Proteomanalyse: Neue Wege zur verbesserten Behandlung der diabetischen Nephropathie

Zusammenfassung

Chronische Nierenerkrankungen sind gekennzeichnet durch einen langsam fortschreitenden Verlust der Nierenfunktion, der schließlich zum Nierenversagen führt. Betroffene Patienten benötigen im Endstadium eine Nierenersatztherapie in Form der Dialyse und/oder Nierentransplantation mit erheblichen Konsequenzen sowohl für Mortalität als auch für die Lebensqualität der Patienten. Da die Prävalenz des Diabetes kontinuierlich deutlich steigt, nimmt gegenwärtig die diabetische Nephropathie (DN) als Dialyseursache zahlenmäßig den höchsten Rang ein. Die individuelle Behandlung der DN sowie der resultierenden kardiovaskulären Komplikationen in der frühen und damit einer Therapie zugänglichen Erkrankungsphase ist derzeit deutlich erschwert, da es an einer effektiven, nichtinvasiven, validen Routinediagnostik dieser Patienten mangelt. Die derzeit verwendeten Marker Serum-Kreatinin/eGFR und Albumin im Urin sind geeignet, um die DN in späteren Stadien abzubilden, jedoch sind sie von geringer Aussagekraft in der Erkennung von frühen Stadien. Eine neue diagnostische Methode ist die Analyse des Proteoms, der Gesamtheit aller Proteine und Peptide. Die Proteomanalyse hat die Identifikation von 273 Biomarkern im Urin zur Diagnostik chronischer Nierenerkrankungen ermöglicht. Ein auf diesen Biomarkern beruhender Klassifikator, CKD273, ermöglicht eine im Verhältnis zu den derzeit verwendeten Biomarkern signifikant bessere Identifizierung der DN. Die Daten zeigen vor allem eine Verbesserung der Früherkennung und Prognostik. Dies ermöglicht eine frühzeitige und gezielte Therapie und damit eine wesentlich verbesserte Option den fortschreitenden Verlust der Nierenfunktion aufzuhalten.

Abstract

Chronic kidney diseases are characterized by a slow progressive loss of renal function leading to kidney failure. At end-stage renal disease, affected patients require renal replacement therapy, dialysis or kidney transplantation, with considerable consequences for mortality and quality of life of the patients. Since the prevalence of diabetes is increasing continuously in the general population, diabetic nephropathy is currently the number one cause of dialysis. The individual treatment of diabetic nephropathy and its resulting cardiovascular complications in the early and thus therapy-accessible phase of the disease is impeded by the lack of effective, non-invasive, valid routine diagnostic procedures for these patients. The currently used standard biomarkers serum creatinine/eGFR and urinary albumin are suitable to display DN in later stages, but they are of low significance in the detection of early stages. A new diagnostic method is based on the analysis of the proteome, the entirety of all proteins and peptides. Proteome analysis enabled the identification of 273 urinary biomarkers for the diagnosis of chronic renal disease. A classifier based on these biomarkers, CKD273, allows a significantly better identification of DN compared to the currently used biomarkers. The data specifically indicate an improvement in early diagnosis and prognosis. This allows an early and targeted therapy and therefore a significantly improved possibility to stop the progressive loss of renal function.

Schlüsselwörter

diabetische Nephropathie - CKD273 - Diagnose - Prognose

Key words

diabetic nephropathy - CKD273 - diagnosis - prognosis

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