Alexandra Scholze | University of Southern Denmark (original) (raw)

Papers by Alexandra Scholze

Oxidative Medicine and Cellular Longevity (Web), 2016

Antioxidants, Apr 14, 2023

Oxidative Medicine and Cellular Longevity, 2016

American Journal of Nephrology, Oct 24, 2007

Background: Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. W... more Background: Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics. Methods: Arterial vascular properties were quantified by the reflective index using digital photoplethysmography in 260 patients with CKD. Patients were grouped according to estimated glomerular filtration rate (eGFR). Additional measurements were performed in 50 healthy control subjects. Results: In patients with CKD stage 1 and 2 (n = 115; age 65 ± 1 years) the reflective index was 30 ± 1%, whereas in patients with CKD stage 3 and 4 (n = 60; age 72 ± 1 years) the reflective index was 36 ± 1%, and in patients with CKD stage 5 (n = 85; age 64 ± 1 years) the reflective index was 36 ± 1% (p < 0.01 by Kruskal-Wallis test) indicating increased arterial stiffness in advanced CKD. Arterial vascular reactivity was significantly impaired in patients with advanced stages of CKD (stage 1 and 2, 78 ± 12%; stage 3 and 4, 32 ± 12%; stage 5, 33 ± 12%; p < 0.01). Univariate analysis showed a significant correlation of the reflective index and eGFR (Pearson r = –0.24; p < 0.0001). Multivariate regression analysis showed an independent association of the reflective index and eGFR (adjusted correlation coefficient, –0.24; p < 0.001). Conclusion: The advanced stages of CKD are associated with increased vascular stiffness and impaired vascular reactivity and these changes are already present in CKD stage 3 and 4.

Microvascular Research, Mar 1, 2009

Transplantation, Nov 1, 2012

Journal of Hypertension, Jun 1, 2004

Antioxidants & Redox Signaling, Mar 1, 2012

The regulation of calcium influx through transient receptor potential canonical type 6 (TRPC6) ch... more The regulation of calcium influx through transient receptor potential canonical type 6 (TRPC6) channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine (HC) or acetylcysteine (ACC) affect TRPC6 expression in human monocytes. We observed that patients with chronic renal failure had significantly elevated HC levels and TRPC6 mRNA expression levels in monocytes compared with control subjects. We further observed that administration of HC or ACC significantly increased TRPC6 channel protein expression compared with control conditions. We, therefore, hypothesize that cysteine residues increase TRPC6 channel protein expression in humans. Antioxid. Redox Signal. 16, 452-457.

American Journal of Nephrology, 2009

Background: We determined whether attainment of classical clinical performance measures for hemod... more Background: We determined whether attainment of classical clinical performance measures for hemodialysis care improves survival in hemodialysis patients with increased arterial stiffness. Methods: We performed a prospective cohort study of 538 hemodialysis patients with a median follow-up of 19 months (interquartile range 8–30). Arterial stiffness was measured using applanation tonometry. Clinical performance measure targets were hemoglobin value ≥110 g/l, serum albumin value ≥37 g/l and measured single-pool Kt/V urea value ≥1.2. Results: During follow-up, 217 patients (40%) died. In non-survivors, arterial stiffness of large arteries (S1) was significantly higher compared with survivors (p = 0.0002). An analysis of hemodialysis patients who were alive 18 months after inclusion into the study showed that survival was significantly longer in those patients that met ≥2 clinical performance measure targets compared with patients that met ≤1 target (χ2 4.13; p = 0.04). Better attainment of classical clinical performance measures showed a 54% mortality risk reduction. Conclusion: S1 predicted mortality in hemodialysis patients. However, better attainment of classical clinical performance measures significantly improved long-term outcome in hemodialysis patients despite their pronounced increase in arterial stiffness.

Antioxidants, Jun 3, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Amino Acids, Oct 8, 2010

We analyzed proteomic profiles in monocytes of chronic kidney disease (CKD) patients and healthy ... more We analyzed proteomic profiles in monocytes of chronic kidney disease (CKD) patients and healthy control subjects. Two-dimensional electrophoresis (2-DE) and silver staining indicated differences in protein pattern. Among the analyzed proteins, superoxide dismutase type 1 (SOD1), which was identified both by MS/MS mass-spectrometry and immunoblotting, was reduced in kidney disease. We characterized SOD1 protein amount, using quantitative in-cell Western assay and immunostaining of 2-DE gel blots, and SOD1 gene expression, using quantitative real-time polymerase chain reaction (PCR), in 98 chronic hemodialysis (HD) and 211 CKD patients, and 34 control subjects. Furthermore, we showed that different SOD1 protein species exist in human monocytes. SOD1 protein amount was significantly lower in HD (normalized SOD1 protein, 27.2 ± 2.8) compared to CKD patients (34.3 ± 2.8), or control subjects (48.0 ± 8.6; mean ± SEM; P < 0.05). Analysis of SOD1 immunostaining showed significantly more SOD1 protein in control subjects compared to patients with CKD or HD (P < 0.0001, analysis of main immunoreactive protein spot). SOD1 gene expression was significantly higher in HD (normalized SOD1 gene expression, 17.8 ± 2.3) compared to CKD patients (9.0 ± 0.7), or control subjects (5.5 ± 1.0; P < 0.0001). An increased SOD1 gene expression may indicate increased protein degradation in patients with CKD and compensatory increase of SOD1 gene expression. Taken together, we show reduced SOD1 protein amount in monocytes of CKD, most pronounced in HD patients, accompanied by increased SOD1 gene expression.

Journal of the American Heart Association, Jun 5, 2018

Background-Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular... more Background-Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. Methods and Results-We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level metaanalysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, À0.23 to0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, À0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. Conclusions-Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.

Nephrology Dialysis Transplantation, Jul 20, 2012

Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels ... more Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 2002; 53: 1029-1034. 30. Wypasek E, Undas A, Sniezek-Maciejewska M et al. The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6-174G > C gene polymorphism.

Medizinische Klinik - Intensivmedizin Und Notfallmedizin, Feb 1, 2009

ABSTRACT Im Hochsommer wird eine 76-jährige Patientin mit zunehmender Schwäche und Unwohlsein ein... more ABSTRACT Im Hochsommer wird eine 76-jährige Patientin mit zunehmender Schwäche und Unwohlsein eingewiesen. Bei der Patientin besteht eine essentielle arterielle Hypertonie, die mit einem Thiaziddiuretikum behandelt wird. Die Patientin weist einen verminderten Hautturgor auf, der Blutdruck beträgt 114/76 mmHg, der Puls 88/min. Die Laborwerte bei Aufnahme zeigen ein Serumnatrium von 127 mmol/l, eine Urinosmolalität von 213 mosmol/kg sowie ein Urinnatrium von 30 mmol/l. Die Serumkaliumkonzentration beträgt 3,9 mmol/l, die Nüchternglucosekonzentration 100 mg/dl, das thyreoideastimulierende Hormon (TSH basal) liegt im Normbereich. Nach Pausieren des Thiaziddiuretikums und Gabe von isotoner Kochsalzlösung kommt es zu einer langsamen Normalisierung der Hyponatriämie und zu einer Verbesserung des klinischen Zustands der Patientin.

American Journal of Kidney Diseases, Nov 1, 2010

Intravenous voriconazole therapy was unsuccessful. Local irrigation of amphotericin has been repo... more Intravenous voriconazole therapy was unsuccessful. Local irrigation of amphotericin has been reported to successfully treat funguria 6 ; therefore, a solution of liposomal amphotericin B in normal saline solution was delivered through the nephrostomy tube. To avoid further hydrostatic damage behind the fluid infusion, an intracranial pressure monitor was connected to the nephrostomy tube. Intrapelvic pressure was measured at the onset of local irrigation and hourly. Nephrostomy delivery of the amphotericin B solution was titrated to 40 mL/h with pressures Ͻ20 cm H 2 O. During the first day of irrigation, urine began to flow through the indwelling bladder catheter. After 6 days of treatment, a nephrostogram showed brisk contrast flow through the collecting system (Fig 1B). Re-examination of urine showed it was sterile, and serum creatinine level normalized.

Kidney & Blood Pressure Research, 2011

globulin light chains predicted mortality in hemodialysis patients. Conclusion: Higher serum leve... more globulin light chains predicted mortality in hemodialysis patients. Conclusion: Higher serum levels of free plus immunoglobulin light chains ameliorate survival in hemodialysis patients.

Therapeutic Apheresis and Dialysis, Jun 1, 2009

It is still controversial whether the mode of dialysis or preexisting comorbidities may influence... more It is still controversial whether the mode of dialysis or preexisting comorbidities may influence the prognosis of patients with chronic kidney disease stage 5. Therefore, we performed a prospective case control study to evaluate whether the mode of dialysis may influence outcome. We found 25 cases on peritoneal dialysis (PD) treatment and 75 age and sex-matched controls on hemodialysis (HD) treatment for more than 3 months. Analysis was by intention-to-treat. During the follow up of 58 months, 6 out of 25 patients (24%) died in the PD group, whereas in the HD group 26 out of 75 patients (35%) died (relative risk 0.69 [95% CI 0.32 to 1.49]; P = 0.46). Survival was not significantly different between the groups as indicated by Mantel-Cox log-rank test (hazard ratio 0.52 [95% CI 0.25 to 1.10]; P = 0.11). Multiple variable regression showed that age and diabetes mellitus, but not mode of dialysis, predicted death in patients with chronic kidney disease. It is concluded that age and comorbidities but not mode of dialysis are important to predict survival in patients with chronic kidney disease stage 5.

Oxidative Medicine and Cellular Longevity (Web), 2016

Antioxidants, Apr 14, 2023

Oxidative Medicine and Cellular Longevity, 2016

American Journal of Nephrology, Oct 24, 2007

Background: Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. W... more Background: Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics. Methods: Arterial vascular properties were quantified by the reflective index using digital photoplethysmography in 260 patients with CKD. Patients were grouped according to estimated glomerular filtration rate (eGFR). Additional measurements were performed in 50 healthy control subjects. Results: In patients with CKD stage 1 and 2 (n = 115; age 65 ± 1 years) the reflective index was 30 ± 1%, whereas in patients with CKD stage 3 and 4 (n = 60; age 72 ± 1 years) the reflective index was 36 ± 1%, and in patients with CKD stage 5 (n = 85; age 64 ± 1 years) the reflective index was 36 ± 1% (p < 0.01 by Kruskal-Wallis test) indicating increased arterial stiffness in advanced CKD. Arterial vascular reactivity was significantly impaired in patients with advanced stages of CKD (stage 1 and 2, 78 ± 12%; stage 3 and 4, 32 ± 12%; stage 5, 33 ± 12%; p < 0.01). Univariate analysis showed a significant correlation of the reflective index and eGFR (Pearson r = –0.24; p < 0.0001). Multivariate regression analysis showed an independent association of the reflective index and eGFR (adjusted correlation coefficient, –0.24; p < 0.001). Conclusion: The advanced stages of CKD are associated with increased vascular stiffness and impaired vascular reactivity and these changes are already present in CKD stage 3 and 4.

Microvascular Research, Mar 1, 2009

Transplantation, Nov 1, 2012

Journal of Hypertension, Jun 1, 2004

Antioxidants & Redox Signaling, Mar 1, 2012

The regulation of calcium influx through transient receptor potential canonical type 6 (TRPC6) ch... more The regulation of calcium influx through transient receptor potential canonical type 6 (TRPC6) channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine (HC) or acetylcysteine (ACC) affect TRPC6 expression in human monocytes. We observed that patients with chronic renal failure had significantly elevated HC levels and TRPC6 mRNA expression levels in monocytes compared with control subjects. We further observed that administration of HC or ACC significantly increased TRPC6 channel protein expression compared with control conditions. We, therefore, hypothesize that cysteine residues increase TRPC6 channel protein expression in humans. Antioxid. Redox Signal. 16, 452-457.

American Journal of Nephrology, 2009

Background: We determined whether attainment of classical clinical performance measures for hemod... more Background: We determined whether attainment of classical clinical performance measures for hemodialysis care improves survival in hemodialysis patients with increased arterial stiffness. Methods: We performed a prospective cohort study of 538 hemodialysis patients with a median follow-up of 19 months (interquartile range 8–30). Arterial stiffness was measured using applanation tonometry. Clinical performance measure targets were hemoglobin value ≥110 g/l, serum albumin value ≥37 g/l and measured single-pool Kt/V urea value ≥1.2. Results: During follow-up, 217 patients (40%) died. In non-survivors, arterial stiffness of large arteries (S1) was significantly higher compared with survivors (p = 0.0002). An analysis of hemodialysis patients who were alive 18 months after inclusion into the study showed that survival was significantly longer in those patients that met ≥2 clinical performance measure targets compared with patients that met ≤1 target (χ2 4.13; p = 0.04). Better attainment of classical clinical performance measures showed a 54% mortality risk reduction. Conclusion: S1 predicted mortality in hemodialysis patients. However, better attainment of classical clinical performance measures significantly improved long-term outcome in hemodialysis patients despite their pronounced increase in arterial stiffness.

Antioxidants, Jun 3, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Amino Acids, Oct 8, 2010

We analyzed proteomic profiles in monocytes of chronic kidney disease (CKD) patients and healthy ... more We analyzed proteomic profiles in monocytes of chronic kidney disease (CKD) patients and healthy control subjects. Two-dimensional electrophoresis (2-DE) and silver staining indicated differences in protein pattern. Among the analyzed proteins, superoxide dismutase type 1 (SOD1), which was identified both by MS/MS mass-spectrometry and immunoblotting, was reduced in kidney disease. We characterized SOD1 protein amount, using quantitative in-cell Western assay and immunostaining of 2-DE gel blots, and SOD1 gene expression, using quantitative real-time polymerase chain reaction (PCR), in 98 chronic hemodialysis (HD) and 211 CKD patients, and 34 control subjects. Furthermore, we showed that different SOD1 protein species exist in human monocytes. SOD1 protein amount was significantly lower in HD (normalized SOD1 protein, 27.2 ± 2.8) compared to CKD patients (34.3 ± 2.8), or control subjects (48.0 ± 8.6; mean ± SEM; P < 0.05). Analysis of SOD1 immunostaining showed significantly more SOD1 protein in control subjects compared to patients with CKD or HD (P < 0.0001, analysis of main immunoreactive protein spot). SOD1 gene expression was significantly higher in HD (normalized SOD1 gene expression, 17.8 ± 2.3) compared to CKD patients (9.0 ± 0.7), or control subjects (5.5 ± 1.0; P < 0.0001). An increased SOD1 gene expression may indicate increased protein degradation in patients with CKD and compensatory increase of SOD1 gene expression. Taken together, we show reduced SOD1 protein amount in monocytes of CKD, most pronounced in HD patients, accompanied by increased SOD1 gene expression.

Journal of the American Heart Association, Jun 5, 2018

Background-Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular... more Background-Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. Methods and Results-We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level metaanalysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, À0.23 to0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, À0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. Conclusions-Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.

Nephrology Dialysis Transplantation, Jul 20, 2012

Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels ... more Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 2002; 53: 1029-1034. 30. Wypasek E, Undas A, Sniezek-Maciejewska M et al. The increased plasma C-reactive protein and interleukin-6 levels in patients undergoing coronary artery bypass grafting surgery are associated with the interleukin-6-174G > C gene polymorphism.

Medizinische Klinik - Intensivmedizin Und Notfallmedizin, Feb 1, 2009

ABSTRACT Im Hochsommer wird eine 76-jährige Patientin mit zunehmender Schwäche und Unwohlsein ein... more ABSTRACT Im Hochsommer wird eine 76-jährige Patientin mit zunehmender Schwäche und Unwohlsein eingewiesen. Bei der Patientin besteht eine essentielle arterielle Hypertonie, die mit einem Thiaziddiuretikum behandelt wird. Die Patientin weist einen verminderten Hautturgor auf, der Blutdruck beträgt 114/76 mmHg, der Puls 88/min. Die Laborwerte bei Aufnahme zeigen ein Serumnatrium von 127 mmol/l, eine Urinosmolalität von 213 mosmol/kg sowie ein Urinnatrium von 30 mmol/l. Die Serumkaliumkonzentration beträgt 3,9 mmol/l, die Nüchternglucosekonzentration 100 mg/dl, das thyreoideastimulierende Hormon (TSH basal) liegt im Normbereich. Nach Pausieren des Thiaziddiuretikums und Gabe von isotoner Kochsalzlösung kommt es zu einer langsamen Normalisierung der Hyponatriämie und zu einer Verbesserung des klinischen Zustands der Patientin.

American Journal of Kidney Diseases, Nov 1, 2010

Intravenous voriconazole therapy was unsuccessful. Local irrigation of amphotericin has been repo... more Intravenous voriconazole therapy was unsuccessful. Local irrigation of amphotericin has been reported to successfully treat funguria 6 ; therefore, a solution of liposomal amphotericin B in normal saline solution was delivered through the nephrostomy tube. To avoid further hydrostatic damage behind the fluid infusion, an intracranial pressure monitor was connected to the nephrostomy tube. Intrapelvic pressure was measured at the onset of local irrigation and hourly. Nephrostomy delivery of the amphotericin B solution was titrated to 40 mL/h with pressures Ͻ20 cm H 2 O. During the first day of irrigation, urine began to flow through the indwelling bladder catheter. After 6 days of treatment, a nephrostogram showed brisk contrast flow through the collecting system (Fig 1B). Re-examination of urine showed it was sterile, and serum creatinine level normalized.

Kidney & Blood Pressure Research, 2011

globulin light chains predicted mortality in hemodialysis patients. Conclusion: Higher serum leve... more globulin light chains predicted mortality in hemodialysis patients. Conclusion: Higher serum levels of free plus immunoglobulin light chains ameliorate survival in hemodialysis patients.

Therapeutic Apheresis and Dialysis, Jun 1, 2009

It is still controversial whether the mode of dialysis or preexisting comorbidities may influence... more It is still controversial whether the mode of dialysis or preexisting comorbidities may influence the prognosis of patients with chronic kidney disease stage 5. Therefore, we performed a prospective case control study to evaluate whether the mode of dialysis may influence outcome. We found 25 cases on peritoneal dialysis (PD) treatment and 75 age and sex-matched controls on hemodialysis (HD) treatment for more than 3 months. Analysis was by intention-to-treat. During the follow up of 58 months, 6 out of 25 patients (24%) died in the PD group, whereas in the HD group 26 out of 75 patients (35%) died (relative risk 0.69 [95% CI 0.32 to 1.49]; P = 0.46). Survival was not significantly different between the groups as indicated by Mantel-Cox log-rank test (hazard ratio 0.52 [95% CI 0.25 to 1.10]; P = 0.11). Multiple variable regression showed that age and diabetes mellitus, but not mode of dialysis, predicted death in patients with chronic kidney disease. It is concluded that age and comorbidities but not mode of dialysis are important to predict survival in patients with chronic kidney disease stage 5.