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Acta Physiologica Hungarica
Authors: János Peti-Peterdi, L. Navar, P. Darwin Bell, D. Casellas, P. Carmines, E. Inscho, and S. Oparil

This article pays tribute to the tremendous achievements of Dr. László Rosivall in renal (patho)physiology research and nephrology education in Hungary on the occasion of his 60th birthday. For the past several decades Dr. Rosivall has been a charismatic leader of academic institutions, national and international societies, foundations in physiology, nephrology and hypertension, but the most important of his many contributions, is his role as a scientist. He earned his MD with Summa cum Laude at Semmelweis University (1973) and was invited immediately after that to join the laboratory of Hársing. He studied the distribution of intra-renal blood flow employing then state-of-the-art methods as well as developed his own technique at Semmelweis University and at the University of Bergen with Knut Aukland. This led to his PhD thesis and degree in 1980. An important determinant of his early basic scientific training and development was his postdoctoral research fellowship and later many visiting professorships in the Nephrology Research and Training Center (NRTC) at the University of Alabama at Birmingham, Birmingham, AL, USA between 1981 and 1983. Actually, this research fellowship not only impacted his own future career, but it also cleared the path for many other young Hungarian scientists who later trained with Dr. Rosivall and then at UAB. The early 1980s were the years of significant scientific discoveries and the NRTC team at UAB made important contributions by their studies on renal and glomerular hemodynamics, the renin-angiotensin system (12, 19, 22) and by the development of classic experimental techniques like renal micropuncture, microperfusion, and the juxtamedullary nephron preparation (3) that are still being used worldwide. When Dr. Rosivall joined UAB in the 1980s, the team at the NRTC included Drs. Navar, Bell, Inscho, Carmines, Casellas, and Oparil, among many others, who share their fond memories of working with Dr. Rosivall in this article.

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Abstract

Objective

In this observational study we addressed accelerated arteriosclerosis (AS) in patients with chronic renal failure (CRF) on hemodialysis (HD) by measuring vascular stiffness (VS) parameters and attempted to relate them to pro-inflammatory and protective factors.

Patients

96 consecutive patients receiving regular HD were included. 20 adult patients without major renal, cardiovascular or metabolic morbidities served as controls.

Methods

AS parameters (carotid-femoral pulse wave velocity – PWV, aortic augmentation index – Aix) were measured by using applanation tonometry (SphygmoCor, AtCor Medical, Sidney). In addition to routine laboratory tests 25(OH) vitamin D3 (vitamin D3) and high-sensitivity C-reactive protein (hsCRP) were quantified by immunometric assay; whereas fetuin-A, α-Klotho, tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) were determined by ELISA.

Results

Pro-inflammatory biomarkers (hsCRP, TNF-α and TGF-β1) were markedly elevated (P < 0.01), while anti-inflammatory factors (fetuin-A: P < 0.05, α-Klotho: P < 0.01, vitamin D3: P < 0.01) significantly depressed in HD patients when compared to controls. PWV was significantly affected only by total cholesterol, fetuin-A and dialysis time. Multiple linear regression analyses revealed that several clinical and laboratory parameters were associated with pro- and anti-inflammatory biomarkers rather than VS. The impact of baseline clinical and biochemical variables on outcome measures were also analyzed after three-year follow-up, and it was demonstrated that low levels of vitamin D, α-Klotho protein and fetuin-A were related to adverse cardiovascular outcomes, whereas all-cause mortality was associated with elevated hsCRP and depressed vitamin D.

Conclusions

Our results provide additional information on the pathomechanism of accelerated AS in patients with CRF, and documented direct influence of pro- and anti-inflammatory biomarkers on major outcome measures.

Open access