Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.

• MeSH
• COVID-19 * immunology   prevention & control   MeSH
• Adult MeSH
• Spike Glycoprotein, Coronavirus immunology   MeSH
• Immunity, Humoral MeSH
• Middle Aged MeSH
• Humans MeSH
• Antibodies, Neutralizing * blood   immunology   MeSH
• Transplant Recipients * MeSH
• Antibodies, Viral * blood   immunology   MeSH
• SARS-CoV-2 * immunology   MeSH
• Immunization, Secondary MeSH
• Aged MeSH
• Kidney Transplantation * adverse effects   MeSH
• BNT162 Vaccine immunology   administration & dosage   MeSH
• COVID-19 Vaccines immunology   administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Ormond's disease is a systemic autoimmune disease with serious complications. We present our retrospective analysis of 83 patients diagnosed with and treated for idiopathic retroperitoneal fibrosis (Ormond's disease) in our department from 1997 to 2023. In this retrospective study, we analysed the diagnostic approaches, the clinical history and surgical and immunosuppressive therapies, and their subsequent effects on our patients. Patients with established disease activity were given immunosuppressive treatment, using corticosteroids alone or in combination with azathioprine, in patients with exacerbation of the disease mycophenolate mofetil. Three patients with Ormond's disease and systemic complications (IgG4-related disease) were treated with rituximab. In the entire cohort, 83 patients received immunosuppressive therapy; the next 5 patients did not receive this treatment because they did not present inflammatory activity from the disease. In these 83 patients, computed tomography showed that immunosuppressive treatment resulted in partial or complete regression of the inflammatory infiltrate. Out of the 83 patients, 10 patients experienced disease exacerbation 7 and 24 months after the immunosuppressive treatment was discontinued. The follow-up ranged from 24 months to 26 years.

• MeSH
• Adult MeSH
• Immunosuppressive Agents * therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Retroperitoneal Fibrosis * diagnosis   drug therapy   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Pemphigoid, Benign Mucous Membrane * diagnostic imaging   drug therapy   pathology   MeSH
• Cyclophosphamide administration & dosage   MeSH
• Hyperemia drug therapy   MeSH
• Drug Therapy, Combination MeSH
• Mycophenolic Acid administration & dosage   MeSH
• Humans MeSH
• Conjunctival Diseases * diagnostic imaging   drug therapy   pathology   MeSH
• Prednisolone administration & dosage   MeSH
• Rituximab administration & dosage   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

Mycophenolate mofetil (MMF) is an immunosuppressant drug approved for prophylaxis of transplant rejection in patients undergoing solid organ transplantation and is further employed in management of various autoimmune disorders. MMF exhibits notable pharmacokinetic inter- and intraindividual variability necessitating tailored therapeutic approaches to achieve optimal therapeutic outcomes while mitigating risks of adverse effects. The objective of this review was to summarize factors that influence the pharmacokinetics of MMF and its active metabolite mycophenolic acid in order to deduce recommendations for personalized treatment strategies. Presumed predictors were analysed in relation to each of the four pharmacokinetic phases, providing tools and targets for MMF dosing optimization amenable to clinical implementation.

• MeSH
• Immunosuppressive Agents * pharmacokinetics   administration & dosage   MeSH
• Precision Medicine MeSH
• Mycophenolic Acid * pharmacokinetics   administration & dosage   MeSH
• Humans MeSH
• Graft Rejection prevention & control   MeSH
• Organ Transplantation * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

ntersticiální plicní onemocnění (ILD) je poměrně častou manifestací systémových revmatických onemocnění, zejména u systémové sklerodermie (SSc), revmatoidní artritidy, idiopatických zánětlivých myopatií, systémového lupus erythematodes, primárního Sjögrenova syndromu a mikroskopické polyangiitidy ze skupiny ANCA asociovaných vaskulitid. Přítomny mohou být nejrůznější typy postižení, nejčastěji se jedná o nespecifickou intersticiální pneumonii (NSIP); u pacientů s revmatoidní artritidou a s mikroskopickou polyangiitidou bývá častější výskyt obvyklé intersticiální pneumonie (UIP). Ve screeningu ILD jsou využívány funkční plicní testy a zobrazovací metody (prostá radiografie hrudníku, HRCT plic), důležitá je včasná identifikace pacientů vyžadujících léčbu a správný výběr terapie s ohledem na její možnou toxicitu. U převažujícího zánětlivého postižení je možné použít kortikosteroidy, cyklofosfamid, mykofenolát mofetil, azathioprin, kalcineurinové inhibitory, B-depleční terapii či tocilizumab. U převážně fibrotizujících forem se naopak uplatňují antifibrotické léky, zejména nintedanib.

Interstitial lung disease (ILD) is a relatively frequent manifestation of systemic autoimmune rheumatic disorders, especially in systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren ́s syndrome and microscopic polyangitis from the group of ANCA associated vasculitis. ILD may present different patterns, most commonly nonspecific interstitial pneumonia (NSIP); usual interstitial pneumonia (UIP) is more often present in patients with rheumatoid arthritis and microscopic polyangitis. Functional lung testing and imaging methods (plain radiography, HRCT) are used for screening of ILD, identifying patients who need treatment and choosing appropriate therapy is important to minimize the risk of therapy-related toxicity. For inflammatory forms of the disorders it is possible to use glucocorticoids, cyclophosphamide, mycophenolate mofetil, azathioprine, calcineurin inhibitors, B-depletion therapy or tocilizumab. There is an indication for the use of antifibrotic drugs, especially nintedanib in predominantly fibrotic forms of the disease.

BACKGROUND: Infliximab selectively targets recently activated effector cells and, as an induction agent, might enable the safe elimination of mycophenolate from maintenance immunosuppression in kidney transplantation. METHODS: This is a phase II international multicenter open-label single-arm confidence interval (CI)-based clinical trial of the BIO-DrIM EU consortium aimed at assessing the efficacy and safety of rabbit antithymocyte globulin and infliximab induction in kidney transplantation. Sixty-seven primary kidney transplant recipients at low risk (panel-reactive antibodies <20%, no donor-specific antibodies [DSA]) received rabbit antithymocyte globulin (2 × 1.5 mg/kg, postoperative days 0 and 1) and infliximab (5 mg/kg, postoperative day 2), followed by mycophenolate-free tacrolimus-based immunosuppression for 12 mo. The primary endpoint was efficacy failure, defined as a composite of acute rejection, graft loss, or poor graft function (estimated glomerular filtration rate <40 mL/min) at 12 mo and was based on the endpoint of the comparator study. Additionally, a historical propensity-matched control cohort was established. RESULTS: Primary endpoint occurred in 22 of 67 patients (32.84%), with upper bound of an exact 1-sided 95% CI of 43.47%, which met the predefined criteria (efficacy failure of <40% and upper-bound 95% CI of <50%) and was similar in the historical matched cohort. By 12 mo, 79.1% of patients remained on the study protocol. Lower rates of BK replication (6% versus 22.4%; P = 0.013) but higher rates of de novo DSAs (11.9% versus 1.5%; P = 0.039) were observed in the study cohort. CONCLUSIONS: A similar efficacy of the study immunosuppression regimen to the comparator study and the historical matched cohort was found. However, a higher de novo DSA emergence points to an increased risk of antibody-mediated rejection (NCT04114188).

• MeSH
• Antilymphocyte Serum * MeSH
• Immunosuppressive Agents adverse effects   MeSH
• Immunosuppression Therapy MeSH
• Infliximab adverse effects   MeSH
• Enzyme Inhibitors MeSH
• Humans MeSH
• Graft Survival MeSH
• Antibodies MeSH
• Graft Rejection prevention & control   MeSH
• Tacrolimus * adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Multicenter Study MeSH

Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n = 1844) or unrelated donor (UD, n = 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality. CI of severe grade III-IV acute GVHD was lower with TAC (6.6% vs. 9.1%, p = 0.02), without difference in grade II-IV acute GVHD or grade III-IV acute GVHD/severe chronic GVHD, relapse-free survival (GRFS). In multivariate analysis, TAC was associated with a lower risk of severe grade III-IV acute GVHD solely with haploidentical donors (HR 0.64 [95% CI, 0.42-0.98], p = 0.04), but not UD (HR 0.49 [95% CI, 0.2-1.21], p = 0.12). There was no significant difference for chronic GVHD. In conclusion, PT-Cy/MMF-based GVHD prophylaxis resulted in favorable OS and GRFS, irrespective of the CNI added. In haploidentical HCT, TAC seemed to prevent severe acute GVHD more effectively than CSA without impact on other outcome parameters.

• MeSH
• Leukemia, Myeloid, Acute * therapy   mortality   MeSH
• Cyclophosphamide * therapeutic use   MeSH
• Cyclosporine * therapeutic use   MeSH
• Child MeSH
• Adult MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Remission Induction MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Graft vs Host Disease * prevention & control   mortality   etiology   MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Tacrolimus * therapeutic use   MeSH
• Hematopoietic Stem Cell Transplantation * methods   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Comparative Study MeSH

Voklosporin je nový kalcineurinový inhibitor, který se aktuálně dostává do léčby lupusové nefritidy v České republice. Jde o první a jediný preparát z této skupiny léků, který je oficiálně schválený pro léčbu této diagnózy. Voklosporin byl u lupusové nefritidy testován v klinické studii fáze 2 (AURA-LV), klinické studii fáze 3 (AURORA 1) a v pokračující dvouleté studii AURORA 2. Všechny tři studie ukázaly, že kombinace voklosporinu s mykofenolát mofetilem a kortikosteroidy je účinnější v porovnání s mykofenolát moferilem, kortikody a placebem v dosažení renální odpovědi (kompletní i primární efektivní léčebná odpověď). Léčba navíc byla dobře tolerována. Na základě těchto studií se proto kombinační léčba voklosporin, mykofenolát mofetil a kortikosteroidy stala dle aktuálních nefrologických i revmatologických doporučení jednou ze čtyř možných variant léčby lupusové nefritidy, a to jak v indukční, tak udržovací fázi léčby. Předkládané stanovisko skupiny expertů má za cíl seznámit širší veřejnost s lékem Lupkynis (účinná látka voklosporin) v léčbě pacientů s lupusovou nefritidou. Adresa pro korespondenci: prof. MUDr. Romana Ryšavá, CSc. Klinika nefrologie 1. LF UK a VFN U Nemocnice 2 128 00 Praha 2 e-mail: romana.rysava@vfn.cz Autoři prohlašují, že nejsou v konfliktu zájmů. Do redakce doručeno: 23. 12. 2024

Voclosporin is a new calcineurin inhibitor that is currently being introduced in the treatment of lupus nephritis in the Czech Republic. It is the first and only drug in this class officially approved for the treatment of this condition. Voclosporin has been tested in lupus nephritis in a phase 2 clinical trial (AURA-LV), a phase 3 clinical trial (AURORA 1), and an ongoing two-year study (AURORA 2). All three studies demonstrated that the combination of voclosporin with mycophenolate mofetil and corticosteroids is more effective than mycophenolate mofetil, corticosteroids, and placebo in achieving a renal response (both complete and primary effective therapeutic response). Moreover, the treatment was well tolerated. Based on these studies, the combination therapy of voclosporin, mycophenolate mofetil, and corticosteroids has become one of the four possible treatment options for lupus nephritis according to current nephrology and rheumatology guidelines, both in the induction and maintenance phases of treatment. The present position statement from a group of experts aims to inform the broader public about the drug Lupkynis (active compound: voclosporin) in the treatment of patients with lupus nephritis.

• Keywords
• voclosporin,
• MeSH
• Immunosuppressive Agents pharmacology   therapeutic use   MeSH
• Calcineurin Inhibitors * administration & dosage   pharmacology   classification   therapeutic use   MeSH
• Humans MeSH
• Lupus Nephritis * diagnosis   drug therapy   MeSH
• Practice Guidelines as Topic MeSH
• Lupus Erythematosus, Systemic drug therapy   complications   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH