Background: Multidisciplinary care is recommended for patients with advanced chronic kidney disease (CKD). A formalized, risk-based approach to CKD management is being adopted in some jurisdictions. In Ontario, Canada, the eligibility criteria for multidisciplinary CKD care funding were revised between 2016 and 2018 to a 2 year risk of kidney replacement therapy (KRT) greater than 10% calculated by the 4-variable Kidney Failure Risk Equation (KFRE). Implementation of the risk-based approach has led to the discharge of prevalent CKD patients. Objective: The primary objective of this study was to determine the frequency of occurrence of death and KRT initiation in patients discharged from CKD clinic. Design: Retrospective cohort study Setting: Single center multidisciplinary CKD clinic in Ontario, Canada Patients: Four hundred and twenty five patients seen at least once in 2013 at the multidisciplinary CKD clinic Measurements: Outcomes included discharge status, death, re-referral and KRT initiation. Reasons for discharge were recorded. Methods: Outcomes were extracted from available electronic medical records and the provincial death registry between the patient’s initial clinic visit in 2013 and January 1, 2020. KFRE-2 scores were calculated using the 4-variable KFRE equation. The hazard rates of death and KRT after discharge due to stable eGFR/low KFRE were compared to patients who remained in the clinic. Results: Of the 425 CKD patients, 69 (16%) and 19 (4%) were discharged to primary care and general nephrology, respectively. Of those discharged, 7 (8%) were re-referred to nephrology or CKD clinic, while only 2 (2%) discharged patients required subsequent KRT. The hazard of mortality was reduced after discharge from the clinic due to stable eGFR/low KFRE (adjusted HR = 0.45 [95% CI, 0.25-0.78, P = .005]). Limitations: Single center, observational retrospective study design and unknown kidney function over time post discharge for most patients Conclusions: Discharge of low risk patients from multidisciplinary CKD clinic appears feasible and safe, with fewer than 1 in 40 discharged patients subsequently initiated on KRT over the following 7 years.

Background and Aims Clinical differentiation of pregnancy-associated thrombotic microangiopathies is challenging and can occur in conjunction with or mimic conditions including hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, pre-eclampsia (PET), thrombotic thrombocytopenia purpura (TTP) and atypical HUS (aHUS). aHUS that occurs during pregnancy classically presents in the third trimester. When kidney transplantation is performed in aHUS patients, disease recurrence is high and can be associated with transplant failure. Here, we report a unique case of aHUS that presented early during pregnancy where the patient subsequently underwent kidney transplantation. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 30 year old G2P0A1 diabetic African American woman presents at 9 weeks gestation with new hypertension. At 18 weeks, she developed acute kidney injury and proteinuria. Further investigations revealed hemoglobin 68 g/L, platelets 120 x 109/L, increased LDH 588 U/L, undetectable haptoglobin and schistocytes on blood smear. Creatinine was 88 umol/L, increased from a baseline of 50 umol/L, and proteinuria greater than 1 g/day. Pre-eclampsia was ruled out as her presentation began at 9 weeks gestation, prior to placental implantation. Placental growth factor levels at 24 and 28 weeks remained >100 pg/mL. HELLP syndrome was excluded given the timing in pregnancy and normal liver enzymes. TTP was excluded with a normal ADAMTS13. Complement Factor H autoantibody was negative. Complement studies revealed grossly elevated soluble C5b-9 level (sC5b-9) of 1.05 (normal <0.3 mg/L). aHUS was diagnosed and she began treatment with eculizumab (ECU). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed and was severely abnormal pre-treatment with ECU (activated 223%, normal <150%), and normalized with ECU therapy (activated 123%, normal <150%). Genetic testing eventually revealed a Complement Factor I mutation, NM_000204.3:c.550G/A, p. Vall84Met reported as likely pathogenic and confirming primary aHUS. Due to worsening renal function, she delivered a healthy boy at 30 weeks gestation by Caesarean section. A renal biopsy performed 3 weeks post-partum demonstrated features of TMA, mainly chronic (i.e. treated) and severe diabetic nephropathy with advanced glomerular sclerosis. Six months post-partum, she required dialysis. She remained on ECU and had an unrelated living kidney transplantation 1.5 years later. Her kidney transplantation included basiliximab and methylprednisolone induction. Calcineurin inhibitors were prescribed in standard fashion. Given severity of original multiorgan aHUS and CFI mutation, she was treated with eculizumab 1200 mg the day prior to surgery and another 1200 mg on post operative day 1. Subsequently she was given eculizumab 900 mg weekly for 4 weeks then 1200 mg every 2 weeks. Eculizumab drug level for adequacy of complement blockade was measured on day 4 post transplant and was 279 (therapeutic >100 mcg/mL) and sC5b-9 was 1504 (normal < 244). Repeated ECU level pre 900 mg dose was 189 and sC5b-9 was 392. 6 months post transplant she has excellent graft function without proteinuria (urine ACR 2.2 mg/mmol) or evidence of aHUS recurrence. Conclusion aHUS, although described to occur late in pregnancy or post-partum, presented here during the first trimester. Thus, TMA in pregnancy is not always PET or HELLP. aHUS is a treatable condition in pregnancy, and should be considered as a possibility particularly for presentations occurring prior to 20 weeks gestation. Complement function studies may aid in aHUS diagnosis. Despite extra ECU dosing and therapeutic ECU levels for this patient post kidney transplantation, she had evidence of massive C5 release (grossly elevated sC5b-9 level). sC5b-9 measurement post transplantation may be useful to guide ECU dosing.

Background and Aims HELLP (hemolysis, elevated liver enzymes, low platelets) is a severe variant of preeclampsia whose pathogenesis remains unknown but likely involves abnormal placentation, endothelial dysfunction and release of vasoactive substances. Complement dysregulation is implicated in the pathogenesis of atypical hemolytic uremic syndrome (aHUS) and there is growing evidence to support its role in HELLP syndrome. Here we present a case of postpartum thrombotic microangiopathy (TMA) in the setting of HELLP syndrome. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 22 year old G1P1 Caucasian woman presents at 37 weeks gestation with abdominal pain and severe hypertension. Labs demonstrated TMA including hemoglobin 95, platelets 30, LDH 2597, and schistocytes. She had severe transaminitis with AST 1845 and ALT 830, and proteinuric acute kidney injury. She was diagnosed with HELLP syndrome and treated with anti-hypertensives and emergency Caesarean section. Unfortunately, the infant did not survive, and there was no placental abruption. Platelets recovered by day 5 postpartum, LDH by day 7. However, renal function worsened and by day 6 postpartum, she required hemodialysis. A renal biopsy revealed acute and chronic TMA. She did not have cortical necrosis. Further workup revealed normal C3, C4 and ADAMTS13 levels. Dialysis was stopped after two weeks. By 6 months, her renal function and proteinuria returned to normal. Complement function testing revealed negative complement factor H autoantibody, but elevated soluble C5b-9 (sC5b-9) level (0.42 mg/L, normal <0.3). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed both on resting (182%, normal <150%) and on ADP-activated endothelial cells (273%, normal <150%). This test was repeated 6 months postpartum when renal function had normalized, and results were persistently abnormal both on resting (215%, normal <150%) and on ADP-activated endothelial cells (282%, normal <150%). aHUS genetic testing was negative. Conclusion Results from Burwick et al suggest that this patient had a very high likelihood of clinical aHUS in association with HELLP syndrome (elevated LDH >1832 U/L and creatinine >1.9 mg/dL) [1]. Identifiable aHUS genetic mutations only occur in 50% of aHUS patients. Complement function testing is not routinely assessed for postpartum HELLP; however, the severity of her HELLP syndrome prompted further investigation (C5b-9 deposition testing). The persistence of increased C5b-9 deposition 6 months postpartum for this patient mimics the findings of patients who have confirmed aHUS [2]. Our patient's unique results suggest the patient may be at risk for recurrent TMA/aHUS in her lifetime, particularly if another pregnancy is being considered. Future research should explore which pregnancy associated TMA patients may benefit from anti-complement therapy.