortic haemodynamics (central pressures [SphygmoCor], aortic tract outflow [echocardiography]), and the impact of controlled BP (SBP/DBP<140/90 mm Hg or SBP/DBP<130/80 mm Hg) between stable systolic HF patients (n=42) and age and sex-matched community participants (n=298). Systolic HF patients had lower central PP and Pb (p<0.005) and higher HR (p<0.005) than community participants. However, no other differences were noted. When assessing the impact of BP control (SBP/DBP<140/90 mm Hg), HF patients with uncontrolled BP had higher Zc (p<0.005), Pf (p<0.05), and systemic vascular resistance (SVR) (p<0.05) than both HF patients and community participants with controlled BP. Moreover, despite similar peripheral and central PP to community participants with uncontrolled BP, Zc (p<0.005) and SVR (p<0.05) were higher in HF patients with uncontrolled BP. However, when assessing more intense BP control (SBP/DBP<130/80 mm Hg), the differences in Zc, QxZc, and SVR between the systolic HF patients with uncontrolled BP and the community participants with uncontrolled BP were eliminated. In conclusion, a lower aortic PP, which was not due to decreased SV, was observed in stable systolic HF patients. However, in the presence of uncontrolled BP (SBP/DBP≥140/90 mm Hg), but not SBP/DBP≥130/80 mm Hg, Zc, QxZc and SVR were increased in patients with systolic HF. Hence, BP control and its level of control are imperative in patients with systolic HF to protect the heart from the detrimental effects of increased afterloads.Item Investigating the mechanism of action of Aristea ecklonii’s suspected antipyretic properties(University of the Witwatersrand, Johannesburg, 2024) Muller, Miles ChristopherAristea ecklonii (A. ecklonii) (Baker) is an indigenous, evergreen perennial medicinal plant used amongst South Africans to treat fever. This study aimed to investigate the antipyretic properties of aqueous A. ecklonii root extracts. Male Sprague-Dawley rats (250 – 300 g) received a subcutaneous (s.c.) injection of zymosan (300 mg/kg) or saline before receiving an intraperitoneal injection (i.p.) of paracetamol (50 mg/kg), aqueous A. ecklonii root extract (55 mg/kg) or saline. The i.p. injection was administered 15 h after the s.c. injection. Abdominal temperature was measured using temperature sensitive radio-transmitters. Blood, cerebrospinal fluid (CSF) and hypothalamic tissue was collected 90 min after the i.p. injection for the measurement of cytokines, prostaglandin E2 (PGE2) and enzymes involved in PGE2 synthesis. Zymosan increased abdominal temperature which peaked at 39.42 ± 0.14 °C. Compared to rats that received saline, rats receiving zymosan had increased concentrations of blood plasma IL- 1β and IL-6, increased PGE2 in the CSF and increased hypothalamic expression of COX-2 and mPGES1 (P < 0.05). Paracetamol and aqueous A. ecklonii root extract reduced the zymosan- induced fevers. Rats that received saline, followed by an i.p. injection of aqueous A. ecklonii root extract, had a decrease in abdominal temperature and an increase in blood plasma IL-1β, IL-6, TNF-α and IL-10 concentrations compared to rats that received saline (P < 0.05). Thus, the antipyretic properties of the A. ecklonii root extract seems to be related to its ability to induce systemic inflammation and not reduce the synthesis of hypothalamic PGE2 and thus should be used with caution in ill individuals.Item Sexual dimorphism and renin-angiotensin-aldosterone system (RAAS) in hypertension and left ventricular hypertrophy in Spontaneously Hypertensive Rat (SHR)(University of the Witwatersrand, Johannesburg, 2024) Selebano, KopanoBackground: The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and is linked to hypertensive left ventricular hypertrophy. Sex differences in the involvement of the RAAS in the development of hypertension and left ventricular hypertrophy are unclear, specifically in spontaneously hypertensive rats (SHRs). This study aimed to investigate the sexual difference in the RAAS effects on hypertension and ventricular remodelling in spontaneously hypertensive rats (SHRs). Methods: Thirty SHRs and Wistar Kyoto rats (WYKs) were assigned to four groups, namely; male SHR (n=8), female SHR (n=8), male WKY (n=7), and female WKY (n=7). Body weight, blood pressure and echocardiography parameters were measured before termination. Concentrations of RAAS parameters were measured using enzyme-linked immunosorbent assays (ELISA) at termination (after 7 months). The picrosirius red stain was used to determine collagen content in the left ventricle. Results: SHRs, in comparison to WKYs, had significantly higher blood pressure, greater heart and left ventricular mass, greater heart wall thickness, greater area of collagen and impaired left ventricular relaxation (reduced lateral e’), and increased filling pressures (increased E/e’) (p<0.05). SHRs also had significantly reduced end- diastolic volume, stroke volume and mid-wall fractional shortening (p<0.05). Females, in comparison to males, had reduced end-diastolic volume, stroke volume and mid- wall fractional shortening but had greater physiological growth (p<0.05). Female SHRs exhibited higher conscious and anaesthetised systolic and diastolic blood pressures, along with greater plasma concentrations of angiotensin II (ANG II) compared to other groups (p<0.05). v Conclusion: Compared to WKYs, SHRs developed concentric hypertrophy, impaired diastolic and systolic function. Compared to males, females developed greater physiological left ventricular growth with lower left ventricular relaxation and systolic function. The physiological cardiac differences may partly be influenced by factors such as body weight and blood volume. Additionally, female SHRs had elevated blood pressure, which may be due to increased plasma concentrations of ANG II.Item Determination of Characteristic Impedance in a Retrospective Cohort of Coronary Artery Disease in South Africa(University of the Witwatersrand, Johannesburg, 2024) Els, Danelle; Peterson , Vernice R.; Peters, FerandeThe relationship between coronary artery disease (CAD) and proximal aortic stiffness-induced increases in central arterial forward wave pressures (Pf) is uncertain. Using central pressure and aortic velocity and diameter measurements, we compared aortic characteristic impedance (Zc) (n=71) and central arterial pressure wave morphology (n=189) in patients with CAD to central arterial function in 210 age- and sex-matched controls from a community study. The results showed that Zc was markedly increased in patients with CAD compared to community controls (p<0.0001). In addition, after adjustment for mean arterial pressure and aortic root diameter, the early systolic pressures generated by the product of peak aortic flow (Q) and Zc (PQxZc) and Pf were markedly increased in patients with CAD as compared to controls (p<0.0001). This increase in Pf was accounted for by an enhanced PQxZc at peak PPc rather than increases in re-reflected wave pressures. Further adjustments for either brachial PP or systolic blood pressure (SBP) showed that higher Pf values were retained in the CAD patients (p<0.05, p<0.01, p<0.0001). After adjusting for conventional risk factors, peak central aortic PPc was higher in patients with CAD as compared to controls (p<0.05, p<0.005, p<0.0001). However, after adjusting for brachial SBP and confounders, central aortic PPc did not differ between the groups. Thus, increases in stiffness-associated proximal aortic Zc in patients with CAD translate into marked increases in Pf, but not peak PPc beyond brachial BP. These findings suggest that pulsatile load responsible for CAD is beyond brachial BP and poorly indexed by peak PPc.Item The Impact of Urinary Uromodulin (Tamm-Horsfall Protein) on Renal Function and Haemodynamic Factors in a Community Sample with a High Prevalence of Hypertension(University of the Witwatersrand, Johannesburg, 2024) Charles, Aaliah; Peterson, VernicePopulations of African ancestry have a high prevalence of primary hypertension and its comorbidities. As they primarily exhibit a volume-dependent form of hypertension, the role of nephron components needs to be explored. Uromodulin is a potential biomarker for renal function and tubular reserve; however, its relationship with renal function, haemodynamic parameters, and hypertension in a population of African ancestry is unknown. I therefore explored the relationship between urinary uromodulin (uUMOD) concentration and renal as well as hemodynamic parameters in an African community with a high prevalence of volume-dependent hypertension. Haemodynamics (central pressures [SphygmoCor], echocardiographic aortic velocity and diameter in the outflow tract), uUMOD concentrations (ELISA assay), renal function (creatinine clearance from 24-hour urine [n = 370]) were determined in a community of African ancestry (n = 397). No relationships between uUMOD concentrations and renal function, age, BMI, BP or hypertension were noted. However, uUMOD concentrations were higher in females than males, even after adjusting for confounders (P = 0.0007). An inverse relationship was observed between stroke volume (SV) and uUMOD (P = 0.0023). This inverse relationship was independent of confounders and present in hypertensives (P= 0.007) but not normotensives (P = 0.43). Hypertensives had a higher SV than normotensives (P = 0.047). In a community sample with a high prevalence of volume-dependent primary hypertension, uUMOD was inversely related to SV, particularly in hypertensives. Although uUMOD is not a biomarker for renal function in this population, these data suggest the need to investigate mechanisms linking uUMOD to SV to assist in identifying novel pathways to better treat volume-dependent hypertension.