Doctoral Degrees (Physiological Sciences)

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Browsing Doctoral Degrees (Physiological Sciences) by browse.metadata.advisor "Myburgh, Kathryn Helen"

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    Neutrophil gelatinase-associated lipocalin and associated damage markers in a chronic kidney disease model and an acute muscle injury model.
    (Stellenbosch : Stellenbosch University, 2024-03) Mahachi, Carol Batsirai; Myburgh, Kathryn Helen; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Molecular markers of chronic pathology or acute tissue injury may be generalised or specific. Kidney and muscle are complex multicellular tissues predisposed to injury. The human immunodeficiency virus (HIV) causes kidney damage (KD) including neutrophil activation, as does acute exercise- induced muscle damage. This study aimed to assess the roles of matrix metalloproteinase 9 (MMP9), neutrophil gelatinase-associated lipocalin (NGAL) and fibroblast growth factor 21 (FGF21) in these conditions. Biobanked plasma and urine samples were obtained from 56 patients with confirmed KD and 10 healthy participants. Patient groups were HIV+ no KD, HIV⁺ with associated nephropathy (HIVAN), HIV⁺ with focal segmental glomerular sclerosis (FSGS) and KD-FSGS. Pathology data and laboratory data were collected from patients’ hospital records. Plasma and urine were analysed for MMP9, NGAL and FGF21. Immunohistochemistry staining was done on 6 kidney biopsies and 12 muscle biopsies to detect granulocytes (CD15), MMP9 and NGAL. The young healthy participants undertook plyometric exercise to induce acute muscle tissue damage. Blood was collected at baseline, post exercise, at 2 and 24 hours post exercise and analysed for the same biomarkers. Baseline and 24 hours post exercise muscle biopsies were stained using the same protocol as for the kidney biopsy samples. HIVAN patients had significantly higher urinary NGAL ng/mg compared to HIV-NKD (p<0.01), HIV-FSGS (p<0.05) and KD-FSGS (p<0.05). Similarly, plasma NGAL was significantly higher in HIVAN (p<0.05). Both plasma and urine MMP9 were variable in HIVAN and only significantly higher than HIV-NKD (p<0.05), not HIV-FSGS or KD-FSGS. HIVAN had a significantly higher urine MMP9/NGAL-complex ng.mg than HIV-NKD (p<0.05). Plasma MMP9/NGAL complex was significantly lower in the HIV-NKD group than in the HIVAN group and the HIV-FSGS group (p<0.01 and p<0.01 respectively). In the exercise study, NGAL and MMP9 were significantly higher post exercise than baseline (p<0.01 and p<0.05). Only MMP9 remained higher 2 hours post exercise (p<0.01). Elevations in NGAL after exercise-induced muscle damage did not reach the high levels seen with chronic KD, HIVAN. Similarly, p FGF21 was higher in HIVAN than at any time point after exercise. In contrast, MMP-9 for the HIVAN group was significantly lower than at 2 hours post exercise (p<0.05). MMP9 and NGAL colocalised in renal tissue of HIVAN participants. The overlap coefficient for MMP9 and NGAL was not significantly different to the other KD groups. In the HIVAN participants, the spatial ratio of MMP9 was significantly more than in the healthy control p<0.01. In HIVAN, the spatial ratio of NGAL was significantly more than healthy kidneys (p<0.01). In HIVAN, MMP9 and NGAL, colocalised more than healthy kidneys (p<0.001). Even in mild inflammation, the spatial ratio of MMP9 was more than in healthy kidneys (p<0.01) In muscle, the spatial ratio of MMP9 decreased significantly from baseline to 24 hours post exercise (p<0.05). In conclusion, NGAL, MMP9 and FGF21 are useful markers to differentiate between chronic diseases. In acute settings, NGAL, MMP9 and FGF21 increase. MMP9 and NGAL return to baseline levels after 24 hours. These markers are useful in following up on the recovery after an acute event.