Haemoglobinuria for the early identification of aHUS relapse: data from the ItalKId-HUS Network

Abstract

Background

Atypical haemolytic uremic syndrome (aHUS) is at high risk of relapse at any time, therefore patients require lifelong monitoring. The most appropriate way to monitor patients is not yet clear. Patients could be monitored for relapse by urine dipstick testing for haemoglobinuria based on the hypothesis that thrombotic microangiopathy involving the glomerulus and associated with renal damage (like aHUS) cannot occur without haematuria.

Methods

The aim of this retrospective study is to analyse our experience with this approach in aHUS patients who have never previously been treated, who are currently on treatment or who have discontinued C5 inhibition. The records of all aHUS patients (children and adults) managed by or referred to our Centre from January 2009 to March 2020 were included and the analysis for the presence of haemoglobinuria was restricted to the period following primary remission. A positive test was defined as haemoglobin ≥ 1 + . Patients reporting positive urine dipstick tests underwent laboratory investigations to rule in or out the diagnosis of aHUS relapse.

Results

Eighty-four patients were included with 1517 determinations of haemoglobinuria during a cumulative observation period of 8904 patient-months. Haemoglobinuria for the early diagnosis of ongoing aHUS relapse shows a sensitivity of 100% and a specificity of 87.4% with a positive predictive value (PPV) of 10.5% and a negative predictive value (NPV) of 100%. The accuracy of the test was 87.6%.

Conclusion

Haemoglobinuria is a very sensitive and acceptably specific marker of aHUS relapse. This finding and its validation may have a positive impact on patients’ quality of life and on the outcome of this life threatening disease via early diagnosis of relapse.

Graphic abstract