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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-01112022-153524


Thesis type
Tesi di dottorato di ricerca
Author
GAROFOLO, MONIA
URN
etd-01112022-153524
Thesis title
Toward better phenotyping and risk stratification in patients with Diabetic Kidney Disease (DKD): the role of biomarkers of kidney damage and of morphological features
Academic discipline
MED/13
Course of study
SCIENZE CLINICHE E TRASLAZIONALI
Supervisors
tutor Prof. Penno, Giuseppe
Keywords
  • Biomarkers
  • Cardiovascular Outcomes
  • Diabetes
  • Diabetic Kidney Disease
  • Kidney Ultrasound
  • Mortality
  • Renal Failure
Graduation session start date
18/01/2022
Availability
Full
Summary
The natural history of DKD is changing, with the non-albuminuric DKD (Alb-DKD) becoming prevalent. The project aims to better define DKD phenotypes and enhance risk stratification for ESRD, CV events and mortality. The “epidemiological study”, i.e. the prospective evaluation of a cohort of 961 T2D subjects (13-year follow-up) demonstrated that the Alb-DKD was associated with higher all-cause mortality, with the highest death rate in Alb+DKD subjects. Alb-DKD, even after adjustment for confounders, was also associated with significantly increased incidences of coronary events, and hospitalization for HF, with no excess risk for ESRD. With respect to the “molecular and imaging phenotyping study”, morphological and vascular kidney parameters have been analyzed in 256 T2D subjects [67 no-DKD; 63 DKD 1-2; 62 Alb-DKD; 64 Alb+DKD], by 2D standard ultrasound scan and 3D volumes with X-matrix array technology. By both techniques, Alb-DKD showed significantly smaller total and parenchymal renal volumes. Furthermore, in the same subjects we use a panel of selected soluble biomarkers to shed light on the heterogeneity of DKD phenotypes with the aim of identify, tracing and distinguishing putatively underlying pathogenic mechanism. Inflammatory, tubulo-interstitial and glomerular biomarkers seem to differently contribute to the specific features of each DKD phenotype. In particular, some biomarkers appear to be differently associated with the Alb-DKD and Alb+DKD. These data suggest that different DKD phenotypes may recognize different prognosis in terms of CV and renal outcomes, as well distinctive traits in kidney morphology and biomarkers profile.
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