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. 2022 Apr 25;37(5):869-875.
doi: 10.1093/ndt/gfab027.

Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2

Prince Singh  1 , Jason K Viehman  2 , Ramila A Mehta  2 , Andrea G Cogal  1 , Linda Hasadsri  3 , Devin Oglesbee  3 , Julie B Olson  1 , Barbara M Seide  1 , David J Sas  1   4 , Peter C Harris  1   5 , John C Lieske  1   3 , Dawn S Milliner  1   4
Affiliations

Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2

Prince Singh et al. Nephrol Dial Transplant. .

Abstract

Background: Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2.

Methods: Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62).

Results: PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P < 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P < 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients.

Conclusions: Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.

Keywords: nephrocalcinosis; oxalate; primary hyperoxaluria; stone.

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Figures

FIGURE 1
FIGURE 1
Stone events per patient per year during each decade of follow-up in PH3 (top panel), PH1 (middle panel) and PH2 (lower panel). The mean for each decade is shown as a black diamond.
FIGURE 2
FIGURE 2
Scatter plot showing 24 h urine oxalate corrected for 1.73 m2 body surface area at first measurement in patients with PH1, PH2 and PH3 across the three groups of PH. Urine oxalate remains elevated at all ages in all PH types.
FIGURE 3
FIGURE 3
Scatter plot showing correlation between urinary HOG and age in PH3 patients (normal limit <10 mg/g Cr).
FIGURE 4
FIGURE 4
Kaplan–Meier curve showing ESKD for the three PH groups with ESKD defined as eGFR <15 mL/min/1.73 m2, initiation of dialysis or kidney transplant.
See this image and copyright information in PMC

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