Abstract: PO1637
Recovery from Dialysis in Responsive Primary Hyperoxaluria Type 1 (PH1) Patients After Initiation of Pyridoxine
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Lorenz, Elizabeth C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Seide, Barbara M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Olson, Julie B., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Mehta, Ramila A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Milliner, Dawn S., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Introduction
PH1 is a genetic disorder characterized by hepatic overproduction of oxalate and eventual end-stage kidney disease (ESKD). The only established treatment to reduce hepatic oxalate production is the use of pharmacologic doses of pyridoxine in responsive patients including those with G170R mutations, though emerging therapies to block specific hepatic enzymes are under clinical trial and appear promising. However, whether reducing oxalate production can result in recovery of kidney in a subset of patients with advanced chronic kidney disease (CKD) is unknown. Here we report a series of three G170R homozygous patients with ESKD who experienced recovery of kidney function that allowed dialysis discontinuation following treatment with pyridoxine.
Case Description
Data from the Rare Kidney Stone Consortium PH Registry was reviewed. Among the 41 G170R homozygous patients, 23 progressed to ESKD, including those who are the subject of this report. Median age at initiation or resumption of pyridoxine treatment following ESKD among these three patients was 37 years (range 20-53), and pyridoxine dose was 8.8 mg/kg/d (range 6.8-14.0 mg/kg/d). Median duration of dialysis prior to renal recovery was 10 months (range 5-19). Plasma oxalate (POx) improved after recovery of renal function even while still on dialysis. At a median of 3 months (range 2-46) following discontinuation of dialysis, estimated glomerular filtration rate was 34 ml/min/1.73 m2 (range 23-52), POx was 8.8 µmol/L (4.6-11.3), and UOx was 0.93 mmol/24 hours (0.47-1.03). Kidney function was maintained during a median of 3.2 yrs (range 1.3-3.8) of follow-up.
Discussion
Our findings challenge the conventional wisdom that ESKD in PH1 is always irreversible. Rather, in selected PH cases advanced CKD could potentially be reversed if hepatic oxalate production is reduced promptly after dialysis initiation. Thus new or emerging treatments may prevent the need for kidney transplantation in a subset of PH1 patients, even after ESKD ensues.
Baseline characteristics of G170R homozygous PH1 patients who recovered renal function after treatment with pyridoxine
| Patient | Age at PH1 symptom1 onset (years) | Age at dialysis initiation (years) | Pyridoxine initiation or resumption | Initial POx (µmol/L) | UOx before pyridoxine (mmol/24 hrs) |
| 1 | 25 | 37 | 3 months after dialysis initiation | 47.2 on dialysis, prior to pyridoxine initiation | 0.95 |
| 2 | 2.5 | 20 | At time of dialysis initiation | 26.6 on dialysis, 6 weeks after pyridoxine initiation | 2.34 |
| 3 | 33 | 53 | Within 1 week after dialysis initiation | 67.9 on dialysis, 6 weeks after pyridoxine resumption | 1.87 |