In the clinical context of end-stage renal disease (ESRD), thrombosis and bleeding risks are simultaneously increased and may have devastating consequences. While anticoagulant and antiplatelet drugs are indispensable for the prevention of thromboembolic events, the significantly higher bleeding risk makes their handling extremely complicated. In ESRD, they are frequently administered for a wide array of conditions. For example, atrial fibrillation is quite common in ESRD and warrants the use of anticoagulants like warfarin. Unfractionated heparin and low molecular weight heparins are typically used for clotting prevention in the hemodialysis extracorporeal circuit. The antithrombotics use dilemma has worsened because ESRD patients have been excluded from major clinical trials that defined standard indications, contraindications and optimal management of these medications. That limits our knowledge and results in that the process of decision-making depends on weaker data. Besides the substantial bleeding risk, warfarin may also increase cardiovascular risk because it is implicated in the pathogenesis of vascular calcifications in ESRD. The present article attempts to offer a comprehensive overview of practical considerations for the use of the most common antithrombotic medications in ESRD linking them, at the same time, to the best available evidence from randomized controlled trials and observational studies.

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Background and Aims C1q nephropathy is an immune glomerular disease in which dominant C1q electron-dense deposits are identified in the mesangium.It commonly presents with nephrotic syndrome, while nephritic syndrome or isolated haematuria are less common. Biopsy findings vary, from no glomerular lesion identified as in minimal change disease (MCD) to focal segmental glomerulosclerosis (FSGS) and immune-mediated proliferative glomerulonephritis. Steroids are the mainstay and other agents have been tried. Rituximab is an anti-CD 20 human/mouse chimeric monoclonal antibody and one of the drugs used in managing C1q nephropathy. We present 3 cases of biopsy-proven C1q nephropathy that presented with nephrotic syndrome. They responded initially to steroids and achieved remission after treatment with rituximab. Method Case Scenarios: Case (1): A 30-year-old man had been diagnosed with steroid sensitive nephrotic syndrome since he was 18 months. Renal biopsy confirmed the diagnosis of C1q nephropathy, more in the spectrum of MCD. He was managed with steroids, and rituximab in 2011 and achieved remission for the last 7 years after 5 doses. His renal function had always remained normal. He presented to our department in 2020 with another relapse and heavy proteinuria (urine protein creatinine ratio (UPCR) was 1300 mg/mmol) but unchanged renal function. Repeat kidney biopsy showed C1q nephropathy in the spectrum of FSGS. He showed good response to oral steroids. On relapse while weaning steroids, Rituximab was considered. He had 2 doses of rituximab of 1 gram 2 weeks apart in July 2021. He achieved full remission over the last 2 years. Case (2): A 77-year-old female presented in 2020 with nephrotic syndrome (UPCR of 660 mg/mmol) and acute kidney injury (AKI) (creatinine 400 μmol/l). Her kidney biopsy showed C1q nephropathy with FSGS features. She was started on haemodialysis due continuous kidney function deterioration. She recovered on steroid therapy to normal kidney function and negative proteinuria, but she relapsed with weaning steroids. So steroid dose was increased and tacrolimus was added. Her renal function remained intact. Following that she had another flare in May 2021 with mild kidney impairment and worse proteinuria (UPCR 500 mg/mmol) while she was on small dose steroid and tacrolimus. She was then started on rituximab. After 2 doses 1 gm 2 weeks apart she achieved remission and her kidney function normalised. She received 2 more doses of 1 gram rituximab 6 months apart with excellent response. She has been in complete remission since. Case (3): A 28-year-old male presented to our department in July 2020 with nephrotic syndrome (urine PCR >900 mg/mmol) and preserved renal function. His kidney biopsy was initially reported as MCD and he was managed with oral steroids. He showed a good response with complete resolution of his proteinuria 3 weeks later and remained in remission for 2 years. However, in August 2022- he suffered a second severe relapse (UPCR 4000 mg/mmol) with preserved renal function. His kidney biopsy was therefore rereviewed and immunofluorescence was added which revealed C1q nephropathy. He had another course of steroids and was initiated on rituximab infusions. He showed full remission after 2 doses (1 gram IV 2 weeks apart) and is on ongoing 6 monthly infusions. Results Rituximab was effective in inducing remission in our patients with nephrotic syndrome due to C1q nephropathy. They were all steroid sensitive. It was effective in both steroid-sensitive and steroid-dependent cases. The first and second cases had biopsy findings in the spectrum of FSGS while the third case histological picture in the spectrum of MCD. They all achieved full resolution of their proteinuria and preserved their renal function finally. Conclusion Rituximab was effective in inducing remission in both steroid-responsive and steroid dependant relapsed patients with C1q nephropathy, despite differences in biopsy results. Kidney function was preserved. More solidified data, including multi-centre randomized controlled trials, are needed to establish clear guidelines for the position of rituximab in the management of the disease and the proper dose to use.

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