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Physical activity, kidney function and kidney injury

Junglee, Naushad Ali (2015) Physical activity, kidney function and kidney injury. PhD thesis, Prifysgol Bangor University.

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Abstract

This PhD sought to exploit the acute effects of exercise upon the kidneys to make tenable links to pathological states such as acute kidney injury (AKI) and chronic kidney disease (CKD). It is surprising that such associations with their potential clinical implications have received limited attention so far despite the ever-increasing number of healthy individuals participating in vigorous and physiologically challenging activities. The work herein has shown how experimental in-vivo exercise models may be used to simulate a “stressed” kidney with features that resemble diseased states. Summarising the key findings briefly, the first study (chapter 2) demonstrated that maximal-intensity exercise in the form of an 800 metre sprint resulted in increased urinary concentrations of an AKI biomarker (neutrophil gelatinase-associated lipocalin / NGAL), suggesting mild kidney stress or a concentrating effect. However, plasma NGAL concentrations decreased and urinary rises were independent of post-exercise proteinuria. There was also an inverse relationship between urinary volume and urinary NGAL concentrations – an observation that is also seen in oliguric AKI. The systematic review in the second study (chapter 3) found promise in post-exercise proteinuria as a predictor for CKD progression. Five studies (N = 351) that met inclusion criteria, examined prospective cohorts of Type I diabetics who were at risk of CKD. Through combining the results of the primary outcome in four studies (N = 318), the presence of post-exercise proteinuria was highly associated with elevated resting proteinuria at follow-up (χ2 test, P < 0.0001) and significant odds ratios (developing CKD following a positive exercise test vs. not developing CKD) were noted in each of these four studies (OR 2.3-52.0). However, there was great variability and questionable validity in the interventions that did not permit meta-analysis. It was evident that exercise interventions need to be refined and standardised before applying to other at-risk CKD populations. In the third study (chapter 4), it was demonstrated that a prior bout of muscle-damaging exercise established a pro-inflammatory state with elevated plasma interleukin-6 (IL-6) concentrations, and that with subsequent endurance-based exercise in the heat there was increased kidney stress as measured by increased urinary NGAL and plasma creatinine concentrations. The latter elevations met clincial criteria for AKI. Also, plasma IL-6 and plasma NGAL concentrations were positively correlated. Lastly, the final study (chapter 5) extended the findings of chapter 4 by isolating the role of pro-inflammatory IL-6 in AKI. Through infusion of recombinant IL-6 in healthy males to concentrations above 100 pg/ml, elevations in plasma NGAL concentrations were shown but not to AKI ranges. In addition, there were no changes to plasma concentrations of other AKI biomarkers such as creatinine or cystatin C. Overall, this suggests that IL-6 is able to modulate NGAL but is not responsible per se for AKI or kidney dysfunction. Thus, it is likely that additional physiological aberrations are needed.

Item Type: Thesis (PhD)
Subjects: Degree Thesis
Departments: College of Health and Behavioural Sciences > School of Sport, Health and Exercise Sciences
Degree Thesis
Date Deposited: 28 Oct 2016 09:10
Last Modified: 28 Oct 2016 09:10
URI: http://e.bangor.ac.uk/id/eprint/8114
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