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Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are associated with defects in primary cilium structure and function. To identify genes mutated in NPHP-RC, we performed homozygosity mapping and whole-exome sequencing for >100 individuals, some of whom were single affected individuals born to consanguineous parents and some of whom were siblings of indexes who were also affected by NPHP-RC. We then performed high-throughput exon sequencing in a worldwide cohort of 800 additional families affected by NPHP-RC. We identified two ADAMTS9 mutations (c.4575_4576del [p.Gln1525Hisfs∗60] and c.194C>G [p.Thr65Arg]) that appear to cause NPHP-RC. Although ADAMTS9 is known to be a secreted extracellular metalloproteinase, we found that ADAMTS9 localized near the basal bodies of primary cilia in the cytoplasm. Heterologously expressed wild-type ADAMTS9, in contrast to mutant proteins detected in individuals with NPHP-RC, localized to the vicinity of the basal body. Loss of ADAMTS9 resulted in shortened cilia and defective sonic hedgehog signaling. Knockout of Adamts9 in IMCD3 cells, followed by spheroid induction, resulted in defective lumen formation, which was rescued by an overexpression of wild-type, but not of mutant, ADAMTS9. Knockdown of adamts9 in zebrafish recapitulated NPHP-RC phenotypes, including renal cysts and hydrocephalus. These findings suggest that the identified mutations in ADAMTS9 cause NPHP-RC and that ADAMTS9 is required for the formation and function of primary cilia.
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Proteína ADAMTS9/genética , Ciliopatias/genética , Mutação , Doenças Renais Policísticas/genética , Proteína ADAMTS9/metabolismo , Animais , Cílios/patologia , Ciliopatias/patologia , Feminino , Humanos , Masculino , Fenótipo , Doenças Renais Policísticas/patologia , Esferoides Celulares , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
The objective of this study was to inform the pediatric nephrologists of recent advances in acute kidney injury (AKI) epidemiology, pathophysiology, novel biomarkers, diagnostic tools, and management modalities. Studies were identified from PubMed, EMBASE, and Google Scholar for topics relevant to AKI. The bibliographies of relevant studies were also reviewed for potential articles. Pediatric (0-18 years) articles from 2000 to May 2020 in the English language were included. For epidemiological outcomes analysis, a meta-analysis on data regarding AKI incidence, mortality, and proportion of kidney replacement therapy was performed and an overall pooled estimate was calculated using the random-effects model. Other sections were created highlighting pathophysiology, novel biomarkers, changing definitions of AKI, evolving tools for AKI diagnosis, and various management modalities. AKI is a common condition seen in hospitalized children and the diagnosis and management have shown to be quite a challenge. However, new standardized definitions, advancements in diagnostic tools, and the development of novel management modalities have led to increased survival benefits in children with AKI. IMPACT: This review highlights the recent innovations in the field of AKI, especially in regard to epidemiology, pathophysiology, novel biomarkers, diagnostic tools, and management modalities.
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Injúria Renal Aguda , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-NascidoRESUMO
BACKGROUND: Invasive mucormycosis (IM) is a life-threatening fungal infection occurring mostly in solid organ transplant (SOT) recipients, patients with hematological malignancies, and diabetes. A sudden spurt of mucormycosis has been reported in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in India; however, there is little data about coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) in kidney transplant recipients (KTRs). METHODS: We describe the clinical presentations, risk factors, treatment and outcomes of 11 mucormycosis cases in KTRs post-COVID-19 infection from February 2020 to June 2021 at a single center in India. RESULTS: Mucormycosis was seen in 11/102 (10.7%) KTRs during the pandemic. Six patients had mild disease and rest five had moderate disease. Seven patients had pre-existing diabetes mellitus and four developed new onset hyperglycemia after receiving steroids for COVID-19 infection. All had poorly controlled sugars at the time of presentation. Most common presentation was rhino-orbital-cerebral mucormycosis (ROCM) in 10/11 (89%) patients and one has pulmonary mucormycosis. All patients received combination of amphotericin B and surgical debridement/excision of affected tissue followed by posaconazole prophylaxis. Nine patients recovered, however two patients succumbed to their illness after median of 14 (7-21) days from diagnosis. One patient developed acute T-cell-mediated rejection during the course of recovery. At last follow up, the mean serum creatinine was 2.05 mg/dl as compared to 1.4 mg/dl at presentation. CONCLUSIONS: IM is a common fungal infection in transplant recipients in India after COVID-19. Early diagnosis and prompt treatment with combination of surgical debridement and liposomal amphotericin B are key to better outcomes in CAM. Judicious use of steroids and control of hyperglycemia is key to avoid flaring up of the fungal infection.
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COVID-19 , Infecções Oculares Fúngicas , Transplante de Rim , Mucormicose , Doenças Orbitárias , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Transplante de Rim/efeitos adversos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/tratamento farmacológico , Fatores de Risco , SARS-CoV-2 , TransplantadosRESUMO
BACKGROUND AND OBJECTIVES: Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical hemolytic uremic syndrome. We have conducted a systematic review on the aHUS biomarkers: C3, C5a, C5b-9, factor B, complement factor B, H, and I, CH50, AH50, D-dimer, as well as anti-CFH antibodies. METHODS: An exhaustive literature search was conducted for aHUS patient population plasma/serum, collected/reported at the onset of diagnosis. A total of 60 studies were included with the data on 837 aHUS subjects, with at least one biomarker reported. RESULTS: The biomarkers C3 [mean (SD): 72.1 (35.0), median: 70.5 vs. reference range: 75-175 mg/dl, n = 752]; CH50 [28.3 (32.1), 24.3 vs. 30-75 U/ml, n = 63]; AH50 [27.6% (30.2%), 10% vs. ≥ 46%, n = 23]; and CFB [13.1 (6.6), 12.4, vs. 15.2-42.3 mg/dl, n = 19] were lower among aHUS subjects as compared with the reference range. The biomarkers including C4 [mean (SD): 20.4 (9.5), median: 20.5 vs. reference range: 14-40 mg/dl, n = 343]; C4d [7.2 (6.5), 4.8 vs. ≤ 9.8 µg/ml, n = 108]; CFH [40.2 (132.3), 24.5 vs. 23.6-43.1 mg/dl, n = 123 subjects]; and CFI [8.05 (5.01), 6.55 mg/dl vs. 4.4-18.1 mg/dl, n = 38] were all observed to be within the reference range among aHUS subjects. The biomarkers C5a [mean (SD): 54.9 (32.9), median: 48.8 vs. reference range: 10.6-26.3 mg/dl, n = 117]; C5b-9 [466.0 (401.4), 317 (186-569.7) vs. ≤ 250 ng/ml, n = 174]; Bb [2.6 (2.1), 1.9 vs. ≤ 1.6 µg/ml, n = 77] and D-dimer [246 (65.05), 246 vs. < 2.2 ng/ml, 2, n = 2 subjects] were higher among patients with aHUS compared with the reference range. CONCLUSION: If a comprehensive complement profile were built using our data, aHUS would be identified by low levels of C3, CH50, AH50, and CFB along with increased levels of C5a, C5b-9, Bb, anti-CFH autoantibodies, and D-dimer. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Síndrome Hemolítico-Urêmica Atípica , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Autoanticorpos , Biomarcadores , Fator B do Complemento , Fator H do Complemento , Complexo de Ataque à Membrana do Sistema Complemento , HumanosRESUMO
Renal cystic disease encompasses a large variety of illnesses with various phenotypic expressions that can manifest in utero, in infancy, and in childhood. These diseases may be unilateral or bilateral and present with single or multiple cysts. Various cystic diseases may also progress to chronic kidney disease (CKD), including kidney failure, and hepatic disease, thus potentially being life threatening. The prevalence and serious complications of CKD in the pediatric population make it vital that health care providers detect these conditions early and provide effective management. This installment of AJKD's Core Curriculum in Nephrology discusses various genetic and sporadic kidney cystic diseases, including multicystic dysplastic kidney, nephronophthisis, cystic dysplasia, hepatocyte nuclear factor 1-ß (HNF1-ß) nephropathy, Bardet-Biedl syndrome, Meckel-Gruber syndrome, Zellweger syndrome, calyceal diverticulum, autosomal recessive polycystic kidney disease (ARPKD), and autosomal dominant polycystic kidney disease (ADPKD). This article discusses the epidemiology, genetics and pathophysiology, diagnosis, presentation, and management for each of these renal cystic diseases, with particular attention to prenatal care and pregnancy counseling.
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Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/terapia , Currículo , Humanos , Recém-Nascido , Nefrologia/educaçãoRESUMO
OBJECTIVES: To study the clinical profile and risk factors of cerebral edema and acute kidney injury in children with diabetic ketoacidosis. DESIGN: Retrospective review of medical records. PATIENTS: Fifty consecutive patients (age <18 years) admitted to our pediatric intensive care unit with a diagnosis of diabetic ketoacidosis over 5 years. MATERIALS AND METHODS: Retrospective analysis of medical records was done, and data including patients' age, sex, presenting features, biochemical profile including blood glucose, osmolality, urea, creatinine, and venous blood gas, electrolytes were recorded at admission, at 12 and 24 hours. Treatment details including fluid administration, rate of fall of glucose, time to resolution of diabetic ketoacidosis were noted. Complications such as cerebral edema and acute kidney injury were recorded. Patients with and without cerebral edema and acute kidney injury were compared. Variables that were significant on univariate analysis were entered in a multiple logistic regression analysis to determine the independent predictors for cerebral edema and acute kidney injury. Odds ratio and 95% confidence interval were calculated using SPSS version 22. MEASUREMENTS AND MAIN RESULTS: Between November 2015 and 2020, 48 patients were admitted for a total of 50 episodes of diabetic ketoacidosis. Two patients had recurrent diabetic ketoacidosis. Median age was 9.5 years (range 1-17). Thirty-one patients (62%) had new-onset type I diabetes mellitus. Twenty-two patients (44%) presented with severe diabetic ketoacidosis. Cerebral edema and acute kidney injury were seen in 11 (22%) and 15 (30%) patients, respectively. On multiple logistic regression analysis, higher blood urea level, lower serum bicarbonate level, and higher corrected sodium levels at admission were identified to be variables independently associated with risk of cerebral edema. CONCLUSIONS: Higher corrected sodium, higher urea level, and lower serum bicarbonate levels at admission are predictive of cerebral edema in patients presenting with diabetic ketoacidosis. The severity of dehydration and acidosis in DKA appears to be a common factor responsible for the development of dysfunction of both brain and kidney. HOW TO CITE THIS ARTICLE: Raghunathan V, Jevalikar G, Dhaliwal M, Singh D, Sethi SK, Kaur P, et al. Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis. Indian J Crit Care Med 2021;25(12):1446-1451.
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The intrinsic similarity shared between the members of the complement factor H family, which comprises complement factor H and five complement factor H-related (CFHR) genes, leads to various recombination events. In turn these events lead to deletions of some genes or abnormal proteins, which are found in patients with atypical hemolytic uremic syndrome or C3 glomerulopathies. Here we describe a novel genetic rearrangement generated from a heterozygous deletion spanning 146 Kbp involving multiple CFHR genes leading to a CFHR1-R5 hybrid protein. This deletion was found in four family members presenting with a familial dominant glomerulopathy histologically classified as an overlap of dense deposit disease and C3 glomerulonephritis. Affected patients exhibited permanently low C3 and factor B levels and high amounts of activation fragments sC5b9 and Bb, indicating a systemic alternative pathway dysregulation. The abnormal protein, characterized by Western blot and immunoprecipitation, was shown to circulate in association with CFHR1 and CFHR2, attributable to its two N-terminal dimerization motifs. The presence of this protein is associated with a perturbation of Factor H activity on the C3 convertase decay. Thus, our study highlights the role of CFHRs in the physiopathology of C3 glomerulopathies and stresses the importance of screening CFHRs in all familial C3 glomerulopathies. Such hybrids described till now were always associated with familial forms.
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Síndrome Hemolítico-Urêmica Atípica/genética , Complemento C3/análise , Proteínas Inativadoras do Complemento C3b/genética , Proteínas do Sistema Complemento/genética , Glomerulonefrite Membranoproliferativa/genética , Adulto , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/patologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Criança , Convertases de Complemento C3-C5/metabolismo , Fator B do Complemento/análise , Fator H do Complemento/metabolismo , Via Alternativa do Complemento/genética , Feminino , Fusão Gênica , Rearranjo Gênico , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite Membranoproliferativa/terapia , Humanos , Lactente , Rim/patologia , Masculino , Linhagem , Deleção de SequênciaRESUMO
BACKGROUND: Removal of anti-ABO is an important component of the preconditioning regimen for ABO-incompatible (ABOi) renal transplant. Cascade plasmapheresis (CP) is one of the extracorporeal methods of antibody removal, others being conventional plasma exchange (PE) and immunoadsorption. There is no previous published experience with CP in this context. The purpose of this study was to present an early experience with this approach. STUDY DESIGN AND METHODS: Consecutive ABOi renal transplant recipients in whom CP was used for pre- and posttransplant anti-ABO removal were included. All the patients received intravenous rituximab 2 weeks before transplant. After 1 week, CP was started along with oral tacrolimus and mycophenolate sodium. Alternate-day CP was done to attain immediate pretransplant antibody titer of not more than 8. RESULTS: Fifteen ABOi renal transplant recipients had baseline (pretreatment) antibody titers ranging from 16 to 512. Desensitization rate was 100%. The mean number of procedures before transplant to achieve titer of not more than 8 was 3.27 ± 1.39. Patient survival was 93% and death-censored graft survival was 87%. Biopsy-proven acute rejection was seen in three patients (20%), one (6.67%) being acute antibody mediated rejection. The complication rate during CP was 4% and two patients had bleeding complication after surgery. Posttransplant infection rate was 13%. CONCLUSION: Based on limited number of patients, we conclude that CP is a safe and effective extracorporeal method for pretransplant ABO antibody removal in patients undergoing ABOi transplant. Patients undergoing CP met target preoperative antibody titers and the clinical outcomes were acceptable.
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Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Transplante de Rim/métodos , Plasmaferese/métodos , Insuficiência Renal Crônica/terapia , Condicionamento Pré-Transplante/métodos , Sistema ABO de Grupos Sanguíneos/sangue , Adulto , Idoso , Incompatibilidade de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/mortalidade , Criança , Feminino , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Plasmaferese/efeitos adversos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/mortalidade , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked multi-systemic disorder, almost always characterized by the triad of congenital cataract, cognitive and behavioral impairment and a proximal tubulopathy. METHODS: Twenty-eight novel patients with suspected Lowe syndrome were studied. RESULTS: All patients carried OCRL gene defects with mutational hot spots at CpG dinucleotides. Mutations previously unknown in Lowe syndrome were observed in ten of the 28 patients, and carriership was identified in 30.4 % of the mothers investigated. Mapping the exact breakpoints of a complete OCRL gene deletion revealed involvement of several flanking repeat elements. We noted a similar pattern of documented clinically relevant symptoms, and even though the patient cohort comprised relatively young patients, 32 % of these patients already showed advanced chronic kidney disease. Thrombocytopenia was seen in several patients, and hyperosmia and/or hyperacusis were reported recurrently. A p.Asp523Asn mutation in a Polish patient, associated with the typical cerebrorenal spectrum but with late cataract (10 year), was also evident in two milder affected Italian brothers with ocular involvement of similar progression. CONCLUSIONS: We have identified clinical features in 28 patients with suspected Lowe syndrome that had not been recognized in Lowe syndrome prior to our study. We also provide further evidence that OCRL mutations cause a phenotypic continuum with selective and/or time-dependent organ involvement. At least some of these mutants might exhibit a genotype-phenotype correlation.
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Mutação , Síndrome Oculocerebrorrenal/diagnóstico , Síndrome Oculocerebrorrenal/genética , Monoéster Fosfórico Hidrolases/genética , Adolescente , Catarata/diagnóstico , Catarata/genética , Criança , Pré-Escolar , Pontos de Quebra do Cromossomo , Ilhas de CpG , Análise Mutacional de DNA , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Hereditariedade , Heterozigoto , Humanos , Hiperacusia/diagnóstico , Hiperacusia/genética , Índia/epidemiologia , Lactente , Masculino , Síndrome Oculocerebrorrenal/epidemiologia , Linhagem , Fenótipo , Valor Preditivo dos Testes , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Fatores de Tempo , Adulto JovemRESUMO
Mutations in the HNF-1ß gene have been found to be associated with renal cysts and diabetes syndrome (RCAD), also known as MODY5. The mutation is inherited in an autosomal dominant fashion, although sporadic mutations can be seen. Pediatric cases of HNF - 1ß mutations are more likely to present with renal involvement like renal failure or renal hypoplasia. In young individuals, the detection of renal abnormalities usually pre-date the diagnosis of diabetes with a mean age of 24 years. We report a 5 year old, end stage kidney disease patient with renal cysts and hypertriglyceridemia (in the absence of overt diabetes) with a known pathogenic mutation in the Hepatocyte Nuclear Factor-1ß (HNF-1ß) gene on chromosome 17q12. This case expands the clinical spectrum of HNF-1ß mutation disorders with a take home message, that end stage renal disease patients with unexplained hypertriglyceridemia (even in absence of diabetes mellitus) should alert a clinician for HNF-1ß mutational analysis.
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Background: The role of induction in low-risk, living-donor kidney transplants being treated with tacrolimus, mycophenolate mofetil, and prednisolone is debatable. Materials and Methods: This was a retrospective study that consisted of patients undergoing living kidney transplantation between February 2010 and June 2021 with a related haplomatch donor, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil, and prednisolone. High-risk transplants, such as second or more transplants, immunologically incompatible transplants, and steroid-free transplants, were excluded. Patients were divided into three groups: no induction, basiliximab induction, and thymoglobulin induction, and the outcomes of all three were compared. Results: A total of 350 transplants were performed. There was a significant difference in the recipient sex distribution (P = 0.0373) and the number of preemptive transplants (P = 0.0272) between the groups. Other parameters were comparable. Biopsy-proven acute rejection (BPAR) was significantly less frequent in the thymoglobulin group than in the no-induction (5.3% vs. 17.5%; P = 0.0051) or basiliximab (5.3% vs. 18.8%; P = 0.0054) group. This persisted even after we performed multivariate regression analysis (thymoglobulin vs. no-induction group, P = 0.0146; thymoglobulin vs. basiliximab group, P = 0.0237). There was no difference in BPAR between the basiliximab and no-induction groups. There were no differences in other outcomes between the groups. Conclusion: In a low-risk haplomatch, related, living-donor kidney transplant on tacrolimus, mycophenolate mofetil, and prednisolone, BPAR was significantly lower with thymoglobulin as opposed to no induction or basiliximab induction with a similar short-term patient and death-censored graft survival and infection rates. Basiliximab did not provide any benefit over no induction.
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BACKGROUND: Nutrition plays a vital role in the outcome of critically ill children, particularly those with AKI. Currently, there are no established guidelines for children with AKI treated with continuous RRT (CRRT). A thorough understanding of the metabolic changes and nutritional challenges in AKI and CRRT is required. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with AKI receiving CRRT. METHODS: PubMed, MEDLINE, Cochrane, and Embase databases were searched for articles related to the topic. Expertise of the authors and a consensus of the workgroup were additional sources of data in the article. Available articles on nutrition therapy in pediatric patients receiving CRRT through January 2023. RESULTS: On the basis of the literature review, the current evidence base was examined by a panel of experts in pediatric nephrology and nutrition. The panel used the literature review as well as their expertise to formulate clinical practice points. The modified Delphi method was used to identify and refine clinical practice points. CONCLUSIONS: Forty-four clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with AKI and on CRRT on the basis of the existing literature and expert opinions of a multidisciplinary panel.
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Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Humanos , Criança , Consenso , Estado Terminal/terapia , Injúria Renal Aguda/terapia , Estado NutricionalRESUMO
OBJECTIVES: Nutrition plays a vital role in the outcome of critical illness in children, particularly those with acute kidney injury. Currently, there are no established guidelines for children with acute kidney injury treated with continuous kidney replacement therapy. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with acute kidney injury receiving continuous kidney replacement therapy. METHODS: An electronic search using PubMed and an inclusive academic library search (including MEDLINE, Cochrane, and Embase databases) was conducted to find relevant English-language articles on nutrition therapy for children (<18 y of age) receiving continuous kidney replacement therapy. RESULTS: The existing literature was reviewed by our work group, comprising pediatric nephrologists and experts in nutrition. The modified Delphi method was then used to develop a total of 45 clinical practice points. The best methods for nutritional assessment are discussed. Indirect calorimetry is the most reliable method of predicting resting energy expenditure in children on continuous kidney replacement therapy. Schofield equations can be used when indirect calorimetry is not available. The non-intentional calories contributed by continuous kidney replacement therapy should also be accounted for during caloric dosing. Protein supplementation should be increased to account for the proteins, peptides, and amino acids lost with continuous kidney replacement therapy. CONCLUSIONS: Clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with acute kidney injury and on continuous kidney replacement therapy based on the existing literature and expert opinions of a multidisciplinary panel.
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Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Estado Terminal , Avaliação Nutricional , Humanos , Injúria Renal Aguda/terapia , Estado Terminal/terapia , Criança , Terapia de Substituição Renal Contínua/métodos , Estado Nutricional , Pré-Escolar , Adolescente , Terapia de Substituição Renal/métodos , Calorimetria Indireta/métodos , Técnica DelphiRESUMO
During the coronavirus disease 2019 (COVID-19) pandemic, acute kidney injury (AKI) was a common sequela of COVID-19 infection and predicted disease severity and mortality. Extracorporeal blood purification techniques involving blood filtration devices are an emerging treatment for AKI in the setting of severe COVID-19 infections. In this review, we discuss potential mechanisms for the development of AKI in COVID-19 patients as well as the various available blood filtration devices and the role they may play in managing the AKI in COVID-19 patients. A total of seven blood filters currently available were compared based on their potential in treating AKI in COVID-19 patients. Blood filtration devices show potential as an emerging treatment modality for COVID-19-induced AKI, but further clinical trials are necessary before their widespread adoption and usage.
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Exploration into the causes of hereditary renal cystic diseases demonstrates a deep-rooted connection with the proteomic components of the cellular organelle cilia. Cilia are essential to the signaling cascades, and their dysfunction has been tied to a range of renal cystic diseases initiating with studies on the oak ridge polycystic kidney (ORPK) mouse model. Here, we delve into renal cystic pathologies that have been tied with ciliary proteosome and highlight the genetics associated with each. The pathologies are grouped based on the mode of inheritance, where inherited causes that result in cystic kidney disease phenotypes include autosomal dominant and autosomal recessive polycystic kidney disease, nephronophthisis (Bardet-Biedl syndrome and Joubert Syndrome), and autosomal dominant tubulointerstitial kidney disease. Alternatively, phakomatoses-, also known as neurocutaneous syndromes, associated cystic kidney diseases include tuberous sclerosis (TS) and Von Hippel-Lindau (VHL) disease. Additionally, we group the pathologies by the mode of inheritance to discuss variations in recommendations for genetic testing for biological relatives of a diagnosed individual.
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Lecithin-cholesterol acyltransferase (LCAT) is a liver enzyme necessary for the formation of cholesteryl esters in plasma from free cholesterol. The rare autosomal recessive disease resulting from familial deficiency of this enzyme can lead to nephropathy with kidney involvement generally being the most common cause of death. In addition, the disease process can engender corneal opacity, very low high-density lipoprotein, normochromic anemia, and nephropathy. We present this case of a 35-year-old male who initially visited for a second opinion for renal failure and nephrotic range proteinuria. He underwent renal biopsy which displayed focal segmental glomerulosclerosis-type injury pattern and was started on futile high-dose steroid therapy. A second renal biopsy coincided with the development of corneal opacity leading to a confirmatory testing of LCAT deficiency through biochemistry panel.
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Opacidade da Córnea , Nefropatias , Deficiência da Lecitina Colesterol Aciltransferase , Síndrome Nefrótica , Masculino , Humanos , Adulto , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Lipoproteínas VLDL , Opacidade da Córnea/diagnóstico , Opacidade da Córnea/etiologia , Deficiência da Lecitina Colesterol Aciltransferase/complicações , Deficiência da Lecitina Colesterol Aciltransferase/diagnóstico , Nefropatias/complicações , Lipoproteínas HDLRESUMO
[This corrects the article DOI: 10.3389/fped.2021.833205.].
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Pediatric acute kidney injury (AKI) is a frequently missed complication. AKI has a significant impact on both short- and long-term outcomes in children. Within the last decade, there have been major landmark developments in this field of critical care pediatric nephrology. The topic was searched by two independent researchers using Google Scholar and PubMed and related studies published in the last 10 years. The terms used for the search were 'pediatric acute kidney injury,' 'pediatric acute renal failure,' 'pediatric dialysis,' 'biomarkers,' 'nephrotoxins,' 'nephrotoxicity in children,' and 'pediatric critical care nephrology.' We found that AKI is common in critically ill neonates and children. Among the various definitions, the Kidney Disease: Improving Global Outcomes (KDIGO) definition is most commonly used. In addition, it is imperative to risk stratify sick children at admission in the hospital to predict AKI and worse outcomes as this aids in early management. There are now major landmark trials that describe the epidemiology, prevention, and management guidelines in this field and health care professionals need to be aware they should diagnose AKI early. Overall, this review highlights the landmark studies in the last decade and shows that early diagnosis and management of AKI in 'at risk' children can improve outcomes.
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Acute kidney injury continues to be a highly occurring disease in the intensive care unit, specifically affecting up to a third of critically ill neonates as per various studies. Although first-line treatments of acute kidney injury are noninvasive, kidney replacement therapy (KRT) is indicated when conservative management modes fail. There are various modalities of KRT which can be used for neonatal populations, including peritoneal dialysis, hemodialysis, and continuous KRT. However, these KRT modalities present their own challenges in this specific patient population Thus, it is the aim of this review to introduce each of these KRT modalities in terms of their challenges, advances, and future directions, with specific emphasis on new technology including the Cardio-Renal Pediatric Emergency Dialysis Machine, Newcastle infant dialysis and ultrafiltration system, and the Aquadex system for ultrafiltration.