Birgit Rudolph

Charité Universitätsmedizin Berlin | Charité · Institute of Pathology

Background Transplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated. Methods 282 kidney allograft recipients with biopsy-pr...

The Banff 2017 report permits the diagnosis of pure chronic antibody-mediated rejection (cAMR) in absence of microcirculation inflammation. We retrospectively investigated renal allograft function and long-term outcomes of 67 patients with cAMR, and compared patients who received antihumoral therapy (cAMR-AHT, n = 21) with patients without treatmen...

Background: Transplant glomerulopathy (TG) is one of the main causes of post-transplant proteinuria (PU). The features and possible risk factors for proteinuria in TG patients are uncertain. Methods: We investigated all patients who had biopsy-proven TG from 2000 to 2018 in our center. The clinical and histological data were compared between two gr...

Background Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance. Methods A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudicati...

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. About 30 % of patients with NAFLD progress to the more severe condition of nonalcoholic steatohepatitis (NASH), which is typically diagnosed using liver biopsy. Liver stiffness (LS) quantified by elastography is a promising imaging marker...

Proteinuria and transplant glomerulopathy (TG) are common in kidney transplantation. To date, there is limited knowledge regarding proteinuria in different types of TG and its relationship to allograft survival. A retrospective cohort analysis of TG patients from indication biopsies was performed to investigate the relationship of proteinuria, hist...

Non-alcoholic fatty liver disease (NAFLD) is a significant health burden in obese children for which there is currently no specific therapy. Preclinical studies indicate that epoxyeicosanoids, a class of bioactive lipid mediators that are generated by cytochrome P450 (CYP) epoxygenases and inactivated by the soluble epoxide hydrolase (sEH), play a...

Background: Mycophenolic acid (MPA) is a standard immunosuppressant in organ transplantation. A simple monitoring biomarker for MPA treatment has not been established so far. Here, we describe inosine 5'-monophosphate dehydrogenase (IMPDH) monitoring in erythrocytes and its application to kidney allograft recipients. Methods: IMPDH activity meas...

Antibody‐mediated rejection (ABMR) is a major cause of graft loss in renal transplantation. We assessed the predictive value of clinical, pathological and immunological parameters at diagnosis for graft survival. We investigated 54 consecutive patients with biopsy‐proven ABMR. Patients were treated according to our current standard regimen followed...

Epoxy-fatty-acids (EpFAs), cytochrome P450 dependent arachidonic acid derivatives, have been suggested to have anti-inflammatory properties, though their effects on autoimmune diseases like systemic lupus erythematosus (SLE) have yet to be investigated. We assessed the influence of EpFAs and their metabolites in lupus prone NZB/W F1 mice by pharmac...

Objectives: Today, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults alike. Yet, the noninvasive evaluation of disease severity remains a diagnostic challenge. In this study, we apply multifrequency magnetic resonance elastography (mMRE) for the quantification of liver steatosis and fibrosis i...

The use of once‐daily tacrolimus in de novo kidney transplantation is increasingly common. Therefore, we were interested in bioavailability aspects of novel once‐daily tacrolimus (LCPT, Envarsus) and once‐daily tacrolimus extended‐release formulation (ER‐Tac, Advagraf) compared with twice‐daily immediate‐release tacrolimus (IR‐Tac, Prograf). Furthe...

We present a 42-year-old man with a BMI of 32, who was referred because of proteinuria and decreased renal function. We were impressed by his markedly muscular physique. A renal biopsy was performed, which showed focal segmental glomerular sclerosis (FSGS). Is this patient merely an obese person with FSGS or is something else going on here? We perf...

Purpose To measure in vivo liver stiffness by using US time-harmonic elastography in a cohort of pediatric patients who were overweight to extremely obese with nonalcoholic fatty liver disease (NAFLD) and to evaluate the diagnostic value of time-harmonic elastography for differentiating stages of fibrosis associated with progressive disease. Materi...

The Eurotransplant Senior Program has been implemented to utilize kidneys from elderly donors for age-matched recipients, but concerns have been raised about the longterm outcome. We investigated the outcomes of all elderly patients in our center. All candidates for kidney transplantation ≥ 65 years were identified. Patients entering the waitlist f...

Background: Current evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. Methods: Steroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W)...

Background: De novo donor specific anti-HLA antibodies (dnDSA) may cause graft loss in renal transplant recipients. The capability to bind the complement may help to stratify the risk for inferior outcomes associated with dnDSA. We developed a modified C1q-binding assay and hypothesized that C1q-binding dnDSA could differentiate between indolent a...

Objective: To analyze the composition of known plasmacytosis in systemic lupus erythematosus (SLE) to obtain further insight into the nature of underlying mechanisms. Methods: Plasmablasts from patients with active SLE, patients with inactive/treated SLE, and healthy controls were characterized by flow cytometry, enzyme-linked immunospot assay,...

Background: Antibody-mediated rejection (ABMR) is a major risk for renal allograft survival. Throughout decades, cyclophosphamide treatment has been proven to be effective in patients with antibody-associated autoimmune diseases. We investigated, whether cyclophosphamide combined with plasmapheresis (PPH) and intravenous immunoglobulins (IVIG) is...

Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may se...

The potential diagnostic value of circulating free miRNAs in plasma compared to miRNA expression in blood cells for rejection processes after kidney transplantation is largely unknown, but offers the potential for better and timely diagnosis of acute rejection. Free microRNA expression of specific blood cell markers was measured in 160 plasma sampl...

Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may se...

Background Current treatment strategies for antibody-mediated renal allograft rejection (AMR) are not sufficiently effective. In most centers, “standard of care” treatment includes plasmapheresis (PPH) and IVIG preparations. Since several years, modern therapeutics targeting B cells and plasma cells have become available. We investigated, whether c...

Supplementary Figure 1. Arrow A shows a glomerulus with normal capillary loops, regular thickness of mesangial matrix and peripheral capillary basement membrane, and flat podocytes. Arrow B shows a glomerulus with segmental glomerular sclerosis. This glomerulus shows the loss of capillary lumen and the adhesion of sclerotic lesions to the Bowman’s...

Mutations in CD2-associated protein (CD2AP) have been identified in patients with focal segmental glomerulosclerosis (FSGS); however, reports of CD2AP mutations remain scarce. We performed Sanger sequencing in a patient with steroid-resistant FSGS and identified a heterozygous CD2AP mutation (p.T374A, c.1120 A > G). Our patient displayed mild cogni...

Urine is normally nearly devoid of leukocytes. In various renal diseases however, immune cells can be observed in the urine. Flow cytometry is the state-of-the-art technique for analyzing the quantity and qualities of cells in suspension, making this method an ideal approach for investigating urinary immune cells. Increased amounts of urinary T cel...

Background: Antibody-mediated rejection (AMR) can induce and develop thrombotic microangiopathy (TMA) in renal allografts. A definitive AMR (dAMR) co-presents three diagnostic features. A suspicious AMR (sAMR) is designated when one of the three features is missing. Methods: 32 TMA cases overlapping with AMR (AMR+ TMA) were studied, which involv...

Background: Primary focal segmental glomerulosclerosis (FSGS) often causes nephrotic proteinuria and frequently results in end-stage renal disease and recurrence after kidney transplantation. Recent studies describe soluble urokinase-type plasminogen activator receptor (suPAR) as a circulating factor implicated in FSGS. Methods: This single-cent...

Background: MicroRNAs (miRNAs, miR) hold important roles in the post-transcriptional regulation of gene expression. Their function has been correlated with kidney disease, and they might represent a new class of biomarkers for frequent evaluation of renal graft status. We analyzed their potential in identifying severe T cell-mediated vascular rejec...

It is unclear if the category of acute rejection with intimal arteritis (ARV) is relevant to short- and long-term clinical outcomes and if the graft outcomes are affected by the severity of intimal arteritis. One hundred forty-eight ARV episodes were reviewed and categorized according to the 2013 Banff criteria of AMR: T cell-mediated rejection wit...

NZB/W mice spontaneously develop a lupus-like disease leading to lethal immune complex-mediated nephritis. Disease manifestation is accompanied by inflammatory infiltration of the kidneys by lymphocytes. Here, we show that the immigration of B cells is mediated via CXCR5 whereas plasma cell infiltration is differently. Histology was used to analyse...

Purpose: To assess whether ultrasonography (US)-based real-time elastography (RTE) can be used to detect gut fibrosis. Materials and methods: In this institutional review board-approved, prospective, proof-of-concept study, unaffected and affected gut segments in 10 patients with Crohn disease (four women, six men; median age, 49 years) were exa...

Background: Most of membranoproliferative glomerulonephritis (MPGN) raise from the abnormalities in alternative complement pathways. Case presentation: A 3-year-old girl manifested hematuria (HU), proteinuria (PU), and hypocomplementemia (HC) without a known cause; the first renal biopsy indicated MPGN that resembled type I MPGN. After treatment wi...

Urine is normally nearly devoid of leukocytes. In various renal diseases however, immune cells can be observed in the urine. Flow cytometry is the state-of-the-art technique for analyzing the quantity and qualities of cells in suspension, making this method an ideal approach for investigating urinary immune cells. Increased amounts of urinary T cel...

Scientific interest in cardiorenal syndrome (CRS) affecting the native kidneys is increasing. In contrast, no relevant literature exists on CRS after kidney transplantation. Prompted by the clinical course of a renal allograft recipient, who lost his graft because of CRS, we systematically investigated the frequency, the clinical appearance, the un...

Objectives: Whether T-cell-mediated rejection Banff classification type Ib (severe tubulointerstitial rejection) and type IIa (mild vascular rejection) are associated with responses to antirejection therapy and long-term graft survival are unclear. Materials and methods: One hundred ten patients were enrolled who had at least 1 episode of T-cell...

Objectives: To determine the pathologic features of early- and late-onset acute cellular rejection that may contribute to graft loss after kidney transplant. Materials and methods: There were 247 patients who had acute cellular rejection included in the study. The biopsy that showed the highest acute cellular rejection severity was evaluated for...

Background: It is unclear if the severity or the timing of acute cellular rejection (ACR) defined by Banff classification 2009 is associated with graft survival. Methods: Borderline changes, TCMR I (interstitial rejection), and TCMR II/III (vascular rejection) were defined as low, moderate, and high ACR severity, respectively. Approximately 270...

Hepatitis E virus infection is increasingly reported as a cause of chronic hepatitis in organ transplant recipients. Besides reduction of immunosuppressive therapy or pegylated-interferon therapy, promising results have been reported for ribavirin monotherapy of hepatitis E virus after kidney transplant. To our knowledge, this is the first report o...

The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II...

Diabetes mellitus is the most common cause of renal failure in industrialized countries. It is largely unknown why only 20 -40% of patients with diabetes develop diabetic nephropathy. Experimental animal models with histological features of human diabetic nephropathy could help to elucidate new genetic and pathophysiological mechanisms of diabetic...

The case of a 58-year-old male patient who developed a chronic pain syndrome after laparoscopic intraperitoneal onlay mesh for treatment of a large symptomatic umbilical hernia combined with rectus diastasis is reported. Twelve months after an uncomplicated initial surgery, the patient presented with progressive signs of a foreign body sensation an...

: In subtotally nephrectomized rats, we studied to what extent high-dose calcitriol-induced cardiovascular disease can be modulated by almost complete suppression of parathyroid hormone (PTH), mediated by either cinacalcet (CINA) or parathyroidectomy (PTX). : Five groups were studied: sham-operated controls, uremic (U), uremic with calcitriol (U+1,...

Objectives: Chronic heart failure after myocardial infarction is still a serious problem without a fundamental therapy. Direct intramyocardial transplantation of bone marrow cells (BMC) is promising but difficult to perform. Therefore, cardiac effect of experimental intravenous application of BMC after myocardial infarction (MI) is evaluated. Met...

Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus ther...

This letter describes two unrelated patients with membranoproliferative glomerulonephritis type 2 and autoantibodies to the two individual components of C3 convertase, factor B and C3. These autoantibodies enhance C3 convertase activity, probably leading to nephritis.

Celiac sprue is an underdiagnosed chronic intestinal inflammatory disease. Probe-based confocal laser microscopy (CLM) is a novel endoscopic technique for in vivo inspection of the intestinal mucosa that has not been evaluated in celiac sprue yet. To develop CLM criteria most predictive of celiac pathology in a prospective pilot study. Twenty-one p...

Antibody-mediated rejection (ABMR) following kidney transplantation is associated with poor allograft survival. Conventional treatment based on plasmapheresis (PPH) and the administration of intravenous immunoglobulins (IVIG) is not satisfactory. Two compounds, more specifically targeting B cells and plasma cells, may help to improve the prognosis:...

We present the case of a 48-year-old otherwise healthy man who required an urgent liver transplant owing to acute liver failure after flupirtine treatment. After 3 months of daily flupirtine intake as treatment for pseudoradicular pain syndrome, he presented at our institution with signs of jaundice and hepatic encephalopathy. Laboratory results sh...

The lymph node number as benchmark in oncologic operations depends on the patient's anatomy, surgeon's skill and pathologist's accuracy. The influence of the pathologist is barely evaluated. A retrospective analysis of lymph node numbers after 700 laparoscopic lymphadenectomies in correlation to the examining pathologists was done. Three surgeons f...

Einleitung: Flupirtin ist ein zentral-wirkendes, nicht opioides Analgetikum. Verschiedene Auspragungsgrade einer additiven hepatotoxischen Wirkung auf dem Boden einer vorbestehenden Lebererkrankung sind bekannt und eine Behandlung mit Flupirtin ist kontraindiziert bei Patienten mit vorbestehender Lebererkrankung. Ziele: Wir berichten hier den Fall...

We assessed the predictive value of TP53 mutations and prostate-specific antigen (PSA) for tumor progression in prostate cancer (PCa) patients. Ninety tumor tissue samples of patients with PCa from radical prostatectomy were used. Tumor progression was estimated biochemically by the PSA level (> 0.2 microg/l) or by detection of metastases. Screenin...

The purpose of this study was to investigate whether analysis of voxels with the highest perfusion and blood volume (hotspots) within a whole region affected by prostate cancer can improve differentiation of cancerous and normal prostate tissue at pharmacokinetic MRI. Fifty-three patients with biopsy-proven prostate cancer were examined with 1.5-T...

To prospectively determine whether pharmacokinetic magnetic resonance (MR) imaging parameters correlate with histologic mean vessel density (MVD), mean vessel area (MVA), and mean interstitial area (MIA) and whether these parameters enable differentiation of prostate cancer, chronic prostatitis, and normal prostate tissue. This study was approved b...

Arteriovenous aneurysms may be congenital (arteriovenous malformation, AVM) or acquired (arteriovenous fistula, AVF). AVFs after a renal transplant biopsy are seldom, but well recognized, usually harmless complications [1]. Congenital AVMs are usually of the cirsoid (racemose) type [2], characterized by a tangle of tortuous vessels of small diamete...

Endocytoscopy (EC) is a novel technique that allows magnified live inspection of the intestinal mucosa. To evaluate EC for the detection of key pathological findings in patients with celiac sprue. A total of 166 EC recordings were prospectively acquired. Matched videos, images, and biopsy specimens were obtained by duodenal argon beamer labeling of...

We aimed to reassess renal amyloidosis in kidney biopsies with a focus on possibly misclassified or unclassified cases and changes in the prevalence of different amyloid types. Two hundred thirty-three kidney biopsies obtained from 231 patients diagnosed with amyloid during the period from 1990 to 2007 years were included in this retrospective stud...

Elevated levels of BAFF and APRIL are characteristic of patients with systemic lupus erythematosus (SLE). The reasons for enhanced cytokine production are not well understood. This study was undertaken to identify the cells responsible for the overproduction of these cytokines. BAFF expression was analyzed on peripheral blood mononuclear cells by m...

Antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) is a well-described cause of multiple organ involvement including rapidly progressive pauci-immune crescentic glomerulonephritis. Kidney transplantation (KTx) is considered the treatment of choice in patients with end-stage renal disease (ESRD) due to AAV. Patient and graft survival...

Although the incidence of early acute rejection could have been diminished in the past, the long-term renal allograft survival could not benefit from the introduction of more effective immunosuppressive regimens mainly aiming at cellular rejection mechanisms. The cause of chronic rejection is still discussed controversially. Here, we demonstrate to...

Ziele: Bestimmung der Genauigkeit der Mehrzeilen-CT bei der Evaluation von HCC-Patienten vor Lebertransplantation. Methode: Alle HCC-Patienten, die sich zwischen 2001 und 2006 in unserer Klinik einer Lebertransplantation unterzogen und max. 100 Tage vorher eine 3-Phasen-Abdomen-CT (ca. 20/40/80s Delay, Bolustracking), ohne zwischenzeitliche locale...

The present study was conducted to analyze the outcome after liver resection for intrahepatic cholangiocarcinoma (IHC) and to compare the prognostic accuracy of the fifth and sixth editions of the TNM classification of malignant tumors. A comparison of the prognostic accuracy of the fifth and sixth editions of the TNM classification of malignant tu...

Autosomal recessive polycystic kidney disease (ARPKD) [MIM 263200] belongs to a group of congenital hepatorenal fibrocystic syndromes and is caused by mutations in the PKHD1 gene encoding the multidomain protein fibrocystin/polyductin (FPC). The serine-threonine kinase mammalian target of rapamycin (mTOR) is one of the most important gate-keepers i...

The high frequency of CD4+ T cells in interstitial infiltrates of patients with lupus nephritis suggests a contribution of these cells to local pathogenesis. The aim of this study was to examine the role of CXCR3 and the chemokine CXCL10 in recruiting these cells into the kidney and to determine whether the infiltrating T cells could be monitored i...

PURPOSE To determine and quantify MRI parameters that allow calculation of histological mean vessel density (MVD), mean vessel area (MVA), and mean interstitial area (MIA). METHOD AND MATERIALS Thirty-eight consecutive patients with biopsy-proven prostate cancer (PSA: 1.4-31.4ng/ml) were examined with a dynamic contrast-enhanced inversion-prepared...