Muralikrishna Gangadharan Komala

Hereditary thrombotic thrombocytopenic purpura (TTP) is a rare autosomal recessive disorder caused by ADAMTS13 deficiency, typically presenting in childhood or early adulthood. We describe an atypical presentation of hereditary TTP in a 55-year-old man presenting with AKI on a background of diabetic kidney disease, without suggestive history or identifiable triggers. Initial evaluation revealed features of thrombotic microangiopathy (TMA), including hemolysis, thrombocytopenia, with preserved coagulation parameters. Presumptive complement-mediated TMA was treated with eculizumab; however, the patient progressed to dialysis dependence and developed transient neurologic symptoms. ADAMTS13 activity was reduced (8 U/dl) without a detectable inhibitor, prompting treatment with fresh frozen plasma (FFP), which resulted in hematologic and neurologic improvement. Kidney biopsy demonstrated acute TMA superimposed on advanced diabetic and vascular disease. Genetic testing identified a heterozygous pathogenic ADAMTS13 variant (c.587C>T; p.Thr196Ile) without a second pathogenic allele. Additional long-read sequencing detected polymorphisms that may be associated with reduced ADAMTS13 activity; however, current evidence suggests that these are variants of unknown significance. Although these variants have been associated with variation in ADAMTS13 levels in population or functional studies, the contribution of the additional variants remains uncertain. Functional response to FFP with transient correction of ADAMTS13 levels supported a diagnosis of hereditary TTP. The patient was commenced on regular FFP infusions and has been stable without further hematologic or neurologic events. He remains dialysis dependent, awaiting kidney transplantation. This case highlights a late-onset, atypical presentation of hereditary TTP and raises important questions regarding the pathogenicity of heterozygous variants and modifying polymorphisms. It underscores the need to consider ADAMTS13 deficiency in unexplained TMA and kidney failure, even in the absence of classic features or biallelic mutations.

Background: The blockade of immune regulatory sites, cytotoxic T-lymphocyte antigen 4, programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) with immune checkpoint inhibitors has revolutionized survival outcomes in patients with cancer. However, immune checkpoint inhibitors are associated with a range of immune-related adverse events. The aim of this network meta-analysis was to evaluate severe adverse kidney events in patients with oncological or hematological malignancy receiving monotherapy, dual therapy, or combined therapy treatment with immune checkpoint inhibitors when compared with either placebo or standard chemotherapy. Methods: Phase 3 randomized control trials reporting severe grade (3–5) adverse kidney events were identified across five electronic databases from inception to May 2022. This was supplemented with hand searching of medical journals and the National Clinical Trials registry. A Bayesian network meta-analysis was performed for AKI, hypertension, CKD, and the composite of all acute kidney adverse events. The results are reported as per the PRISMA guidelines. Results: Ninety-five randomized control trials reported severe grade adverse kidney events. The risk of developing severe AKI is higher among patients who received PD-1 plus chemotherapy (odds ratio [OR], 1.8; 95% credible interval [CrI], 1.4 to 2.5) and PD-L1 plus chemotherapy (OR, 1.8; 95% CrI, 1.2 to 2.7) compared with standard chemotherapy and placebo (94 studies, 63,357 participants). The risk of developing the composite of all severe acute kidney adverse events is higher among patients who received PD-1 plus chemotherapy (OR, 1.6; 95% CrI, 1.1 to 2.3) and PD-L1 plus chemotherapy (OR, 1.7; 95% CrI, 1.1 to 2.8) when compared with standard chemotherapy and placebo (95 studies, 63,973 participants). Conclusions: The combined regimen of PD-1 plus chemotherapy and PD-L1 plus chemotherapy was associated with higher incidence of severe AKI and the composite of all severe acute kidney adverse events. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_07_10_CJN0000000000000160.mp3

Increased numbers of patients with chronic conditions use nutraceuticals or food-based therapeutics. However, to date, there is no global consensus on the regulatory processes for nutraceuticals. With the increased use, issues of quality and safety have also arisen. This review summarises the current regulations held for nutraceuticals in the USA, European and Australian jurisdictions using regulatory authority sites and databases. The efficacy and safety concerns, product development, gaps in regulation and challenges in ensuring product authenticity are also summarised. The data highlight the complexity that the globalisation of nutraceuticals brings with respect to challenges in regulation and associated claims regarding efficacy and safety. The development of an effective system with integrity is needed to increase vertical collaboration between consumers, healthcare practitioners, and government agencies and the development of international risk assessment criteria and botanical compendia. This will help in greater transparency and improved trust in the process and products. Emerging technologies could play a role in improving systems engineering by information sharing and leveraging the strengths of different countries. In conclusion, nutraceuticals have been poorly regulated leading to spurious claims based on little or no real evidence. This makes it difficult to separate meaningful results from poor data. More stringent regulation and an effective system of integrity are required to ensure efficacy and safety and enable the adequate monitoring and increase consumer and healthcare professionals’ confidence.

The newer antidiabetic medications have revolutionized management of diabetes. These include the sodium–glucose cotransporter 2 (SGLT2) inhibitors and the long-

Background: Sarcopenia is associated with significant morbidity and mortality in patients with chronic kidney disease. The prevalence of sarcopenia in the dialysis population varies from 4% to 63%. However, the prevalence and risk factors of sarcopenia in the Australian dialysis population remain uncertain. Aim: To study the prevalence of sarcopenia in patients on maintenance dialysis by using the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria of sarcopenia and to identify associated risk factors. Methods: We evaluated adult patients on maintenance haemodialysis and peritoneal dialysis in this single-centre cross-sectional study in Australia. Patient’s clinical (age, gender, dialysis modality and diabetic status) and laboratory parameters (serum albumin, calcium, phosphate, 25-hydroxy-vitamin D and parathyroid hormone levels) were investigated. We employed bioimpedance spectroscopy, hand grip dynamometer and the timed up and go test (TUG) to evaluate muscle mass, strength and function, respectively. Results: We evaluated 39 dialysis patients with a median age of 69 years old. The prevalence of sarcopenia was 18%. Sarcopenia was associated with low serum albumin (p = 0.02) and low serum phosphate level (p = 0.04). Increasing age and female sex were potential risk factors for sarcopenia (p = 0.05 and 0.08, respectively). Low lean muscle mass, reduced hand grip strength and prolonged TUG were present in 23.1%, 41% and 40.5%, respectively, of the cohort. The hand grip test had good correlation with lean muscle evaluation and the TUG. Conclusions: Sarcopenia was prevalent in 18% of maintenance haemodialysis patients from an Australian single-centre cohort, with low serum albumin and phosphate as significant risk factors.

We describe the clinical course and response to treatment of atypical haemolytic uraemic syndrome (aHUS) in two sisters presenting to our hospital 6 years apart with a novel complement factor H mutation that has not been described previously in literature and demonstrates the genetic complexity of this ultra-rare disease. The contrast in course and outcome of disease between the two sisters highlights the rapid evolution of management of aHUS, the importance of rapidly establishing a diagnosis, and how minimizing time to eculizumab therapy significantly reduces associated morbidity and mortality.

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.