Natural History of Advanced Primary Hyperoxaluria Type 1: A Retrospective Study.
Publisher DOI
PubMed ID
41209157
Abstract
Rationale & Objective
Characterize the natural history of advanced primary hyperoxaluria type 1 (PH1) in a multinational patient cohort.Study Design
A retrospective chart review.Setting & Participants
Patients, from participating medical centers in North America, Europe, and the Middle East, had ≥ 4 health care visits related to PH1 spanning ≥ 6 months (except deceased patients) on/after January 1, 2000, and ≥ 2 estimated glomerular filtration rate (eGFR) values ≤ 45 mL/min/1.73m2 (if age < 12 months, 2 serum creatinine values elevated for age) were included.Exposure
None (retrospective observational study).Outcomes
Kidney function, liver and/or kidney transplantation, death, plasma oxalate, systemic oxalosis, emergent clinical events, and abnormal clinical laboratory values.Analytical Approach
Patients were categorized as not on dialysis (Cohort A) and receiving hemodialysis (Cohort B). Patients could be in more than one cohort, but not during the same time.Results
Seventy patients were analyzed (up to 21 years of data; Cohort A, n = 54; Cohort B, n = 53). The median age at entry was 11.8 years (Cohort A) and 12.2 years (Cohort B). The eGFR slope was -2.8 mL/min/1.73m2/year (Cohort A). Patients underwent hemodialysis a median of 6 days/week (range, 3-7; Cohort B). Forty-two patients underwent liver and/or kidney transplantation (median age at first transplant, 15.3 years). Nineteen patients died (median age at death, 3.9 years [range, 2.2-34.9]), including 8 who received liver or liver-kidney transplants. Death occurred in 11 of 28 (39.3%) patients without transplant and 8 of 42 (19.0%) patients with transplant. Improvement in skeletal oxalosis after liver-kidney transplantation generally took > 1 year. Limited plasma oxalate and cardiac oxalosis data were available. The most common emergent clinical events were nephrolithiasis (Cohort A [nondialysis]) and fracture (Cohort B [hemodialysis]). The most commonly reported abnormal clinical laboratory values were bicarbonate, creatinine, and eGFR.Limitations
Minimal follow-up in some patients; small sample for some endpoints.Conclusions
Advanced PH1 is associated with high morbidity and mortality rates.Primary hyperoxaluria type 1 (PH1) is a rare disease in which the liver makes too much oxalate. Excess oxalate may damage the kidneys and eventually lead to kidney failure and disease in other organs due to oxalate storage (systemic oxalosis). The course of PH1 is not well understood. We studied 70 patients with PH1 with < 45% kidney function, at a median age of 12 years, using existing data. We found that kidney function declined rapidly in patients who were not yet on dialysis. Nearly 20% of patients with kidney transplants and nearly 40% of patients without kidney transplants died. Skeletal oxalosis, which caused fractures, recovered slowly after transplantation. New treatments may improve kidney function and outcomes in people with PH1.
Characterize the natural history of advanced primary hyperoxaluria type 1 (PH1) in a multinational patient cohort.Study Design
A retrospective chart review.Setting & Participants
Patients, from participating medical centers in North America, Europe, and the Middle East, had ≥ 4 health care visits related to PH1 spanning ≥ 6 months (except deceased patients) on/after January 1, 2000, and ≥ 2 estimated glomerular filtration rate (eGFR) values ≤ 45 mL/min/1.73m2 (if age < 12 months, 2 serum creatinine values elevated for age) were included.Exposure
None (retrospective observational study).Outcomes
Kidney function, liver and/or kidney transplantation, death, plasma oxalate, systemic oxalosis, emergent clinical events, and abnormal clinical laboratory values.Analytical Approach
Patients were categorized as not on dialysis (Cohort A) and receiving hemodialysis (Cohort B). Patients could be in more than one cohort, but not during the same time.Results
Seventy patients were analyzed (up to 21 years of data; Cohort A, n = 54; Cohort B, n = 53). The median age at entry was 11.8 years (Cohort A) and 12.2 years (Cohort B). The eGFR slope was -2.8 mL/min/1.73m2/year (Cohort A). Patients underwent hemodialysis a median of 6 days/week (range, 3-7; Cohort B). Forty-two patients underwent liver and/or kidney transplantation (median age at first transplant, 15.3 years). Nineteen patients died (median age at death, 3.9 years [range, 2.2-34.9]), including 8 who received liver or liver-kidney transplants. Death occurred in 11 of 28 (39.3%) patients without transplant and 8 of 42 (19.0%) patients with transplant. Improvement in skeletal oxalosis after liver-kidney transplantation generally took > 1 year. Limited plasma oxalate and cardiac oxalosis data were available. The most common emergent clinical events were nephrolithiasis (Cohort A [nondialysis]) and fracture (Cohort B [hemodialysis]). The most commonly reported abnormal clinical laboratory values were bicarbonate, creatinine, and eGFR.Limitations
Minimal follow-up in some patients; small sample for some endpoints.Conclusions
Advanced PH1 is associated with high morbidity and mortality rates.Primary hyperoxaluria type 1 (PH1) is a rare disease in which the liver makes too much oxalate. Excess oxalate may damage the kidneys and eventually lead to kidney failure and disease in other organs due to oxalate storage (systemic oxalosis). The course of PH1 is not well understood. We studied 70 patients with PH1 with < 45% kidney function, at a median age of 12 years, using existing data. We found that kidney function declined rapidly in patients who were not yet on dialysis. Nearly 20% of patients with kidney transplants and nearly 40% of patients without kidney transplants died. Skeletal oxalosis, which caused fractures, recovered slowly after transplantation. New treatments may improve kidney function and outcomes in people with PH1.
Date Issued
2025-11
Publication Type
Article
Subject(s)
Subjects
Dialysis
•
kidney
•
liver
•
oxalate
•
oxalosis
•
primary hyperoxaluria type 1
•
transplant
Language(s)
en
Author(s)
Lieske, John C | |
Groothoff, Jaap W | |
Frishberg, Yaacov | |
Garrelfs, Sander F | |
Milliner, Dawn S | |
Magen, Daniella | |
Sellier-Leclerc, Anne-Laure | |
Shasha-Lavsky, Hadas | |
Bakkaloǧlu, Sevcan | |
Lemoine, Sandrine | |
Devresse, Arnaud | |
Cytter-Kuint, Ruth | |
Kajbaf, Farshad | |
Du, Weiming | |
Gansner, John M |
Journal
Kidney medicine
Publisher
Elsevier
ISSN
2590-0595
Related Collection(s)
Access(Rights)
open.access