Ruth J Pepper's research while affiliated with University College London and other places

Publications (63)

Article
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Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investi...
Article
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Introduction: Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults and is characterized by detectable autoantibodies against glomerular antigens, most commonly phospholipase A2 receptor-1 (PLA2R1) and thrombospondin type-1 domain containing 7A (THSD7A). In Europeans genetic variation in at least five loci, PLA2R1, HLA-DR...
Article
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Background Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-...
Article
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Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with widespread immune dysregulation and diverse clinical features. Immune abnormalities might be differentially associated with specific organ involvement or response to targeted therapies. We aimed to identify biomarkers of response to belimumab after rituxim...
Chapter
Nephrotic syndrome (NS) is the combination of oedema, hypoalbuminaemia, proteinuria and hyperlipidaemia and occurs secondary to damage or dysfunction of the podocytes from a variety of causes. These causes can be inherited or acquired, and acquired NS may be due to primary glomerular disorders or secondary to other systemic disease. Whatever the ca...
Chapter
Immunosuppression is used for many forms of inflammatory kidney diseases, and while there have been limited options to date, a significant expansion in types of immunosuppression, combination therapies and regimen durations means that familiarity with the agents and the evidence for their use is increasingly important for nephrologists. Novel combi...
Article
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Membranous nephropathy (MN) is one of the commonest causes of adult-onset nephrotic syndrome. We present two cases of two young women presenting with nephrotic syndrome due to Anti-phospholipase A2 Receptor (PLA2R) negative MN which was found to be associated with benign tumors. Two women in their 20s presented with nephrotic syndrome. They had no...
Article
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Objectives To investigate key factors that may contribute to the variability of rituximab-mediated peripheral and renal B cell depletion (BCD) in Systemic Lupus Erythematosus (SLE). Methods We analysed: 1) CD19+ B cell counts in patients with SLE before and one, two, three and six months after treatment with rituximab, comparing them with Rheumato...
Article
Adult nephrologists often look after patients who have been diagnosed with kidney disease in childhood. This does present unique challenges to the adult nephrologist, who may be unfamiliar with the underlying cause of kidney disease as well as the complications of chronic kidney disease (CKD) that may have accumulated during childhood. This review...
Article
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Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pat...
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Membranous nephropathy is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in a majority of patients changed the management of membranous nephropathy dramatically, and provided a rationale for B cell depleting agents such as rituximab. The efficacy of rituxim...
Article
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Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, r...
Article
Objective Subglottic stenosis (SGS) is a severe, life-threatening disease found in immune-mediated diseases such as granulomatosis with polyangiitis (GPA) and in rare cases of immunoglobulin G4 (IgG4)-related disease. It can result in persistent airway compromise due to the fibrotic response following inflammation. Standard management involves repe...
Conference Paper
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Background Lupus nephritis (LN) is one of the most severe manifestations of Systemic Lupus Erythematosus. Objectives 1) To compare proliferative (PLN), membranous (MLN) and mixed LN regarding clinical and laboratory presentation. 2) To investigate predictors of progression to chronic kidney disease (CKD). Methods Multicentre observational study,...
Article
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Objectives: To compare membranous lupus nephritis (MLN) and proliferative lupus nephritis (PLN) with respect to survival, demographic, clinical and laboratory characteristics; and to investigate predictors of renal and patient survival. Methods: Single-centre retrospective observational study. Patients with biopsy-proven PLN, MLN and mixed lupus...
Article
Background Despite the improvement in survival of patients with lupus nephritis (LN) over the last decades, LN is associated with progression to end-stage renal disease (ESRD) in a significant proportion of patients. We aimed to investigate the factors influencing renal survival in patients with LN. Methods Single-centre retrospective observationa...
Article
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Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10⁻¹²) and IRF4 (rs9405192, OR = 1.29, P = 1.4 ×...
Conference Paper
Full-text available
Background Lupus Nephritis (LN) is one of the most severe manifestations of Systemic Lupus Erythematosus (SLE). We aimed to compare proliferative (PLN), membranous (MLN) and mixed LN regarding clinical and laboratory presentation, and serologic profiles. Previous work suggested that these groups differ in autoantibody profile and complement levels,...
Conference Paper
Full-text available
Background Despite the improvement in survival of patients with lupus nephritis (LN) over the last decades, LN is associated with progression to end-stage renal disease (ESRD) in a significant proportion of patients. We aimed to investigate the factors influencing renal survival in patients with LN. Methods Single-centre retrospective observationa...
Conference Paper
Background The pathogenesis of membranous lupus nephritis (MLN) is poorly understood. Our objectives were to investigate, in patients with MLN, the presence of antibodies to nucleosomes and histones, which have been linked to the pathogenesis of proliferative lupus nephritis (PLN); and antibodies against phospholipase A2 receptor (PLA2R), previousl...
Article
Background: Membranous lupus nephritis (MLN) accounts for 10-20% of the cases of lupus nephritis (LN) but its pathogenesis is not fully understood. Idiopathic membranous nephropathy (IMN), is characterized by glomerular basement membrane subepithelial IgG deposits. Around 70-80% of patients with IMN show seropositivity for an autoantibody targeting...
Article
OBJECTIVES: Glucocorticoids (GCs) are a mainstay of treatment for patients with ANCA-associated vasculitis (AAV) but are associated with significant adverse effects. Effective remission induction in severe AAV using extremely limited GC exposure has not been attempted. We tested an early rapid GC withdrawal induction regimen for patients with sever...
Article
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Oedema is a defining element of the nephrotic syndrome. Its’ management varies considerably between clinicians, with no national or international clinical guidelines, and hence variable outcomes. Oedema may have serious sequelae such as immobility, skin breakdown and local or systemic infection. Treatment of nephrotic oedema is often of limited eff...
Article
Objectives: Glucocorticoids (GCs) are a mainstay of treatment for patients with ANCA-associated vasculitis (AAV) but are associated with significant adverse effects. Effective remission induction in severe AAV using extremely limited GC exposure has not been attempted. We tested an early rapid GC withdrawal induction regimen for patients with seve...
Article
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Introduction IgG4-related disease (IgG4-RD) is a relapsing multisystem fibro-inflammatory disease, which may involve the kidney (IgG4-related kidney disease [IgG4-RKD]) and retroperitoneum (IgG4-related retroperitoneal fibrosis [IgG4-RPF]). The aim of this study was to describe IgG4-RKD and IgG4-RPF in the United Kingdom. Methods We conducted a re...
Data
Structured vignettes documenting history of patients with IgG4-RKD and IgG4-RPF.
Article
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Background Although the prognosis has improved in the last decades, Lupus patients still have a 3-fold increase in mortality, compared with the general population.¹Lupus nephritis (LN) is one of the most severe manifestations of this complex systemic disease, occurring in up to 60% of patients. Objectives 1) To obtain the overall and renal surviva...
Article
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Background Lupus nephritis (LN) is currently classified according to the 2003 International Society of Nephrology/Renal pathology Society (ISN/RPS) classification system, which is based on histology. Most patients have proliferative lupus nephritis (PLN), which has been the most studied type of LN. Membranous lupus nephritis (MLN) is less frequent,...
Article
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Background Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. MN is a clinically heterogeneous disease and it is difficult to accurately predict outcomes (including end stage renal failure) at presentation and whom to treat with potentially toxic therapies. We aimed to identify factors predicting outcome in MN in our...
Article
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Introduction: Quinoline-3-carboximide compounds, such as paquinimod, which targets the protein S100A9, have demonstrated efficacy in treating autoimmune diseases. S100A9, in association with S100A8, forms the heterodimer S100A8/S100A9, known as calprotectin; that has been shown to be upregulated in numerous inflammatory disorders. We had previously...
Article
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Introduction: Quinoline-3-carboximide compounds, such as paquinimod, which targets the protein S100A9, have demonstrated efficacy in treating autoimmune diseases. S100A9, in association with S100A8, forms the heterodimer S100A8/S100A9, known as calprotectin; that has been shown to be upregulated in numerous inflammatory disorders. We had previousl...
Article
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IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of glomerulonephritis and IL-17 deficient mice are protected from nephrotoxic nephritis. However, a regulatory role for IL-17 has recently emerged. We describe a novel protective function for IL-17 in the kidney. Bone marrow chimeras were created using wild-type and IL-17 deficient...
Article
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Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 (MRP8/14,...
Article
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Objectives: B cells are central to the pathology of ANCA-associated vasculitis (AAV), a disease characterized by autoantibodies and effectively treated by rituximab. In addition to promoting inflammation, a subset of B cells act to suppress harmful autoimmune responses (Breg). The balance of effector and regulatory B cell subsets in AAV is not kno...
Article
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Rituximab is effective in inducing remission in ANCA-associated vasculitis (AAV), with randomized evidence to support its use as four infusions of 375 mg/m(2) (the conventional lymphoma dosing schedule). As B cell depletion (BCD) appears to occur very rapidly after the first dose, we questioned the need for repeat dosing and adopted a standard sing...
Chapter
Many forms of glomerular disease are immune mediated and are therefore treated with immunosuppression. The particular regimen that is used may vary depending on the underlying condition, but many protocols are based on combination therapy using glucocorticoids and a second agent, which has historically often been cyclophosphamide. With the introduc...
Article
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Soluble Flt1 (sFlt1) is a potent inhibitor of vascular endothelial growth factor, secreted mainly by the placenta, endothelial cells and monocytes. Increased sFlt1 serum levels correlate with endothelial dysfunction and cardiovascular complications in dialysis patients. However, the impact of dialysis by itself on sFlt1 serum levels remains unknown...
Article
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Objectives Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephro...
Article
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Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory conditions. By immunohistochem...
Conference Paper
Calprotectin, an endogenous toll-like receptor 4 (TLR 4) agonist that is expressed in neutrophils, monocytes, and infiltrating macrophages, promotes endothelial activation and transcription of pro-inflammatory cytokines. We investigated calprotectin in renal biopsy samples and serum of patients with anti-neutrophil cytoplasmic antibody associated v...
Article
Background and objectives: Induction therapy with oral cyclophosphamide (CYP) has been a mainstay of treatment in patients with severe renal failure secondary to ANCA-associated vasculitis (AAV). Recent evidence proposes using pulsed intravenous CYP in less severe disease to minimize adverse events. It is unclear if this can be translated to those...
Article
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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-associated vascu...
Article
To determine a role for antineutrophil cytoplasmic antibody (ANCA)-activated neutrophils in promoting B cell survival through the release of B lymphocyte stimulator (BLyS). Neutrophil BLyS expression was measured by flow cytometry. Concentrations of BLyS in cell supernatants and donor serum samples were measured by ELISA. Cell survival assays were...
Article
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Lupus nephritis is a life-threatening complication of SLE. Treatment regimes include steroids and cyclophosphamide, both associated with significant morbidity. Newer regimes include mycophenolate mofetil (MMF). We report our outcomes in a prospectively monitored cohort of patients receiving our new standard treatment protocol, comprising rituximab...
Article
Large-bore dual lumen in-dwelling venous catheters are used in hemodialysis. These catheters are usually locked with heparin after the treatment. This study addressed the underappreciated postdialysis coagulopathy that can result. Thirty-six patients were included: 7 dialyzed through arterio-venous fistulae, 29 through in-dwelling venous catheters....

Citations

... The circulating B cell population may not represent the total B cell population in MN, as interstitial CD20 positive B cells did not reflect the circulating B cell value in lupus (61). CD20 positive B cell infiltrate in the kidney has also been seen as a marker of poor outcomes in SLE, ANCA, and now MN (62,63). ...
... Capillaries invade glomerular podocyte tufts and deliver blood for filtration, and tubules modify the ultrafiltrate to make definitive urine. Dysplastic kidney malformations (DKMs) are major causes of kidney failure in children (Kohl et al., 2022) and young adults (Pepper et al., 2022). Ultrasonography detects echo-bright organs that, lacking cortical-medullary distinction (Kohl et al., 2022), manifest aberrant nephron morphogenesis and patterning accompanied by deregulated cell turnover (Winyard et al., 1996a and1996b). ...
... Therefore, ORM has been studied as a potential blood biomarker for many diseases (28)(29)(30)(31). ORM has also been studied as a single or combined urinary biomarker of inflammatory diseases and cancer, including lupus nephritis, adult-onset Still's disease, psoriasis, rheumatoid arthritis, sepsis, Crohn's disease, bladder cancer, and hepatocellular carcinoma (32)(33)(34)(35)(36)(37)(38). In one cohort study, urinary ORM showed a significant association with incident hypertension at the 7-year follow-up (39). ...
... Rituximab (RTX) can deplete CD20 + B-cells by apoptosis, complement-mediated cytotoxicity, and antibody-dependent cellular cytotoxicity. Several earlier non-randomized studies indicated that RTX induced clinical remission in 60%-80% Treatment with rituximab and hydroxychloroquine in a patient with membranous nephropathy and diabetic nephropathy: A case report of patients with PMN [3,4]. In terms of side effects, RTX is different from glucocorticoids and immunosuppressants, and it does not have an influence on glucose intolerance. ...
... A differenza degli altri farmaci, la somministrazione di rituximab prevede l'infusione ev di una singola dose, in base al protocollo scelto (375 mg/m 2 o 1000 mg) ed il monitoraggio della proteinuria per un periodo di quattro-sei mesi [24,55]. Un quadro di proteinuria non accompagnato da altri segni clinici quali ipoalbuminemia ed ipervolemia richiede l'esclusione di cause secondarie e, qualora appropriato, di cause genetiche. ...
... Specifically, proteinuria after 12 months of treatment has been recognised as a better predictor than the baseline proteinuria in multiple studies of patients with LN. [21][22][23][24] In our study, the medium proteinuria levels at baseline and 6 months were significantly higher in the ESRD group (table 1). However, proteinuria level at 6 months was not selected by the LASSO regression model, which was also validated by receiver operating characteristic (ROC) curves. ...
... These results have been replicated in both European and non-European cohorts [17][18][19]. Most recently, these results have been replicated including the finding of an additional HLA locus; HLA-DRB1 and two non-HLA loci that contribute a smaller risk to disease; NFKB1 and IRF4 [20]. In Europeans, the strongest association is with the HLA-DQA1 region with an odds ratio (OR) for the risk allele of 3.71 followed by PLA2R1 with an OR of 1.98 [20]. ...
... The renal parenchyma is one of the major targets of immunoglobulin (Ig)G4-related disease (IgG4-RD), with plasma cell-rich tubulointerstitial nephritis (TIN) being a frequent renal manifestation of IgG4-RD, which is called IgG4-TIN [1][2][3]. In addition to the kidneys, IgG4-RD affects various other organs throughout the body, including the lacrimal glands, salivary glands, pancreas, and periaorta/retroperitoneum, with 7.0-24.6% of patients with IgG4-RD having kidney lesions [4][5][6][7][8][9][10][11][12][13][14]. The renal pelvis is also a major target of IgG4-RD, but most renal pelvic lesions result in little damage to patients clinically [1,2]. ...
... At 6 months, the cumulative dose of oral GC in the reduced-dose group was less than 60% of that in the standard group and was associated with less severe infections during the first year of treatment [19]. The combination of CYC and RTX has also been attempted to accelerate GC tapering [20][21][22], with some studies limiting the duration of GC treatment to 2 weeks, although strong evidence with randomized controlled trials (RCTs) is lacking. ...
... With this combination, a rapid glucocorticoid withdraw at 2 weeks was feasible for remission induction in severe renal AAV, exhibiting equivalent outcomes to matched cohorts from EUVAS trials, but with lower total exposure to cyclophosphamide and glucocorticoids and reduced rates of severe infections [29]. Long-term follow up showed excellent remission rates at 4 years while 80% of the patients remained steroid free [46]. PEXIVAS investigated two prednisolone induction regimens. ...