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OBJECTIVES: The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). METHODS: Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. RESULTS: One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72-232) vs 199 (130-371) 109/l], ferritin level on admission [1107 (676-2050) vs 2863 (1193-9562) ng/ml], C-reactive protein level [15.4 (2.9-56) vs 90 (32-160) mg/l], erythrocyte sedimentation rate [13 (3-36) vs 43.5 (13-77) mm/h] and fever duration [5 (4-7.5) vs 10 (7-14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. CONCLUSION: Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.
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OBJECTIVES: To investigate the severe haematological involvement in children with SLE and assess its clinical associations, treatments, outcome and damage accrual. METHODS: The medical charts of children with SLE in whom haematological involvement was observed were reviewed. Severe haematological indices were defined as autoimmune haemolytic anaemia with a haemoglobin concentration < 8 g/dL, thrombocyte count < 30 000/µL, and neutrophil count < 500/µL. RESULTS: Among the 224 patients included, 102 (45.5%) displayed severe indices, predominantly at the initial involvement, and most frequently as severe anaemia in 54 (24.1%) and severe thrombocytopenia in 45 (20.1%). Disease activity did not differ according to the presence of severe disease indices. In addition, the presence of severe indices at initial involvement did not affect the damage accrual. However, a higher rate of damage (51.1% vs. 29.9%, p = 0.002) and steroid-induced damage (28.9% vs. 8.2%, p < 0.001) was evident in patients with flares of the haematological system. Regression analysis revealed that rituximab treatment during the initial episode (OR:4.5, p = 0.006) and the presence of anticardiolipin antibodies (OR:2.3, p = 0.014) significantly increases the odds for haematological system flare. However, severe indices at initial involvement did not increase the odds of a haematological flare. CONCLUSION: Severe haematological indices at onset are common but not related with disease outcomes. Prevention of flares is important to improve outcomes, and a more rigorous maintenance strategy would benefit most to children who display haematological indices refractory to conventional immunosuppressants and those with anti-cardiolipin antibodies.
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BACKGROUND: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. METHOD: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. RESULTS: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. CONCLUSION: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.
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Diabetes Mellitus , Glomerulonefrite , Nefropatias , Transplante de Rim , Adulto , Humanos , Feminino , Masculino , Europa (Continente) , Doadores de Tecidos , Sistema de Registros , Transplantados , Sobrevivência de EnxertoRESUMO
OBJECTIVE: In this study, we aimed to evaluate the characteristics of pediatric rhupus patients including all the related series in the literature. METHODS: Thirty pediatric patients with rhupus syndrome from 12 different centers in Turkey were included in this study. The literature was also reviewed for pediatric patients with rhupus syndrome. RESULTS: The most prominent phenotype of these 30 patients was juvenile idiopathic arthritis (JIA) (60%) at the disease onset and SLE (73.3%) at the last visit. Major SLE-related organ involvements were skin (80%), hematological system (53.3%), and kidney (23.3%). Arthritis was polyarticular (73.3%), asymmetric (66.7%), and erosive (53.3%) in most patients. Hydroxychloroquine (100%), glucocorticoids (86.7%), and mycophenolate mofetil (46.7%) were mostly used for SLE, while glucocorticoids (76.6%), methotrexate (73.3%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (57.6%) were mainly preferred for JIA. Our literature search revealed 20 pediatric patients with rhupus syndrome (75% were RF positive). The most prominent phenotype was JIA (91.7%) at the disease onset and SLE (63.6%) at the last visit. Major SLE-related organ involvements were skin (66.7%), hematological system (58.3%), and kidney (58.3%). Arthritis was polyarticular (77.8%), asymmetric (63.6%), and erosive (83.3%) in most patients. Glucocorticoid (100%), hydroxychloroquine (76.9%), and azathioprine (46.2%) were mostly used for SLE, while methotrexate (76.9%) and NSAIDs (46.2%) were mainly preferred for the JIA phenotype. CONCLUSION: Our study is the largest cohort in the literature evaluating pediatric rhupus cases. Most of the pediatric patients had polyarticular, asymmetric, and erosive arthritis, as well as organ involvements associated with SLE, including the skin, hematological system, and kidney.
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Artrite Juvenil , Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Humanos , Criança , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Estudos Retrospectivos , Metotrexato/uso terapêutico , Artrite Reumatoide/complicações , Artrite Juvenil/complicações , Artrite Juvenil/tratamento farmacológico , Glucocorticoides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: In 2020, the COVID-19 pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe. METHODS: Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017-2019. Also changes occurring during the first and second wave of the pandemic were explored. RESULTS: The incidence of KRT was 6.2% lower in 2020 compared with 2017-2019, with the lowest point (-22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (-5.2%) than in females (-8.2%), and was moderate for peritoneal dialysis (-3.7%) and haemodialysis (-5.4%), but substantial for pre-emptive kidney transplantation (-23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of -80.1% during the first wave, and most for living donor kidney transplants (-30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decline. In dialysis patients, mortality increased by 11.4%, and was highest in those aged 65-74 years (16.1%), in those with diabetes as primary renal disease (15.1%), and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N=317787) resembled that of 2019 (N=317077). CONCLUSION: The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT, and prevalence of KRT in Europe with variations across countries.
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BACKGROUND/AIMS: Two earthquakes on February 6th, 2023 destroyed ten cities in Türkiye. We report our experience with pediatric victims during these catastrophes, with a focus on crush syndrome related-acute kidney injury (Crush-AKI) and death. METHOD: A web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were asked. RESULTS: 903 injured children (median age: 11.62 years) were evaluated. Mean TUR was 13 h (Interquartile range-IQR: 32.5), max 240 h). 31 of 32 patients with a TUR of >120 h survived. The patient who rescued after ten days survived.Two-thirds of the patients were given 50 mEq/L sodium-bicarbonate in 0.45% sodium-chloride solution on admission day. 58% of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% of 3000-4000 mL/m2 BSA, and only 2% of >4000 mL/m2 BSA. 425 patients had surgeries, 48 suffered from major bleeding. Amputations were recorded in 96 patients. Eighty-two and 66 patients required ventilator and inotropic support, respectively.Crush-AKI developed in 314 patients (36% of all patients). 189 patients were dialyzed. Age > 15 years, creatine phosphokinase (CK)≥20 950 U/L, TUR≥10 h, and the first-day IVF volume < 3000-4000 mL/m2 BSA were associated with Crush-AKI development. 22 deaths were recorded, 20 of 22 occurred in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: This is the most extensive pediatric kidney disaster data after an earthquake. Serum CK level was significantly associated with Crush-AKI at the levels of >20 950 U/L, but not with death. Adolescent age and initial IVF of less than 3000-4000 mL/m2 BSA were also asscoiated with Crush-AKI. Given that mildly injured victims can survive longer periods in the disaster field, we suggest uninterrupted rescue activity for at least 10 days.
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Spontaneous tendon or ligament ruptures are quite rare and mostly associated with chronic systemic diseases such as diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, and chronic kidney disease (CKD). In this study, we present the first documented case of a spontaneous rupture of the medial patellofemoral ligament (MPFL) in a pediatric patient. The patient was undergoing long-term peritoneal dialysis (PD) and had a history of severe secondary hyperparathyroidism. Additionally, we discussed spontaneous tendon and ligament ruptures associated with CKD or dialysis through a comprehensive literature review. This case report highlights the importance of recognizing that spontaneous tendon or ligament injuries are not exclusive to adults; children with CKD can also be affected. Several factors including poor parathyroid hormone (PTH) and metabolic acidosis control, prolonged CKD duration and presence of malnutrition play role in the pathogenesis. Early diagnosis is crucial as it allows for timely surgical intervention and leads to a favorable functional recovery.
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Doenças Musculares , Insuficiência Renal Crônica , Traumatismos dos Tendões , Criança , Humanos , Ligamentos/patologia , Doenças Musculares/etiologia , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Traumatismos dos Tendões/diagnóstico , Traumatismos dos Tendões/etiologia , Traumatismos dos Tendões/terapia , Tendões/patologiaRESUMO
BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.
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Glomerulonefrite Membranoproliferativa , Glomerulonefrite , Nefropatias , Falência Renal Crônica , Humanos , Criança , Complemento C3/genética , Ácido Micofenólico/uso terapêutico , Glomerulonefrite Membranoproliferativa/patologia , Mutação , Glomerulonefrite/tratamento farmacológico , Nefropatias/tratamento farmacológicoRESUMO
Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration. CONCLUSIONS: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests. WHAT IS KNOWN: ⢠During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring. WHAT IS NEW: ⢠There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. ⢠This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.
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Antirreumáticos , Padrões de Prática Médica , Reumatologistas , Rituximab , Humanos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Criança , Inquéritos e Questionários , Masculino , Turquia , Feminino , Reumatologia , Doenças Autoimunes/tratamento farmacológico , Pediatras/estatística & dados numéricos , PediatriaRESUMO
AIM: Rituximab (RTX) is a genetically engineered chimeric monoclonal antibody which binds directly to CD20 antigen and mediates inhibition of B cell development. Although RTX has been widely used in paediatric nephrology, there is no routine protocol for its use. In this study, paediatric nephrologists in Türkiye were asked to fill out a questionnaire to understand their practice in using RTX. This study aimed to determine common practices and clarify the uncertainties regarding the use of RTX in paediatric nephrology. METHODS: This was a nationwide, multicenter, retrospective cohort study based on data evaluating the use of RTX in paediatric nephrology practice. An online questionnaire was sent to all paediatric nephrology centers in Türkiye. The questionnaire forms included information about how many patients in total applied RTX treatment, for which indications they use RTX, and whether they made any preparations before using RTX. RESULTS: According to this survey on RTX use in Türkiye, paediatric nephrologists use it most commonly in SSNS and followed by SRNS, ABMR, SLE and AAV, respectively. Dosing was highly standard but there is significant heterogeneity in pre-exposure tests and patient monitoring in the clinical practice of RTX. Also, the rate of encountering RTX-related allergic and infectious side effects at least once during the professional experience of our physicians can be quite high. CONCLUSION: There is an increasing need for the preparation of a guideline on the indications for RTX use for each diagnosis, posology, and the practices to be performed before and after infusion.
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Nefrologia , Criança , Humanos , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , TurquiaRESUMO
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is characterized by increased endogenous oxalate production and deposition as calcium oxalate crystals. The main manifestations are nephrocalcinosis/nephrolithiasis, causing impaired kidney function. We aimed to evaluate the clinical characteristics and overall outcomes of paediatric PH1 patients in Turkey. METHODS: This is a nationwide, multicentre, retrospective study evaluating all available paediatric PH1 patients from 15 different paediatric nephrology centres in Turkey. Detailed patient data was collected which included demographic, clinical and laboratory features. Patients were classified according to their age and characteristics at presentation: patients presenting in the first year of life with nephrocalcinosis/nephrolithiasis (infantile oxalosis, Group 1), cases with recurrent nephrolithiasis diagnosed during childhood (childhood-onset PH1, Group 2), and asymptomatic children diagnosed with family screening (Group 3). RESULTS: Forty-eight patients had a mutation consistent with PH1. The most common mutation was c.971_972delTG (25%). Infantile oxalosis patients had more advanced chronic kidney disease (CKD) or kidney failure necessitating dialysis (76.9% vs. 45.5%). These patients had much worse clinical course and mortality rates seemed to be higher (23.1% vs. 13.6%). Patients with fatal outcomes were the ones with significant comorbidities, especially with cardiovascular involvement. Patients in Group 3 were followed with better outcomes, with no kidney failure or mortality. CONCLUSION: PH1 is not an isolated kidney disease but a systemic disease. Family screening helps to preserve kidney function and prevent systemic complications. Despite all efforts made with traditional treatment methods including transplantation, our results show devastating outcomes or mortality.
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Hiperoxalúria Primária , Hiperoxalúria , Falência Renal Crônica , Nefrocalcinose , Nefrolitíase , Insuficiência Renal , Humanos , Criança , Nefrocalcinose/diagnóstico , Nefrocalcinose/epidemiologia , Nefrocalcinose/etiologia , Estudos Retrospectivos , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/genética , Nefrolitíase/complicações , Nefrolitíase/diagnóstico , Nefrolitíase/genética , Hiperoxalúria/complicaçõesRESUMO
OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is a noninfectious autoinflammatory bone condition that frequently occurs alongside other inflammatory diseases, such as familial Mediterranean fever (FMF). We aimed to determine the demographic, clinical, laboratory, and radiological characteristics of patients diagnosed with both FMF and CNO. METHODS: We reviewed the medical records of pediatric patients with both CNO and FMF at 3 pediatric rheumatology centers in Turkey from December 2008 to 2022. Patients' demographics, laboratory features, imaging findings, and treatment were recorded. RESULTS: Twelve patients with FMF and CNO were included in the study. Half of them were female. The mean ages at onset for FMF and CNO symptoms were 80 and 116 months, whereas the ages at diagnosis for FMF and CNO were 100 and 125 months, respectively. Ten patients (83.3%) had M694V mutation on at least 1 allele of the Mediterranean fever (MEFV) gene. The most common sites of osteitis were the long bones (58.3%), pelvis (50%), and clavicles (25%). Ten patients (83%) received nonsteroidal anti-inflammatory drugs; 8 (66%) received disease-modifying antirheumatic drugs; biological therapy was administered to 5 patients (41%), who did not respond to these treatments; and all patients received colchicine. CONCLUSION: The increased frequency of FMF in patients with CNO is of interest. Because most patients with CNO and FMF carried a homozygous or combined heterozygous M694V mutation, we speculated that the M694V mutation may play a role in the development of osteitis. Further studies are needed to elucidate the link between FMF and CNO.
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OBJECTIVE: The exact effects of MEFV variants on inflammation are still under investigation, and reports on variants of unknown significance, particularly the E148Q variant, have been conflicting. Therefore, this study aims to investigate patients exhibiting E148Q heterozygosity, focusing on diagnoses and disease courses to assist physicians in interpreting the variant. METHODS: Data of pediatric patients presenting to the Pediatric Rheumatology clinic between November 2016 and September 2023, exhibiting only E148Q heterozygosity in MEFV gene analysis, were extracted. Patients who were lost before 9 months of follow-up have been excluded to ensure the completion of initial diagnostic tests and evaluations. RESULTS: Among the 119 patients with E148Q variant, the diagnoses were as follows: healthy, 51.3%; IgA vasculitis, 10.1%; Familial Mediterranean Fever (FMF), 7.6%; Periodic fever, Aphtous stomatitis, Pharyngitis, Adenitis (PFAPA), 6.7%; and other diagnoses, 19.3%. IgA vasculitis patients experienced articular, gastrointestinal, and renal involvement at rates of 91.7%, 58.3%, and 16.7%, respectively. Complete response, partial response, and no response to colchicine were 37.5%, 12.5%, and 50%, respectively, in PFAPA patients. All FMF patients responded to colchicine treatment resulting in reduced mean FMF episode counts in 6 months from 3.22 ± 0.92 to 0.56 ± 0.52. CONCLUSIONS: The E148Q variant may amplify inflammation and modify disease courses. Patients with the E148Q variant experiencing typical FMF episodes should receive colchicine, but clinicians should exercise caution regarding alternative diagnoses. Additionally, the E148Q variant may increase acute phase reactants and disease severity in IgA vasculitis. However, to reach definitive conclusions on its treatment-modifying role in PFAPA, universal diagnosis and treatment response criteria should be adopted.
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OBJECTIVES: We aimed to outline the demographic data, clinical spectrum, and treatment approach of sarcoidosis in a large group of patients and sought to figure out the variations of early-onset (EOS) and late-onset paediatric sarcoidosis (LOS). METHODS: The study followed a retrospective-descriptive design, with the analysis of medical records of cases diagnosed as paediatric sarcoidosis. RESULTS: Fifty-two patients were included in the study. The median age at disease onset and follow-up duration were 83 (28.2-119) and 24 (6-48) months, respectively. Ten (19.2%) cases had EOS (before 5th birthday) and 42 (80.7%) cases had LOS. The most common clinical findings at the time of the disease onset were ocular symptoms (40.4%) followed by joint manifestation (25%), dermatological symptoms (13.5%), and features related to multi-organ involvement (11.5%). Anterior uveitis was the most common (55%) one among ocular manifestations. Patients with EOS displayed joint, eye, and dermatological findings more commonly than patients with LOS. The recurrence rate of disease in patients with EOS (5.7%) and LOS (21.1%) were not statistically different (P = .7). CONCLUSIONS: Patients with EOS and LOS may present with variable clinical features and studies addressing paediatric sarcoidosis cases in collaboration between disciplines will enhance the awareness of this rare disease among physicians and assist early diagnosis with lesser complications.
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Sarcoidose , Uveíte , Humanos , Criança , Uveíte/diagnóstico , Uveíte/etiologia , Estudos Retrospectivos , Turquia , Sarcoidose/diagnóstico , Sarcoidose/terapia , Sarcoidose/complicaçõesRESUMO
RATIONALE & OBJECTIVE: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease. STUDY DESIGN: Phase 3, open-label, single-arm trial. SETTING & PARTICIPANTS: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age <12 months), and POx ≥20 µmol/L at screening, including patients with or without systemic oxalosis. INTERVENTION: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing. OUTCOME: Primary end point: percent change in POx from baseline to month 6 (cohort A; not receiving hemodialysis at enrollment) and percent change in predialysis POx from baseline to month 6 (cohort B; receiving hemodialysis at enrollment). Pharmacodynamic secondary end points: percent change in POx area under the curve between dialysis sessions (cohort B only); absolute change in POx; percent and absolute change in spot urinary oxalate-creatinine ratio; and 24-hour urinary oxalate adjusted for body surface area. RESULTS: All patients (N = 21; 43% female; 76% White) completed the 6-month primary analysis period. Median age at consent was 8 (range, 0-59) years. For the primary end point, least-squares mean reductions in POx were 33.3% (95% CI, -15.2% to 81.8%) in cohort A (n = 6) and 42.4% (95% CI, 34.2%-50.7%) in cohort B (n = 15). Improvements were also observed in all pharmacodynamic secondary end points. Most adverse events were mild or moderate. No patient discontinued treatment or withdrew from the study. The most commonly reported lumasiran-related adverse events were injection-site reactions, all of which were mild and transient. LIMITATIONS: Single-arm study without placebo control. CONCLUSIONS: Lumasiran resulted in substantial reductions in POx with acceptable safety in patients with PH1 who have advanced kidney disease, supporting its efficacy and safety in this patient population. FUNDING: Alnylam Pharmaceuticals. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT04152200 and at EudraCT with study number 2019-001346-17. PLAIN-LANGUAGE SUMMARY: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive hepatic oxalate production that frequently causes kidney failure. Lumasiran is an RNA interference therapeutic that is administered subcutaneously for the treatment of PH1. Lumasiran has been shown to reduce oxalate levels in the urine and plasma of patients with PH1 who have relatively preserved kidney function. In the ILLUMINATE-C study, the efficacy and safety of lumasiran were evaluated in patients with PH1 and advanced kidney disease, including a cohort of patients undergoing hemodialysis. During the 6-month primary analysis period, lumasiran resulted in substantial reductions in plasma oxalate with acceptable safety in patients with PH1 complicated by advanced kidney disease.
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Hiperoxalúria Primária , Hiperoxalúria , Nefropatias , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Hiperoxalúria Primária/complicações , Nefropatias/complicações , OxalatosRESUMO
Chronic kidney disease (CKD) is diagnosed when glomerular filtration rate (GFR) falls below 60 ml/min/1.73 m2 or urinary albumin:creatinine ratio (UACR) reaches ≥30 mg/g, as these two thresholds indicate a higher risk of adverse health outcomes, including cardiovascular mortality. CKD is classified as mild, moderate or severe, based on GFR and UACR values, and the latter two classifications convey a high or very high cardiovascular risk, respectively. Additionally, CKD can be diagnosed based on abnormalities detected by histology or imaging. Lupus nephritis (LN) is a cause of CKD. Despite the high cardiovascular mortality of patients with LN, neither albuminuria nor CKD are discussed in the 2019 European League Against Rheumatism (EULAR)/European Renal Association-European Dialysis and Transplant Association recommendations for the management of LN or the more recent 2022 EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases. Indeed, the proteinuria target values discussed in the recommendations may be present in patients with severe CKD and a very high cardiovascular risk who may benefit from guidance detailed in the 2021 European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice. We propose that the recommendations should move from a conceptual framework of LN as an entity separate from CKD to a framework in which LN is considered a cause of CKD and evidence generated from large CKD trials applies unless demonstrated otherwise.
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Doenças Cardiovasculares , Nefrite Lúpica , Insuficiência Renal Crônica , Doenças Reumáticas , Humanos , Nefrite Lúpica/complicações , Nefrite Lúpica/terapia , Nefrite Lúpica/diagnóstico , Ácido Edético , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Taxa de Filtração Glomerular , Doenças Reumáticas/complicações , Doenças Cardiovasculares/complicaçõesRESUMO
Serum osmolality is the sum of the osmolalities of every single dissolved particle in the blood such as sodium and associated anions, potassium, glucose, and urea. Under normal conditions, serum sodium concentration is the major determinant of serum osmolality. Effective blood osmolality, so-called blood tonicity, is created by the endogenous (e.g., sodium and glucose) and exogenous (e.g., mannitol) solutes that are capable of creating an osmotic gradient across the membranes. In case of change in effective blood osmolality, water shifts from the compartment with low osmolality into the compartment with high osmolarity in order to restore serum osmolality. The difference between measured osmolality and calculated osmolarity forms the osmolal gap. An increase in serum osmolal gap can stem from the presence of solutes that are not included in the osmolarity calculation, such as hypertonic treatments or toxic alcoholic ingestions. In clinical practice, determination of serum osmolality and osmolal gap is important in the diagnosis of disorders related to sodium, glucose and water balance, kidney diseases, and small molecule poisonings. As blood hypertonicity exerts its main effects on the brain cells, neurologic symptoms varying from mild neurologic signs and symptoms to life-threatening outcomes such as convulsions or even death may occur. Therefore, hypertonic states should be promptly diagnosed and cautiously managed. In this review, the causes and treatment strategies of hyperosmolar conditions including hypernatremia, diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, hypertonic treatments, or intoxications are discussed in detail to increase awareness of this important topic with significant clinical consequences.
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Manitol , Ureia , Humanos , Concentração Osmolar , Sódio , GlucoseRESUMO
BACKGROUND: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. METHODS: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. RESULTS: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). CONCLUSION: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Doenças Ósseas , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Nefrologia , Insuficiência Renal Crônica , Lactente , Humanos , Criança , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Cálcio/uso terapêutico , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Fosfatos , MineraisRESUMO
BACKGROUND: Automated peritoneal dialysis (APD) is increasingly preferred worldwide. By using a software application (Homechoice with Claria sharesource system (CSS)) with a mod-M added to the APD device, details of the home dialysis treatment become visible for PD nurses and physicians, allowing for close supervision. We aimed to evaluate the perceptions of patients/caregivers, PD nurses, and physicians about the advantages and disadvantages of CSS. METHODS: Three different web-based questionnaires for patients/caregivers, nurses, and physicians were sent to 15 pediatric nephrology centers with more than 1 year of experience with CSS. RESULTS: Respective questionnaires were answered by 30 patients/caregivers, 22 pediatric nephrologists, and 15 PD nurses. Most of the nurses and physicians (87% and 73%) reported that CSS improved patient monitoring. A total of 73% of nurses suggested that CCS is not well known by physicians, while half of them reported reviewing CSS data for all patients every morning. Sixty-eight percent of physicians thought that CSS helps save time for both patients/caregivers and healthcare providers by reducing visits. However, only 20% of patients/caregivers reported reduced hospital visits. A total of 90% of patients/caregivers reported that being under constant monitoring made them feel safe, and 83% stated that the patient's sleep quality improved. CONCLUSIONS: A remote monitoring APD system, CSS, can be successfully applied with children for increased adherence to dialysis prescription by giving shared responsibility and may help increase the patient's quality of life. This platform is more commonly used by nurses than physicians. Its potential benefits should be evaluated in further well-designed clinical studies with larger patient groups. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Diálise Peritoneal , Médicos , Humanos , Criança , Diálise Renal , Cuidadores , Qualidade de VidaRESUMO
BACKGROUND: Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. METHODS: We included patients < 20 years starting KRT in 33 European countries from 1995-2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) < -1.88 and tall stature as height SDS > 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. RESULTS: We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. CONCLUSIONS: Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.