Deciphering Diabetes Mellitus in Chronic Kidney Disease - from Posttransplant Hyperglycemia to Precision Medicine Urinary Proteomics
The present project aims at deciphering diabetes mellitus in patients with chronic kidney disease (CKD) and combines our previous expertise in Post-Transplant Diabetes Mellitus (PTDM) with specific goals of a recently approved precision medicine grant, dealing with fluid management in hemodialysis (HD) patients in general, but urinary proteomics in particular. The proteomics approach will pursue the following two objectives:
- To investigate the proteome of urine and used dialysate. The hypothesis is that biomarkers for outcomes (such as thymosine-beta-4) might be identifiable in dialysate and urine, which may ultimately allow tailoring the HD session (Objective 1).
- To analyze the urinary proteome of CKD patients with diabetes mellitus. A simultaneously ongoing classification of these patients into various subtypes might improve our understanding of the pathophysiology of kidney function decline and could identify further urinary markers (Objective 2).
Simultaneously, analyses of kidney transplanted patients with and without PTDM during following-up of the ITP-NODAT (Insulin Therapy for the Prevention of New-Onset Diabetes After Transplantation) study, we will analyze oral glucose tolerance test-derived read-outs of insulin secretion and insulin sensitivity, pursuing the objective:
- To investigate if beta-cell function (as opposed to insulin sensitivity) improved in patients who adhered to the basal insulin therapy protocol and declined in patients who deteriorated to PTDM. Further, to assess the effect of high versus low steroid doses in ITP-NODAT patients, and to describe the particular effect of insulin pump therapy (a side-arm of the ITP-NODAT study (=SAPT-NODAT; unpublished, as of yet; Objective 3).
Methods and Skills:
Mass spectrometry and analysis of proteomics; clinical studies on PTDM
Schwaiger E, Krenn S, Kurnikowski A, Bergfeld L, Perez-Sáez MJ, Frey A, Topitz D, Bergmann M, Hödlmoser S, Bachmann F, Halleck F, Kron S, Hafner-Giessauf H, Eller K, Rosenkranz AR, Crespo M, Faura A, Tura A, Song PXK, Port FK, Pascual J, Budde K, Ristl R, Werzowa J, Hecking M: Early postoperative basal insulin therapy versus standard of care for the prevention of diabetes mellitus after kidney transplantation: A multicenter, randomized trial." JASN (accepted for publication 2021)
Müller MM, Schwaiger E, Kurnikowski A, Haidinger M, Ristl R, Tura A, Pacini G, Werzowa J, Hecking M: Glucose metabolism after kidney transplantation: insulin release and sensitivity with tacrolimus- versus belatacept-Based immunosuppression. Am J Kidney Dis 77: 462-464, 2021
Berner C, Marculescu R, Frommlet F, Kurnikowski A, Schairer B, Aigner C, Bieglmayer C, Hecking M: Parathyroid hormone concentrations in maintenance hemodialysis: longitudinal evaluation of intact and biointact assays. Kidney Med 3: 343-352.e1, 2021
Kurnikowski A, Nordheim E, Schwaiger E, Krenn S, Jenssen TG, Hecking M: Diagnostic criteria for post-transplant diabetes mellitus after kidney transplantation: an analysis through 2 years in patients from the Itp-Nodat study. Abstract and poster presented at the EASD annual meeting 2020, 2020.
Hödlmoser S, Winkelmayer WC, Zee J, Pecoits-Filho R, Pisoni RL, Port FK, Robinson BM, Ristl R, Krenn S, Kurnikowski A, Lewandowski M, Ton A, Carrero JJ, Schernhammer ES, Hecking M: Sex differences in chronic kidney disease awareness among US adults, 1999 to 2018. PloS One 15: e0243431, 2020