A rare complication of pauci-immune crescentic glomerulonephritis in a child: Answers
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CLINICAL QUIZ
A rare complication of pauci-immune crescentic glomerulonephritis in a child: Answers Sidharth Kumar Sethi 1 & Abhyuday Rana 2 & Shyam Bihari Bansal 2 & Alka Rana 3 & Dinesh Kumar Yadav 2 & Kritika Soni 2 & Marie-Agnès Dragon-Durey 4 & Rupesh Raina 5 & Vijay Kher 2 Received: 22 August 2020 / Accepted: 15 September 2020 # IPNA 2020
Keywords Child . Pauci-immune crescentic glomerulonephritis . Thrombotic microangiopathy . aHUS . Alternative complement pathway . Anti-factor H antibodies . CFHR1 and CFHR3 duplication
Answers 1. Activation of alternative complement pathway should be kept in mind in a selected subset of patients with ANCAnegative pauci-immune crescentic glomerulonephritis (PICGN) who present with hemolysis and thrombocytopenia. 2. Investigations for evaluation of alternative complement pathway genes, anti-factor H antibodies, and multiplex ligation probe amplification for deletions in CFHR genes. 3. Complement blocker eculizumab or plasma exchanges (with plasma as replacement fluid) should be initiated as soon as possible. Plasma exchanges were restarted in the child, but this time, she received plasma replacement instead of albumin. A Both Sidharth Sethi and Abhyuday Rana shall be first authors This refers to the article that can be found at https://doi.org/10.1007/ s00467-020-04784-0. * Sidharth Kumar Sethi [email protected] 1
Pediatric Nephrology, Kidney Institute, Medanta the Medicity, Gurgaon, Haryana 122001, India
2
Kidney Institute, Medanta the Medicity, Gurgaon, Haryana 122001, India
3
Department of Pathology, Medanta the Medicity, Gurgaon, Haryana 122001, India
4
Université de Paris, Hôpital Européen Georges Pompidou, APHP, INSERM UMRS1138, Paris, France
5
Pediatric Nephrology, Akron Children’s Hospital, Cleveland, OH, USA
detailed complement assay yielded anti-factor H antibodies (Table 1) with a titer of 295 A U /L. The decision to start eculizumab therapy was withheld due to monetary constraints. After 5 sessions of total plasma exchanges (TPE) with plasma replacement hemolysis resolved, the patient’s condition improved gradually thereafter (serum creatinine (sCr) stabilized at 2.2 mg/dL; Hb 8.4 g/dL) (Fig. 1), and on achieving hematological remission, she was discharged with advice to continue alternate day TPE, monthly intravenous cyclophosphamide, and daily oral steroids. Repeat anti-factor H antibodies sent on discharge showed a rise of titer to 960 AU /L. She was lost to follow-up and expired 2 months later at home. The clinical exome sequencing report came back later and showed no mutations in genes of complement H, I, B, CD46, thrombomodulin, or DGKE. Multiplex ligation-dependent probe amplification (MLPA) revealed homozygous duplications in CFHR1 and CFHR3 genes with a probe ratio of 1.8–2.17. The duplication involved the upstream region; exons 1, 2, 3, and 6 and intron 4 of CFHR3 gene; and exons 3, 5, and 6 of CFHR1 gene.
Commentary Complement proteins provide an important line of defense, which on activation generates several fragments that have pro-infla
