From Patterns to Proteins: Mass Spectrometry Comes of Age in Glomerular Disease.

Laser capture microdissection and mass spectrometry (LCM/MS) is a technique that involves dissection of glomeruli from paraffin-embedded biopsy tissue, followed by digestion of the dissected glomerular proteins by trypsin, and subsequently mass spectrometry to identify and semiquantitate the glomerular proteins. LCM/MS has played a crucial role in the identification of novel types of amyloidosis, biomarker discovery in fibrillary GN, and more recently discovery of novel target antigens in membranous nephropathy (MN). In addition, LCM/MS has also confirmed the role for complement proteins in glomerular diseases, including C3 glomerulopathy. LCM/MS is now widely used as a clinical test and considered the gold standard for diagnosis and typing amyloidosis. For the remaining glomerular diseases, LCM/MS has remained a research tool. In this review, we discuss the usefulness of LCM/MS in other glomerular diseases, particularly MN, deposition diseases, and diseases of complement pathways, and advocate more routine use of LCM/MS at the present time in at least certain diseases, such as MN, for target antigen detection. We also discuss the limitations of LCM/MS, particularly the difficulties faced from moving from a research-based technique to a clinical test. Nonetheless, the role of LCM/MS in glomerular diseases is expanding. Currently, LCM/MS may be used to identify the etiology in certain glomerular diseases, but in the future, LCM/MS can play a valuable role in determining pathways of complement activation, inflammation, and fibrosis.

Apolipoprotein E is enriched in dense deposits and is a marker for dense deposit disease in C3 glomerulopathy.

C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), both of which are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy (EM), DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known. We performed laser microdissection (LCM) of glomeruli followed by mass spectrometry (MS) in 12 cases each of DDD, C3GN, and pretransplant kidney control biopsies. LCM/MS showed marked accumulation of complement proteins C3, C5, C6, C7, C8, C9 and complement regulating proteins CFHR5, CFHR1, and CFH in C3GN and DDD compared to controls. C3, CFH and CFHR proteins were comparable in C3GN and DDD. Yet, there were significant differences. First, there was a six-to-nine-fold increase of C5-9 in DDD compared to C3GN. Secondly, an unexpected finding was a nine-fold increase in apolipoprotein E (ApoE) in DDD compared to C3GN. Most importantly, immunohistochemical and confocal staining for ApoE mirrored the dense deposit staining in the GBM in DDD but not in C3GN or control cases. Validation studies using 31 C3G cases confirmed the diagnosis of C3GN and DDD in 80.6 % based on ApoE staining. Overall, there is a higher burden of terminal complement pathway proteins in DDD compared to C3GN. Thus, our study shows that dense deposits in DDD are enriched with ApoE compared to C3GN and control cases. Hence, ApoE staining may be used as an adjunct to EM for the diagnosis of DDD and might be valuable when EM is not available.

A comprehensive model for assessing and classifying patients with thrombotic microangiopathy: the TMA-INSIGHT score.

BACKGROUND: Thrombotic Microangiopathy (TMA) is a syndrome characterized by the presence of anemia, thrombocytopenia and organ damage and has multiple etiologies. The primary aim is to develop an algorithm to classify TMA (TMA-INSIGHT score). METHODS: This was a single-center retrospective cohort study including hospitalized patients with TMA at a single center. We included all consecutive patients diagnosed with TMA between 2012 and 2021. TMA was defined based on the presence of anemia (hemoglobin level < 10 g/dL) and thrombocytopenia (platelet count < 150,000/µL), signs of hemolysis, and organ damage. We classified patients in eight categories: infections; Malignant Hypertension; Transplant; Malignancy; Pregnancy; Thrombotic Thrombocytopenic Purpura (TTP); Shiga toxin-mediated hemolytic uremic syndrome (STEC-SHU) and Complement Mediated TMA (aHUS). We fitted a model to classify patients using clinical characteristics, biochemical exams, and mean arterial pressure at presentation. RESULTS: We retrospectively retrieved TMA phenotypes using automatic strategies in electronic health records in almost 10 years (n = 2407). Secondary TMA was found in 97.5% of the patients. Primary TMA was found in 2.47% of the patients (TTP and aHUS). The best model was LightGBM with accuracy of 0.979, and multiclass ROC-AUC of 0.966. The predictions had higher accuracy in most TMA classes, although the confidence was lower in aHUS and STEC-HUS cases. CONCLUSION: Secondary conditions were the most common etiologies of TMA. We retrieved comorbidities, associated conditions, and mean arterial pressure to fit a model to predict TMA and define TMA phenotypic characteristics. This is the first multiclass model to predict TMA including primary and secondary conditions.

Thrombotic microangiopathy in children.

The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ involvement. It comprises a spectrum of underlying etiologies that may differ in children and adults. In children, apart from ruling out shigatoxin-associated hemolytic uremic syndrome (HUS) and other infection-associated TMA like Streptococcus pneumoniae-HUS, rare inherited causes including complement-associated HUS, cobalamin defects, and mutations in diacylglycerol kinase epsilon gene must be investigated. TMA should also be considered in the setting of solid organ or hematopoietic stem cell transplantation. In this review, acquired and inherited causes of TMA are described with a focus on particularities of the main causes of TMA in children. A pragmatic approach that may help the clinician tailor evaluation and management is provided. The described approach will allow for early initiation of treatment while waiting for the definitive diagnosis of the underlying TMA.

APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses.

BACKGROUND: APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort. METHODS: Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m2] and slow/non-progressors (eGFR > 30 mL/min/1.73 m2 through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy. RESULTS: Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-risk-genotype (LRG) children in the whole NS cohort (p = 0.001) and the three subgroups. In SRNS and biopsied patients, a single risk variant was associated with trends of higher CKD progression risk. CONCLUSIONS: Novel discoveries include a substantial prevalence of HRG among patients self-reported White, worse kidney outcomes in HRG versus LRG children in the FSGS subgroup, and a trend of higher CKD progression risk associated with a single risk variant in the SRNS cohort. These findings suggest APOL1-associated NS extends beyond patients self-reported non-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS.

Collaborative Brazilian pediatric renal transplant registry (CoBrazPed-RTx): A report from 2004 to 2018.

The Brazilian collaborative registry for pediatric renal transplantation began in 2004 as a multicenter initiative aimed at analyzing, reporting, and disseminating the results of pediatric renal transplantation in Brazil. Data from all pediatric renal transplants performed from January 2004 to May 2018 at the 13 participating centers were analyzed. A total of 2744 pediatric renal transplants were performed in the thirteen participating centers. The median age at transplantation was 12.2 years, with the majority being male recipients (56%). The main underlying diseases were CAKUT (40.5%) and glomerulopathy (28%). 1981 (72%) of the grafts were from deceased donors (DD). Graft survival at one year (censored by death) was 94% in the live donor group (LD) and 91% in the DD group (log-rank test P < 0.01). The patient's survival at one and 5 years was 97% and 95% for the LD group and 96% and 93% for the DD group (log-rank test P = 0.02). The graft loss rate was 19% (n = 517), more frequently caused by vascular thrombosis (n = 102) and chronic graft nephropathy (n = 90). DD recipients had 1.6 (1.0-2.2) times greater chance of death and 1.5 (1.2-1.8) times greater chance of graft loss compared to LD recipients. The mortality rate was 5.4% (n = 148), mainly due to infection (n = 69) and cardiovascular disease (n = 28). The results of this collaborative pediatric renal transplant record are comparable to other international registries, although we still have a high infection rate as a cause of death.

Overlap of C3 Glomerulopathy and Thrombotic Microangiopathy: A Case Series.

Introduction: Dysregulation of alternative complement pathway underlies the pathogenesis of both C3 glomerulopathy (C3G) and thrombotic microangiopathy (TMA). In this study, we describe both disease entities occurring in 5 patients. Methods: We identified 114 patients at our institution from 2007 to 2016 with C3G in native kidney biopsies and those with concurrent TMA were included. Results: The median age at diagnosis was 58 years (range: 28-69); all were male. Median serum creatinine and proteinuria at presentation were 2.3 mg/dl and 2089 mg/d, respectively. Three cases presented with TMA-predominant phenotype and 2 with C3G-predominant phenotype. Immunofluorescence (IF) showed bright C3 staining in mesangium and/or capillary walls. Electron microscopy showed marked subendothelial expansion by fluffy material in the capillary loops without associated deposits. However, capillary wall deposits were present in other loops in 4 cases. Mesangial deposits were present in all cases. Four cases showed low C3, of which 2 showed low C4. Complement evaluation in 3 cases showed pathogenic CFH mutation in 1 case, and multiple variant of unknown significance along with factor B autoantibody and C4 nephritic factor in 1 case. One patient negative for complement abnormalities had a monoclonal gammopathy. Three cases were treated with steroids and/or immunosuppressants. One case progressed to end-stage renal disease (ESRD) at 38.3 months; the remaining showed median serum creatinine and proteinuria of 2.5 mg/dl and 1169 mg/d, respectively at median follow-up of 17.5 months. Conclusion: Overlap of C3G and TMA is rare and can clinically present as C3G-predominant or TMA-predominant phenotype. The significance of concurrent C3G/TMA findings on long-term renal survival remains to be explored.

Proteomic Analysis of Complement Proteins in Glomerular Diseases.

Introduction: Complement plays an important role in the pathogenesis of glomerulonephritis (GN). Even though the underlying etiology of GN might be different, complement activation with subsequent glomerular deposition of complement proteins result in glomerular injury and progression of the lesions. Routine immunofluorescence microscopy (IF) includes staining for only complement factors C3c and C1q. Therefore, with regard to evaluation of the complement pathways, routine kidney biopsy provides only limited information. Methods: In this study, using laser microdissection of glomeruli followed by mass spectrometry, complement proteins and pathways involved in GN were analyzed. Results: We found that C3 followed by C9 are the most abundant complement proteins in GN, indicating activation of classical or lectin or alternative, and terminal pathways, either exclusively or in a combination of pathways. Furthermore, depending on the type of GN, C4A and/or C4B were also present. Therefore, membranous nephropathy (MN), fibrillary GN, and infection-related GN showed C4A dominant pathways, whereas lupus nephritis (LN), proliferative GN with monoclonal Ig deposits, monoclonal Ig deposition disease (MIDD), and immunotactoid glomerulopathy showed C4B dominant pathways. Significant deposition of complement regulatory proteins, factor H-related protein-1 (FHR-1) and factor H-related protein-5 (FHR-5), were also detected in most GN. Conclusions: This study shows accumulation of specific complement proteins in GN. The complement pathways, complement proteins, and the amount of complement protein deposition are variable in different types of GN. Selective targeting of complement pathways may be a novel option in the treatment of GN.

The challenges of the pandemic and the vaccination against covid-19 in pediatric patients with kidney disease.

The covid-19 vaccine confers direct protection and reduces transmission rates of the virus and new variants. Vaccines from Pfizer/BioNTech and CoronaVac have been cleared for children in Brazil. They are safe, effective, and immunogenic. There are no known complications associated with the use of steroids or vaccines in pediatric patients with covid-19 and nephrotic syndrome. With or without immunosuppression, these patients are not at increased risk of severe covid-19, and steroids are safe for them. A milder form of covid-19 occurs in patients with chronic kidney disease without the need for hospitalization. The vaccine response may be reduced and/or the duration of antibodies after vaccination may be shorter than in the general population. However, considering risk of exposure, vaccination against covid-19 is recommended. It is believed that patients with hemolytic-uremic syndrome are at higher risk of severe covid-19. Vaccination is recommended, although specific data on the safety and efficacy of the covid-19 vaccine are limited. There is agreement that the benefits of induced immunity outweigh the risks of immunization. Vaccination against covid-19 is recommended for children and adolescents needing kidney transplantation or who have undergone transplantation. These patients present decreased immune response after vaccination, but immunization is recommended because the benefits outweigh the risks of vaccination. Current recommendations in Brazil stipulate the use of the messenger RNA vaccine. This paper aims to provide pediatric nephrologists with the latest knowledge about vaccination against covid-19 for children with kidney disease.

Eculizumab in low-middle income countries: how much does a life cost?

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease and eculizumab was approved as first line therapy in 2011 by the Food and Drug Administration. Access to eculizumab in low-middle income countries is challenging. We discuss access to eculizumab in Brazil that was made possible by judicialization or compassionate use. We showed a nationwide cohort of unplanned eculizumab interruptions resulted in higher rates of aHUS relapse. Similar to the French cohort, the use of eculizumab after transplantation showed superior graft survival compared to conventional treatment. We speculate a possible solution to the higher cost of eculizumab in which the government negotiates with the manufacturers. In this process, the government should compromise to ensure validated protocols of drug use, and the pharmaceutical companies, on the other hand, should reduce prices, especially in low-income countries. We also suggest a price adjustment based on gross domestic product.

Pediatric peritoneal dialysis in Brazil: a discussion about sustainability. A document by the Brazilian Society of Nephrology, the Brazilian Society of Pediatrics, the Brazilian Association of Organ Transplantation, and the Brazilian Association of Dialysis and Transplant Centers.

INTRODUçÃO: A diálise peritoneal (DP) é importante para a pediatria. Este estudo mostrou dados de centros brasileiros que utilizam DP pediátrica. MÉTODO: Estudo transversal, observacional, descritivo com questionário eletrônico. Incluiu-se pacientes de 0-18 anos em DP cadastrados nos bancos de dados dos diversos centros. Questionário preenchido anonimamente, sem dados de identificação. Foi adotada metodologia quantitativa. RESULTADOS: 212 pacientes estão em DP no Brasil (agosto, 2021). 80% têm menos de 12 anos de idade. A maioria realiza DP automatizada e 74% são dependentes do Sistema Único de Saúde. Em 25% dos centros faltou material de DP e em 51% os pacientes pediátricos foram convertidos de DP para HD. CONCLUSÃO: A maioria dos pacientes tinha menos de 12 anos e era dependente do SUS. A escassez de insumos aconteceu em 25% dos centros. Esses dados apontam para o problema da sustentabilidade de DP, única alternativa de TRS em crianças muito pequenas.

Baseline characteristics and evolution of Brazilian patients with atypical hemolytic uremic syndrome: first report of the Brazilian aHUS Registry.

Background: Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease. Therefore, studies involving large samples are scarce, making registries powerful tools to evaluate cases. We present herein the first analysis of the Brazilian aHUS Registry (BRaHUS). Methods: Analysis of clinical, laboratory, genetic and treatment data from patients inserted in the BRaHUS, from 2017 to 2020, as an initiative of the Rare Diseases Committee of the Brazilian Society of Nephrology. Results: The cohort consisted of 75 patients (40 adults and 35 pediatric). There was a predominance of women (56%), median age at diagnosis of 20.7 years and a positive family history in 8% of cases. Renal involvement was observed in all cases and 37% had low C3 levels. In the <2 years of age group, males were predominant. Children presented lower levels of hemoglobin (P = .01) and platelets (P = .003), and higher levels of lactate dehydrogenase (LDH) (P = .004) than adults. Genetic analysis performed in 44% of patients revealed pathogenic variants in 66.6% of them, mainly in CFH and the CFHR1-3 deletion. Plasmapheresis was performed more often in adults (P = .005) and 97.3% of patients were treated with eculizumab and its earlier administration was associated with dialysis-free after 3 months (P = .08). Conclusions: The cohort of BRaHUS was predominantly composed of female young adults, with renal involvement in all cases. Pediatric patients had lower hemoglobin and platelet levels and higher LDH levels than adults, and the most common genetic variants were identified in CFH and the CFHR1-3 deletion with no preference of age, a peculiar pattern of Brazilian patients.

Complement in Secondary Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a condition characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) with varying degrees of organ damage in the setting of normal international normalized ratio and activated partial thromboplastin time. Complement has been implicated in the etiology of TMA, which are classified as primary TMA when genetic and acquired defects in complement proteins are the primary drivers of TMA (complement-mediated TMA or atypical hemolytic uremic syndrome, aHUS) or secondary TMA, when complement activation occurs in the context of other disease processes, such as infection, malignant hypertension, autoimmune disease, malignancy, transplantation, pregnancy, and drugs. It is important to recognize that this classification is not absolute because genetic variants in complement genes have been identified in patients with secondary TMA, and distinguishing complement/genetic-mediated TMA from secondary causes of TMA can be challenging and lead to potentially harmful delays in treatment. In this review, we focus on data supporting the involvement of complement in aHUS and in secondary forms of TMA associated with malignant hypertension, drugs, autoimmune diseases, pregnancy, and infections. In aHUS, genetic variants in complement genes are found in up to 60% of patients, whereas in the secondary forms, the finding of genetic defects is variable, ranging from almost 60% in TMA associated with malignant hypertension to less than 10% in drug-induced TMA. On the basis of these findings, a new approach to management of TMA is proposed.

Atypical hemolytic uremic syndrome in Brazil: clinical presentation, genetic findings and outcomes of a case series in adults and children treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and kidney injury caused by a dysregulation of the alternative complement pathway. METHODS: We conducted a multicenter nonregistry study aimed at collecting clinical, laboratory and genetic information of patients with aHUS in Brazil. Demographic data, genetic findings, treatments and outcomes are presented. RESULTS: Thirty-four patients were included, 62% were female and 67% were Caucasian. Half of the patients had the first manifestation of aHUS before the age of 18 years (pediatric group). Among the 17 patients who had the first manifestation after the age of 18 years (adult group), 6 were kidney transplant patients. Overall, 22 patients (65%) received plasma exchange/plasma infusion (PE/PI) and 31 patients (91%) received eculizumab. Eculizumab was started later in the adult group compared with the pediatric group. Two patients stopped dialysis after PE/PI and 19 patients stopped dialysis after eculizumab despite a late start. A pathogenic/likely pathogenic variant was found in 24.3% of patients. A coexisting condition or trigger was present in 59% of patients (infections, pregnancy, hypertension, autoimmune disease and transplant), especially in the adult group. There was a 30% relapse rate after stopping eculizumab, irrespective of genetic status. CONCLUSION: This is the largest case series of aHUS in Brazil involving a wide range of patients for which eculizumab was the main treatment. Although eculizumab was started later than advised in the guidelines, most patients were able to stop dialysis at variable intervals. Discontinuation of eculizumab was associated with a 30% relapse of aHUS.

Thrombotic microangiopathy after kidney transplantation: Analysis of the Brazilian Atypical Hemolytic Uremic Syndrome cohort.

BACKGROUND: Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab. METHODS: This was a multicenter retrospective cohort study including kidney transplant patients diagnosed with aHUS. We collected data from 118 transplant centers in Brazil concerning aHUS transplanted patients between 01/01/2007 and 12/31/2019. Patients were stratified into three groups: no use of eculizumab (No Eculizumab Group), use of eculizumab for treatment of after transplantation TMA (Therapeutic Group), and use of eculizumab for prophylaxis of aHUS recurrence (Prophylactic Group). RESULTS: Thirty-eight patients with aHUS who received kidney transplantation were enrolled in the study. Patients' mean age was 30 years (24-40), and the majority of participants was women (63% of cases). In the No Eculizumab Group (n = 11), there was a 91% graft loss due to the TMA. The hazard ratio of TMA graft loss was 0.07 [0.01-0.55], p = 0.012 in the eculizumab Prophylactic Group and 0.04 [0.00-0.28], p = 0.002 in the eculizumab Therapeutic Group. CONCLUSION: The TMA graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients. This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients. Cost optimization analysis and the early access to C5 inhibitors are suggested, especially in low-medium income countries.

Eculizumab interruption in atypical hemolytic uremic syndrome due to shortage: analysis of a Brazilian cohort.

BACKGROUND: The risk of eculizumab therapy discontinuation in patients with atypical hemolytic uremic syndrome (aHUS) is unclear. The main objective of this study was to analyze the risk of aHUS relapse after eculizumab interruption due to drug shortage in Brazil. METHODS: We screened all the registered dialysis centers in Brazil (n = 800), willing to participate in the aHUS Brazilian shortage cohort, through electronic mail and formal invitation by the Brazilian Society of Nephrology. We included patients with aHUS whose eculizumab therapy underwent unplanned discontinuation for at least 30 days between January 1st, 2016 and December 31st, 2019 during the maintenance phase of treatment. Relapse was defined by the development of thrombocytopenia, hemolytic anemia, acute kidney injury or thrombotic microangiopathy (TMA) in a kidney biopsy. RESULTS: We analyzed 25 episodes of exposure to risk of relapse, from 24 patients. Median age was 33 (6-53) years, 18 (72%) were female, 9 (36%) had a functioning renal graft, 5 (20%) were undergoing dialysis. CFH variant was found in 8 (32%) episodes. There were 11 relapses. The risk of relapse was 34%, 44.5% and 58% at 114, 150 and 397 days, respectively. No baseline variable was related to relapse in Cox multivariate analysis, including CFH variant. CONCLUSIONS: In this study, the cumulative incidence of aHUS relapse at 397 days was 58% after eculizumab interruption. The presence of complement variant does not seem to be associated with a higher relapse rate. The eculizumab interruption was deemed not safe, considering that the rate of relapse was high.

Recommendations from the Brazilian Society of Nephrology regarding the use of cloth face coverings, by chronic kidney patients in dialysis, during the new coronavirus pandemic (Covid-19).

These recommendations were created after the publication of informative note 3/2020- CGGAP/DESF/SAPS/MS, of April 4, 2020, in which the Brazilian Ministry of Health recommended the use of a cloth mask by the population, in public places. Taking into account the necessary prioritization of the provision of Personal Protective Equipment (PPE) for patients with suspected or confirmed disease, as well as for healthcare professionals, the SBN is favorable concerning the wear of cloth masks by chronic kidney patients in dialysis, in public settings, except in the dialysis setting. The present recommendations have eleven items, related to this rationale, the procedures, indications, contraindications, as well as appropriate fabrics for the mask, and hygiene care to be adopted. These recommendations may change, at any time, in the light of new evidence.

Recommendations from the Brazilian Society of Nephrology for approaching Covid-19 Diagnostic Testing in Dialysis Units.

The Covid-19 pandemic brought several challenges to the healthcare system: diagnosis, treatment and measures to prevent the spread of the disease. With the greater availability and variety of diagnostic tests, it is essential to properly interpret them. This paper intends to help dialysis units concerning the use of clinical criteria and diagnostic tests for decision making regarding the discontinuation of isolation of patients with suspected or confirmed Covid-19, as well as the return to work activities for employees with suspected or confirmed Covid-19.

Recommendations Of The Brazilian Society Of Nephrology Regarding Pediatric Patients On Renal Replacement Therapy During The Covid-19 Pandemic.

INTRODUCTION: The impact of the new coronavirus (SARS-COV-2) and its worldwide clinical manifestations (COVID-19) imposed specific regional recommendations for populations in need of specialized care, such as children and adolescents with kidney diseases, particularly in renal replacement therapies (RRT). We present the recommendations of the Brazilian Society of Nephrology regarding the treatment of pediatric patients with kidney diseases during the COVID-19 pandemic. METHODS: Articles and documents from medical societies and government agencies on specific recommendations for children on RRT in relation to COVID-19 as well as those focused on epidemiological aspects of this condition in Brazil Were evaluated and analyzed. RESULTS: We present recommendations on outpatient care, transportation to dialysis centers, peritoneal dialysis, hemodialysis, and kidney transplantation in children and adolescents during the COVID-19 pandemic in Brazil. DISCUSSION: Despite initial observations of higher mortality rates in specific age groups (the elderly) and with comorbidities (obese, diabetics, and those with cardiovascular diseases), patients with chronic kidney disease (CKD) on RRT are particularly prone to develop COVID-19. Specific measures must be taken to reduce the risk of contracting SARS-CoV-2 and developing COVID-19, especially during transport to dialysis facilities, as well as on arrival and in contact with other patients.