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
V populaci diabetiků 2. typu je častěji než v běžné populaci diagnostikováno jak srdeční selhání, tak i chronické onemocnění ledvin (CKD). Screening CKD musí směřovat k časnému záchytu onemocnění s cílem zvrátit, nebo alespoň významně zpomalit jeho průběh a oddálit přechod do selhání ledvin s nutností chronické dialyzační anebo transplantační léčby. Finerenon je nesteroidní, selektivní antagonista mineralokortikoidního receptoru. Efekty finerenonu u nemocných s diabetem 2. typu byly zkoumány ve velkých registračních klinických studiích fáze III FIDELIO-DKD, FIGARO-DKD a následně v jejich sdružené analýze FIDELITY. Na základě výsledků publikovaných prospektivních randomizovaných kontrolovaných studií s finerenonem je jeho použití u pacientů s CKD a diabetem 2. typu zmíněno v několika recentních doporučeních. Zástupci expertního panelu zahrnujícího Českou nefrologickou společnost, Českou diabetologickou společnost ČLS JEP, Českou internistickou společnost ČLS JEP a Českou kardiologickou společnost v souladu s recentními mezinárodními doporučeními považují finerenon za jeden z pilířů léčby pacientů s chronickým onemocněním ledvin a diabetem 2. typu pro jeho nefroprotektivní a kardioprotektivní účinky.
Both heart failure and chronic kidney disease (CKD) are detected more often in the type 2 diabetic population than in the general population. CKD screening should focus on its early detection to reverse, or at least significantly slow down its course and delay stage 5 CKD with the need for chronic dialysis or transplant treatment. Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist. The effects of finerenone in patients with type 2 diabetes were investigated in the large registration phase III clinical trials FIDELIO-DKD, FIGARO-DKD and subsequently in their pooled analysis FIDELITY. Based on the results of published prospective randomized controlled trials with finerenone, its use in patients with CKD and type 2 diabetes is mentioned in several recent recommendations. Representatives of an expert panel including the Czech Nephrological Society, the Czech Diabetological Society, the Czech Internal Medicine Society and the Czech Cardiology Society, in accordance with recent international recommendations, consider finerenone to be one of the pillars of the treatment of patients with chronic kidney disease and type 2 diabetes for its nephroprotective and cardioprotective effects.
- Klíčová slova
- finerenon,
- MeSH
- chronická renální insuficience * farmakoterapie prevence a kontrola MeSH
- diabetes mellitus 2. typu * farmakoterapie komplikace MeSH
- dialýza ledvin MeSH
- komplikace diabetu farmakoterapie MeSH
- lidé MeSH
- naftyridiny farmakologie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé 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
Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Chronické onemocnění ledvin (CKD) postihuje 10 % populace vyspělých zemí a významným způsobem ovlivňuje zdravotní stav populace. Vedle známých nástrojů renoprotekce zpomalujících progresi CKD se do klinické praxe na základě výsledků rozsáhlých studií nově zavedly SGLT2 inhibitory, a to jak pro diabetiky, tak i pro nediabetiky. Tento materiál diskutuje klasifikaci CKD, současné možnosti renoprotekce a recentní roli SGLT2 inhibitorů v péči o nemocné s CKD.
Chronic kidney disease (CKD) affects 10% of the population of developed countries and significantly affects the population health. In addition to the well-known renoprotection tools slowing down the progression of CKD, SGLT2 inhibitors have been newly introduced into clinical practice based on the results of extensive studies, both in diabetics and non-diabetics. This expert opinion discusses the classification of CKD, current renoprotection options, and the recent role of SGLT2 inhibitors in the care of patients with CKD.
