Florian Knoll - Academia.edu (original) (raw)

Papers by Florian Knoll

Variable mechanisms of vascular calcification in different segments of the arterial tree in patients with chronic kidney disease

Kidney International, 2014

Coumarins and survival in incident dialysis patients

Nephrology Dialysis Transplantation, 2011

The benefit and risk of oral anticoagulation in dialysis patients are debated controversially. We... more The benefit and risk of oral anticoagulation in dialysis patients are debated controversially. We prospectively followed 235 dialysis patients of the INVOR Study (Study of Incident Dialysis Patients in Vorarlberg) for up to 7 years and analysed the prevalence and incidence of atrial fibrillation (AF) and the impact of coumarin therapy on survival. Oral anticoagulation was monitored frequently. A total of 748 person-years were recorded with a median follow-up of 2.84 years. Twelve patients (5.1%) had AF at the start of dialysis. During follow-up, 40 patients (17.0%) developed AF, representing an incidence of 5.85 per 100 person-years. AF was positively associated with mortality (P = 0.004). Forty-six (19.6%) of the 235 patients were treated with coumarins. The majority (93.7%) had a clear indication for oral anticoagulation. In 65% of our patients, AF was the indication for coumarins. Patients without coumarins and without AF represented our reference group. The mortality risk of the coumarin-treated patients with AF or an alternative indication for coumarins was slightly lower compared to the reference group [hazard ratio (HR) 95% confidence interval (CI): 0.80 (0.28-2.29), P = 0.679 and 0.42 (0.16-1.10), P = 0.078, respectively]. No patient under sufficient oral anticoagulation experienced a stroke or a fatal bleeding event. Patients with AF and a contraindication for coumarins had a significantly higher mortality risk compared to the reference group [HR (95% CI): 3.90 (2.16-7.04), P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001]. Our data suggest that coumarins might be less harmful than previously anticipated when clearly indicated and closely monitored.

PLoS ONE, 2014

Background: Studies on the association between iron supplementation and mortality in dialysis pat... more Background: Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting. Methods: In our observational single-center cohort study (INVOR study) we prospectively studied 235 incident dialysis patients. Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and allcause mortality, cardiovascular and sepsis-related mortality. Furthermore, the timedependent association of ferritin levels with mortality in patients with normal Creactive protein (CRP) levels (,0.5 mg/dL) and elevated CRP levels ( §0.5 mg/dL) was evaluated by using non-linear P-splines to allow flexible modeling of the association. Results: One hundred and ninety-one (81.3%) patients received intravenous iron, 13 (5.5%) patients oral iron, whereas 31 (13.2%) patients were never supplemented with iron throughout the observation period. Eighty-two (35%) patients died during a median follow-up of 34 months, 38 patients due to cardiovascular events and 21 patients from sepsis. Baseline CRP levels were not different between patients with and without iron supplementation. However, baseline serum ferritin levels were lower in patients receiving iron during follow up (median 93 vs 251 ng/mL, p,0.001). Iron supplementation was associated with a significantly reduced all-cause mortality [HR (95%CI): 0.22 (0.08-0.58); p50.002] and a reduced cardiovascular and sepsis-related mortality [HR (95%CI): 0.31 (0.09-1.04); p50.06]. Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality, whereas in patients with elevated CRP values ferritin levels.800 ng/mL were linked with increased mortality. Conclusions: Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients. While serum ferritin levels up to 800 ng/mL appear to be safe, higher ferritin levels are associated with increased mortality in the setting of concomitant inflammation. Shown for each model are estimated HRs for the linear component of the non-linear P-spline and HRs for ferritin measurements per 100 ng/mL increase. * Adjusted for age, sex, diabetes mellitus and time-dependent albumin and hemoglobin. ** Cardiovascular or sepsis mortality: myocardial infarction (MI), heart failure, sudden death, ischemic stroke, hemorrhagic stroke, sepsis.

PLoS ONE, 2011

High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional p... more High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are associated with clinical outcomes in the general population. Data in patients with chronic kidney disease are sparse. We therefore investigated the association of MR-proANP and MR-proADM levels with all-cause and cardiovascular (CV) mortality, CV events and peripheral arterial disease in 201 incident dialysis patients of the INVOR-Study prospectively followed for a period of up to more than 7 years. The overall mortality rate was 43%, thereof 43% due to CV events. Both baseline MR-proANP and MR-proADM were associated with higher risk of all-cause (HR = 1.44, p = 0.001 and HR = 1.32, p = 0.002, respectively) and CV mortality (HR = 1.75, p,0.001 and HR = 1.41, p = 0.007, respectively) after adjustment for age, sex, previous CV events, diabetes mellitus and time-dependent type of renal replacement therapy. We then stratified patients in high risk (both peptides in the upper tertile), intermediate risk (only one of the two peptides in the upper tertile) and low risk (none in the upper tertile). Although demographic, clinical and laboratory variables were similar among the intermediate and high risk group, to be with both parameters in the upper tertile was associated with a 3-fold higher risk for all-cause (HR = 2.87, p,0.001) and CV mortality (HR = 3.58, p = 0.001). In summary, among incident dialysis patients MR-proANP and MR-proADM were shown to be associated with all-cause and CV mortality, with the highest risk when both parameters were in the upper tertiles.

Clinical Journal of the American Society of Nephrology, 2011

Background and objectives Hypoalbuminemia and hyperphosphatemia have been shown to be strong pred... more Background and objectives Hypoalbuminemia and hyperphosphatemia have been shown to be strong predictors of mortality in dialysis patients that might not be independent from each other. We prospectively investigated the relationship and interaction between serum albumin and phosphorus with all-cause mortality in an inception cohort of incident dialysis patients.

BMC Nephrology, 2012

Background: Complement activation products are present in atherosclerotic plaques. Recently, bind... more Background: Complement activation products are present in atherosclerotic plaques. Recently, binding of complement to elastin and collagen in the aortic wall has been demonstrated, suggesting a role of complement in the development aortic stiffness and atherosclerosis. The definitive role of complement in atherosclerosis and arteriosclerosis, however, remains unclear. Case presentation: We here describe a patient with hereditary complete deficiency of complement C4 suffering from Henoch-Schoenlein purpura and on renal replacement therapy for twenty-eight years. The patient had the full range of risk factors for vascular damage such as hypertension, volume overload, hyperphosphatemia and hyperparathyroidism. Despite that, his carotid artery intima media thickness was below the normal range and his pulse wave velocity was normal. In contrast, the patient's coronary and peripheral muscular arteries were heavily calcified. Conclusion: This case supports the hypothesis that complement plays an important role in the development of stiffness of elastic arteries. We speculate that inability to activate complement by the classical or lectin pathways protected the patient from atherosclerosis, arteriosclerosis, stiffening and calcification of the aorta and carotid arteries. Inhibition of complement activation may be a potential target for prophylactic and therapeutic interventions.

Vitamin D deficiency is associated with poor response to active hepatitis B immunisation in patients with chronic kidney disease

Vaccine, 2012

Vitamin D deficiency is highly prevalent in patients suffering from chronic kidney disease. At pr... more Vitamin D deficiency is highly prevalent in patients suffering from chronic kidney disease. At present it is not known whether this condition is associated with poor response to hepatitis B vaccination in these patients. We performed a retrospective analysis of 200 patients with chronic kidney disease stages 3-5D, who had undergone hepatitis B vaccination with three 40 μg recombinant hepatitis B vaccine doses in a single centre. Anti-HBs antibody titres and 25-hydroxyvitamin D (25(OH)D) levels were measured by chemiluminescence immunoassays. Vitamin D deficiency with serum levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 ng/mL was found in 35.5% of patients. These patients had a lower seroconversion rate than did patients with levels ≥10 ng/mL (45% vs 64%; P=0.011) and their median (25th, 75th percentile) anti-HBs antibody titres were lower (0 (0, 117)IU/L vs 48 (0, 236.5)IU/L). Non-responders had lower 25(OH)D concentrations than did responders (12.9±6.5 ng/mL vs 15.1±7.4 ng/mL; P=0.034). Treatment with a vitamin D receptor activator had no influence on the immune response. In a multiple logistic regression analysis vitamin D deficiency (OR 0.480; P=0.023) and diabetes (OR 0.496; P=0.038) remained independent and significant negative predictors of seroconversion. In conclusion, in patients with chronic kidney disease vitamin D deficiency is associated with a poor antibody formation upon hepatitis B vaccination.