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Deficiency of Complement Factor H Related (CFHR) plasma proteins and Autoantibody Positive Hemolytic Uremic Syndrome (DEAP-HUS) is a subtype of atypical hemolytic uremic syndrome, known to be associated with significant morbidity. Its pathogenesis is linked to the production of IgG autoantibodies against complement factor H, a regulator of the alternative complement pathway. The binding of the autoantibodies to the C terminal of complement factor H interferes with its regulatory function, leading to increased activation of the alternative complement pathway and consequent endothelial cellular damage. Early diagnosis and initiation of appropriate therapy is reported to lead to favorable outcomes. Institution of plasma exchange therapy within 24 h of diagnosis has been shown to rapidly lower antibody levels, leading to clinical improvement. Adjunctive immunosuppression therapy suppresses antibody production and helps in maintaining long-term clinical remission of the disease. Available data advocates a treatment regimen that combines plasma therapy (preferably plasma exchange) and immunosuppression to halt disease process and sustain long-term disease remission., Author(s): Franca Iorember [sup.1] , Anjali Nayak [sup.1] Author Affiliations: (1) grid.417276.1, 0000 0001 0381 0779, Division of Nephrology, Phoenix Children's Hospital, , Phoenix, AZ, USA Introduction Hemolytic uremic syndrome [...]

Background Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients. Methods We examined seven patients with treatment-refractory C4d + AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and anti-metabolite. Estimated glomerular filtration rate (eGFR) calculated by the Schwartz equation, biopsy findings assessed by 2013 Banff criteria, and human leukocyte antigen (HLA) donor-specific antibodies (DSA) performed using the Luminex single antigen bead assay were monitored pre- and post- bortezomib therapy. Results Seven patients (86 % male, 86 % with [greater than or equal to]6/8 HLA mismatch, and 14 % with pre-formed DSA) age 5 to 19 (median 15) years developed refractory C4d + AMR between 1 and 145 (median 65) months post-transplantation. All patients tolerated bortezomib. One patient had allograft loss. Of the six patients with surviving grafts (86 %), mean pre-bortezomib eGFR was 42 ml/min/1.73 m.sup.2 and the mean 1 year post-bortezomib eGFR was 53 ml/min/1.73 m.sup.2. Five of seven (71 %) had improvement of histological findings of AMR, C4d staining, and/or acute cellular rejection. Reduction in HLA DSAs was more effective for class I than class II. Conclusions Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric kidney transplant patients with refractory C4d + AMR., Author(s): Meghan H. Pearl[sup.1] , Anjali B. Nayak[sup.1] , Robert B. Ettenger[sup.1] , Dechu Puliyanda[sup.2] , Miguel Fernando Palma Diaz[sup.3] , Qiuheng Zhang[sup.3] , Elaine F. Reed[sup.3] , Eileen W. [...]

Background Kidney transplantation is the treatment of choice for end-stage renal disease. However, since pediatric patients have long projected life-years, it is also optimal for them to get well-matched transplants to minimize long-term sensitization. In North America, pediatric kidney transplantation is largely dependent upon the use of deceased donor organs, making it challenging to identify timely, well-matched transplants. Pediatric recipients may have willing living donors who are either HLA- or ABO-incompatible (ABOi); therefore, one solution is to utilize ABOi transplants and paired exchange programs to enhance HLA matching and living donation. Case-diagnosis/treatment We adopted this approach for a highly sensitized patient with cPRA 90 %, who received a successful ABOi paired exchange transplant. The recipient received pre-transplant immunomodulation until an acceptable isohemagglutinin titer Conclusions This case highlights the safety and efficacy of using paired exchange in combination with ABOi transplants in pediatric kidney transplantation to optimize HLA matching, minimize wait times, and enhance allograft survival., Author(s): Anjali B. Nayak[sup.5] , Robert B. Ettenger[sup.1] , Suzanne McGuire[sup.2] , Gerald S. Lipshutz[sup.2] , Elaine F. Reed[sup.3] , Jeffrey Veale[sup.4] , Eileen W. Tsai[sup.1] Author Affiliations: (1) Department [...]

Background Exposure to gadolinium-based contrast agents (GBCA) in patients with chronic kidney disease (CKD) has been associated with the development of a potentially fatal disorder, nephrogenic systemic fibrosis (NSF). Although contrast-enhanced computed tomography (CT) is an alternative to magnetic resonance imaging (MRI), it carries the risk of radiation exposure and further reduction of residual renal function. Therefore we sought to assess the feasibility of ferumoxytol as an alternative to GBCA for contrast-enhanced MR angiography (MRA) in a pediatric cohort with CKD. Ferumoxytol is a parenteral iron supplement that contains ultrasmall superparamagnetic iron oxide (USPIO) and is a potent relaxivity agent for MRI. Methods We describe the MRI findings in ten pediatric patients who needed detailed vascular mapping. Ferumoxytol (4 mg/kg) was administered intravenously for contrast-enhanced MRA. The patients tolerated the procedure without complications. Results Resulting studies were highly diagnostic and were pivotal in guiding patient management. The images were notable for clear delineation of multiple vascular occlusions. Conclusions Given the concerns associated with the use of GBCAs in renal failure, ferumoxytol is an excellent alternative contrast agent in pediatric end stage renal disease (ESRD) patients. Future studies are needed in order to further evaluate safety and efficacy of ferumoxytol in this patient population. Keywords Children * Chronic kidney disease * Ferumoxytol * Vascular imaging, Introduction Pediatric patients with chronic kidney disease (CKD) require detailed vascular imaging as a prelude to line placement as well as renal transplantation. Contrast-enhanced magnetic resonance venography and arteriography (ceMRV [...]

Providing safe drinking water for the entire world's population is essential for ensuring sustainable development. The presence of harmful compounds in aquifers, majorly toxic elements, is a serious environmental concern around the globe. This research aimed to quantify for the initial period the amounts of toxic elements in freshwater in the Dehradun Industrial Region of Uttrakhand, India, as well as the associated health risks. The PTEs (potentially toxic elements) Fe, Cd, Mn, Cu, Cr and Pb, Zn, Ni is measured by AAS and compared to BIS and WHO requirements for drinking safety. The order of mean trace element values in all groundwater samples were determined as Fe > Zn > Cu > Ni > Co > Cd > Pb. HPI was discovered to be higher than high class during the research period (HPI > 30), but under the severe contamination criterion of 100. Iron's MI and PI values were consistently over the threshold limit during the research period, and certain toxic elements were discovered exceptionally near the threshold limit, indicating a severe future influence on groundwater quality. According to PCA (principal component analysis), CM (correlation matrix), and potential health hazard, maximum levels of toxic elements in groundwater in the Dehradun region are attributed to land use patterns, anthropogenic activity, industrial activity, fertilizer and pesticide leaching, and residential waste into the aquifer system. The findings of this study could aid local planners and policymakers in preventing health risks from contaminated aquifers through the deployment of suitable monitoring and mitigation measures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Groundwater pollution of the watershed is mainly influenced by the multifaceted interactions of natural and anthropogenic process. To analyse the spatial-temporal variation and pollution source identification and apportionment, the dataset was subjected to a globally acknowledged coherent technique using water quality indices and chemometric techniques (principal component analysis (PCA) and cluster analysis. The bulk of the samples tested were below the BIS's permissible levels. Groundwater samples from the pre- and post-monsoon seasons mostly contained the anions HCO - 3  > Cl -  > SO 2- 4  > NO - 3 , while the primary cations were Ca 2+  > Mg 2+  > Na +  > K + . Groundwater was alkaline and hard at most of the sites. According to hydro-geochemical facies and relationships, Piper diagrams, and principal component analysis, weathering, dissolution, leaching, ion exchange, and evaporation were the key mechanisms influencing groundwater quality. The hydrochemical facies classified the groundwater samples into the Ca-Mg-HCO 3 type. For all the sampling locations, PIG was determined to be 0.43, 0.52, 0.47, 0.48, 1.00, and 0.70; respectively. The majority of the test locations fell into the low to medium contamination zone, as determined by the groundwater pollution index (PIG) and contamination index. Three principal components, which together account for 93.8% of the total variance, were identified via PCA. The study's findings confirm the value of these statistical techniques in interpreting and understanding large datasets and offering reliable information to reduce the time and expense of programmes for monitoring and evaluating water quality., Competing Interests: Conflict of interestInapplicable., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)