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
- antilymfocytární sérum * MeSH
- imunosupresiva škodlivé účinky MeSH
- imunosupresivní léčba MeSH
- infliximab škodlivé účinky MeSH
- inhibitory enzymů MeSH
- lidé MeSH
- přežívání štěpu MeSH
- protilátky MeSH
- rejekce štěpu prevence a kontrola MeSH
- takrolimus * škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
BACKGROUND: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs. METHODS: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology. RESULTS: Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eβ] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eβ 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eβ1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19. CONCLUSIONS: Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).
- Publikační typ
- časopisecké články MeSH
Tento článek shrnuje poznatky v oboru nefrologie za poslední rok. Studie EMPA ‐KIDNEY potvrdila výrazný renoprotektivní efekt SGLT‐2 inhibitorů u nemocných bez diabetu, zatímco renoprotektivní efekt u nemocných s diabetem byl potvrzen u finerenonu. Studie STOP ‐ACEi ukázala, že přerušování léčby inhibitory systému renin‐angiotesin‐aldosteron nemá smysl u pokročilého chronického onemocnění ledvin. Studie CHAP prokázala významný efekt včasné léčby krevního tlaku při jeho vzestupu nad 140/90 mm Hg u těhotných žen. Dále bylo potvrzeno, že jak systémová, tak topická kortikoterapie představuje možnosti léčby IgA nefropatie. Rovněž ve studii CONVINCE bylo prokázáno, že hemodiafiltrace má mortalitní benefity oproti hemodialýze. Studií NOSTONE byla zpochybněna role thiazidových diuretik v prevenci urolitiázy. Potenciálně zásadní novinkou pro vysoce senzitizované pacienty čekající na transplantaci ledviny představuje IgG ‐degradující enzym Streptococcus pyogenes – imlifidáza. Tyto nové poznatky dávají pacientům naději na zpomalení progrese chronického onemocnění ledvin a rovněž zlepšují jejich vyhlídky v případě nutnosti zahájení náhrady funkce ledvin.
This article summarizes the latest developments in the field of nephrology over the past year. The EMPA-KIDNEY study confirmed a significant renoprotective effect of SGLT-2 inhibitors in patients without diabetes, while a renoprotective effect in patients with diabetes was confirmed for finerenone. The STOP-ACEi study showed that discontinuation of renin-angiotensin-aldosterone system inhibitors does not confer benefit in patients with advanced chronic kidney disease. The CHAP study showed a significant beneficial effect of early treatment of hypertension above 140/90mmHg in pregnant women. It has also been confirmed that both systemic and topical corticosteroids represent viable treatment options for IgA nephropathy. Furthermore, the CONVINCE study showed that hemodiafiltration has mortality benefits over hemodialysis. The role of thiazide diuretics in the prevention of urolithiasis has been questioned by the NOSTONE study. The IgG-degrading enzyme of Streptococcus pyogenes - imlifidase - is a potentially crucial innovation for highly sensitized patients awaiting kidney transplantation. These new findings give patients hope for slowing the progression of chronic kidney disease and also improves their prospects if the need for renal replacement therapy arises.
INTRODUCTION: There is a strong impetus for the use of telemedicine for boosting early detection rates and enabling early treatment and remote monitoring of COVID-19 cases, particularly in chronically ill patients such as kidney transplant recipients (KTRs). However, data regarding the effectiveness of this practice are lacking. METHODS: In this retrospective, observational study with prospective data gathering we analyzed the outcomes of all confirmed COVID-19 cases (n = 955) in KTRs followed at our center between March 1, 2020, and April 30, 2022. Risk factors of COVID-19 related mortality were analyzed with focus on the role of early referral to the transplant center, which enabled early initiation of treatment and remote outpatient management. This proactive approach was dependent on the establishment and use of a telemedicine system, which facilitated patient-physician communication and expedited diagnostics and treatment. The main exposure evaluated was early referral of KTRs to the transplantation center after confirmed or suspected COVID-19 infection. The primary outcome was the association of early referral to the transplantation center with the risk of death within 30 days following a COVID-19 diagnosis, evaluated by logistic regression. RESULTS: We found that KTRs who referred their illness to the transplant center late had a higher 30-day mortality (4.5 vs. 13.6%, p < 0.001). Thirty days mortality after the diagnosis of COVID-19 was independently associated with late referral to the transplant center (OR 2.08, 95% CI 1.08-3.98, p = 0.027), higher age (OR 1.09, 95% CI 1.05-1.13, p < 0.001), higher body mass index (OR 1.06, 95% CI 1.01-1.12, p = 0.03), and lower eGFR (OR 0.96, 95% CI 0.94-0.98, p < 0.001) in multivariable logistic regression. Furthermore, KTRs who contacted the transplant center late were older, had longer time from transplantation, lived farther from the center and presented with higher Charlson comorbidity index. DISCUSSION: A well-organized telemedicine program can help to protect KTRs during an infectious disease outbreak by facilitating pro-active management and close surveillance. Furthermore, these results can be likely extrapolated to other vulnerable populations, such as patients with chronic kidney disease, diabetes or autoimmune diseases requiring the use of immunosuppression.
- Publikační typ
- časopisecké články MeSH
Dlouhodobé následky prodělání onemocnění covid‐19, tzv. syndrom dlouhého covidu (long covid), patří mezi relativně časté a svízelné komplikace infekce virem SARS‐CoV‐2. V následujícím textu jsou shrnuty problematika nejčastějších klinických otázek, nové pohledy na patofyziologii vzniku tohoto onemocnění a v neposlední řadě jeho dopad na ledviny a pacienty s chronickým onemocněním ledvin.
- Publikační typ
- abstrakt z konference MeSH
PURPOSE: Advanced age is associated with an impaired humoral immune response to SARS-CoV-2 mRNA vaccination in kidney transplant recipients (KTR). The mechanisms are, however, poorly understood. Frailty syndrome assessment may determine the most vulnerable population. METHODS: This study is a secondary analysis of a prospective study (NCT04832841) regarding seroconversion after BNT162b2 vaccination, including 101 SARS-CoV-2 naïve KTR 70 years and older. The Fried frailty components were evaluated, and antibodies against S1 and S2 subunits of SARS-CoV-2 were examined > 14 days after the second dose of BNT162b2 vaccine. RESULTS: Seroconversion was observed in 33 KTR. Male gender, eGFR, MMF-free immunosuppression, and a lower frailty score were associated with higher seroconversion rates in univariable regression. Concerning frailty components, physical inactivity had the most negative effect on seroconversion (OR = 0.36, 95% CI 0.14-0.95, p = 0.039). In a multivariable regression adjusted for eGFR, MMF-free immunosuppression, time from transplant and gender, pre-frail (OR = 0.27, 95% CI 0.07-1.00, p = 0.050), and frail status (OR = 0.14, 95% CI 0.03-0.73, p = 0.019) were associated with an increased risk of unresponsiveness to SARS-CoV-2 vaccines. CONCLUSION: Frailty was associated with an impaired humoral response to SARS-CoV-2 mRNA vaccination in older SARS-CoV-2 naïve KTR. TRAIL REGISTRATION: This study is registered under the identifier NCT04832841 on ClinicalTrials.gov.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- křehkost * MeSH
- křehký senior MeSH
- lidé MeSH
- messenger RNA MeSH
- příjemce transplantátu MeSH
- prospektivní studie MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- vakcína BNT162 MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Přestože byly inhibitory kotransportéru pro sodík a glukózu 2 (sodium-glucose co-transporter 2, SGLT2) původně vyvinuty jako nová třída antidiabetik, jejich výrazné kardioprotektivní a nefroprotektivní účinky výrazně rozšířily spektrum jejich využití. Zde shrnujeme farmakologické vlastnosti inhibitorů SGLT2, výsledky hlavních klinických studií s nefrologickými cíli, novinky v indikačních kritériích a budoucí perspektivy jejich využití. Inhibitory SGLT2 se tak stávají základními prostředky renoprotekce a kardioprotekce u většiny nemocných s chronickým onemocnění ledvin či chronickým srdečním selháním nehledě na přítomnost diabetu.
Although sodium-glucose co-transporter 2 (SGLT-2) inhibitors were originally developed as a new class of antidiabetic drugs, their significant cardioprotective and nephroprotective effects have greatly expanded the spectrum of their use. Here, we summarize the pharmacological properties of SGLT-2 inhibitors, the results of major clinical trials with renal outcomes, novel indication criteria, and future perspectives of their use. SGLT-2 inhibitors are now becoming to be considered as novel cornerstones of nefroprotective and cardioprotective therapies in patients in with chronic kidney disease or chronic heart failure regardless of the presence of diabetes.
Nemocní po transplantaci ledviny jsou ve vyšším riziku závažných projevů nemoci covid-19. Po prodělání nemoci byla u nemocných po transplantaci ledviny popsána solidní míra sérokonverze (vytvoření specifických protilátek). Imunosupresivní terapie, především mykofenolová kyselina, limituje schopnost vytvoření specifických protilátek nebo specifických T – lymfocytů jako odpověď na očkování doporučenými mRNA vakcínami. Posilující třetí dávka mRNA vakcíny dále zvyšuje šanci na sérokonverzi bez ohledu na zvolený typ vakcíny. Očkování po proběhlém onemocnění vede k vytvoření protilátek ve vysokém titru u většiny nemocných. Vyšetření humorální nebo celulární imunity je ale jenom pomocným nástrojem k posouzení specifické imunokompetence u nemocných léčených imunosupresí.
Kidney transplant recipients are at high risk of severe covid-19. Seroconversion rates comparable to those of the general population were previously described after the natural course of the disease in kidney transplant recipients. Immunosuppressive therapy, such as mycophenolic acid, limits the production of specific T-cells and antibodies following mRNA vaccination. A third booster dose significantly improves the humoral response regardless of the vaccine type chosen. Furthermore, vaccination following covid-19 infection results in high levels of specific antibodies in the majority of patients. However, the testing of humoral or cellular immune response in kidney transplant recipients is only an auxiliary tool in assessing their immunocompetence.
