This paper is born from the intimate belief that solutions for the future are to be found in the past. No transformation is irreversible enough to destroy the experiences of the past, unified as a ...core in tradition. Those come into light whenever the proper conditions are created. From the point of view of architecture, representation is the basis for the transmission of knowledge, ideas, feelings, etc. The method of the paper is to put in antithesis two concepts which define the present world of representation： real （associated to transcendent revelation） and virtual （understood as result of human imagination）. An itinerary through the philosophy of Plato and Plotin, ancient Greek, Byzantine, Gothic architecture, etc., is proposed, until encountering the moment of the death of revelation and the birth of the arbitrary, which is connected to the supremacy of the image. This journey through aesthetic conceptions brought major changes in art and society during the centuries. Recuperation of the involvement of all human senses into perception of space and understanding of the built environment of life as revelation, and not as a simple interface of images, may lead now to a revolution of urban spirit, based on a relationship with the city inspired from the values promoted by Socrates and later developed into Christianity, that proved their permanence across the millenniums.
INTRODUCTIONThere is no published experience with the use of Meltdose Tacrolimus (M-TAC) in pediatric transplant population. Theoretically, this new drug should not only improve adherence to ...treatment, but it could also offer better pharmacokinetics than once-daily extended-release tacrolimus (ER-TAC) with less side effects.
PATIENTS AND METHODSThis is a retrospective study of a single centre experience with the use of M-TAC in pediatric stable kidney transplant recipients who were selectively converted from other tacrolimus (TAC) formulae to M-TAC. Sixteen patients (44% boys, mean age at transplant 9.3∓5.6 years, mean time after transplant of 2.7 years) were switched from Advagraf(R) or Prograf(R) to M-TAC. The reasons for conversion wereimprove TAC pharmacokinetics (56%), improve patientʼs adherence to treatment (25%) or reduce TAC adverse events (19%).The immunossupression regime prior to conversion was TAC and prednisone based-triple therapy in 81% of them and double therapy in 19%.
RESULTSMean pre-conversion TAC dose was 7.03∓4.3 mg/day. Mean post-conversion TAC dose was 5.03∓2.9 mg/day, with a mean Conversion Factor of 0.73∓0.08. Mean pre-conversion TAC through blood level was 7.52∓2.75 ng/ml (range 4.4 - 12.7) and the post-conversion mean level was 7.81∓2.78 ng/ml (range 3.2 - 15.4)At a mean time of 15 months of follow-up after conversion 94% of the patients are still on M-TAC treatment. A new onset diabetes (NODAT) was diagnosed 3 months after conversion and it disappeared after the M-TAC withdrawal. No clinical acute rejection events have been diagnosed after the conversion in this population. No beneficial effect was observed in 3 patients who persist showing high variability on TAC through blood levels.(Table is included in full-text article.)
CONCLUSIONSThe switch from other TAC formulae to Meltdose TAC using the recommended conversion factor of 0.7 can be safely done also in children. The through blood levels obtained after conversion are quite predictable and stable. The switch can be done without increasing the risk of rejection episodes.
Abstract Background and Aims Neuroblastoma is the most common extracranial solid tumor in children, harboring a poor survival for those with high-risk (HR) tumors. Naxitamab (hu3F8) is a humanized ...monoclonal anti-disialoganglioside (GD2) antibody approved for the treatment of patients older than 1-year with refractory/relapsed HR-neuroblastoma limited to bone and/or bone marrow. First naxitamab (DanyelzaR) infusion was in 2017 in our institution and since then a large experience has been acquired with its use through several clinical trials as well as an expanded named patient access program. The objective is to describe the renal toxicity profile associated to naxitamab in patients with HR-neuroblastoma. Method Retrospective descriptive study including 244 patients treated with naxitamab (either on monotherapy or associated to chemotherapy) from June 2017 to December 2022 in whom renal involvement and/or hypertension (HT) was evaluated. Results Mean age of the cohort was 8 years (41% female -101- and 59% male -143-), presenting nephrotoxicity of some type up to 26.6% (n = 65): AHT (11.9%), acute renal damage (ARD 10.2%) and proteinuria (5.3%), developing all during the first 3 cycles. All of them were classified as mild adverse events (1-2) according to the Common Terminology Criteria for Adverse Events (CTCAE) scale, except for one patient with ARD grade 3 and two patients with HT grade 3. In the case of HT only in 6 patients an Ambulatory Blood Pressure Monitoring (ABPM) was performed, observing: 2 nocturnal-HT, 2 diurnal-HT without specific-pattern and 2 disautonomic-patterns. Among the ARD, all cases were tubular except for two patients who presented acute tubule-interstitial nephritis (AIN) (one with clinical-analytical pattern and another confirmed by biopsy). Eight of them (32%) had potential confounding factors (previous chemotherapy, ibuprofen or radiotherapy). Among patients with proteinuria (none in the nephrotic range): 38% tubular, 38% glomerular and 23% mixed. Two patients presented ARD + HT and 3 a combination of HT + ARD + proteinuria. All patients received prior chemotherapy and 2 developing chronic renal damage (CKD stage 2 and 3). Conclusion Short-and long-term follow-up, the systematic performance of ABPM, and the use of early markers of renal damage, could lead to a more efficient management of complications derived from this new treatment.
Abstract
Background and Aims
Ravulizumab is a long-acting C5 inhibitor that has recently demonstrated its effectiveness in adult and pediatric patients for the control of hemolytic uremic syndrome ...compared to eculizumab, allowing average annual infusion times of up to 70% less. There is still little evidence in the literature of naïve treatment with this drug in pediatrics.
Method
We present the first two pediatric cases worldwide with the use of de novo Ravulizumab: the first one in the onset of the disease and the second one, post-kidney transplant
Results
13-year-old girl referred from another country with 1 week history of acute gastroenteritis with bloody stools, vomiting and compromise of consciousness. Deterioration of general condition, with laboratory tests compatible with thrombotic microangiopathy (TMA), evolves to anuria and convulsive episode requiring invasive mechanical ventilation, corticosteroid boluses, 6 plasmapheresis sessions and 4 intermittent hemodialysis. One Eculizumab dose (600 mg) was administered in the center of origin and STEC was isolated. At admission presented compromised renal function (AKI III), hemolytic anemia, thrombocytopenia, normal ADAMTS-13, negative direct Coombs and decreased complement. Brain MRI study shows images compatible with multiple foci of necrosis. Due to the persistent requirement of renal replacement therapy and persistent TMA, Ravulizumab was started with a loading dose (2400 mg) and a second dose after 2 weeks. The need for renal replacement therapy ceased with improvement of hemolysis and renal function. Genetic study showed mutation of uncertain significance in heterozygosis in exon 6 (c.881_883, p.Ala292del) with risk polymorphism for HUSa (deletion CFHR3-CFHR1)
Case 2: 7-year-old girl (stage 5 CKD) in chronic hemodialysis 3 times/week secondary to aHUS (CD46 mutation) was admitted for kidney transplant from a living donor (father), performing hemodialysis session before surgical intervention. Low-intermediate immunological risk (PRA 0%, 9 HLA matches) and high CMV infectious risk (valganciclovir prophylaxis). Induction treatment: Basiliximab, tacrolimus, mycophenolate and steroids. First dose of Ravulizumab was infused the day before transplantation (900mg), well tolerated. 36 hours after presented acute pulmonary edema as well as a drop in hemoglobin (4g/dL). With normal laboratory hemolysis parameters, urgent abdominal-pelvic CT was performed due to suspicion of bleeding, confirming an active bleeding. Surgical reintervention was decided due to ureteral bleeding and the tunnel was redone with good results. The patient has had a favorable evolution of renal function, with a normal value of creatinine at discharge (0.43 mg/dl). Protein/Creatinine urine ratio (iPr/Cr) increases to a maximum of 8 mg/mg. Negative DSA levels but the option of renal biopsy was assessed and ruled out due to a decrease in proteinuria (iPr/Cr 0.51 mg/mg). She received second dose of ravulizumab after 2 weeks, remain stable with no data on recurrence of her underlying disease today.
Conclusión: In the two patients, the initial treatment with Ravulizumab was satisfactory, both in the acute phase of the disease and in the immediate post-transplantation. In the first case we observed a functional recovery from the first dose with no notable adverse effects up today, as in the post-transplant patient, maintaining a good control of TMA despite more spaced dosing (8 weeks). The inclusion of this drug in the therapeutic arsenal opens a new safe treatment route in pediatric patients with HUSa
Abstract
Background and Aims
Tubulointerstitial nephritis (TIN) in pediatrics represents 7% of the causes of acute kidney injury (AKI) and a syndrome with a variety of manifestations, even with ...oligosymptomatic pictures, with the classic triad (fever, eosinophilia and exanthema) being observed in only 10%.the causes are multiple (pharmacological 70%) and can be associated with clinical syndromes. The diagnosis is defined by histology, but renal biopsy is not always performed due to the rapid and good evolution of some patients. The pathogenic mechanism is immune-mediated, self- limited, reversible and acute, and can evolve to tubulointerstitial fibrosis and CKD. the aim of our study is to describe the clinical characteristics of patients with TIN.
Method
Retrospective descriptive study conducted during 9 years (2013-2022) of a series of cases with a diagnosis of TIN (with/without biopsy), evaluating demographic, etiological, clinical-analytical, evolution and treatment parameters. Patients with previous renal disease or renal transplantation were excluded. KDIGO 2012 criteria were used to evaluate ARD, glomerular filtration rate was estimated using the Schwartz 2009 equation (0.413) in >1 year, and by CKD-EPI in >12 years. Regarding Cystatin C, the estimation was performed by the Filler formula. Proteinuria was expressed as IPr/Cr (mg/mg) and Alb/Cr (mg/mmol).Fractional excretion of solutes was analyzed, using urinary Beta-2-microglobulin (ug/ml) as a marker of tubular injury.
Results
Eighteen cases were identified, with a median age of 14 years (2-7 years). 11 renal biopsies were performed (61.1%), with the reason for indication generally being persistent ARD of non-filial etiology despite supportive treatment.11 pharmacological cases were identified (61.1%),3 infectious (bacterial,2 by Mycoplasma Pneumoniae),2 TINU and 2 idiopathic. The most common symptom was abdominal pain (94%) and the most frequent sign was fever (94%), with prolonged febrile syndrome in 4 children. The most common symptom was abdominal pain (94%) and the most frequent sign was fever (44.4%), with prolonged febrile syndrome in 4 children. The classic triad was detected in two cases (11.1%).On admission, all patients had normal BP, with only one patient oliguric on debut. The delay from clinical onset to diagnosis was a median of 8.5 days (IQR 20.5). Renal ultrasound showed renal hyperechogenicity (25%) and associated nephromegaly (12.5 %).median eGFR at one month was 79.72 mL/min/1.73 m2, with only 1 case of recurrence and 2 of chronicity.7 cases received treatment with corticosteroids and 2 of them with immunosuppressants.
Conclusión
In every child with ARD, acute tubulointerstitial nephritis is one of the causes that we must always keep in mind in our differential diagnosis.in the series we confirm the wide forms of presentation of the disease and its various etiologies. Likewise, the evolution of the disease and the prognosis will depend on the cause and the early diagnosis, conditioning the treatment.
Abstract
Background and Aims
Patients monitored in the cardiovascular risk (CVR) consultation usually present overweight/obesity, metabolic syndrome, tendency to hypertension (HT), poor eating habits ...and sedentary lifestyle, with great resistance to change, great influence of the environment and, frequently, psychosocial limitations. We asked whether home confinement for COVID-19 (March-May 2020) could have negative effects in relation to CVR in these patients. The main objective of this work is to assess this hypothesis with respect to HTN and the use of antihypertensive drugs in these patients. As a secondary objective, we assessed changes in other parameters: body mass index (BMI), level of physical activity and diet.
Method
Retrospective cohort study with review of 738 ambulatory blood pressure monitoring (ABPM) between 2019-2022 obtaining, after applying the exclusion criteria (no overweight/obesity, poor therapeutic compliance, underlying renal pathology or failure to perform two ABPM in the study period), a final cohort of 46 patients divided into two groups (23 each): one group exposed to home confinement (G1) with one ABPM before and after home confinement and another group not exposed to confinement (G2) with two ABPM in different periods between 2021-2022. Blood pressure (BP) percentile values, dipper pattern, variability and blood pressure load, as well as the rest of the CVR parameters were compared in both periods.
Results
The mean age was 13 years (13.8 G1/13.2 G2) with a mean time between the 1st and 2nd ABPM of 11 months (11.08 G1/10.95 G2) and a greater reduction in BMI in G2 than in G1 (1.05 G1/1.21 G2). Despite this, the results were not statistically significant. Nor were the results significant in terms of differences in AT or worsening of the dipper pattern (30.4% in G1 and 21.7% in G2). We did observe differences (p<0.022) in the use of antihypertensive drugs, although contrary to our initial hypothesis, with greater use of drugs in G2.
Conclusion
Although the low sample size, the biases inherent in the design and the lack of previous studies make the interpretability and statistical significance of some results difficult, they reinforce that the measures during confinement did not contemplate all spheres of health and the need to implement specific CVR consultations. Obesity and its associated pathologies are an important public health problem that pediatricians have the responsibility to address.
Introduction
HLA sensitization is a growing problem in children awaiting kidney transplantation. In some cases, finding an immunologically compatible donor entails contemplating the option of an ABO ...incompatible transplant or paired transplant.
Methods
Patient with genetic nephrotic syndrome and progressive chronic kidney disease, with a previous thrombosis of a first kidney transplant, resulting hypersensitized and remaining for a long‐time on hemodialysis. Despite a desensitization strategy, family members were incompatible and deceased donation options must be ruled out due to the presentation of donor‐specific antibodies (DSA). After 4 years, the possibility arises to perform a kidney paired transplant with a 62‐year‐old woman with an incompatible blood group. Although the current cytotoxicity‐ and cell‐based crossmatches were negative, history of DSA were recorded.
Results
An intensive ABO and HLA desensitization protocol was performed in order to combat the isohemagglutinin antibodies and on the memory‐HLA, based on rituximab, apheresis sessions, and immunoglobulins. Despite the donor being older in terms of pediatric transplantation, the donor‐recipient weight difference, and immunological risk, the transplant was completed successfully. Maintenance of titration of up to 1/2 was confirmed after 3 weeks post‐transplant (IgM and IgG). Kidney biopsy at 2 weeks and 6 months without signs of rejection. The patient is currently 12 months post‐transplant and has not presented any signs of transplant rejection and has proper renal function.
Conclusions
Kidney paired transplantation is an excellent solution for hypersensitized children, and ABO incompatibility can be considered to increase their options to find a good donor, without thereby obtaining worse results.
Abstract
Background and Aims
Ofatumumab (OFA) is an anti-CD-20 monoclonal antibody useful in nephrotic syndrome refractory to conventional treatments and rituximab (RTX). Our objective is to evaluate ...the response and safety in patients with nephrotic syndrome (NS) treated with Ofatumumab.
Method
A prospective descriptive study of 2 years duration (2017-2019) in children with NS refractory to first-line therapies who received treatment with anti-CD20 monoclonal antibodies. To do this, we divided the cohort into 3 groups: Patients with corticodependent NS (CDNS) without response or with adverse effects associated with first-line treatment that preclude its use (Group 1); Corticosteroid-resistant SN (CRNS) (Group 2) and SN with post-transplant recurrence (Group 3). In them, the results of safety and remission rate were evaluated.
Results
Thirty-three patients (21 with SNCD, 11 with SNCR, and 1 with SN recurrence in transplantation) were included and administered anti-CD20. The male / female ratio was 2: 1 and the mean age at diagnosis was 5.2 years. 100% of the children (33) received RTX and 18.2% (6) OFA. The RTX achieved complete remission in 87.9% (29) and 48.3% of these did not present new relapses after 70 months of follow-up. 100% of Group 1 presented complete remission after RTX, although 52.4% (11) presented at least 1 relapse after 22.9 months (mean 2.5 relapses). In group 2, 72.72% (8) complete remission and 27.2% (3) partial, with persistent proteinuria. 36.4% (4) presented relapse after 17 months of treatment (mean 1 relapse). Of the 6 who received OFA, 83.3% presented complete remission (1 SNCR and 4 SNCD) and 1 patient (SNCD) presented relapse at 24 months (mean follow-up 1 year). The other case, a 13-year-old girl with recurrence of focal segmental glomerulosclerosis (FSGS) in kidney transplantation, presented partial remission after one year of treatment in association with immunoadsorption sessions. Regarding safety, adverse reactions occurred in 6% (2): allergic reaction with 2nd dose of RTX and cytokine release syndrome with 1st dose of OFA.
Conclusion
Ofatumumab in our series has proven to be an effective and safe drug in difficult-to-manage NS, achieving complete remission in 5 patients who had not previously responded to Rituximab
Abstract
Background and Aims
To report the response to different treatments and the renal prognosis in a cohort of patients with corticosteroid-resistant nephrotic syndrome (CRNS).
Method
...Retrospective observational study in patients with CRNS. For this, the results of the histology, the different treatment guidelines used in each case and the evolution of renal function were collected, determining the results in terms of remission and renal survival in the different groups.
Results
Of the initial cohort of 37 patients, 33 were included, excluding 4 patients with Finnish-type genetic CRNS. The mean age at diagnosis was 6.1 years. 54.5% were women. Regarding the initial biopsy, 45.5% corresponded to minimal changes (15 patients), 27.3% (9) focal and segmental glomerulosclerosis, 15.1% (5) diffuse mesangial proliferation and 12.1% (4) others. The mean follow-up was 53 months (3-115 months). 27 patients (84.4%) received cyclosporine (CyA), 66.7% (18) of them presented complete remission and 22.2% (6) partial response. Of the patients in complete remission, 33% had at least one relapse after 17 months of treatment (7–27 months). Rituximab was administered in 12 patients (37.5%), of which 7 had not previously responded to immunosuppressants. 100% of frequent relapsers presented complete remission after administration of Rituximab, although 3 had subsequent relapses (60%) after 21 months of treatment (12-34 months). 57% of the patients who did not respond to immunosuppressants did not respond to Rituximab either, with Ofatumumab allowing complete remission in one of them. When relating the results with the histology, we saw how the remission in minimal changes and diffuse mesangial proliferation was 100% and 80%, respectively, although it was 33.3% in focal and segmental glomerulosclerosis. Similarly, renal failure was more frequent in patients with focal segmental glomerulosclerosis (77.7%). Of the remissions (24; 72.7%), 3 were partial (9.1%) and 6 (18.2%) did not respond to any immunosuppressive treatment, with the need for kidney transplantation in 2 of them (6%) and with 1 deceased due to an infectious cause (3%).
Conclusion
Histology and, especially, focal and segmental glomerulosclerosis, play a prognostic role in the CRNS with a lower remission rate and a greater deterioration in renal function and the need for associated kidney transplantation.
A superficial perspective on architecture may induce the impression that it consists in the analysis of a long series of “containers”, conceived to shelter activities, technically named “programmes”. ...This inaccurate interpretation is distanced from the inner sense of “frozen music”, as defined by Goethe. Seen as an engine of civilizations across history, architecture acts as a phenomenon, answering to a dynamics defined both on a social scale and on a family or individual scale. We use today pedantic terms, such as “conversion”, “resilience” or the English term “adaptive re-use”, with the impression that these are conquests of our present thinking. But this process was followed as well when Roman amphitheaters were transformed into living areas or when Greek and Roman temples sheltered Christian basilicas since every epoch had its own conception on the pragmatism of reusing a pre-existing built fund.
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