Background The pathogenesis of autoantibody generation in anti-factor H (FH) antibody associated atypical hemolytic uremic syndrome (aHUS) is unknown and is perhaps triggered by an infectious or environmental agent. We observed an unusual increase of patients with anti-FH antibody associated aHUS coinciding with the second pandemic wave in New Delhi and suspected that SARS-CoV-2 infection might be a potential trigger. Methods We screened for SARS-CoV-2 infection using reverse transcriptase polymerase chain reaction (RT-PCR) and serology in 13 consecutive patients with anti-FH antibody associated aHUS during the past year in New Delhi. Results We report 5 patients, 4–13 years old, who presented with a febrile illness without respiratory symptoms during the second pandemic wave. Of these, 3 patients presented with a relapse 25–85 months following the initial episode of aHUS. SARS-CoV-2 was detected by RT-PCR in 1 patient and by serology in 4 patients (median titer 47.1 cut-off index). Patients had high titers of anti-FH antibodies (median 2,300 AU/ml). Genetic studies, done in 3 of the 5 patients, showed homozygous CFHR1 deletion without other significant genetic abnormalities. Specific management comprised plasma exchanges and oral prednisolone, combined with either cyclophosphamide or mycophenolate mofetil. At median follow-up of 3.3 months, the estimated glomerular filtration rate in 4 patients ranged from 62 to 110 ml/min/1.73 m 2 ; one patient was dialysis-dependent. Conclusion Increased vigilance is required during the pandemic, especially in patients with anti-FH associated aHUS, who might relapse despite quiescent disease for a prolonged period. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information. Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05390-4.

Renal transplantation is associated with abnormalities of the structure and function of the musculoskeletal system. No data are available on bone health in Indian patients with end-stage renal disease (ESRD) and its evolution after transplantation. Consecutive ESRD patients who underwent living donor renal transplantation were studied prospectively. Bone mineral density (BMD) was measured at lumbar vertebrae using quantitative computed tomography (CT) scan before transplantation and after 3 and 6 months. T and Z scores were calculated by comparing with normal control data, and values were correlated with various clinical and biochemical parameters. Of the 56 patients enrolled (mean age, 33.7 years; 47 males), 40 completed the 6-month follow-up. The vertebral trabecular bone density at the time of transplantation was 172±53 mg/cc and the average Z score was 0.26±1.7. There was a significant decline in BMD at 3 months (11.8%; P<0.0001) and 6 months (16%; P<0.0001) after transplantation. Both T and Z scores showed a significant decline at 3 and 6 months. There was a significant decline in intact parathormone (iPTH) levels after transplantation, but 15 (37.5%) patients continued to have raised iPTH 6 months after transplantation. The iPTH levels at 6 months had significant correlation with BMD decline (r=0.43, P=0.006). We conclude that Indian ESRD patients have relatively well-preserved BMD, but the density declines rapidly after transplantation. A significant proportion of patients exhibit persistent hyperparathyroidism 6 months after transplantation, which correlates with bone loss.

Background Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. Methods We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015–2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). Results Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3–14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7–2.0] over 2.0 years (95% CI 1.2–3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8–2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01–0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17–0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02–0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of &lt;9–10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy. Conclusions Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.

Haemolytic uraemic syndrome (HUS) includes the triad of nonimmune haemolytic anaemia, acute kidney injury and thrombocytopenia. 1 Presence of schistocytes in peripheral blood smear, a characteristic finding and diagnostic criteria in HUS, is due to microvascular haemolysis. 2 The International Council for Standardization of Haematology (ICSH) framed guidelines for reporting the presence of schistocytes. 3 However, it still has interobserver bias. 4 Moreover, requirement of expertise for reporting makes it difficult in suburban areas. Automated fragmented RBC count and the derived percentage (FRC %) has been studied in haemolysis due to various clinical conditions like thrombotic microangiopathy (TMA) in post-transplantation and thrombotic thrombocytopenic purpura (TTP). 5,6 However, evaluation of its role in paediatric HUS is scarce. We performed this study to assess the role of automated FRC% in children with HUS.

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