Bernd Hohenstein

• MD
• Nephrologisches Zentrum Villingen-Schwenningen

According to the latest Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on glomerular diseases, rare forms of glomerulonephritis (GN) mediated by the complement system are categorized under glomerulonephritis with a membranoproliferative GN (MPGN) pattern. Insights into the pathophysiology suggest that these represent a spectrum of sec...

Background Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However,...

Introduction Large-scale trials showed positive outcomes of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in adults with chronic kidney disease (CKD). Whether the use of SGLT2i is safe and effective in patients with the common hereditary CKD Alport syndrome (AS) has not yet been investigated specifically in larger cohorts. Methods This observ...

Introduction: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cyto-plasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m 2 in the avacopan group and 4.1 ml/min per 1.73 m 2 in the pred...

Since the publication of the latest Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on glomerular diseases, rare complement-mediated forms of glomerulonephritis (GN) have again been sorted primarily into the group of GN with a membranoproliferative GN (MPGN) pattern: however, the growing knowledge about the pathophysiological relations...

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, rando...

During 2012–2020, 89 German apheresis centers collected retrospective and prospective observational data of 2028 patients undergoing regular lipoprotein apheresis (LA) for the German Lipoprotein Apheresis Registry (GLAR). More than 47 500 LA sessions are documented in GLAR. In 2020, all patients treated with LA showed a high immediate median reduct...

A continual increase in cases of Long Covid constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggests that up to 20% of people with confirmed with SARS-CoV-2 suffer from clinically relevant symptoms of Long Covid several weeks to mo...

Aim: The PERI-DYS study aims to characterize two groups of patients with dyslipidaemia at very high CV risk: PCSK9i receivers and patients qualifying for but not receiving PCSK9i. Methods: This is an observational study by office-based and clinic-based physicians, mainly cardiologists and other internists in Germany, with data extracted from pat...

Elevated plasma concentrations of asymmetric dimethylarginine (ADMA) are associated with an increased risk of mortality and adverse cardiovascular outcomes. ADMA can be metabolized by dimethylarginine dimethylaminohydrolases (DDAHs) and by alanine-glyoxylate aminotransferase 2 (AGXT2). Deletion of DDAH1 in mice leads to elevation of ADMA in plasma...

Purpose: Patients suffering from chronic kidney disease (CKD) are in general at high risk for severe coronavirus disease (COVID-19) but dialysis-dependency (CKD5D) is poorly understood. We aimed to describe CKD5D patients in the different intervals of the pandemic and to evaluate pre-existing dialysis dependency as a potential risk factor for mort...

Background The reasons why patients are treated or not with PCSK9 inhibitors (PCSK9i) are incompletely understood. In Germany, access to PCSK9i is limited by local regulations and many high-risk cardiovascular patients do not receive these therapies. The PERI-DYS study aims to describe and compare two groups of dyslipidaemia patients at very high C...

ZUSAMMENFASSUNG In der SARS-CoV-2-Pandemie sind Patienten mit chronischen Nierenerkrankungen und hierbei besonders chronische Dialysepatienten einem hohen Infektionsrisiko und im Falle einer Infektion mit Abstand dem höchsten Mortalitätsrisiko aller prädisponierenden Erkrankungen ausgesetzt. Ambulante Dialyseeinrichtungen erbringen dabei den Großte...

Purpose The ongoing pandemic caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has stressed health systems worldwide. Patients with chronic kidney disease (CKD) seem to be more prone to a severe course of coronavirus disease (COVID-19) due to comorbidities and an altered immune system. The study’s aim was to identify factors p...

Objective: Elevated plasma concentrations of asymmetric dimethylarginine (ADMA) are associated with an increased risk of mortality and adverse cardiovascular outcomes. ADMA can be metabolized by dimethylarginine dimethylaminohydrolases (DDAHs) and by alanine-glyoxylate aminotransferase 2 (AGXT2). Deletion of DDAH1 in mice leads to elevation of ADMA...

According to the current state of knowledge, the group of diseases composed of immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) form a disease spectrum, which is very heterogeneous in terms of pathophysiology and the clinical course, but the representatives frequently show an MPGN histological p...

ZUSAMMENFASSUNG Für Diabetes mellitus als eine der kostenintensivsten Erkrankungen weltweit entstand in vielen Jahrzehnten durch zahlreiche Studien ein detailliertes Bild von der optimierten Therapie hinsichtlich mikro- und makrovaskulärer Folgeerkrankungen. Neben der Kontrolle der Hyperglykämie kommt vor allem der RAS-Blockade eine wichtige Bedeut...

Background: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective...

Closed micro-physiological systems (MPS) are miniaturized, chip-sized platforms that can be used as cellularized organoid systems to study cellular processes like migration, regeneration or proliferation in vitro. Due to the limited accessibility of the cells inside of closed MPS, the establishment of a well-defined mechanism to induce specific cel...

Membranoproliferative glomerulonephritis (MPGN) and glomerulopathy with dominant C3 deposits are very rare autoimmune disorders of the kidney that had been classified in its current form in 2010 due to a better understanding of the underlying pathophysiology. Today, the immune complex-associated membranoproliferative glomerulonephritis (IC-MPGN) an...

Lipoprotein(a) (Lp(a)) consists of an LDL particle whose apolipoprotein B (apoB) is covalently bound to apolipoprotein(a) (apo[a]). An increased Lp(a) concentration is a causal, independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and a predictor of incident or recurrent cardiovascular events. Although Lp(a) was first describe...

Background and aims: Cardiovascular disease is nowadays the major cause of mortality and morbidity worldwide. The risk of developing cardiovascular disease is significantly increased in patients with diabetic nephropathy. It has been suggested that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthases (NOS), may play an impor...

Background: The metabolic syndrome is a cluster of cardiovascular risk factors and is highly predictive for development of cardiovascular diseases. An association between elevated plasma levels of the endogenous inhibitor of nitric oxide synthases asymmetric dimethylarginine (ADMA) and risk of cardiovascular diseases has been demonstrated in numer...

Background: Although lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5-10% of high-risk cardiovascular patients reach the target values recommended by internati...

Background: Lipoprotein apheresis (LA) can effectively lower lipoproteins but is an invasive procedure. Objective: The objective of this study was to evaluate whether evolocumab can reduce LA requirement in patients undergoing chronic LA. Methods: Patients on regular weekly or every-2-week LA and moderate- to high-intensity statin (if tolerate...

Chronic kidney disease (CKD) is a global health problem that affects around 11 to 13% of the world’s population and more than 18% of European citizens. Characteristic syndromes of CKD during all stages of the disease are proteinuria and ongoing glomerular dysfunction caused by cellular damages at the glomerular filtration barrier. While some rare c...

Aims: The potential influence of angiotensin-receptor blockers (ARBs) on carcinogenesis is a much-debated topic. Both observational, as well as preclinical studies in rodent carcinogenic assays, suggest a major role of the Renin-Angiotensin-Aldosterone-System (RAAS) in cancer development. Therefore, a systematic review and meta-analysis with avail...

Background Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and is associated with the induction and sustaining of atherosclerotic cardiovascular diseases (ASCVD). Since 2008 Lp(a) along with progressive CVD has been approved as an indication for regular lipoprotein apheresis (LA) in Germany. The German Lipoprotein A...

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Basierend auf dem zunehmend besseren pathophysiologischen Verständnis der vergangenen 10 Jahre wurde im Jahr 2010 die neue Klassifikation einer Glomerulonephritis mit dominanten oder kodominanten C3-Ablagerungen eingeführt, deren wesentliche Untergruppe die C3-Glomerulopathie (C3G) darstellt. Nach derzeitigem Verständnis bildet die Erkrankungsgrupp...

In the present study a functional renal proximal tubule cell culture model suitable for drug testing assays was established. TEER and direct 2-NDGB transport assays were used to identify potential nephrotoxic effects of antibiotic treatments in vitro. In further experiments the Insert will be integrated into in micro fluidic system.

Mimicking the physiology of the proximal tubule in vitro seems an adequate way to study secretion and reabsorption of metabolites in the kidney. Here we present an cell based micro physiological model system that can be used to emulate drug transport along the proximal tubule in vitro. To prove that, the effect of SGLT2-inhibition on the glucose tr...

Endothelial cells (EC) frequently undergo primary or secondary injury during kidney disease such as thrombotic microangiopathy or glomerulonephritis. Renin Lineage Cells (RLCs) serve as a progenitor cell niche after glomerular damage in the adult kidney. However, it is not clear whether RLCs also contribute to endothelial replenishment in the glome...

Background: There is evidence for beneficial effects of lipoprotein apheresis (LA) in terms of reduction of cardiovascular events and interventions, but quality of life (QOL) in LA patients has only been explored in small samples. Objective: In this study, both LA- or treatment-related and health-related QOL (HRQOL) were assessed in 206 LA patie...

Introduction Lipoprotein apheresis (LA) represents the only effective therapeutic option for patients with elevated Lipoprotein(a) (Lp(a)) levels. We aimed at analyzing the Lp(a) reduction, rebound rates as well as mean interval values between two weekly apheresis sessions, since this might be important for the prediction of the residual cardiovasc...

We reported earlier that PPAR-gamma regulates renin transcription through a human-specific atypical binding sequence termed hRen-Pal3. Here we developed a mouse model to investigate the functional relevance of the hRen-Pal3 sequence in vivo since it might be responsible for the increased renin production in obesity and thus for the development of a...

Zusammenfassung Bei der Apherese handelt es sich um ein der Hämodialyse ähnliches und in der Regel von Nephrologen durchgeführtes extrakorporales Eliminationsverfahren. Daher liegt es nahe, die pflegerischen Aufgaben ebenfalls in die Hände von nephrologischem Fachpersonal zu legen. Allerdings sind die Erfahrungen mit der therapeutischen Apherese au...

In recent years more and more artificial but complex microphysiological systems (MPS) were used to investigate physiological processes and renal diseases. Our MPS are perfused, miniaturized chipsized platforms which can be used as cellularized human organoid systems to examine cell processes like regeneration, proliferation and cell-cell interactio...

Intracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gsα in...

Renin lineage cells (RLCs) serve as a progenitor cell reservoir during nephrogenesis and after renal injury. The maintenance mechanisms of the RLC pool are still poorly understood. Since RLCs were also identified as a progenitor cell population in bone marrow we first considered that these may be their source in the kidney. However, transplantation...

Background Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effe...

Introduction Immunoadsorption (IA) is increasingly used instead of plasma exchange due to lower risk of side effects and a higher selectivity. As a consequence of the reduction of immunoglobulins (Ig), the rate of infectious complications might increase in those patients. We therefore aimed to investigate the infection rate following IA without int...

ABO incompatible (ABOi) organ transplantation requires pre-transplant reduction of the recipient's IgG and IgM isoagglutinin titer against the donor to prevent hyperacute rejection. Over the past four years we primarily used unspecific IgG immunoadsorption (IA) for this purpose and combined this selectively with membrane filtration (IAc) to reduce...

Background Monocytes can be differentiated into subpopulations depending on their expression profile of CD14 and CD16. CD16-positive monocytes are associated with coronary artery disease. Up to now, no data exist about the effect of lipoprotein apheresis (LA) on the distribution of monocyte subpopulations. Methods 80 patients who underwent LA at t...

Objective Beyond its well-established efficacy in lowering atherogenic lipids and lipoproteins, DALI (Direct Adsorption of Lipids) apheresis has been shown to have acute anti-inflammatory and endothelium-protective effects. In the present study, we investigated long-term effects of DALI procedures on circulating oxidative stress markers. Methods T...

Background Dyslipidemia is a well-known risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). While low density lipoprotein cholesterol (LDL-C) is well-established and taken into consideration for risk management and therapy, lipoprotein(a) is another established CVD risk factor frequently not undergoing screening due to a la...

Background and aims Cardiovascular disease is the major cause of morbidity and mortality in the world. Diabetes and its complications, such as diabetic nephropathy, dramatically increase cardiovascular risk. Association studies suggest that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, plays a role in the pa...

Background Severe forms of mono- and polygenetic hypercholesterolemia as well as elevated Lipoprotein (a) (LP(a)) with progressing cardiovascular (CV) disease are indication for lipoprotein apheresis (LA) in Germany. Many studies investigated pleiotropic effects of LA that might contribute to beneficial effects in advanced atherosclerosis. The pres...

Background Pemphigus vulgaris is a chronic autoimmune disease characterized by blisters and erosions forming in the mucous membranes and the skin. Many patients are severely impaired by pain, weight loss and increased risk of infections. The disease is mediated by specific autoantibodies directed against desmogleins that contribute to connect kerat...

Background and aim Lipoprotein-apheresis (LA) is a therapeutic approach used against severe forms of dyslipidemia in patients who are non-responders or intolerant to pharmacological treatments. However, little is known about the potential pleiotropic effects of LA, particularly regarding the immune system and its regulation. Thus, in an attempt to...

Objectives Lipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus...

Lipoprotein apheresis (LA) has been the last-resort therapeutic option in patients suffering from limited pharmaceutical options to lower highly elevated low density lipoprotein cholesterol (LDL-C) levels. Facing the introduction of the proprotein convertase subtilisin/kexine type 9 (PCSK-9) inhibitors, it has been speculated that they might replac...

Background: It has been demonstrated in various studies that ADMA (asymmetric dimethylarginine), an inhibitor of nitric oxide synthase, is associated with the increased risk of cardiovascular diseases. There are two known pathways of ADMA metabolism: hydrolysis to citrulline by dimethylarginine dimethylaminohydrolases (DDAH) and transamination by a...

Mit der therapeutischen Apherese (TA) steht dem Nephrologen neben den Nierenersatzverfahren ein zusätzliches Arsenal an Blutreinigungsverfahren mit teils hoher Selektivität zur Verfügung. Allen Aphereseverfahren ist gemeinsam, dass Patienten formal über einen venovenösen Zugang behandelt werden können, da nur niedrige Blutflussraten (≤100 ml/min) n...

In contrast to existing EAS/ESC guidelines on the management of lipid disorders, current recommendations from nephrological societies are very conservative and restrictive with respect to any escalation of lipid lowering/statin therapy. Furthermore, lipoprotein(a) (Lp(a)) – an established cardiovascular risk factor – has not even been mentioned. Wh...

The thorough investigation of peritubular capillary changes during renal fibrosis presented in this issue provides novel insights, not only into the value of elaborate methodological approaches, but also the necessity to carefully dissect pathophysiology using current techniques. This study strengthens the existing view of a uniform progression of...

Microfluidic systems are small, chip-sized platforms which can be used as cellularized organoid systems to study cell processes and cell-cell interactions. Due to the limited accessibility, the induction of specific cell damage within the channel system to study regenerative processes is difficult. We recently established a microfluidic platform to...

Various complement-mediated renal disorders are currently treated with the complement inhibitor eculizumab. By blocking the cleavage of C5 this monoclonal antibody prevents cell damage caused by complement-mediated inflammation. We included 23 patients with atypical hemolytic uremic syndrome (aHUS, n=12), C3 glomerulopathies (C3G, n=9) and acute an...

As a major event in the field of therapeutic apheresis, lipidology and immune-modulating extracorporeal treatments, Dresden hosted the 4th International Symposium on Therapeutic Apheresis 17–19 March 2016. In conjunction with the newly founded European Group – International Society for Apheresis, this meeting attracted more than 300 clinicians and...

Today's 3D printing technologies offer great possibilities for biomedical researchers to create their own specific laboratory equipment. With respect to the generation of ex vivo vascular perfusion systems this will enable new types of products that will embed complex 3D structures possibly coupled with cell loaded scaffolds closely reflecting the...

Microfluidic systems are small, chip-sized platforms, which can be used as cellularized organoid systems to studycell processes and cell-cell interactions. Due to the limited accessibility, the establishment of specific cell damage within thechannel system to study regenerative processes is difficult. We recently established a microfluidic platform...

Aim To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly as...

Background: Elevation of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) has been shown to be associated with increased risk of cardiovascular diseases. There are two major pathways of ADMA catabolism: hydrolysis to citrulline by dimethylarginine dimethylaminohydrolases (DDAH) and transamination by alanine-glyox...

Background: Many patients with heterozygous familial hypercholesterolemia (HeFH) fail to reach optimal low-density lipoprotein cholesterol (LDL-C) levels with available lipid-lowering medications, including statins, and require treatment using alternative methods such as lipoprotein apheresis. Objective: To evaluate the efficacy of alirocumab 15...

Background Increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are associated with cardiovascular and renal diseases. We and others have shown that both ADMA and SDMA can be Nα-acetylated to form asymmetric and symmetric Nα-acetyldimethylarginine (Ac-ADMA and Ac-SDMA). The current study further investigated...

Since the last update in this context, substantial progress has been made with respect to the classification and therapeutic aspects of rare types of glomerulonephritis. This includes the reclassification of diseases formerly categorized as membranoproliferative glomerulonephritis (MPGN) into the two separate entities of C3 glomerulopathy (C3G) and...

Background: ADMA (asymmetric dimethylarginine), an inhibitor of nitric oxide synthase, has been shown to be associated with the risk of cardiovascular diseases. There are two known pathways for ADMA catabolism: hydrolysis to citrulline by dimethylarginine dimethylaminohydrolases (DDAH) and transamination by alanine-glyoxylate aminotransferase 2 (AG...

Endothelial progenitor cells (EPCs) may be relevant contributors to endothelial cell (EC) repair in various organ systems. In this study, we investigated the potential role of EPCs in renal EC repair. We analyzed the major EPC subtypes in murine kidneys, blood, and spleens after induction of selective EC injury using the concanavalin A/anti-concana...