Nephrological Research in Context with Kidney Replacement Therapy

Prevention of hypotensive episodes while improving fluid status in dialysis patients is a delicate balance act and requires novel, highly adaptive treatment algorithms. Answering the Precision Medicine Call by the Vienna Science and Technology Fund (WWTF), investigators from the Medical Univerity of Vienna, AIT Austrian Institute of Technology, and the Institute for Molecular Pathology have initiated a research consortium to tackle this challenge.

Intravenous fluid therapy is used frequently and ubiquitously across clinical disciplines and is considered indispensable for the treatment of various serious diseases. Nevertheless, the question of the most adequate procedure for fluid replacement, in both acute situations as well as in long-term therapy, is currently one of the most controversial debates in intensive care medicine. Although intravenous fluid therapy is probably the most common intervention in medicine, the question arises as to whether enteral fluid administration would be more physiological.

Kidney failure requiring replacement therapies predispose patients for various cardiovascular diseases, exemplarily measurable as an increase in left ventricular mass after the onset of hemodialysis. Therapeutic options are limited with progressing kidney disease through occurring events of hyperkalemia.

Mineral bone disease (MBD) affects nearly all patients with kidney failure requiring dialysis and requires surveillance of serum phosphate, serum calcium and parathyroid hormone (PTH) levels at regular intervals. Considerable controversy exists over the question which diagnostic assay should be used to measure and monitor PTH. The existence of PTH fragments, which became known to be detected by first and second generation PTH assays (second generation, also entitled “intact” PTH assays) led to the development of full-length PTH assays (third generation, also entitled “biointact” PTH assays) that detect only full length PTH (1-84).

While hundreds of laboratory parameters can be readily analyzed in blood, serum or plasma by standard clinical laboratories, available diagnostic parameters in urine are comparably sparse. Clinical decisions regarding stratification into risk-groups or even treatment of patients frequently need to rely on coarse markers of kidney damage such as the overall protein:creatinine ratio or the albumin:creatinine ratio of urine, supplementing clinical information and the results of kidney biopsy. A quantitative analysis of the protein content of urine appears appealing, as kidney diseases likely leak a protein fingerprint into urine. We will therefore establish state-of-the art technology based on mass spectrometry to compare individual rather than total protein ratios in urine, with the goal of correlating these values to states of health and disease. In the future, such markers may assist clinicians in risk stratification or treatment decisions regarding nephrological patients.

Fluid status in haemodialysis is strongly associated with acute symptoms, hospitalization and cardiovascular mortality. Despite technological advances, routine fluid management practice (target weight estimation; interdialytic weight gain control) have changed little in decades. Our consortium frames fluid management as a complex intervention requiring systems level support that integrates routinely collected dialysis data with patient reported symptoms to enable truly shared, patient centered decisions. A transnational approach (Ireland, Scotland, Austria) enhances generalizability and device agnostic implementation. The intervention design is under-pinned by behavioral theory, drawing specifically on Social Cognitive Theory and established behavior-change mechanisms related to self-efficacy, feedback, and shared decision-making.

The study of posttransplant diabetes mellitus (PTDM) is a primary focus of the HD & Co Research Group. At the Medical University of Vienna, the first projects and research ideas in this area started in the year 2007 under the leadership of Marcus Säemann and primarily involved our former colleagues Johannes Werzowa and Michael Haidinger, besides Manfred Hecking.