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Rationale: Thrombotic microangiopathy (TMA) is a spectrum of rare diseases characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. Differentiating pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome and atypical hemolytic uremic syndrome (aHUS) during pregnancy may be diagnostically challenging yet important as the treatment pathways differ. Most cases of aHUS are associated with dysregulation of the complement alternative pathway, for which current guidelines recommend prompt treatment with complement C5 inhibitor to prevent chronic sequelae. Here, we report a case of pregnancy-associated aHUS (p-aHUS) to highlight the challenging aspects of the diagnostic process and the importance of prompt treatment with complement inhibition to reduce the risk of poor outcomes. Presenting concerns: A 28-year-old woman was admitted to a local hospital for induction of vaginal delivery of twins at 34 weeks and 3 days of gestational age, due to intrauterine growth restriction (IUGR). She was previously healthy, and this current pregnancy was uncomplicated, except for the IUGR. Approximately, 10 hours after her induced delivery, she developed vomiting, epigastric pain, and hypertension. Diagnosis: She was initially suspected of having fulminant liver failure in the context of acute fatty liver of pregnancy versus pre-eclampsia/HELLP syndrome, due to evidence of elevated liver enzymes, acute kidney injury (AKI), thrombocytopenia, and hemoglobin levels trending down, for which the patient was initially treated conservatively. On day 2 post-delivery, she was transferred to our hospital for possible liver biopsy and management of liver failure. Upon transfer, dialysis was started due to anuric AKI; at the same time, her liver function spontaneously improved, while platelet count remained very low and hemoglobin levels continued to trend down. A full TMA work-up revealed low C3 levels; secondary causes of TMA were ruled out. The patient received a final diagnosis of p-aHUS. Complement genetic tests were also performed and did not identify any pathogenic variants. Interventions: Given the final diagnosis of p-aHUS, the patient was started on a C5 inhibitor (day 8 post-delivery). Her platelet count quickly normalized 2 days after the first dose, while the hemoglobin levels remained low for a longer period, likely due to retained products of conception. Outcomes: The patient was able to completely discontinue dialysis after approximately 3 months, however, her kidney function did not recover completely, despite all the other TMA markers normalizing (platelets count in range, negative hemolysis markers, and normal hemoglobin levels). Her estimated glomerular filtration rate (eGFR) was 23 mL/min/1.73 m 2 at the 6-month follow-up. Teaching points: The diagnosis of p-aHUS can be challenging due to frequent overlapping symptoms and signs with other forms of pregnancy-associated TMA, leading to a delay of the treatment, which can affect the patient’s outcome. Failure of TMA to improve in the postpartum period or occurring at this time, with negative ADAMTS13 and antiphospholipid antibody syndrome (APLAS) serologies should favor the diagnosis of p-aHUS. Early treatment with C5 inhibition should be considered in women with a diagnosis of p-aHUS. Patients need multidisciplinary and likely tertiary/quaternary care at centers where clinical experience, access to diagnostics and treatment initiation can begin without delay.

Purpose of Program: Glomerulonephritis (GN) is a group of rare kidney diseases that is increasingly being managed with higher cost immunosuppressive (IS) agents in Canada. Ontario Health’s Ontario Renal Network (ORN) oversees the management and delivery of GN services in the province. Stakeholder surveys previously conducted by ORN identified that both clinicians and patients do not perceive access to GN medications as comprehensive or timely. The program conducted a focused jurisdictional scan among 7 provinces to inform ORN initiatives to improve access to GN medications. Specifically, the program examined clinician experience with GN access, public drug coverage criteria, and timelines for public coverage for select IS agents (ie, tacrolimus, cyclosporine, mycophenolate mofetil [MMF], mycophenolate sodium, rituximab, and eculizumab) used to manage GN in adults who live in Canada. Methods: For the selected IS agents, a focused jurisdictional scan on medication access was conducted by ORN in 2018 and updated in July 2022. Information was obtained by searching the gray literature and/or credible online sources for public funding policies and eligibility criteria. Findings were supplemented by personal communications with provincial drug programs and consulting GN clinical experts from 7 provinces (ie, Alberta, British Columbia, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Quebec). Key Findings: Clinicians from different provinces prescribe IS agents similarly for GN indications, despite distinctions in public drug funding policies. While patients can obtain public funding for many IS agents, for GN, most provinces rely on case-by-case review processes. In addition, provinces can vary in their funding criteria and which IS agents are listed on the public formulary. For IS agents that require prior authorization or case-by-case review, timelines vary by province with decisions taking a few days to weeks. British Columbia, with a GN-specific drug formulary, had the most integrated and efficient system for patients and prescribers. Limitations: This scan primarily relied on publicly available information for drug coverage criteria and clinician experience with access in their province. Since this scan was conducted, public drug coverage criteria and/or application processes may have changed. Implications: While patients in most provinces have similar needs and nephrologists similar prescribing patterns, gaps still exist for publicly funded GN medications. Interprovincial differences in the drugs funded, funding criteria, and application process may affect timely and equitable access to GN medications across Canada. Given the rarity of GN, a pan-Canadian funding approach may be warranted to improve the current state.

Background: Glomerulonephritis (GN) is a leading cause of kidney failure and accounts for 20% of incident cases of end-stage kidney disease (ESKD) in Canada annually. Reversal of kidney injury and prevention of progression to kidney failure is possible; however, limited knowledge of underlying disease mechanisms and lack of noninvasive biomarkers and therapeutic targets are major barriers to successful therapeutic intervention. Multicenter approaches that link longitudinal clinical and outcomes data with serial biologic specimen collection would help bridge this gap. Objective: To establish a national, patient-centered, multidimensional web-based clinical database and federated virtual biobank to conduct human-based molecular and clinical research in GN in Canada. Design: Multicenter, prospective observational registry, starting in 2019. Setting: Nine participating Canadian tertiary care centers. Patients: Adult patients with a histopathologic pattern of injury consistent with IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy, C3 glomerulopathy, and membranoproliferative GN recruited within 24 months of biopsy. Measurements: Initial visits include detailed clinical, histopathological, and laboratory data collection, blood, urine, and tonsil swab biospecimen collection, and a self-administered quality of life questionnaire. Follow-up clinical and laboratory data collection, biospecimen collection, and questionnaires are obtained every 6 months thereafter. Methods: Patients receive care as defined by their physician, with study visits scheduled every 6 months. Patients are followed until death, dialysis, transplantation, or withdrawal from the study. Key outcomes include a composite of ESKD or a 40% decline in estimated glomerular filtration rate (eGFR) at 2 years, rate of kidney function decline, and remission of proteinuria. Clinical and molecular phenotypical data will be analyzed by GN subtype to identify disease predictors and discover therapeutic targets. Limitations: Given the relative rarity of individual glomerular diseases, one of the major challenges is patient recruitment. Initial registry studies may be underpowered to detect small differences in clinically meaningful outcomes such as ESKD or death due to small sample sizes and short duration of follow-up in the initial 2-year phase of the study. Conclusions: The Canadian Glomerulonephritis Registry (CGNR) supports national collaborative efforts to study glomerular disease patients and their outcomes. Trial registration: NCT03460054.

Rationale: Synthetic adrenocorticotropic hormone (Tetracosactide) has been used in the treatment of refractory glomerular diseases. Literature surrounding the use of this medication is limited to small case series and there is conflicting data on the rate of adverse events associated with this medication. Presenting concerns of the patient: Glomerulonephritis not in remission after at least 6 months of treatment with conservative care. Stable doses of concurrent immunosuppression were permitted. Diagnoses: Membranous nephropathy, IgA nephropathy, minimal change disease, and focal and segmental glomerulosclerosis. Intervention: Intramuscular synthetic adrenocorticotropic hormone (Tetracosactide, Synacthen Depot) with doses of either 1 mg weekly or 1 mg twice weekly. Outcomes: Five of 12 patients had at least a partial remission with Tetracosactide. Median time to response was 6 months for responders. Five of the 12 patients had adverse events documented, 2 of which led to treatment discontinuation. No patients with focal and segmental glomerulosclerosis responded to treatment. Lessons Learned: Higher rate of adverse events than previously reported with synthetic adrenocorticotropic hormone and uncertain treatment efficacy.