Servicenavigation

Detailseite

Zurück

Projekt Druckansicht

Therapeutische Implikationen und pathophysiologische Rolle von Calprotectin beim akuten Nierenversagen

Fachliche Zuordnung Nephrologie
Förderung Förderung von 2011 bis 2018
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 152203169
 
Erstellungsjahr 2019

Zusammenfassung der Projektergebnisse

TP7 aimed at a characterization of calprotectin as a novel biomarker for acute kidney injury (AKI). In the first funding period we performed a proof of concept trial showing that urinary calprotectin is concentrations are substantially increased in intrinsic AKI, whereas they resembled healthy controls in prerenal AKI. This finding was confirmed in a second cohort (validation trial). In the second funding period we demonstrated that urinary calprotectin is able to distinguish prerenal and intrinsic AKI in pediatric populations as well. With regard to the effects of immunosuppression, it remained unclear whether calprotectin had a discriminatory potency in AKI after renal transplantation as well. A further clinical trial addressed this question and revealed a diagnostic potency in this setting. Moreover, urinary calprotectin concentrations obtained early after transplantation demonstrated a predictive value for graft function of the following 12 months. Immunohistochemistry studies identified monocytes and granulocytes as the primary source of calprotectin in the renal interstitium. To determine the timecourse of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, we performed a trial in subjects undergoing nephron sparing surgery for kidney tumours. Calprotectin concentrations started rising within 2 hours after ischaemia/reperfusion-induced kidney injury and remained increased for several days. An interesting collateral finding was that urothelial tumours are associated with increased calprotectin concentrations as well. This finding was separately addressed in a consecutive confirmatory trial including immunohistochemical analyses.8 Pyuria was identified as a further alternative source of urinary calprotectin and has to be taken into account in the interpretation of calprotectin concentrations in AKI. In summary, these findings identified calprotectin as a sensitive but not a specific marker in AKI. Since AKI may also occur in pre-established chronic kidney disease (“acute on chronic AKI“), a further clinical trial investigated urinary calprotectin in different forms of CKD. Only inflammatory kidney diseases, e. g. vasculitis, were consistently associated with increased calprotectin concentrations. Noninflammatory diseases were associated with low calprotectin concentrations thereby allowing a diagnostic use in the setting of acute on chronic AKI. A prognostic value for a future deterioration of renal function could not be demonstrated. This aspect was additionally investigated in the international multicenter randomized controlled ”STOP-IgAN“ trial. In accordance with the above mentioned data calprotectin did neither demonstrate a predictive value for a deterioration of renal function, nor for a response to immunosuppressive therapy in IgA nephropathy. In the meantime other groups confirmed our central finding and moreover indicated that calprotectin plays a pathophysiological role in AKI. Very recently, the clinical trials on the use of urinary calprotectin for the discrimination of intrinsic and prerenal AKI were summarized in a first meta-analysis. The findings of the first funding period led to an international patent application. Currently, the following projects are ongoing: We investigated the pathophysiological role of calprotectin in acute ischemia/reperfusion injury using S100A9 -/- mice. The experiments have been successfully finished. Moreover, we performed a clinical trial on the diagnostic use of calprotectin to identify subjects at increased risk for contrast induced nephropathy. In summary, the two funding periods were used to successfully perform an in-depth characterization of the diagnostic use, the dynamics and the source of urinary calprotectin in acute and chronic kidney injury in different populations.

Projektbezogene Publikationen (Auswahl)

 
 

Zusatzinformationen

© 2024 DFG Kontakt / Impressum / Datenschutz

Textvergrößerung und Kontrastanpassung