Publications by authors named "Vladimir Tesar"

223 Publications

Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis.

Nephrol Dial Transplant 2021 Apr 29. Epub 2021 Apr 29.

Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.

Background: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and characterized by an imbalanced extracellular matrix remodeling. Endotrophin (ETP) is a signaling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with IgA nephropathy (IgAN) and patients with ANCA-associated vasculitis (AAV).

Methods: We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the ELISA PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores.

Results: S-ETP and U-ETP/Cr levels correlated with kidney function, increased with CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort.

Conclusions: We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.
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http://dx.doi.org/10.1093/ndt/gfab163DOI Listing
April 2021

Rituximab in Membranous Nephropathy.

Kidney Int Rep 2021 Apr 13;6(4):881-893. Epub 2021 Jan 13.

Division of Nephrology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.

Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of "the new standard."
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http://dx.doi.org/10.1016/j.ekir.2020.12.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071613PMC
April 2021

Reduction of arteriovenous access blood flow leads to biventricular unloading in haemodialysis patients.

Int J Cardiol 2021 Jul 30;334:148-153. Epub 2021 Apr 30.

Department of Nephrology, 1(st) Faculty of Medicine, Charles University and General University Hospital in Prague, U Nemocnice 2, 128 08 Prague, Czech Republic.

Aims: Patients on chronic haemodialysis have a wide range of changes in cardiac function and structure, including left ventricular hypertrophy, dilation and diastolic dysfunction or pulmonary hypertension. All these changes were linked to increased mortality in previous studies. High-flow arteriovenous fistulas (AVF) are supposed to be a factor contributing to their development. This study investigated the early effect of surgical AVF blood flow (Qa) reduction on these changes in patients with or without heart failure changes.

Methods And Results: Forty-two patients in chronic haemodialysis programme with high-flow AVF (Qa over 1500 mL/min), indicated for surgery for ≥1 of the following indications: 1.manifest heart failure; 2.hand ischemia; 3.advanced structural heart changes detected by echocardiography. The patients underwent echocardiography on selection visit, before blood flow reducing surgery and six weeks thereafter. The Qa reduction led to decrease of left ventricular mass (p = 0.02), end-diastolic volume (p = 0.008), end-diastolic diameter (p = 0.003) and left atrial volume (p = 0.0006). Diastolic function improved. Similarly, right ventricular diameter and right atrial volume decreased (p = 0.000001 and 0.00009, respectively) together with the decrease of estimated pulmonary artery systolic pressure. 81% of patients suffered from pulmonary hypertension prior to surgery, only 36% thereafter.

Conclusion: The surgical restriction of the hyperkinetic circulation leads to several improvements of heart structure and function, which was linked to higher mortality in other studies. The beneficial effect of Qa reduction is present even in patients without symptoms of heart failure. The contribution of AVF must be considered with structural or functional heart changes.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.027DOI Listing
July 2021

Autoantibodies in the Diagnosis, Monitoring, and Treatment of Membranous Nephropathy.

Front Immunol 2021 22;12:593288. Epub 2021 Mar 22.

Department of Nephrology, 1st Faculty of Medicine, General University Hospital, Charles University, Prague, Czechia.

The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease. Evaluation of serum levels of anti-podocyte antibodies paved the way for non-invasive diagnosis and helped distinguish between primary and secondary MN although the relationship between anti-podocyte antibodies and cancer remains to be elucidated. Serum levels of anti-PLA2R antibodies directed against the major podocyte autoantigen are related to MN activity and the decrease in serum levels of anti-PLA2R antibodies in response to treatment (immunologic remission) also serves as an early indicator of the later putative proteinuric remission, enabling personalization of the treatment. The serum levels of anti-podocyte antibodies also enable the prediction of renal outcomes in terms of both remission and the risk of progression to end-stage renal disease. The positivity of anti-PLA2R antibodies before renal transplantation is associated with the risk of recurrence of MN. It remains to be established if all these relations observed in patients with anti-PLA2R antibodies are also valid for expanding spectrum of antibodies directed against recently discovered minor antigens (e.g., THSD7A, NELL-1, semaphorin 3B).
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http://dx.doi.org/10.3389/fimmu.2021.593288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019786PMC
March 2021

The effect of high-flow arteriovenous fistulas on systemic haemodynamics and brain oxygenation.

ESC Heart Fail 2021 Jun 23;8(3):2165-2171. Epub 2021 Mar 23.

Department of Nephrology, General University Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Aims: High-flow arteriovenous fistula (AVF) for haemodialysis leads to profound haemodynamic changes and sometimes to heart failure (HF). Cardiac output (CO) is divided between the AVF and body tissues. The term effective CO (COef) represents the difference between CO and AVF flow volume (Qa) and better characterizes the altered haemodynamics that may result in organ hypoxia. We investigated the effects of Qa reduction on systemic haemodynamics and on brain oxygenation.

Methods And Results: This is a single-centre interventional study. Twenty-six patients on chronic haemodialysis with high Qa (>1500 mL/min) were indicated for surgical Qa reduction for HF symptoms and/or signs of structural heart disease on echocardiography. The included patients underwent three sets of examinations: at 4 months and then 2 days prior and 6 weeks post-surgical procedure. Clinical status, echocardiographical haemodynamic assessment, Qa, and brain oximetry were recorded. All parameters remained stable from selection to inclusion. After the procedure, Qa decreased from 3.0 ± 1.4 to 1.3 ± 0.5 L/min, P < 0.00001, CO from 7.8 ± 1.9 to 6.6 ± 1.5 L/min, P = 0.0002, but COef increased from 4.6 ± 1.4 to 5.3 ± 1.4 L/min, P = 0.036. Brain tissue oxygen saturation increased from 56 ± 11% to 60 ± 9%, P = 0.001.

Conclusions: Qa reduction led to increased COef. This was explained by a decreased proportion of CO running through the AVF in patients with Qa > 2.0 L/min. These observations were mirrored by higher brain oxygenation and might explain HF symptoms and improved haemodynamics even in asymptomatic high Qa patients.
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http://dx.doi.org/10.1002/ehf2.13305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120398PMC
June 2021

Recommendations for the use of COVID-19 vaccines in patients with immune-mediated kidney diseases.

Nephrol Dial Transplant 2021 Mar 9. Epub 2021 Mar 9.

Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Coronavirus Disease 19 (COVID-19) vaccine platforms are becoming available and are the most promising strategy to curb the spread of SARS-CoV-2 infections. However, numerous uncertainties exist regarding the pros and cons of vaccination, especially in patients with (immune-mediated) kidney diseases on immunosuppressive drugs. Here, members of the Immunonephrology Working Group (IWG) of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) discuss thirteen frequently-asked questions regarding safety and efficacy of the most promising vaccine candidates. Post-marketing surveillance should be performed to estimate the rate of vaccine response (humoral and cellular) of different vaccine platforms, and surveillance of disease activity following administration of COVID-19 vaccines. Some of the candidates induce signaling pathways which also promote autoimmune kidney diseases, e.g. type I interferons in systemic lupus erythematosus. Efficacy estimates would thus far favor the use of selected COVID-19 vaccines, such as BNT162b2, mRNA-1273 or Gam-COVID-Vac. Humoral immune response after vaccination should be monitored using appropriate assays. Even in the absence of neutralizing antibodies patients might be protected by a sufficient cellular immune response capable to reduce severity of COVID-19. A reduced vaccine response after the use of CD20-depleting agents is anticipated, and it is particularly important to discuss strategies to improve vaccine response with these patients. Distancing and shielding measures remain important as not all vaccines fully protect from coronavirus infection. In-depth information about the most pressing vaccine questions is essential to reduce vaccine hesitancy of patients.
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http://dx.doi.org/10.1093/ndt/gfab064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989374PMC
March 2021

A roadmap for optimizing chronic kidney disease patient care and patient-oriented research in the Eastern European nephrology community.

Clin Kidney J 2021 Jan 22;14(1):23-35. Epub 2020 Dec 22.

Division of Nephrology, Ambroise Paré University Hospital, APHP, University of Paris Ouest-Versailles-St-Quentin-en-Yvelines (UVSQ) av G De Gaulles Boulogne-Billancourt/Paris, x, FR 92100; Inserm U1018, CESP Team 5-Epidemiology of Renal and Cardiovascular Disease, Villejuif, France.

Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3-5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease-related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.
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http://dx.doi.org/10.1093/ckj/sfaa218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857792PMC
January 2021

Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study.

Rheumatology (Oxford) 2021 Feb 1. Epub 2021 Feb 1.

Department of Medicine, University of Cambridge, Cambridge, UK.

Objective: To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK, and North America.

Methods: Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centers. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Over a median follow up of 63 (29; 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype (granulomatosis with polyangiitis: 9.8%; 95% CI 8.3-11.6, microscopic polyangiitis: 9.6%; 95% CI 7.9-11.4, and eosinophilic granulomatosis with polyangiitis: 9.8%; 95% CI 7.0-13.3). Most VTE (65.6%) were reported in the first-year post diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI 1.01-2.92), pulmonary (OR 1.78, 95% CI 1.04-3.14) and kidney involvement (eGFR 15-60 mL/min/1.73 m2, OR 2.86, 95% CI 1.27-6.47; eGFR < 15 mL/min/1.73 m2, OR 6.71, 95% CI 2.94-15.33) were independent variables associated with a higher occurrence of VTE.

Conclusion: Two thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.
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http://dx.doi.org/10.1093/rheumatology/keab071DOI Listing
February 2021

Plasma exchange in ANCA-associated vasculitis: the pro position.

Nephrol Dial Transplant 2021 01;36(2):227-231

Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia.

Plasma exchange (PLEX) is capable of removing significant amounts of circulating antibodies. In anti-neutrophil cytoplasmic antibody-associated vasculitis, PLEX was reserved for patients with severe presentation forms such as rapidly progressive glomerulonephritis and pulmonary haemorrhage. The Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial included all comers with a glomerular filtration rate <50 mL/min/1.73 m2 and thus aimed to answer the question of whether PLEX is an option for patients with no relevant kidney function impairment or not. PEXIVAS revealed that after a follow-up of almost 3 years, routine administration of PLEX does not provide an additional benefit to reduce the rate of a composite comprising end-stage kidney disease or death. In the absence of histological parameters, it is tempting to speculate whether PLEX is effective or not in those with a potential for renal recovery. A subset of patients presented with alveolar haemorrhage, and there was a trend towards a better outcome of such cases receiving PLEX. This would be in line with observational studies reporting a recovery of alveolar haemorrhage following extracorporeal treatment. In this PRO part of the debate, we highlight the shortcomings of the PEXIVAS trial and stimulate further research paths, which in our eyes are necessary before abandoning PLEX from the therapeutic armamentarium.
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http://dx.doi.org/10.1093/ndt/gfaa311DOI Listing
January 2021

Availability, coverage, and scope of health information systems for kidney care across world countries and regions.

Nephrol Dial Transplant 2020 Dec 22. Epub 2020 Dec 22.

Department of Medicine, Faculty of Medicine, King Chulalong Memorial Hospital, Chulalongkorn University, Bangkok,Thailand.

Background: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas.

Methods: As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT).

Results: Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups.

Conclusions: These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.
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http://dx.doi.org/10.1093/ndt/gfaa343DOI Listing
December 2020

Availability, Accessibility, and Quality of Conservative Kidney Management Worldwide.

Clin J Am Soc Nephrol 2020 12 15;16(1):79-87. Epub 2020 Dec 15.

Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

Background And Objectives: People with kidney failure typically receive KRT in the form of dialysis or transplantation. However, studies have suggested that not all patients with kidney failure are best suited for KRT. Additionally, KRT is costly and not always accessible in resource-restricted settings. Conservative kidney management is an alternate kidney failure therapy that focuses on symptom management, psychologic health, spiritual care, and family and social support. Despite the importance of conservative kidney management in kidney failure care, several barriers exist that affect its uptake and quality.

Design, Setting, Participants, & Measurements: The Global Kidney Health Atlas is an ongoing initiative of the International Society of Nephrology that aims to monitor and evaluate the status of global kidney care worldwide. This study reports on findings from the 2018 Global Kidney Health Atlas survey, specifically addressing the availability, accessibility, and quality of conservative kidney management.

Results: Respondents from 160 countries completed the survey, and 154 answered questions pertaining to conservative kidney management. Of these, 124 (81%) stated that conservative kidney management was available. Accessibility was low worldwide, particularly in low-income countries. Less than half of countries utilized multidisciplinary teams (46%); utilized shared decision making (32%); or provided psychologic, cultural, or spiritual support (36%). One-quarter provided relevant health care providers with training on conservative kidney management delivery.

Conclusions: Overall, conservative kidney management is available in most countries; however, it is not optimally accessible or of the highest quality.
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http://dx.doi.org/10.2215/CJN.09070620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792657PMC
December 2020

Urine proteomics for prediction of disease progression in patients with IgA nephropathy.

Nephrol Dial Transplant 2020 Dec 14. Epub 2020 Dec 14.

Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.

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.
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http://dx.doi.org/10.1093/ndt/gfaa307DOI Listing
December 2020

Mass spectrometry-based proteomic exploration of the small urinary extracellular vesicles in ANCA-associated vasculitis in comparison with total urine.

J Proteomics 2021 02 9;233:104067. Epub 2020 Dec 9.

Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:

ANCA-associated vasculitis (AAV) is a rare, but potentially severe autoimmune disease, even nowadays displaying increased mortality and morbidity. Finding early biomarkers of activity and prognosis is thus very important. Small extracellular vesicles (EVs) isolated from urine can be considered as a non-invasive source of biomarkers. We evaluated several protocols for urinary EV isolation. To eliminate contaminating non-vesicular proteins due to AAV associated proteinuria we used proteinase K treatment. We investigated the differences in proteomes of small EVs of patients with AAV compared to healthy controls by label-free LC-MS/MS. In parallel, we performed an analogous proteomic analysis of urine samples from identical patients. The study results showed significant differences and similarities in both EV and urine proteome, the latter one being highly affected by proteinuria. Using bioinformatics tools we explored differentially changed proteins and their related pathways with a focus on the pathophysiology of AAV. Our findings indicate significant regulation of Golgi enzymes, such as MAN1A1, which can be involved in T cell activation by N-glycans glycosylation and may thus play a key role in pathogenesis and diagnosis of AAV. SIGNIFICANCE: The present study explores for the first time the changes in proteomes of small extracellular vesicles and urine of patients with renal ANCA-associated vasculitis compared to healthy controls by label-free LC-MS/MS. Isolation of vesicles from proteinuric urine samples has been modified to minimize contamination by plasma proteins and to reduce co-isolation of extraluminal proteins. Differentially changed proteins and their related pathways with a role in the pathophysiology of AAV were described and discussed. The results could be helpful for the research of potential biomarkers in renal vasculitis associated with ANCA.
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http://dx.doi.org/10.1016/j.jprot.2020.104067DOI Listing
February 2021

Emerging Modes of Treatment of IgA Nephropathy.

Int J Mol Sci 2020 Nov 28;21(23). Epub 2020 Nov 28.

1st Faculty of Medicine, General University Hospital, Department of Nephrology, Charles University, 128 08 Prague, Czech Republic.

IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance. In this review, we summarize treatment options for patients with IgA nephropathy including the drugs currently under evaluation in randomized control trials. An early initiation of immunosupressive regimens in patients with IgA nephropathy at risk of progression should result in the slowing down of the progression of renal function to end stage renal disease.
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http://dx.doi.org/10.3390/ijms21239064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730306PMC
November 2020

English-Latin nomenclature conundrum: should we use kidneylogy, kidneylogist?

Kidney Int 2020 11;98(5):1352-1353

Department of Nephrology, General University Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic.

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http://dx.doi.org/10.1016/j.kint.2020.08.015DOI Listing
November 2020

Why Target the Gut to Treat IgA Nephropathy?

Kidney Int Rep 2020 Oct 20;5(10):1620-1624. Epub 2020 Aug 20.

Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.

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http://dx.doi.org/10.1016/j.ekir.2020.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569689PMC
October 2020

Proteinuria from an internists point of view.

Vnitr Lek 2020 ;66(3):90-92

A basal level of proteinuria is about 30-100 mg/day, the upper limit of basal proteinuria does not exceed 150 mg/day which is considered non-pathology. Albumin accounts approximately 15 % of basal protein in the urine, other plasma proteins (immunoglobulins, β-2 microglobulin, Tamm-Horsfall mucoprotein) comprise the remaining 85 % of total quantity non-pathology proteinuria. Persistent proteinuria present for more than three months already meets the definition of chronic kidney disease independently of the stage of the estimated glomerular filtration rate. Patients are classified as A1-A3 based on the level of albuminuria. Examination of the albumin in the urine is one of the single sensitive indicators of chronic kidney disease. Proteinuria is an independent risk factor for cardiovascular disease, overall mortality and end stage renal failure both in general population and in population with chronic kidney disease. Presence of the urinary protein is associated with a higher mortality rate in critically ill patients. The degree of proteinuria after kidney transplantation predicts graft and patient survival in this population. Pharmacological and non-pharmacological treatments that attenuate proteinuria have been associated with better prognosis of kidney disease.
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November 2020

Proteinuria from an internists point of view.

Vnitr Lek 2020 ;66(3):87-89

A basal level of proteinuria is about 30-100 mg/day, the upper limit of basal proteinuria does not exceed 150 mg/day which is considered non-pathology. Albumin accounts approximately 15 % of basal protein in the urine, other plasma proteins (immunoglobulins, β-2 microglobulin, Tamm-Horsfall mucoprotein) comprise the remaining 85 % of total quantity non-pathology proteinuria. Persistent proteinuria present for more than three months already meets the definition of chronic kidney disease independently of the stage of the estimated glomerular filtration rate. Patients are classified as A1-A3 based on the level of albuminuria. Examination of the albumin in the urine is one of the single sensitive indicators of chronic kidney disease. Proteinuria is an independent risk factor for cardiovascular disease, overall mortality and end stage renal failure both in general population and in population with chronic kidney disease. Presence of the urinary protein is associated with a higher mortality rate in critically ill patients. The degree of proteinuria after kidney transplantation predicts graft and patient survival in this population. Pharmacological and non-pharmacological treatments that attenuate proteinuria have been associated with better prognosis of kidney disease.
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November 2020

Pulmonaryrenal syndrome.

Vnitr Lek 2020 ;66(5):56-61

Pulmonary syndrome is defined by occurrence of lung involvement (alveolar haemorrhage) in association with renal failure (with a typical crescentic necrotizing rapidly progressive glomerulonephritis). It is caused by an autoimmune disease, most frequently ANCA-associated vasculitides and anti-GBM (glomerular basement membrane) disease. Early establishment of the right diagnosis and immediate treatment are crucial for favourable prognosis of the patients. First choice therapy includes high-dose corticosteroids and cyclophosphamide, usually with plasma exchange added. Newer therapeutic possibilities include especially rituximab even though there is limited experience with its use in the settings of the most severe cases of pulmonary syndrome.
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November 2020

Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?

Autoimmun Rev 2020 Nov 15;19(11):102671. Epub 2020 Sep 15.

Department of Nephrology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

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, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations.
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http://dx.doi.org/10.1016/j.autrev.2020.102671DOI Listing
November 2020

Development and testing of an artificial intelligence tool for predicting end-stage kidney disease in patients with immunoglobulin A nephropathy.

Kidney Int 2021 05 2;99(5):1179-1188. Epub 2020 Sep 2.

Research Laboratory, Fondazione Ricerca Molinette, Torino, Italy.

We have developed an artificial neural network prediction model for end-stage kidney disease (ESKD) in patients with primary immunoglobulin A nephropathy (IgAN) using a retrospective cohort of 948 patients with IgAN. Our tool is based on a two-step procedure of a classifier model that predicts ESKD, and a regression model that predicts development of ESKD over time. The classifier model showed a performance value of 0.82 (area under the receiver operating characteristic curve) in patients with a follow-up of five years, which improved to 0.89 at the ten-year follow-up. Both models had a higher recall rate, which indicated the practicality of the tool. The regression model showed a mean absolute error of 1.78 years and a root mean square error of 2.15 years. Testing in an independent cohort of 167patients with IgAN found successful results for 91% of the patients. Comparison of our system with other mathematical models showed the highest discriminant Harrell C index at five- and ten-years follow-up (81% and 86%, respectively), paralleling the lowest Akaike information criterion values (355.01 and 269.56, respectively). Moreover, our system was the best calibrated model indicating that the predicted and observed outcome probabilities did not significantly differ. Finally, the dynamic discrimination indexes of our artificial neural network, expressed as the weighted average of time-dependent areas under the curve calculated at one and two years, were 0.80 and 0.79, respectively. Similar results were observed over a 25-year follow-up period. Thus, our tool identified individuals who were at a high risk of developing ESKD due to IgAN and predicted the time-to-event endpoint. Accurate prediction is an important step toward introduction of a therapeutic strategy for improving clinical outcomes.
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http://dx.doi.org/10.1016/j.kint.2020.07.046DOI Listing
May 2021

HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients.

Kidney Int 2021 03 2;99(3):671-685. Epub 2020 Sep 2.

Sorbonne Université, Université Pierre et Marie Curie Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S1155, Paris, France; Department of Nephrology (Day Hospital), AP-HP, Tenon Hospital, Paris, France. Electronic address:

Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.
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http://dx.doi.org/10.1016/j.kint.2020.08.007DOI Listing
March 2021

Peritoneal Dialysis Use and Practice Patterns: An International Survey Study.

Am J Kidney Dis 2021 03 12;77(3):315-325. Epub 2020 Aug 12.

Department of Nephrology, General University Hospital, Charles University, Prague, Czech Republic.

Rationale & Objective: Approximately 11% of people with kidney failure worldwide are treated with peritoneal dialysis (PD). This study examined PD use and practice patterns across the globe.

Study Design: A cross-sectional survey.

Setting & Participants: Stakeholders including clinicians, policy makers, and patient representatives in 182 countries convened by the International Society of Nephrology between July and September 2018.

Outcomes: PD use, availability, accessibility, affordability, delivery, and reporting of quality outcome measures.

Analytical Approach: Descriptive statistics.

Results: Responses were received from 88% (n=160) of countries and there were 313 participants (257 nephrologists [82%], 22 non-nephrologist physicians [7%], 6 other health professionals [2%], 17 administrators/policy makers/civil servants [5%], and 11 others [4%]). 85% (n=156) of countries responded to questions about PD. Median PD use was 38.1 per million population. PD was not available in 30 of the 156 (19%) countries responding to PD-related questions, particularly in countries in Africa (20/41) and low-income countries (15/22). In 69% of countries, PD was the initial dialysis modality for≤10% of patients with newly diagnosed kidney failure. Patients receiving PD were expected to pay 1% to 25% of treatment costs, and higher (>75%) copayments (out-of-pocket expenses incurred by patients) were more common in South Asia and low-income countries. Average exchange volumes were adequate (defined as 3-4 exchanges per day or the equivalent for automated PD) in 72% of countries. PD quality outcome monitoring and reporting were variable. Most countries did not measure patient-reported PD outcomes.

Limitations: Low responses from policy makers; limited ability to provide more in-depth explanations underpinning outcomes from each country due to lack of granular data; lack of objective data.

Conclusions: Large inter- and intraregional disparities exist in PD availability, accessibility, affordability, delivery, and reporting of quality outcome measures around the world, with the greatest gaps observed in Africa and South Asia.
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http://dx.doi.org/10.1053/j.ajkd.2020.05.032DOI Listing
March 2021

Hemodialysis Use and Practice Patterns: An International Survey Study.

Am J Kidney Dis 2021 03 13;77(3):326-335.e1. Epub 2020 Aug 13.

Department of Medicine, Faculty of Medicine, King Chulalong Memorial Hospital, Chulalongkorn University, Bangkok, Thailand; Bhumirajanagarindra Kidney Institute, Bangkok, Thailand.

Rationale & Objective: Hemodialysis (HD) is the most common form of kidney replacement therapy. This study aimed to examine the use, availability, accessibility, affordability, and quality of HD care worldwide.

Study Design: A cross-sectional survey.

Setting & Participants: Stakeholders (clinicians, policy makers, and consumer representatives) in 182 countries were convened by the International Society of Nephrology from July to September 2018.

Outcomes: Use, availability, accessibility, affordability, and quality of HD care.

Analytical Approach: Descriptive statistics.

Results: Overall, representatives from 160 (88%) countries participated. Median country-specific use of maintenance HD was 298.4 (IQR, 80.5-599.4) per million population (pmp). Global median HD use among incident patients with kidney failure was 98.0 (IQR, 81.5-140.8) pmp and median number of HD centers was 4.5 (IQR, 1.2-9.9) pmp. Adequate HD services (3-4 hours 3 times weekly) were generally available in 27% of low-income countries. Home HD was generally available in 36% of high-income countries. 32% of countries performed monitoring of patient-reported outcomes; 61%, monitoring of small-solute clearance; 60%, monitoring of bone mineral markers; 51%, monitoring of technique survival; and 60%, monitoring of patient survival. At initiation of maintenance dialysis, only 5% of countries used an arteriovenous access in almost all patients. Vascular access education was suboptimal, funding for vascular access procedures was not uniform, and copayments were greater in countries with lower levels of income. Patients in 23% of the low-income countries had to pay >75% of HD costs compared with patients in only 4% of high-income countries.

Limitations: A cross-sectional survey with possibility of response bias, social desirability bias, and limited data collection preventing in-depth analysis.

Conclusions: In summary, findings reveal substantial variations in global HD use, availability, accessibility, quality, and affordability worldwide, with the lowest use evident in low- and lower-middle-income countries.
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http://dx.doi.org/10.1053/j.ajkd.2020.05.030DOI Listing
March 2021

Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis.

Clin J Am Soc Nephrol 2020 08 28;15(8):1103-1111. Epub 2020 Jul 28.

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Background And Objectives: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN.

Design, Setting, Participants, & Measurements: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score.

Results: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (<0.001). These survival percentages are higher compared with the percentages in the original study.

Conclusions: The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.
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http://dx.doi.org/10.2215/CJN.14561119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409752PMC
August 2020

The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and associated with defective CD46 expression.

Nephrol Dial Transplant 2020 Jun 24. Epub 2020 Jun 24.

Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.

The proteasome to immunoproteasome (iPS) switch consists of β1, β2 and β5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4 years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/β5 and LMP2/β1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/β5 (P < 0.0001). The LMP7/β5 switch was significantly associated with the rate of eGFR loss (P = 0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR >75th centile, i.e. -1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/β5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/β5 and low CD46 expression.
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http://dx.doi.org/10.1093/ndt/gfaa092DOI Listing
June 2020

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis.

Ann Rheum Dis 2020 09 24;79(9):1243-1249. Epub 2020 Jun 24.

University of Pittsburg, Pittsburg, Pennsylvania, USA.

Objectives: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial.

Methods: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse.

Results: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19-89), prior disease duration 5.0 years (range 0.4-34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections.

Conclusions: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.
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http://dx.doi.org/10.1136/annrheumdis-2019-216863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456549PMC
September 2020

Treatment of Granulomatosis with Polyangiitis and Microscopic Polyangiitis: Should Type of ANCA Guide the Treatment?

Clin J Am Soc Nephrol 2020 10 29;15(10):1519-1521. Epub 2020 May 29.

Department of Nephrology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.

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http://dx.doi.org/10.2215/CJN.15861219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536742PMC
October 2020