Privat-docent thesis
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Development of Non-Invasive Tools in Nephrology

ContributorsBerchtold, Lena
Number of pages117
Defense date2024-04-26

Chronic kidney disease (CKD) is characterized by abnormal kidney structure and/or function lasting more than three months. It is a prevalent condition, affecting approximately 10% of the global population. Terminal renal disease is, fortunately, much less frequent, with a prevalence estimated to be around 1 in 1000 patients. CKD is, therefore, a significant public health concern. Early identification, prevention, and management of CKD can substantially mitigate this progression in the patients with the highest risk, necessitating early identification. Regular monitoring is essential for CKD patients to prevent and manage complications. Therefore, the development of non-invasive tools in nephrology is paramount, both for enhancing diagnostic capabilities and for closely monitor patients to improve their prognosis.

In our studies, we first optimized a diffusion magnetic resonance imaging (MRI) sequence for quantifying renal fibrosis in collaboration with radiologist. We validated this novel sequence on healthy volunteers and two animal models of renal disease. Subsequently, we included patients with primary renal disease or an allograft and successfully demonstrated that diffusion MRI enables the quantification of renal fibrosis and detects a significant percentage of renal fibrosis. Our research further revealed that diffusion MRI can track the progression of renal fibrosis over time. Notably, it also possesses the ability to predict the evolution of renal function, independently of baseline proteinuria and renal function. We have thus developed diffusion MRI as a non-invasive tool for quantifying renal fibrosis, monitoring renal fibrosis and predicting renal outcomes in CKD patients. We are very optimistic that this advancement will considerably enhance the management of CKD patients and potentially become a routine clinical tool in the future.

Moreover, we have worked on the development of several biomarkers. Our investigation focused on assessing whether phosphocalcic markers could serve as indicators of interstitial fibrosis and vascular lesions in kidney allograft recipients. We have been able to show a significant association between PTH, vitamin D, calcification propensity (T50), and interstitial fibrosis, as well as vascular lesions in kidney allograft recipients, irrespective of renal function. Subsequently, we explored the predictive capacity of phosphocalcic markers in relation to rapid declines in renal function in the same population. We have shown that only T50 predicts a rapid decline of renal function in kidney transplant recipients. Additionally, we delved into the connection between hyponatremia post-renal transplantation and mortality, decline in renal function, and graft loss. Notably, we found no substantial link between hyponatremia at 6 months post-transplant and mortality, renal function decline, or graft loss.

As other non invasiv tools, we developed a genetic risk score in a specific nephropathy : primary membranous nephropathy. Membranous nephropathy stands as the leading cause of nephrotic syndrome in adults without diabetes. Post-kidney transplantation, recurrence of membranous nephropathy is observed in a subset of patients. Our research underscored that donor genetics can predict the risk of glomerulonephritis recurrence following kidney transplantation. This discovery is a significant advancement in our comprehesion of this disease.

Citation (ISO format)
BERCHTOLD, Lena. Development of Non-Invasive Tools in Nephrology. 2024. doi: 10.13097/archive-ouverte/unige:176808
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Creation05/03/2024 11:44:41 AM
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