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Mineral abnormalities are a common complication of heart failure (HF). In particular, dyskalaemia, hyponatraemia, and hypomagnesaemia are prevalent, with hypo- and hyperkalaemia observed in over 40 % of HF patients, hyponatraemia in 18-27 %, hypomagnesaemia in 7-52 %, and phosphate imbalance in 13 %. These abnormalities serve as indicators of the severity of HF and are strongly associated with an increased risk of morbidity and mortality. The neurohumoral activation, including the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system, and vasopressin, HF medications such as diuretics and RAAS inhibitors, amd concomitant diseases such as chronic kidney disease, can disrupt mineral homeostasis. Iron deficiency (ID) is another of the most common mineral abnormalities, affecting up to 60 % of HF patients. ID is significantly associated with adverse clinical outcomes such as reduced quality of life and exercise capacity, HF re-hospitalization, and all-cause mortality. Various pathways contribute to the development of ID in HF, including reduced iron intake due to anorexia, increased hepcidin levels associated with chronic inflammation and hepatic congestion, and occult gastrointestinal bleeding due to the concomitant use of antithrombotic agents. The efficacy of iron replacement therapy has been demonstrated in clinical trials, particularly in heart failure with reduced ejection fraction (HFrEF), whilst more recently, it has also been shown to improve exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). This review focuses on potassium and phosphate abnormalities, hyponatraemia, hypomagnesaemia, and ID in HF, providing a comprehensive overview of the mechanisms, clinical significance, and intervention strategies with the latest findings., Competing Interests: Conflict of Interest statement R.S reports grants from Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad, during the conduct of the study. M.K has received speaking honoraria and research grants from CVRx. M.K is a member of the CVRx Barostim Hypertension Registry Steering Committee. S.v.H has been a paid consultant for and/or received honoraria payments from AstraZeneca, Bayer, Boehringer Ingelheim, BRAHMS, Edwards Lifesciences, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, and Vifor. S.v.H reports research support from Amgen, Boehringer Ingelheim, Pharmacosmos, IMI, and the German Center for Cardiovascular Research (DZHK)., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Arterial hypertension (aHTN) plays a fundamental role in the pathogenesis and prognosis of heart failure with preserved ejection fraction (HFpEF). The risk of heart failure increases with therapy-resistant arterial hypertension (trHTN), defined as inadequate blood pressure (BP) control ≥140/90 mmHg despite taking ≥3 antihypertensive medications including a diuretic. This study investigates the effects of the BP lowering baroreflex activation therapy (BAT) on cardiac function and morphology in patients with trHTN with and without HFpEF., Methods: Sixty-four consecutive patients who had been diagnosed with trHTN and received BAT implantation between 2012 and 2016 were prospectively observed. Office BP, electrocardiographic and echocardiographic data were collected before and after BAT implantation., Results: Mean patients' age was 59.1 years, 46.9% were male, and mean body mass index (BMI) was 33.2 kg/m 2 . The prevalence of diabetes mellitus was 38.8%, atrial fibrillation was 12.2%, and chronic kidney disease (CKD) stage ≥3 was 40.8%. Twenty-eight patients had trHTN with HFpEF, and 21 patients had trHTN without HFpEF. Patients with HFpEF were significantly older (64.7 vs. 51.6 years, P < 0.0001), had a lower BMI (30.0 vs. 37.2 kg/m 2 , P < 0.0001), and suffered more often from CKD-stage ≥3 (64 vs. 20%, P = 0.0032). After BAT implantation, mean office BP dropped in patients with and without HFpEF (from 169 ± 5/86 ± 4 to 143 ± 4/77 ± 3 mmHg [P = 0.0019 for systolic BP and 0.0403 for diastolic BP] and from 170 ± 5/95 ± 4 to 149 ± 6/88 ± 5 mmHg [P = 0.0019 for systolic BP and 0.0763 for diastolic BP]), while a significant reduction of the intake of calcium-antagonists, α 2 -agonists and direct vasodilators, as well as a decrease in average dosage of ACE-inhibitors and α 2 -agonists could be seen. Within the study population, a decrease in heart rate from 74 ± 2 to 67 ± 2 min -1 (P = 0.0062) and lengthening of QRS-time from 96 ± 3 to 106 ± 4 ms (P = 0.0027) and QTc-duration from 422 ± 5 to 432 ± 5 ms (P = 0.0184) were detectable. The PQ duration was virtually unchanged. In patients without HF, no significant changes of echocardiographic parameters could be seen. In patients with HFpEF, posterior wall diameter decreased significantly from 14.0 ± 0.5 to 12.7 ± 0.3 mm (P = 0.0125), left ventricular mass (LVM) declined from 278.1 ± 15.8 to 243.9 ± 13.4 g (P = 0.0203), and e' lateral increased from 8.2 ± 0.4 to 9.0 ± 0.4 cm/s (P = 0.0471)., Conclusions: BAT reduced systolic and diastolic BP and was associated with morphological and functional improvement of HFpEF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Renal venous congestion due to backward heart failure leads to disturbance of renal function in acute decompensated heart failure (ADHF). Whether decongestion strategies have an impact on renal venous congestion is unknown. Objective was to evaluate changes in intrarenal hemodynamics using intrarenal Doppler ultrasonography (IRD) in patients with heart failure with reduced ejection fraction (HFrEF) and ADHF undergoing recompensation., Methods: Prospective observational study in patients with left ventricular ejection fraction (LV-EF) ≤ 35% hospitalized due to ADHF. IRD measurement was performed within the first 48 h of hospitalisation and before discharge. Decongestion strategies were based on clinical judgement according to heart failure guidelines. IRD was used to assess intrarenal venous flow (IRVF) pattern, venous impedance index (VII) and resistance index (RI). Laboratory analyses included plasma creatinine, eGFR and albuminuria., Results: A number of 35 patients with ADHF and LV-EF ≤ 35% were included into the study. IRD could be performed in 30 patients at inclusion and discharge. At discharge, there was a significant reduction of VII from a median of 1.0 (0.86-1.0) to 0.59 (0.26-1.0) (p < 0.01) as well as improvement of IRVF pattern categories (p < 0.05) compared to inclusion. Albuminuria was significantly reduced from a median of 78 mg/g creatinine (39-238) to 29 mg/g creatinine (16-127) (p = 0.02) and proportion of patients with normoalbuminuria increased (p = 0.01). Plasma creatinine and RI remained unchanged (p = 0.73; p = 0.43)., Discussion: This is the first study showing an effect of standard ADHF therapy on parameters of renal venous congestion in patients with HFrEF and ADHF. Doppler sonographic evaluation of renal venous congestion might provide additional information to guide decongestion strategies in patients with ADHF., (© 2023. The Author(s).)

Patients with resistant hypertension (HTN) demonstrate an increased risk of chronic kidney disease and progression to end-stage renal disease; however, the individual course of progression is hard to predict. Assessing the stress-induced, urinary glycoprotein Dickkopf-3 (uDKK3) may indicate ongoing renal damage and consecutive estimated glomerular filtration rate (eGFR) decline. The present study aimed to determine the association between uDKK3 levels and further eGFR changes in patients with resistant HTN. In total, 31 patients with resistant HTN were included. Blood pressure and renal function were measured at baseline and up to 24 months after (at months 12 and 24). uDKK3 levels were determined exclusively from the first available spot urine sample at baseline or up to a period of 6 months after, using a commercial ELISA kit. Distinctions between different patient groups were analyzed using the unpaired t-test or Mann-Whitney test. Correlation analysis was performed using Spearman's correlation. The median uDKK3 level was 303 (interquartile range (IQR) 150-865) pg/mg creatinine. Patients were divided into those with high and low eGFR loss (≥3 vs. <3 mL/min/1.73 m²/year). Patients with high eGFR loss showed a significantly higher median baseline uDKK3 level (646 (IQR 249-2555) (n = 13) vs. 180 (IQR 123-365) pg/mg creatinine (n = 18), p = 0.0412 (Mann-Whitney U)). Alternatively, patients could be classified into those with high and low uDKK3 levels (≥400 vs. <400 pg/mg creatinine). Patients with high uDKK3 levels showed significantly higher eGFR loss (-6.4 ± 4.7 (n = 11) vs. 0.0 ± 7.6 mL/min/1.73 m 2 /year (n = 20), p = 0.0172 (2-sided, independent t-test)). Within the entire cohort, there was a significant correlation between the uDKK3 levels and change in eGFR at the latest follow-up (Spearman's r = -0.3714, p = 0.0397). In patients with resistant HTN, high levels of uDKK3 are associated with higher eGFR loss up to 24 months later.

A relevant number of patients with resistant hypertension do not achieve blood pressure (BP) dipping during nighttime. This inadequate nocturnal BP reduction is associated with elevated cardiovascular risks. The aim of this study was to evaluate whether a nighttime intensification of BAT might improve nocturnal BP dipping. In this prospective observational study, non-dippers treated with BAT for at least 6 months were included. BAT programming was modified in a two-step intensification of nighttime stimulation at baseline and week 6. Twenty-four hours ambulatory BP (ABP) was measured at inclusion and after 3 months. A number of 24 patients with non- or inverted dipping pattern, treated with BAT for a median of 44 months (IQR 25-52) were included. At baseline of the study, patients were 66 ± 9 years old, had a BMI of 33 ± 6 kg/m 2 , showed an office BP of 135 ± 22/72 ± 10 mmHg, and took a median number of antihypertensives of 6 (IQR 4-9). Nighttime stimulation of BAT was adapted by an intensification of pulse width from 237 ± 161 to 267 ± 170 μs (p = .003) while frequency (p = .10) and amplitude (p = .95) remained unchanged. Uptitration of BAT programming resulted in an increase of systolic dipping from 2 ± 6 to 6 ± 8% (p = .03) accompanied with a significant improvement of dipping pattern (p = .02). Twenty four hours ABP, day- and nighttime ABP remained unchanged. Programming of an intensified nighttime BAT interval improved dipping profile in patients treated with BAT, while the overall 24 h ABP did not change. Whether the improved dipping response contributes to a reduction of cardiovascular risk beyond the BP-lowering effects of BAT, however, remains to be shown., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Therapy adherence significantly determines the success of antihypertensive therapy, especially in patients with resistant hypertension. Our study investigates the impact of drug adherence on the efficacy of Baroreflex-activation-therapy (BAT). In this retrospective analysis, the authors measured blood pressure (BP) and antihypertensive medication adherence (by gas chromatography-mass spectrometry [GC-MS] urine analysis) before and 6 months after BAT initiation. Adherence was defined as detection of ≥80% intake of prescribed medication at the time of follow-up. Response to BAT was defined as BP drop ≥5 mmHg in systolic 24 h-ambulatory BP (ABP) after 6 months. Overall patients (n = 38) median medication adherence was low, but rose from 60% (IQR 25%-100%) to 75% (IQR 38%-100%; p = .0194). After 6 months of BAT, mean systolic and diastolic office BP (-21 ± 25 mmHg and -9 ± 15 mmHg; p < .0001 and .0004) as well as 24 h-ABP dropped significantly (-9 ± 17 mmHg and -5 ± 12 mmHg; p = .0049 and .0280). After 6 months of BAT, 21 patients (60%) could be classified as responders. There was neither significant difference in mean office systolic (-21 ± 23 mmHg vs. -21 ± 28 mmHg; p = .9581) nor in 24 h-systolic ABP decrease (-11 ± 19 mmHg vs. -7 ± 15 mmHg; p = .4450) comparing adherent and non-adherent patients. Whereas Antihypertensive Therapeutic Index (ATI) was unchanged in non-responders, it significantly decreased in responders (from 50 ± 16 to 46 ± 16; p = .0477). These data are the first to show that BAT-initiation leads to a clear BP reduction independently of patients´ medication adherence. Response to BAT is associated with a significant lowering of ATI, which might contribute to an underestimation of BAT efficacy., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification., Methods: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models., Results: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81)., Conclusions: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Lymphoma-associated Hemophagocytic lymphohistiocytosis (HLH) represents a severe complication of disease progression, mediated through cytokine release from the lymphoma cells. Cytokine adsorption may contribute as a supportive treatment to stabilize organ function by reduction of cytokine levels. So far, no experiences of cytokine adsorption and simultaneous stem cell transplantation were published. We report the case of a patient with aggressive lymphoma secondary to chronic lymphocytic leukemia with rapidly progressive HLH (Richter's transformation) upon conditioning chemotherapy prior to allogeneic stem cell transplantation (ASCT). Continuous hemodiafiltration was initiated in the treatment of shock with acute renal failure, lactacidosis and need for high-dose catecholamine therapy, integrating an additional cytokine-adsorbing filter (CytoSorb®) to reduce cytokine levels. This was followed by scheduled allogenic stem cell transplantation. We observed a marked decrease in interleukin-6 plasma levels, associated with a reduced need for vasopressor therapy and organ function stabilization. Hematopoietic engraftment was present at day 14 post-ASCT, leading to disease-free discharge at day 100 post-transplantation. Cytokine adsorption may serve as a safe adjunct to HLH/sepsis treatment during allogeneic stem cell transplantation. Clinical studies are required to make future treatment recommendations., (© 2021. The Author(s).)

(1) Background: Arterial hypertension (HTN) is one of the most relevant cardiovascular risk factors. Nowadays multiple pharmaceutical treatment options exist with novel interventional methods (e.g., baroreflex activation therapy (BAT)) as a last resort to treat patients with resistant HTN. Although pathophysiology behind resistant HTN is still not fully understood. There is evidence that selected biomarkers may be involved in the pathophysiology of HTN. (2) Methods: We investigated serum SDC4-levels in patients suffering from resistant HTN before and 6 months after BAT implantation. We collected 19 blood samples from patients with resistant HTN and blood pressure above target and measured serum SDC4-levels. (3) Results: Our results showed high serum SDC4-levels in patients with resistant HTN as compared to a healthy population. Patients with both, resistant HTN and diabetes mellitus type II, demonstrated higher serum SDC4-levels. β-blockers had lowering effects on serum SDC4-levels, whereas calcium channel blockers were associated with higher levels of serum SDC4. BAT implantation did not lead to a significant difference in serum SDC4-levels after 6 months of therapy. (4) Conclusion: Based on our results we propose SDC4 is elevated in patients suffering from resistant HTN. Thus, SDC4 might be a potential marker for endothelial dysfunction in patients with resistant hypertension.

Multiple sclerosis (MS) is an inflammatory disease mainly affecting the central nervous system. In MS, abnormal immune mechanisms induce acute inflammation, demyelination, axonal loss, and the formation of central nervous system plaques. The long-term treatment involves options to modify the disease progression, whereas the treatment for the acute relapse has its focus in the administration of high-dose intravenous methylprednisolone (up to 1000 mg daily) over a period of three to five days as a first step. If symptoms of the acute relapse persist, it is defined as glucocorticosteroid-unresponsive, and immunomodulation by apheresis is recommended. However, several national and international guidelines have no uniform recommendations on using plasma exchange (PE) nor immunoadsorption (IA) in this case. A systematic review and meta-analysis was conducted, including observational studies or randomized controlled trials that investigated the effect of PE or IA on different courses of MS and neuromyelitis optica (NMO). One thousand, three hundred and eighty-three patients were included in the evaluation. Therapy response in relapsing-remitting MS and clinically isolated syndrome was 76.6% (95%CI 63.7-89.8%) in PE- and 80.6% (95%CI 69.3-91.8%) in IA-treated patients. Based on the recent literature, PE and IA may be considered as equal treatment possibilities in patients suffering from acute, glucocorticosteroid-unresponsive MS relapses.

Objective: Baroreflex activation therapy (BAT) reduces office blood pressure (BP) in patients with resistant hypertension (HTN). Whereas sustained effects from the BAT Rheos device have already been reported, no long-term data on 24-h ambulatory BP (ABP) are currently available for the unilateral BAT Neo device., Methods: Patients treated with the BAT neo device for resistant hypertension were prospectively included into this observational study. Office and ABP measurements were performed before BAT implantation as well as 6, 12 and 24 months after initiation of BAT., Results: A total of 60 patients with resistant HTN (office BP 172 ± 25/90 ± 17 mmHg, 24-h ABP 150 ± 16/80 ± 12 mmHg, median of antihypertensive drugs 7 (IQR 6-8)) were included. After 24 months, there was a significant reduction of - 25 ± 33/- 9 ± 18 mmHg (n = 50, both p < 0.01) in office BP and - 8 ± 23/- 5 ± 13 mmHg (n = 46, both p = 0.02) in 24-h ABP, while the number of antihypertensive medications was reduced to a median of 5 (4-6) drugs (p < 0.01). Patients with isolated systolic HTN (ISH) experienced a BP-lowering effect in office BP, but not in ABPM at month 24. Using unadjusted BP values, BAT seems to be more effective in combined hypertension (CH) than in ISH. After adjustment for baseline BP values, there was no significant difference in BP reduction between ISH and CH patients. Ambulatory SBP at baseline was the only independent correlate of BP response at month 24., Conclusion: BAT reduced office BP and improved relevant parameters of ABP, which is associated with a high cardiovascular risk, in patients with resistant HTN, whereas, after adjustment for baseline BP, BP reduction was not different in patients with CH compared with patients with ISH. However, randomized controlled trials are needed to confirm the effects of BAT on 24-h ABP.

Objective: Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion., Methods: From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed., Results: Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27 mmHg and 148 ± 16 mmHg despite a median intake of 7(3-9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29 mmHg (p < 0.01), 24-h systolic BP to 142 ± 22 mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83 mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43-1.47] to 0.92% [0.61-1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015)., Conclusion: The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.

Background: Plasma exchange (PE) and immunoadsorption (IA) are alternative treatments of steroid-refractory relapses of multiple sclerosis (MS) or neuromyelitis optica (NMO)., Methods: Adverse events and neurological follow-ups in 127 MS- (62 PE, 65 IA) and 13 NMO- (11 PE, 2 IA) patients were retrospectively analyzed. Response was defined by improvements in either expanded disability status scale (EDSS) by at least 1.0 or visual acuity (VA) to 0.5, confirmed after 3 and/or 6 months., Results: Hundred and forty patients were included in safety analysis, 102 patients provided sufficient neurological follow-up-data. There were no significant differences between IA and PE in side effects (3.9% vs 3.6%, P = .96) or response-rate (P = .65). Responders showed significant lower age (P = .02) and earlier apheresis-initiation (P = .01). Subgroup-analysis confirmed significant lower age in patients with relapsing-remitting MS (RRMS) /clinical isolated syndrome (CIS)., Conclusion: IA and PE seem equally safe and effective in steroid-resistant MS- or NMO-relapses. Early apheresis and low patient age are additional prognostic factors., (© 2019 Wiley Periodicals, Inc.)

In addition to the early detection of an acute kidney injury (AKI), several problems or questions have to be addressed. These include the identification of the etiology, the severity (functional or structural), the prognosis (recovery or transition to chronic renal failure), the course of the disease (dialysis or not), and the identification of specific treatment options for AKI. The following article provides an overview of established and new AKI biomarkers as well as an outlook on the potential of future biomarker-associated models of AKI.

Background: Due to rising vascular comorbidities of patients undergoing dialysis, the prevalence of permanent hemodialysis catheters as hemodialysis access is increasing. However, infection is a major complication of these catheters. Therefore, identification of potential predicting risk factors leading to early infection related complications is valuable, in particular the significance the CRP (C-reactive protein)-value is of interest., Methods: In this retrospective study 151 permanent hemodialysis catheters implanted in 130 patients were examined. The following data were collected at the time of catheter implantation: CRP-value, history of catheter-related infection, microbiological status, immunosuppression and diabetes mellitus. The primary outcomes were recorded over the 3 months following the implantation: catheter-related infection, days of hospital stay and death. Catheter removal or revision, rehospitalization and use of antibiotics were identified as secondary outcomes., Results: We identified a total of 27 (17.9%) infections (systemic infection: 2.26 episodes/ 1000 catheter days, local infection: 0.6 episodes/ 1000 catheter days). The development of an infection was independent of the CRP-value (p = 0.66) as well as the presence of diabetes mellitus (p = 0.64) or immunosuppression (p = 0.71). Univariate analysis revealed that infection was more frequent in patients with MRSA-carriage (p < 0.001), in case of previous catheter-related infection (p < 0.05) and of bacteremia or bacteriuria in the period of 3 months before catheter implantation (p < 0.001). Catheter removal or revision (p = 0.002), rehospitalization (p = 0.001) and use of antibiotics (p = 0.02) were also more often observed in patients with MRSA-carriage., Conclusions: The CRP-value at the time of implantation of a permanent hemodialysis catheter is not associated with the development of early catheter related infections, but an individual history of catheter-related infection, MRSA-carriage and bacteremia or bacteriuria in the period of 3 months prior to catheter implantation are significant risk factors.

Though drug adherence is supposed to be low in hypertensive crisis (HTN-C), there are no data available from direct adherence assessments. The aim of the present study was to evaluate adherence to prescribed antihypertensives and potential interactions of concomitant drugs and foods with prescribed antihypertensives in patients with HTN-C by a direct evaluation via biochemical urine analysis. In the present cross-sectional study, 100 patients with HTN-C, admitted to the emergency department (ED), were included. A biochemical urine analysis using gas chromatography-tandem mass spectrometry was performed. Out of 100 patients, 86 received antihypertensives. Urine analyses could be evaluated unambiguously in 62 patients. In 15 of these 62 patients (24%), a nonadherence could be demonstrated, and in 21 patients (34%), a partial nonadherence could be demonstrated. Patients with nonadherence or partial nonadherence showed a longer hypertension history (15[5-22] vs 10[3-15] years, P = 0.04) were prescribed more general medication (number 7.1 ± 3.4 vs 3.4 ± 1.8; P < 0.01) as well as antihypertensive drugs (number 2.8 ± 1.1 vs 1.5 ± 0.7, P < 0.01). A potential BP-raising trigger by medications or food interaction was frequently detectable, predominantly with nonsteroidal anti-inflammatory drugs (NSAIDs; n = 38), glucocorticoids (n = 8), antidepressants (n = 10), and licorice (n = 10). Nonadherence and partial nonadherence to prescribed antihypertensives might play a crucial role for the occurrence of HTN-C. However, further case-controlled studies are needed to confirm the present findings. Ingestion of concurrent over-the-counter drugs such as NSAIDs but also prescribed drugs as well as aliments may lead to critical BP elevation. In order to prevent HTN-C, the present findings emphasize the importance for clinicians to pay attention to the issue of adherence and co-medication., (©2018 Wiley Periodicals, Inc.)

Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty-two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response., (©2018 Wiley Periodicals, Inc.)

Baroreflex activation therapy (BAT) is a sympathoinhibitory procedure for treatment of therapy-resistant hypertension (rsHTN) and severe heart failure with reduced ejection fraction (HFrEF) that been available for several years. The double-blind, randomized Rheos Pivotal Trial demonstrated a blood pressure lowering effect in patients with rsHTN for the first-generation BAT device. A smaller randomized study in heart failure showed that the Barostim Neo system is safe and can improve heart failure symptoms and decrease neuroendocrine activation. However, for this unilateral system, which is currently in clinical use, no data from large randomized trials exist. Despite existing data for BAT in rsHTN and HFrEF, large randomized trials, showing reduction of blood pressure and cardiovascular events are still lacking. Therefore, BAT's efficacy and safety cannot be conclusively assessed.

Activation of baroreceptors in the carotid modulates the autonomic nervous system. Baroreflex activation therapy (BAT), which activates baroreceptors in the carotid, has become available in the treatment of resistant hypertension. Besides this, a carotid implant modulating baroreceptors as well as pharmacological modulation of carotid bodies were quite recently presented. This review will underscore currently available and promising approaches that activate baroreceptors in the carotid, and thereby contribute to beneficial effects in patients with arterial hypertension, and discusses potential organoprotective BAT effects beyond blood pressure (BP) reduction. A systematic review and meta-analysis was conducted including observational studies or randomized controlled trials that investigated the effect of BAT on BP in resistant hypertension. Nine studies, seven observational and two randomized, with a total of 444 patients, were included in the evaluation. Analysing the longest follow-up visit from the different studies, there was a significant reduction of systolic BP after BAT of -36 mmHg [95% confidence interval (CI) -42 to -30 mmHg]. Separate meta-analysis of the short-term (1-6 months) and long-term effects (≥12 months) revealed a reduction of -21 mmHg (95% CI -26 to -17 mmHg) and -38 mmHg (95% CI -46 to -30 mmHg), respectively. There are promising data both in the experimental and the clinical application for BAT. Though the present meta-analysis suggests beneficial effects of BAT on BP, the results must be interpreted extremely carefully. Considering that evidence from controlled trials is very limited, it is evident that there is a strong need for further investigation.

Objective: Unlike safety data of baroreflex activation therapy device (Rheos), only few data of the currently used second device (Barostim neo) are available and little is reported about common side effects., Methods: We prospectively analyzed patients with resistant hypertension treated with Barostim neo. A standardized interview regarding side effects of the therapy was performed in routine follow-up visits after device implantation in 42 patients to determine adverse events staged into three degrees., Results: Within 6 months of baroreflex activation therapy, the office mean arterial blood pressure decreased from 169 ± 27 to 148 ± 29 mmHg systolic (P < 0.001), respectively, to 145 ± 24 mmHg after 1 year (P < 0.001), whereas the number of prescribed antihypertensive classes decreased from 6.6 ± 1.5 to 5.6 ± 1.8 (P < 0.001). Adverse events were combination of the following field depending on the severity (I° mild: local discomfort, clinical observation only, no intervention indicated; II° moderate: medically significant such as occurrence of hypertensive crisis, syncope, arrhythmias; III° severe: life-threatening events or urgent medical intervention indicated). Adverse events I° were present in almost all patients (97.6%), and occurred mainly within first 6 months after device activation. Device-related events were most frequently and could be resolved by optimization of device parameters. Most procedure-related adverse events were directly related to the incision or anesthetic procedure. Adverse events II° occurred in 28.6% patients treated with Barostim neo, whereas patients' elevated individual risks might be potential triggers. Because of individual diversity of blood pressure response and the occurrence of adverse events, no standardization of parameters of implantable pulse generator could be found. By adapting the pulse generator settings individually, most of adverse events I° resolved without sequel., Conclusion: Though there are common side effects, Barostim neo significantly lowers blood pressure in resistant hypertension and provides an adequate safety profile. Regular patient visits are necessary to register side effects.

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

Heart failure and kidney dysfunction are common comorbidities with overlapping and synergizing mechanisms. Coincidence of both pathologies aggravates disease progression rates, symptoms, and outcomes. The treatment of patients with advanced renal insufficiency is faced with limited evidence for therapies that are standard of care in patients with normal and moderate kidney failure, frequent deterioration of kidney function during therapy, and onset of hyperkalemia, which pose challenges for clinical care, requiring intensified physician-patient contacts. A special challenge is the so-called diuretic resistance, which may require extracorporeal drainage.

Detection of renal artery stenosis (RAS) using Doppler is difficult to evaluate, particularly under conditions such as bilateral RAS or difficultly accessible renal arteries (RA). The objective of the present study was to assess the utility of splenic arterial compared to renal flow as an additional parameter in the Doppler evaluation of RAS. The difference between the resistive indices (RI) determined in renal and splenic parenchymal arteries (ΔRI K-S ) was evaluated in 181 hypertensive subjects without any evidence of RAS. Subsequently 47 RA in 24 patients with suspected RAS were angiographically assessed. A ΔRI K-S of 0.055 (median) was determined in the population without any evidence of RAS similar to RA with angiographically excluded stenosis (ΔRI K-S 0.068). In contrast, in angiographic proven RAS, ΔRI K-S was significantly lower (-0.050; P < .005). The assessment of the ΔRI K-S , proved to be an easily feasible parameter, which improves the diagnostic accuracy in the detection of RAS., (©2018 Wiley Periodicals, Inc.)

Background: Both baroreflex activation therapy (BAT) and renal denervation modulate sympathetic activity. The aim of this study was to systematically investigate whether additive modulation of autonomic nervous system by BAT lowers blood pressure (BP) in patients who still suffer from uncontrolled resistant hypertension despite prior renal denervation., Methods: From 2012 to January 2015, patients treated with BAT for uncontrolled resistant hypertension, who prior received renal denervation were consecutively analyzed in four German centers for hypertension. Analyses of office BP, 24-h ambulatory BP, central hemodynamics, parameters of renal function were performed., Results: A total of 28 patients, who underwent renal denervation at least 5 months before and still suffer from uncontrolled BP, were subsequently treated with BAT. The office SBP decreased from 182 ± 28 to 163 ± 27 mmHg (P < 0.01) with a responder rate of 68% (office SBP reduction ≥10 mmHg) at month 6, whereas the number of prescribed antihypertensive drug classes remained unchanged (6.2 ± 1.5 vs. 6.0 ± 1.7, P = 0.30). Serum creatinine, estimated glomerular filtration rate and cystatin C remained stable (P = 1.00, P = 0.41 and P = 0.22, respectively), whereas albuminuria was significantly reduced by a median of -29% (P = 0.02). Central SBP (-15 ± 24 mmHg, P = 0.047) and end systolic pressure (-14 ± 20 mmHg, P = 0.03) were significantly reduced., Conclusion: The present data demonstrate that BAT may exert BP-lowering as well as antiproteinuric effects in patients with prior renal denervation. However, precise evaluation of BAT effects in patients with prior renal denervation will need randomized controlled trials using sham procedures.

Baroreflex activation therapy (BAT) has been demonstrated to decrease office blood pressure (BP) in the randomized, double-blind Rheos trial. There are limited data on 24-hour BP changes measured by ambulatory BP measurements (ABPMs) using the first generation rheos BAT system suggesting a significant reduction but there are no information about the effect of the currently used, unilateral BAT neo device on ABPM. Patients treated with the BAT neo device for uncontrolled resistant hypertension were prospectively included into this study. ABPM was performed before BAT implantation and 6 months after initiation of BAT. A total of 51 patients were included into this study, 7 dropped out from analysis because of missing or insufficient follow-up. After 6 months, 24-hour ambulatory systolic (from 148 ± 17 mm Hg to 140 ± 23 mm Hg, P<0.01), diastolic (from 82 ± 13 mm Hg to 77 ± 15 mm Hg, P<0.01), day- and night-time systolic and diastolic BP (all P ≤ 0.01) significantly decreased while the number of prescribed antihypertensive classes could be reduced from 6.5 ± 1.5 to 6.0 ± 1.8 (P=0.03). Heart rate and pulse pressure remained unchanged. BAT was equally effective in reducing ambulatory BP in all subgroups of patients. This is the first study demonstrating a significant BP reduction in ABPM in patients undergoing chronically stimulation of the carotid sinus using the BAT neo device. About that BAT-reduced office BP and improved relevant aspects of ABPM, BAT might be considered as a new therapeutic option to reduce cardiovascular risk in patients with resistant hypertension. Randomized controlled trials are needed to evaluate BAT effects on ABPM in patients with resistant hypertension accurately., (© 2016 American Heart Association, Inc.)

Background/aims: Early initiation of renal replacement therapy (RRT) is recommended in order to improve the clinical outcome of patients who develop an acute kidney injury (AKI). However, markers that guide an early RRT initiation do not really exist currently., Methods: Urine and serum samples were prospectively collected from 120 AKI patients. Depending on the necessity of initiating RRT, patients were divided into 2 different groups: dialysis (n = 52) and non-dialysis (n = 68)., Results: Comparative urinary proteomic analyses identified 4 different proteins (fatty acid binding proteins 1 and 3 (FABP1 and FABP3), β-2-microglobulin (B2M), cystatin-M (CST6)) that discriminate AKI patients with high risk for RRT. Western blot analysis confirmed the proteomics data for FABP1 and FABP3 but not for B2M and CST6. Validation analysis confirmed that the FABP1 and FABP3 fulfilled the requirement of functioning as markers for AKI patients with risk to dialysis (p < 0.001)., Conclusion: The release of high amounts of FABP1 and FABP3 in urine of AKI patients could serve as a diagnostic/prognosis marker for RRT initiation in these patients., (© 2016 S. Karger AG, Basel.)

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition., (© 2015 Wiley Periodicals, Inc.)

Background: Resistant arterial hypertension and chronic kidney disease (CKD) are interlinked via sympathetic overactivity. Baroreflex activation therapy (BAT) is a well tolerated therapy, which has been shown to reduce BP in patients with resistant hypertension. The effects of BAT in patients with resistant hypertension and end stage renal disease have not been reported., Method and Results: We retrospectively analyzed procedural effectiveness and safety in seven CKD stage 5D patients with resistant hypertension who underwent BAT. One year after activation, office SBP decreased significantly from 194 ± 28 to 137 ± 16 mmHg (P < 0.01). Ambulatory SBP showed a trend to be decreased from 167 ± 30 to 137 ± 24 mmHg (P = 0.17), whereas the median number of prescribed antihypertensive classes decreased from 5 (4-9) to 3 (1-4) (P = 0.01). Intraoperative drop of SBP was -34.3 ± 34.4 mmHg (P = 0.04). With respect to adverse events there were minor side-effects (mainly paresthesia and dysphagia) reported in our patients, which occurred according to treatment intensity and modality., Conclusion: BAT is an effective and well tolerated intervention to reduce BP in patients suffering from end-stage renal disease and resistant hypertension. Therefore, BAT might contribute to a reduction of cardiovascular events in those high-risk patients.

Aims: Sympathetic overactivity is one critical factor associated with the development of arterial hypertension, impaired insulin secretion and resistance. Some antihypertensives exert beneficial effects on glucose metabolism, whereas others lead to an impairment of metabolic state with consecutive weight gain. In resistant hypertension, baroreflex activation therapy (BAT) reduces arterial blood pressure (BP) by inhibition of the sympathetic nervous system. The objective of this study was to evaluate whether BAT influences metabolic state in patients with resistant hypertension., Methods: Thirty patients with resistant hypertension (10 with known diabetes mellitus) were prospectively included into this study. Blood pressure, BMI, weight, fasting glucose, insulin, C-peptide, hemoglobin A1c, HOMA-IR, HOMA-β, ISQuickI, and glucose levels during oral glucose tolerance test were measured at baseline and 6 months after BAT activation., Results: Fasting glucose was significantly reduced after 6 months of BAT, whereas mean 2-h glucose levels during oral glucose tolerance test, fasting insulin levels, C-peptide levels, hemoglobin A1c, HOMA-IR, HOMA-β, ISQuickI, weight, and BMI remained unchanged., Conclusion: Despite improvement in fasting glucose, BAT exerts neither sustained additional beneficial effects nor an impairment of metabolic state. Thus, chronic BAT might be an effective interventional method to reduce BP without metabolic disadvantages.

The results of previous studies on blood pressure in acute stroke therapy allow a few generally valid therapeutic recommendations. Efforts should be made to achieve a constant blood pressure level without major fluctuations. An antihypertensive therapy in the acute stage of stroke should be initiated only at highly elevated values. High blood pressure levels can be tolerated in patients with ischemic stroke unless thrombolytic comes into consideration. Should this be desired, the blood pressure must be quickly lowered to a target range of at least < 180 mmHg. In the case of intracerebral hemorrhage a blood pressure reduction appears to be beneficial. The ESO recommends a reduction to < 140 mmHg systolic within one hour, according to recommendations of the ESH and the EUSI but not more than 20 %., (© Georg Thieme Verlag KG Stuttgart · New York.)

Therapeutic apheresis has reached an important value in the treatment of neurologic disorders. In the indication of acute relapses of inflammatory demyelinating conditions plasma exchange (PE) is currently mentioned in guidelines in adults and children. Immunoadsorption (IA) is a younger but more selective apheresis method. Compared to PE, data on IA in these indications are less substantiated. Hitherto existing studies indicate IA as effective and safe with similar response rates versus PE. Our own study of 140 adult patients treated with PE or IA in steroid refractory multiple sclerosis or neuromyelitis optica affirm previous findings showing no significant difference in efficacy and treatment safety. Analogue to adult patients, children seem to benefit from apheresis therapy in steroid resistant inflammatory demyelinating conditions but their treatment implies certain challenges concerning physiology, anatomy and psychological aspects necessitating a multidisciplinary therapeutic setting., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: High central blood pressure, augmentation index and pulse wave velocity are independent cardiovascular risk factors. Little is known of the effect of baroreflex activation therapy on central hemodynamics., Method: In this prospective clinical trial, radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressure and hemodynamic indices (i.e. augmentation pressure, augmentation index, pulse wave velocity, systolic and diastolic pressure time integral, subendocardial viability index) at baseline and 6 months after starting baroreflex activation therapy in 25 patients with resistant hypertension., Results: Apart from peripheral blood pressure reduction, 6 months of baroreflex activation therapy significantly reduced mean central aortic blood pressure from 109.7 ± 20.5 to 97.4 ± 18.8 mm Hg (P < 0.01) and aortic pulse pressure from 62.9 ± 18.6 to 55.2 ± 16.0 mm Hg (P < 0.01). Aortic augmentation pressure and augmentation index at a heart rate of 75 b.p.m. were significantly reduced by 4.3 ± 7.9 mm Hg (P = 0.01) and 3.5 ± 6.8% (P = 0.02). Additionally, pulse wave velocity decreased from 10.3 ± 2.6 to 8.6 ± 1.3 m/s (P < 0.01) 6 months after starting baroreflex activation therapy. Systolic pressure time integral was significantly reduced (P = 0.03), whereas subendocardial viability index remained unchanged., Conclusion: Apart from peripheral blood pressure, baroreflex activation therapy reduces central blood pressure, augmentation index at a heart rate of 75 b.p.m. and pulse wave velocity in patients with resistant hypertension, suggesting strong potential to reduce cardiovascular risk.

Background: AKI frequently develops in sepsis patients, significantly decreasing the overall prognosis. There are currently no diagnostic markers available which reliably predict the prognosis of sepsis-associated AKI. Recently, ATP content of CD4+ T cells (ATP&#95;CD4) has been shown to correlate with survival in sepsis. The aim of the study was to determine ATP&#95;CD4 in sepsis-associated AKI., Methods: Thirty-three patients with sepsis were prospectively analyzed for ATP&#95;CD4 at three different time points. Results were related to survival, renal recovery, and further clinical/laboratory findings., Results: ATP&#95;CD4 tended to lower in concentration at 48 h after onset of sepsis in those patients with complete renal recovery. There were no differences between patients with no AKI and those with AKI of different severity (AKIN 1-3). Urinary NGAL did not correlate with renal prognosis., Conclusion: ATP&#95;CD4 may serve as risk predictor in sepsis-associated AKI. Lower concentrations may indicate a higher chance of complete renal recovery in sepsis.

Lipoprotein apheresis (LA) is believed to exert anti-atherosclerotic effects beyond LDL-cholesterol reduction. We investigated 22 patients undergoing regular LA on a weekly basis (group A) before (AP) and after LA procedure (EP), 15 healthy individuals (group B), and 22 hyperlipoproteinemic patients with concomitant cardiovascular end organ damage treated without LA therapy (group C). Biomarkers of endothelial inflammation (hsCRP), plaque destabilization, and rupture (sVCAM, MMP-9, PAPP-A, ADMA) were quantified. Intergroup comparison revealed a statistically significant lower MMP-9 level in group A (AP and EP) compared with group C (P < 0.01), whereas PAPP-A levels were lower in group B compared with group A and C (P = 0.04). EP ADMA-levels and EP sVCAM levels in group A were statistically lower compared with group B and C. AP and EP values comparison revealed a significant reduction for hsCRP (mean 41.0 ± 16.7%, P < 0.01), sVCAM (mean 69.6 ± 14.0%, P < 0.01), PAPP-A (mean 88.7 ± 20.4%, P < 0.01), ADMA (mean 69.7 ± 18.4% P < 0.01). In conclusion, we observed a transient decrease in the plasma concentrations of several biomarkers expressed during plaque destabilization and elevated cardiovascular risk after a single LA treatment., (© 2013 Wiley Periodicals, Inc.)

Background/aims: Resistant hypertension and chronic kidney disease (CKD) are interlinked via sympathetic overdrive. Baroreflex activation therapy (BAT) has been shown to chronically reduce blood pressure (BP) in patients with resistant hypertension. The effect of BAT on renal function in CKD patients with resistant hypertension has not been reported. The aim of this study was to investigate the effect of sympathetic inhibition on renal function in CKD patients., Methods: 23 CKD patients with resistant hypertension were prospectively treated with BAT. Analyses were performed before and 6 months after the start of BAT. The renal function was analyzed by creatinine, cystatin C, glomerular filtration rate (GFR), renin, aldosterone, fractioned and 24-hour sodium excretion and analyses of urine marker proteins. The purpose of the control group was to investigate the influence of treating patients in a center for hypertension and regression to the mean on investigated variables., Results: The office mean BP decreased from 116.9 ± 20.9 mm Hg to 104.2 ± 22.2 mm Hg (p < 0.01), while the number of prescribed antihypertensive classes decreased from 6.6 ± 1.6 to 6.1 ± 1.7 (p = 0.02). Proteinuria and albuminuria decreased from a median of 283.9 and 47.7 to 136.5 (p = 0.01) and 45.0 mg/g creatinine (p = 0.01) with pronounced effects in higher CKD stage III + IV compared to I + II (p < 0.01). CKD-EPI cystatin C equation improved from 53.6 ± 22.7 to 60.4 ± 26.1 ml/min (p = 0.02). While creatinine and GFR were impaired after a period of 6 months, no changes of proteinuria, albuminuria, or BP were obtained in control patients., Conclusion: The data of this prospective trial demonstrate potential nephroprotective effects of BAT in therapy-resistant hypertension in CKD patients by a reduction of BP, proteinuria and moreover, a stabilization of estimated GFR., (© 2014 S. Karger AG, Basel.)

Background: The assessment of hydration status remains a challenging task in hemodialysis (HD) management. There are only limited data available on the relevance of clinical decisions in the estimation of dialysis overhydration (OH). The objective of this study was to examine the significance of clinical judgment in the assessment of pre-dialysis OH., Methods: We compared the performance of three methods of OH assessment: (1) clinical judgment guided by a single clinical examination with (2) multifrequency bioimpedance analysis (BIA) and (3) complex systematic clinical approach. We additionally studied the associations of these methods with selected laboratory and imaging parameters., Results: Any of the single parameters alone reached a sufficient level of accuracy for reliable prediction of OH. Clinical judgment was the single most important factor in OH estimation, and also had the highest contribution when in combination with other parameters. BIA reliably measured extracellular fluid, but the automatically calculated OHBIA exhibited a substantial degree of inaccuracy that precludes the use of BIA as a standard at present. The combination of clinical judgment with additional clinical parameters had the highest prediction accuracy for OH. Among the parameters studied, vena cava collapsibility index and calf circumference showed the strongest association with OH. Echocardiography, cardiothoracic index, atrial natriuretic peptide levels and spirometry did not have acceptable sensitivity., Conclusion: The systematic clinical approach combining physician and patient inputs, laboratory and imaging data enables an individualized decision and a superior accuracy in OH assessment.

Recombinant interferon α (IFN-α) and interferon β (IFN-β) are efficient drugs for clinical use in multiple sclerosis, hepatitis C virus infection, and malignant diseases. We report a case of a 40-year-old woman with relapsing-remitting multiple sclerosis who was treated with interferon beta-1b for several years before being admitted to our department with nephrotic-range proteinuria (protein excretion, 8.3 g/d) and serum albumin level of 2.9 g/dL without any clinical and laboratory change typical for a systemic autoimmune disease. The kidney biopsy led to the diagnosis of immune complex-mediated membranoproliferative glomerulonephritis with immunoglobulin and complement deposits visible by immunohistology, as well as subendothelial deposits and tubuloreticular inclusions evident by electron microscopy. Subsequently replacing interferon beta-1b with glatiramer acetate resulted in partial remission, with proteinuria decreasing to protein excretion of 1.0 g/d 2 months thereafter. The association of a focal mesangiocapillary glomerular change and immunoglobulin-complement deposits with tubuloreticular inclusions suggests lupus nephritis. To our knowledge, this is the first report of an interferon beta-1b-induced immune complex glomerulonephritis characterized by histologic, immunohistologic, and ultrastructural features that resembled lupus nephritis, but that occurred in a patient without evidence of systemic lupus erythematosus. Our review of experimental data and earlier case reports suggests a pathogenic role of recombinant IFN in some autoimmune diseases, especially those with the potency to induce systemic lupus erythematosus-like syndromes., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The vast majority of patients with end-stage renal disease are treated with intermittent hemodialysis as a form of renal replacement therapy. To investigate the impact of hemodialysis membrane material on vital protein removal, dialysates from 26 well-characterized hemodialysis patients were collected 5 min after beginning, during 5h of treatment, as well as 5 min before ending of the dialysis sessions. Dialysis sessions were performed using either modified cellulose (n=12) (low-flux and high flux) or synthetic Polyflux (n=14) (low-flux and high-flux) dialyzer. Protein removal during hemodialysis was quantified and the dialysate proteome patterns were analyzed by 2-DE, MS and Western blot. There was a clear correlation between the type of membrane material and the amount of protein removed. Synthetic Polyflux membranes exhibit strong interaction with plasma proteins resulting in a significantly higher protein loss compared to modified cellulosic membrane. Moreover, the proteomics analysis showed that the removed proteins represented different molecular weight range and different functional groups: transport proteins, protease inhibitors, proteins with role in immune response and regulations, constructive proteins and as a part of HLA immune complex. The effect of this protein removal on hemodialysis treatment outcome should be investigated in further studies., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The most common immunosuppressive regimens after renal transplantation include calcineurin inhibitors (CNI). However, due to renal toxicity long-term graft survival does not seem to be positively affected by CNIs., Methods: In the present study, we investigated 17 patients, in which the CNI immunosuppression was converted to a CNI-free, mycophenolate sodium (MPS) regimen. Conversion was performed due to progressive impairment of the graft function from suspected CNI toxicity. We retrospectively analyzed graft function as well as toxicity and surrogate markers for 4 years before and 4 years after conversion using a repeated-measures mixed model data analysis and/or a paired sample t-test., Results: The mean time point of therapy conversion was 11.2 ± 4.6 years after transplantation. Within 1 month of CNI discontinuation, allograft function improved significantly, remaining at a significant level for 2 years. The estimated glomerular filtration rate increased from 43.4 ± 14.8 to a maximum of 55.7 ± 21.7 mL/min at 1 year after conversion (P = .0027). After 4 years, the end of the observation period, renal function was similar to the baseline. There were no significant side effects., Conclusion: These data suggested that, when chronic CNI-toxicity is suspected, renal allograft recipients may benefit from CNI withdrawal in favor of a MPS-including immunosuppressive regimen., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Multiple sclerosis (MS) is an autoimmune disorder, with involvement of both the humoral and cellular components of the immune system. The use of plasma exchange (PE) in steroid-refractory relapses has become an integral part of national and international guidelines for the treatment of steroid-resistant relapses of MS with an efficacy of 40-70%. So far, 6 studies of immunoadsorption (IA) treatment in different forms of MS have been published, 4 of them in steroid-refractory MS relapses. These 4 studies revealed a significant clinical improvement in 73-85% of patients with steroid-refractory MS relapses. However in MS patients with non-active relapsing-remitting or secondary progressive course, there was no clinical improvement. Despite the limited number of patients and studies, these data suggest a reasonably similar efficacy of IA in the treatment of steroid-refractory MS relapses compared to PE. More prospective trials are needed to confirm and extend these results., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Backgrounds: Criteria that may guide early renal replacement therapy (RRT) initiation in patients with acute kidney injury (AKI) currently do not exist., Methods: In 120 consecutive patients with AKI, clinical and laboratory data were analyzed on admittance. The prognostic power of those parameters which were significantly different between the two groups was analyzed by receiver operator characteristic curves and by leave-1-out cross validation., Results: Six parameters (urine albumin, plasma creatinine, blood urea nitrogen, daily urine output, fluid balance and plasma sodium) were combined in a logistic regression model that estimates the probability that a particular patient will need RRT. Additionally, a second model without daily urine output was established. Both models yielded a higher accuracy (89 and 88% correct classification rate, respectively) than the best single parameter, cystatin C (correct classification rate 74%)., Conclusions: The combined models may help to better predict the necessity of RRT using clinical and routine laboratory data in patients with AKI.

Background: In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established., Methods: We prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients' sera., Results: After the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA., Conclusions: IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.

Lipid-apheresis (LA) is thought to improve microcirculation. However, limited data are available on the effects on peripheral microcirculation. We investigated upper limb microcirculation of 22 patients undergoing regular LA on a weekly basis before and after LA. Using standardized semiquantitative scales, we analyzed blood flow, vasomotor function, and erythrocyte aggregation by capillary microscopy. In addition, capillary blood flow in quiescence and under heat and cryo-stress was evaluated by photoplethysmographic and laser Doppler anemometry. Moreover, levels of vasoactive mediators adrenalin, noradrenalin, endothelin-1 (ET-1), atrial natriuretic peptide (ANP), asymmetrical dimethyl-arginine (ADMA), as well as total protein and fibrinogen were measured. We found a significant increase in blood flow, the number of perfused capillaries and an improvement of erythrocyte aggregation by capillary microscopy. Using laser Doppler anemometry, we were able to show that this increase was predominantly located in the superficial layer capillaries (Δ44.53 ± 135.81%, n.s.) and less so in deeper layer arterioles (Δ2.75 ± 24.84%, n.s.). Vascular response to heat and cryo stress was also improved after LA but failed to reach significance. LA significantly reduced levels of epinephrin (-33 ± 39.2%), ANP (-28.8 ± 20.2%), ADMA (-74.1 ± 23%), and fibrinogen (-45.4 ± 19.7%) when comparing before LA and after LA values. In summary, we found an improvement in the microcirculation of the upper limbs under LA, which may result from a decrease of vasoconstrictors, improvement of vasomotor function, and a decrease in blood viscosity or erythrocyte aggregation., (Copyright © 2011 Wiley-Liss, Inc.)

Clinical observations revealed an increased prevalence of iron deficiency anemia without chronic bleeding in patients treated with serial low-density lipoprotein (LDL) apheresis. Since several different proteins are adsorbed by LDL apheresis beside pro-atherogenic lipoproteins, we examined the modification of the full blood count, plasma iron, vitamin B12, folic acid, and hemolysis by LDL apheresis. Nineteen patients (55 (50-59) years, 4 female, 15 male) undergoing chronic LDL apheresis due to mixed dyslipidemia (N = 17), homozygous familiar hypercholesterolemia (N = 1) or isolated elevated lipoprotein(a) (N = 1) were included in this study. They were treated with direct adsorption of lipoproteins (DALI; N = 6), heparin-induced LDL-precipitation (HELP; N = 7) or double filtration plasmapheresis (DFPP; N = 6). The patients' full blood count, iron metabolism (plasma iron, ferritin, transferrin, transferrin saturation), vitamins involved in erythropoiesis (vitamin B12 and folic acid), and markers of hemolysis (haptoglobin and free hemoglobin) were analyzed directly before and after LDL apheresis. A single LDL apheresis session significantly decreased the levels (reduction in the median [25(th)-75(th) percentiles] of: ferritin 9.8 [1.3-18] %; P = 0.004), transferrin (12.1 [10.0-15.96] %; P = 0.0005), and vitamin B12 (17.8 [16.2-20.8] %; P = 0.0005). Thereby, transferrin and vitamin B12 were decreased in all (N = 19) and ferritin in 74% (N = 14) of the patients. Twelve out of 19 patients (63.2%) had mild anemia despite iron administration in 14 out of 19 patients (73.7%). LDL apheresis had no significant influence on full blood count, plasma iron, transferrin saturation, folic acid, or hemolysis. Similar changes were observed in all LDL apheresis methods used. LDL apheresis significantly decreases ferritin, transferrin, and vitamin B12, suggesting an influence of serial LDL apheresis on erythropoiesis.