Abstract
Background: Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). Though systemic oxalate deposition is well-known, the natural history of PH1 during RRT has not been systematically described. In this study, we describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT.Methods: Patients with PH1 enrolled in the Rare Kidney Stone Consortium PH Registry who progressed to require RRT, had ≥2 plasma oxalate (pOx) measurements 3–36 months after start of RRT, and at least one pair of pOx measurements between 6 and 18 months apart were retrospectively analyzed. Clinical, echocardiographic, and laboratory results were obtained from the Registry.Results: The 17 PH1 patients in our cohort had a mean total HD hours/week of 17.4 (SD 7.9; range 7.5–36) and a range of age of RRT start of 0.2–75.9 years. The average change in plasma oxalate (pOx) over time on RRT was −0.74 [−2.9, 1.4] μmol/L/month with the mean pOx never declining below 50 μmol/L. Over time on RRT, oxalosis progressively developed in multiple organ systems. Echocardiography performed on 13 subjects showed worsening of left ventricular global longitudinal strain correlated with pOx (p < 0.05).Conclusions: Even when a cohort of PH1 patients were treated with intensified RRT, their predialysis pOx remained above target and they developed increasing evidence of oxalosis. Echocardiographic data suggest that cardiac dysfunction could be related to elevated pOx and may worsen over time.
Highlights
The primary hyperoxalurias are a group of genetic diseases that result in excessive hepatic oxalate production producing increased urinary oxalate excretion, which can cause severe urinary stone disease, nephrocalcinosis, and progressive chronic kidney disease (CKD)
In the cohort of Primary hyperoxaluria type 1 (PH1) patients enrolled in the Rare Kidney Stone Consortium (RKSC) registry, 57% progressed to endstage kidney disease (ESKD) by 40 years of age and 88% by age 60 [1, 2]
Eleven of the 17 members of our cohort had a diagnosis of primary hyperoxaluria (PH) prior to initiation of renal replacement therapy (RRT); 4 were first known to have PH within 3 months before or after starting RRT, and there were 2 in whom the PH diagnosis was made >3 months after the start of dialysis
Summary
The primary hyperoxalurias are a group of genetic diseases that result in excessive hepatic oxalate production producing increased urinary oxalate excretion, which can cause severe urinary stone disease, nephrocalcinosis, and progressive chronic kidney disease (CKD). Systemic oxalosis can occur with endstage kidney disease (ESKD) if patients are maintained on routine renal replacement therapy (RRT) long term. In the cohort of PH1 patients enrolled in the Rare Kidney Stone Consortium (RKSC) registry, 57% progressed to ESKD by 40 years of age and 88% by age 60 [1, 2]. Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). We describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT
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