ESPN 54th Annual Meeting

ESPN 2022


 
RESPONSE TO LUMASIRAN IN PRIMARY HYPEROXALURIA TYPE 1 (PH1): FIRST CLINICAL EXPERIENCES
SINA SAFFE 1 MARKUS J KEMPER 1 MATTHIAS HANSEN 2 NELE KANZELMEYER 3 ANJA B√úSCHER 4 JUN OH 5 KATJA DOERRY 5

1- DEPARTMENT OF PAEDIATRICS, ASKLEPIOS KLINIK NORD, HAMBURG, GERMANY
2- PAEDIATRIC NEPHROLOGY, CLEMENTINE KINDERHOSPITAL, FRANKFURT, GERMANY
3- PAEDIATRIC NEPHROLOGY, MEDIZINISCHE HOCHSCHULE HANNOVER, GERMANY
4- PAEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITAL ESSEN, GERMANY
5- PAEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITAL HAMBURG, GERMANY
 
Introduction:

Primary hyperoxaluria type 1 (PH1) is characterised by hepatic overproduction of oxalate, leading to hyperoxaluria which can result in nephrocalcinosis, urolithiasis and renal failure. Conservative management of PH1 aims to reduce the urinary oxalate concentration (high fluid intake, citrate, pyridoxine). The only curative treatment to date is a liver transplant. Lumasiran is a novel drug that has been approved for use in PH1 patients in November 2020. It reduces the oxalate synthesis in the liver by RNA interference. Data on its effect in routine clinical setting are scarce.

Material and methods:

We present data on 6 patients (3 girls) with genetically confirmed PH1, including 2 on dialysis. 

Results:

Median age at start of treatment was 10.8 (1.8-15.8) years. In those with preserved renal function median reduction of hyperoxaluria was 66% (range 50.4-82%) after 2 months and 58% (4.4-71%) after 6 months. One of these patients had rapid normalization initially but urinary oxalate levels started rising again after the third dose and reached values similar to before the treatment was started. In 2 patients urinary oxalate decreased to healthy control values. In the 2 patients on dialysis, frequency of sessions could be decreased in one patient because plasma oxalate levels decreased but had to be increased in the other due to increasing systemic oxalosis. Treatment was well tolerated, the only noticeable side effects were injection site reactions. 


Conclusions:

Even though there is promising data regarding the benefits of Lumasiran in PH1, this could not be replicated in all of our patients. Our data highlights the need to regularly re-evaluate hyperoxaluria during Lumasiran treatment also in the long-term; registry data seem mandatory for all PH1 patients treated with Lumasiran to monitor effectiveness and side effects.