Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 3;17(5):sfae099.
doi: 10.1093/ckj/sfae099. eCollection 2024 May.

Primary hyperoxaluria in adults and children: a nationwide cohort highlights a persistent diagnostic delay

Romain Pszczolinski  1 , Cécile Acquaviva  2 , Insaf Berrahal  3 , Nathalie Biebuyck  4 , Stéphane Burtey  5   6 , Karine Clabault  7 , Claire Dossier  8 , Matthieu Guillet  9 , Floriane Hemery  10 , Emmanuel Letavernier  11 , Caroline Rousset-Rouvière  12 , Justine Bacchetta  13 , Bruno Moulin  1
Affiliations

Primary hyperoxaluria in adults and children: a nationwide cohort highlights a persistent diagnostic delay

Romain Pszczolinski et al. Clin Kidney J. .

Abstract

Background: Primary hyperoxalurias (PH) are extremely rare genetic disorders characterized by clinical heterogeneity. Delay in diagnosing these conditions can have detrimental effects on patient outcomes. The primary objective of this study is to assess the current diagnostic delay for PH.

Methods: This nationwide, observational and retrospective study included patients who received a genetic diagnosis of PH types 1, 2 and 3 between 1 January 2015 and 31 December 2019. Diagnostic delay was defined as the duration between the onset of symptoms and the time of genetic diagnosis.

Results: A total of 52 patients (34 children and 18 adults) were included in the study, with 40 PH1 (77%), 3 PH2 (6%) and 9 PH3 (17%). At the time of diagnosis, 12 patients (23%) required dialysis. Among the PH1 patients, the predominant symptom at onset in adults was renal colic (79% of cases), whereas symptoms in children were more diverse (renal colic in 17% of cases). The diagnostic delay was significantly shorter in children compared with adults [median (interquartile range)]: 1.2 (0.1-3.0) versus 30 (17-36) years, respectively (P < .0001). RNA interference was utilized in 23 patients (58%). Five individuals (13%) underwent double liver-kidney transplantation, and five (13%) received isolated kidney transplantation, with lumasiran therapy in four patients. For PH2 and PH3 patients, the diagnostic delay ranges from 0 to 3 years, with renal colic as first symptom in 33% of cases.

Conclusion: This extensive and recent cohort of PH underscores the considerable delay in diagnosing PH, particularly in adults, even in a country with a dedicated organization for enhancing the overall management of rare diseases. These findings reinforce the imperative for increased awareness among relevant specialties regarding the evaluation of urolithiasis.

Keywords: diagnostic delay; genetic testing; nephrolithiasis; orphan disease; primary hyperoxaluria.

PubMed Disclaimer

Conflict of interest statement

R.P. received funding from Alnylam Pharmaceuticals to attend a national nephrology congress. C.A. received consulting fees for Alnylam and Novonordisk. N.B. received help for medical writing from Alnylam. S.B. received fees from AstraZeneca, Lilly, CSL Vifor, Bayer and IKI. I.B., K.C., C.D., M.G., F.H. and C.R.-R. declare no conflict of interest. E.L. patented Stiripentol to reduce urine oxalate excretion (WO2017140658A1) and received consulting fees from Biocodex Laboratory. J.B. received travel, consulting and speaker fees from Alnylam Pharmaceuticals, and consulting fees from Dicenra/Novonordisk Pharmaceuticals and Biocodex Pharmaceuticals. B.M. received consulting, travel and speaker fees from Alnylam Pharmaceuticals.

Figures

Figure 1:
Figure 1:
Distribution of symptoms at onset of PH1 in children (A) and in adults (B). Two missing data in adults.
Figure 2:
Figure 2:
Age at onset (white boxes) and age at genetic diagnosis (grey boxes) of PH1 in children (N = 23) and adults (N = 13). Diagnostic delay is indicated with arrows. ****P < .0001.
See this image and copyright information in PMC

References

    1. Hoppe B, Beck BB, Milliner DS. The primary hyperoxalurias. Kidney Int 2009;75:1264–71. 10.1038/ki.2009.32 - DOI - PMC - PubMed
    1. Mandrile G, Beck B, Acquaviva C et al. Genetic assessment in primary hyperoxaluria: why it matters. Pediatr Nephrol 2023;38:625–34. 10.1007/s00467-022-05613-2 - DOI - PMC - PubMed
    1. Hopp K, Cogal AG, Bergstralh EJ et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. J Am Soc Nephrol 2015;26:2559–70. 10.1681/ASN.2014070698 - DOI - PMC - PubMed
    1. Bouzidi H, Majdoub A, Daudon M et al. Hyperoxalurie primitive : une revue de la littérature. Nephrol Ther 2016;12:431–6. - PubMed
    1. Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med 2013;369:649–58. 10.1056/NEJMra1301564 - DOI - PubMed