FP007The Importance of Evaluating for Potential Underlying Causes of Kidney Stones: A Survey of Physician Experiences in Diagnosing Primary Hyperoxaluria Type 1

Abstract

INTRODUCTION: Primary hyperoxaluria type 1 (PHI) is a rare genetic disorder characterized by persistent hepatic overproduction of oxalate. Oxalate crystalizes with calcium and leads to serious manifestations including recurrent kidney stones, nephrocalcinosis, progressive renal failure, and multiorgan damage from systemic oxalosis once disease advances. Among patients with PHI, clinical phenotype is heterogeneous with a wide spectrum of clinical manifestations, including a variable age of presentation and an unpredictable progression rate, leading to delayed diagnosis and increased disease burden. A series of case-based physician interviews was conducted to identify triggers that raised suspicion of PHI and factors that contributed to diagnostic delays throughout the patient journey. METHODS: Key criteria for participants: physicians in practice for 2+ years; active role in diagnosing, treating, or managing 1+ PHI patient within last 5 years; spend ≥ 5 0% of time in direct patient care; see 100+ total patients per year; and able to review PH1 patient medical records. Case history forms served as basis for further probing of details in 60-minute interviews conducted with open-ended questions from a semi-structured interview guide. RESULTS: Physicians from the US (N=10) and Europe (N=8) participated in the study and reported 30 PH 1 patient cases. At diagnosis, age ranged from 1 month-48 years (median 4.5 years);17 patients had preserved renal function and 13 had advanced kidney disease. In many patients, especially adults, diagnostic delay impacted disease progression to more advanced kidney disease. Specialties diagnosing PHI were nephrologists (80%), geneticists/metabolic specialists (17%), and urologists (3%); patients were primarily diagnosed via genetic testing (86%). Physicians identified the following as triggers raising initial suspicion leading to diagnosis (N=28 patients): recurrent kidney stones (50%); nephrocalcinosis (18%, all in pediatric cases); single kidney stone event (14%, all in pediatric cases); ESRD (ll%,allinpediatriccases); family history (11%); acute renal failure (11 %); progressive chronic kidney disease (11%); and failure to thrive (4%, pediatric cases). When asked what, in retrospect, should have triggered suspicion in these cases (regardless of actual events), physicians most commonly identified kidney stone(s), a single event in pediatrics and recurrent events in adults. Physicians identified the following as key factors that contributed to diagnostic delay: symptomatic stones treated with no further evaluation/workup completedand/orlackof awareness/suspicion of PH 1. CONCLUSIONS: Kidney stones were the most common symptom triggering suspicion leading to PH 1 diagnosis. Nonetheless, diagnostic delays were seen in a notable proportion of patients. Despite guidelines indicating medical evaluation in all kidney stone patients, which could have led to earlier diagnosis in patients in this study, diagnostic delay was mainly due to initial symptomatic treatment with no further evaluation and/or lack of awareness/suspicion of PHI. In some cases, patients' kidney disease progressed to ESRD before diagnosis, which demonstrates negative outcomes duetofhelackofPHl diagnosis and management. Although all patients with kidney stones should be evaluated, a single event in children and recurrent events in adults should trigger suspicion and evaluation for an underlying cause such as PHI to ensure they can be appropriately managed to avoid disease progression.