#3141 AN ATYPICAL EXPERIENCE FOR THE WEST OF SCOTLAND
Authors: Groome Ciaran , Padmanabhan Neal 
Published: June 2023

Background and Aims

Haemolytic uraemic syndrome (HUS) is a disease which affects the kidneys presenting with acute kidney injury (AKI), microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. In 90% of cases it is precipitated by shiga-toxin producing E coli [1]. The remaining 10% of cases have been termed atypical haemolytic uraemic syndrome (aHUS) and complement system overactivation is the underlying mechanism [2]. This can take the form of autoantibody production or complement gene mutations [2]. Eculizumab has been proven to significantly ameliorate disease progression [3]. In this series, we sought to explore the West of Scotland's experience with this ultra-rare population evaluating outcomes and access to therapies.

Method

This is a retrospective case series. We extracted data from the west of Scotland renal electronic patient records database Strathclyde Electronic Renal Patient Record (“SERPR”) provided by VitalDataClient. We ran a query to identify patients in whom TMA and/or MAHA and/or HUS was inputted as a diagnosis. 363 patients were identified. Filtering for aHUS in the adult population, 22 patients were identified spanning 19 years.

Results

The incidence rate is 0.43/million of the population. 14 patients had either genetic mutations (n=13) or acquired antibodies. Genetic mutations: C3, n=5; Complement Factor H (CFH) n=5; Complement Factor I (CFI)+CD46 n=1; CFI alone n=1, variants of uncertain significance n=1. One patient with CFH mutation was positive for the nephritic factor; another with CFH mutation had detectable Factor H autoantibodies. The only acquired patient without a genetic mutation had Factor H autoantibodies. The mean levels of biochemical markers at presentation are: Haemoglobin (g/L) 72; Creatinine, (μmol/L) 603; Platelet count, (×109/L) 89; Lactate dehydrogenase (IU/L) 1853; and Total Bilirubin, (µmol/L) 30. Eculizumab is an available treatment for aHUS utilised in coordination with The National Renal Complement Therapeutics Centre. The outcomes of patients with and without genetic defects and/or antibodies, with the number in parenthesis denoting those who received Eculizumab, are listed below, stratified by CKD staging. Those with identifiable genetic/acquired defects: Recovered 2(2); CKD3 3(3); CKD4 1(0); CKD5 1(0); Renal replacement therapy dependent 7(6)*. Total 14(11). Those with no identifiable defect: Recovered 2(2); CKD3 2(0); CKD4 0; CKD5 0; Renal replacement therapy dependent 4(3)**. Total 8(5). *4 of the 6 have successfully functioning transplants. **Of the 3 patients who received Eculizumab, 2 had a brief trial. The third received it after transplantation but the transplant failed.

Conclusion

It is clear from the above data that long term renal outcomes are poor for these patients with the majority being left with residual impairment to some degree. Furthermore, in those for whom transplantation is being considering, it is imperative that Eculizumab is introduced, if already withdrawn, to cover transplantation and is maintained to prevent recurrence in the new organ. Even in those without RRT requirements, use of the C5 inhibitor is necessary to stabilise and allow for recovery of at least some native function. Therefore, clinicians in encountering MAHA and TMA in their practice should always consider aHUS and liaise with the Newcastle centre promptly to ensure diagnostics are sent and treatment can be commenced, otherwise the outcomes can be catastrophic.