Is the atypical hemolytic uremic syndrome risk polymorphism in Membrane Cofactor Protein MCPggaac relevant in kidney transplantation? A case report.

aHUS is a rare disease characterized by episodes of TMA that frequently progresses to CKD and often recurs after KT. The most frequent cause of aHUS is defective regulation of complement activation because of genetic anomalies. Eculizumab interrupts the process of TMA and improves renal function. We describe one female patient with aHUS who debuted in 2005 at 3-mo-old with extrarenal manifestations and progressed to end-stage kidney disease (ESKD) within a year. Her family history included several affected members with similar bad outcomes. Our patient carries a strong aHUS genetic predisposition consisting in a pathogenic gain-of-function mutation in complement factor B concurrent with the MCP aHUS risk haplotype MCPggaac. She received a kidney transplant in 2011 without eculizumab prophylaxis. The graft, which was negative for the MCPggaac risk haplotype, had an unexpected excellent evolution without aHUS recurrence. Different retrospective studies have shown that the risk of aHUS recurrence after KT correlates well with the genetic load of aHUS risk factors. Knowing important contribution of the MCPggaac risk haplotype to the risk of developing aHUS in Factor B mutations carriers, we speculate whether the absence of this polymorphism in the graft that our patient received may have decreased the risk of aHUS recurrence after KT.

Infants Requiring Maintenance Dialysis: Outcomes of Hemodialysis and Peritoneal Dialysis.

BACKGROUND: The impact of different dialysis modalities on clinical outcomes has not been explored in young infants with chronic kidney failure. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: Data were extracted from the ESPN/ERA-EDTA Registry. This analysis included 1,063 infants 12 months or younger who initiated dialysis therapy in 1991 to 2013. FACTOR: Type of dialysis modality. OUTCOMES & MEASUREMENTS: Differences between infants treated with peritoneal dialysis (PD) or hemodialysis (HD) in patient survival, technique survival, and access to kidney transplantation were examined using Cox regression analysis while adjusting for age at dialysis therapy initiation, sex, underlying kidney disease, and country of residence. RESULTS: 917 infants initiated dialysis therapy on PD, and 146, on HD. Median age at dialysis therapy initiation was 4.5 (IQR, 0.7-7.9) months, and median body weight was 5.7 (IQR, 3.7-7.5) kg. Although the groups were homogeneous regarding age and sex, infants treated with PD more often had congenital anomalies of the kidney and urinary tract (CAKUT; 48% vs 27%), whereas those on HD therapy more frequently had metabolic disorders (12% vs 4%). Risk factors for death were younger age at dialysis therapy initiation (HR per each 1-month later initiation, 0.95; 95% CI, 0.90-0.97) and non-CAKUT cause of chronic kidney failure (HR, 1.49; 95% CI, 1.08-2.04). Mortality risk and likelihood of transplantation were equal in PD and HD patients, whereas HD patients had a higher risk for changing dialysis treatment (adjusted HR, 1.64; 95% CI, 1.17-2.31). LIMITATIONS: Inability to control for unmeasured confounders not included in the Registry database and missing data (ie, comorbid conditions). Low statistical power because of relatively small number of participants. CONCLUSIONS: Despite a widespread preconception that HD should be reserved for cases in which PD is not feasible, in Europe, we found 1 in 8 infants in need of maintenance dialysis to be initiated on HD therapy. Patient characteristics at dialysis therapy initiation, prospective survival, and time to transplantation were very similar for infants initiated on PD or HD therapy.

Eculizumab in dense-deposit disease after renal transplantation.

BACKGROUND: Dense-deposit disease (DDD) is a rare glomerulopathy characterized by electron-dense deposits in the glomerular basement membrane. About 50 % of patients with DDD progress to end-stage kidney disease and require dialysis within 10 years of diagnosis, and the disease often recurs after renal transplantation. CASE-DIAGNOSIS/TREATMENT: We describe a 14-year-old girl with recurrent DDD in her transplanted kidney. Clinical onset was at 8 years of age, when steroid-resistant nephrotic syndrome was diagnosed with microhematuria, severe hypocomplementemia and normal kidney function. Although remission was initially observed after several plasma exchanges, nephrotic proteinuria returned and kidney function further declined 1 year later. The patient received a living-related kidney transplant. Initial allograft function was good, but proteinuria reappeared 3 months after transplantation, accompanied by a slight deterioration in kidney function. After histological confirmation of DDD recurrence and subsequent management with plasmapheresis, the patient was treated for 30 months with eculizumab, a humanized monoclonal antibody that binds to C5 complement protein. This intervention proved effective and resulted in complement inhibition, sustained remission of proteinuria and preservation of renal function. A graft biopsy 6 months later showed no progression of the renal lesions. CONCLUSIONS: Early clinical and histological recurrence of DDD in the transplanted kidney in this 14-year-old patient was treated for 30 months with eculizumab. The patient remains asymptomatic, has no proteinuria and her kidney function is intact.

Life after a pediatric kidney transplant.

INTRODUCTION AND OBJECTIVES: There is currently no doubt that a kidney transplant with good function is the best treatment we can offer a child with severe kidney failure, improving their growth, development and life in general. But there are few works that follow these patients over the years to find out what their life is like as adults, their achievements and if there are any difficulties that may have arisen from their illness. That has been the objective of this work. MATERIAL AND METHODS: We have collected the evolution of 287 patients who received at least one kidney transplant in pediatric age, analyzing not only the survival of grafts and recipients but, fundamentally, their current quality of life. RESULTS: Over a 40-year period (1979-2019), 345 kidney transplants were performed in 287 pediatric recipients, with a rate of retransplantation before reaching the age of majority of 16.7%. Survival, both of patients and grafts, has improved remarkably in the last 20 years. The survival of transplanted patients in the period from 1979 to 1996 at 10, 20 and 25 years after the intervention was 83%, 76% and 65% respectively, and 94% and 82% at 10 and 20 years respectively in those transplanted in the period from 1997 to 2019. Graft survival in the period from 1979 to 1996 at 10 and 20 years was 39% and 18%, increasing in the second period to 68% and 34% respectively. Survival of the first living donor graft (LD) at 5 and 10 years was 94% and 89%. Currently 150 of these patients are adults. Of these, 32% have a stable partner and 6.6% have children. The level of training is lower than that of the general population and many of them have other comorbidities. CONCLUSIONS: The life expectancy of pediatric patients with kidney failure transplanted during childhood has improved markedly in recent decades, as has graft survival, being better with a living donor. In general, they consider themselves satisfied with their lives, with great acceptance of their illness and limitations, but -analyzing their testimonies- we conclude that they lack social support, both for themselves and their families, to achieve a higher level of education and better quality of life.

Case report: Cortico-ocular interaction networks in NBA2K.

The sport industry has never seen growth such as eSports'. Using synchronized monitoring of two biological processes on a 25-year-old gamer, we investigated how his brain (via EEG) and eyes (via pupil dilation) interacted dynamically over time as an integrated network during NBA2K playing time. After the spectral decomposition of the different Brain and Eye signals into seven frequency bands, we calculated the bivariate equal-time Pearson's cross-correlation between each pair of EEG/Eye spectral power time series. On average, our results show a reorganization of the cortico-muscular network across three sessions (e.g., new interactions, hemispheric asymmetry). These preliminary findings highlight the potential need for individualized, specific, adaptive, and periodized interventions and encourage the continuation of this line of research for the creation of general theories of networks in eSports gaming. Future studies should recruit larger samples, investigate different games, and explore cross-frequency coordination among other key organ systems.

Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Prospective study of infectious complications in a cohort of pediatric renal transplant recipients.

UNLABELLED: Infections are frequent and serious in pediatric RT recipients; however, the information available is scarce. The aim of this study was to determine the incidence, etiology, and risk factors for infection in these patients. This was a prospective, observational study of a consecutive pediatric RT recipient cohort. Risk factors for infection and descriptive analyses during the first two post-transplantation years were performed. Twenty-one patients (58.3%) had at least one infection (incidence 1.5 episodes/patient/first year of transplantation). There were 33 bacterial infections (73.3%), 11 viral infections (24.4%), and one protozoal infection. UTI was the most common syndrome (48.3%), followed by CMV infection (15.5%). The main microorganisms isolated were Escherichia coli (28.9%), 46.1% of which were ESBL producers, and CMV (20%). Patient and graft survival at the end of follow-up were 97.2% and 83.3%, respectively. The only risk factor for infection was cold ischemia time >800 min (OR 5.7, CI 95% 1.7-19.3). CONCLUSIONS: In pediatric RT recipients, UTI is the most frequent syndrome. Bacterial infections are the most common, with a high rate of ESBL producer strains. Despite their good prognosis, infections are a cause of morbidity that could potentially be reduced by decreasing cold ischemia times.

Masa nasal como único compromiso extrapulmonar de infección por M. Tuberculosis / Nasal mass as the only extrapulmonary compromise of M. Tuberculosis infection / Massa nasal como único compromisso extrapulmonar da infecção por M. Tuberculose

La tuberculosis aún es un problema de salud pública mundial. La infección causada por Mycobacterium tuberculosis se manifiesta de forma principal a nivel pulmonar. Sin embargo, alrededor del 20 % de los casos se presentan en otras localizaciones anatómicas y solo el 2 % tiene afectación del tracto respiratorio superior. Se presenta el caso de una mujer de 75 años, reconsultante al servicio de otorrinolaringología por epistaxis, lesiones postillosas en cavidad nasal y hallazgo de masa nasal. Posterior a la resección quirúrgica de la lesión, se logró la comprobación microbiológica de infección por M. tuberculosis. Se realizan estudios para descartar compromiso pulmonar y de otras localizaciones. Posterior al inicio de tratamiento antituberculoso se logró resolución completa de la lesión y no recurrencia de los síntomas. Las formas extrapulmonares de la infección por M. tuberculosis y, en especial las que afectan la región de la cabeza y el cuello, requieren un alto índice de sospecha para su diagnóstico. Los métodos de diagnóstico como la prueba de PCR y los cultivos de tejidos permiten un óptimo inicio del manejo médico de acuerdo con la epidemiología local y las condiciones del paciente.

Tuberculosis is still a global public health burden. Infection caused by the bacillus Mycobacterium tuberculosis (M. Tuberculosis) manifests mainly in the lungs. However, around 20 % of cases occur in other anatomical locations and only 2 % have upper respiratory tract involvement. We present the case of a 75-year-old female patient, who returned to the otorhinolaryngology service due to epistaxis and postillomous lesions in the nasal cavity with a finding of a nasal mass. After surgical resection of the lesion, microbiological confirmation of M. tuberculosis infection is achieved. Studies are performed to rule-out lung involvement, as well as other locations. After the initiation of tuberculosis treatment, complete resolution of the lesion and no recurrence of symptoms is documented. Extrapulmonary forms of M. tuberculosis infection, and especially those involving the head and neck region, require a high index of suspicion for their diagnosis. Diagnostic methods such as PCR testing and tissue cultures allow optimal initiation of medical management according to local epidemiology and patient conditions.

A tuberculose ainda é um problema de saúde pública global. A infecção causada pelo Mycobacterium tuberculoses manifesta-se principalmente nos pulmões. Entretanto, cerca de 20% dos casos ocorrem em outras localizações anatômicas e apenas 2% apresentam comprometimento do trato respiratório superior. É apresentado o caso de uma mulher de 75 anos que retornou ao serviço de otorrinolaringologia por quadro de epistaxe, lesões com crostas em cavidade nasal e descoberta de massa nasal. Após ressecção cirúrgica da lesão, foi realizada verificação microbiológica de infecção por M. tuberculoses. Estudos são realizados para descartar envolvimento pulmonar e otras localizações. Após início do tratamento antituberculoso, houve resolução completa dalesão e não houve recidiva dos sintomas. As formas extrapulmonares da infecção por M. tuberculoses, especialmente aquelas que acometem a região de cabeça e pescoço, requerem alto índice de suspeita para diagnóstico. Métodos de diagnóstico, como testes de PCR e culturas de tecidos, permitem o início ideal do tratamento médico de acordó com a epidemiologia local e as condições do paciente.

Irreversible temperature gating in trpv1 sheds light on channel activation.

Temperature-activated TRP channels or thermoTRPs are among the only proteins that can directly convert temperature changes into changes in channel open probability. In spite of a wealth of functional and structural information, the mechanism of temperature activation remains unknown. We have carefully characterized the repeated activation of TRPV1 by thermal stimuli and discovered a previously unknown inactivation process, which is irreversible. We propose that this form of gating in TRPV1 channels is a consequence of the heat absorption process that leads to channel opening.