Primary Hyperoxaluria Type 2 Requires Careful Follow-Up

By Will Boggs MD

October 05, 2019

NEW YORK (Reuters Health) - Patients with primary hyperoxaluria type 2 (PH2), a rare inherited disorder, require careful follow-up due to the risk of significant morbidity, according to findings from the European Hyperoxaluria Consortium (OxalEurope).

"Renal outcome in PH2 is worse than was borne out by previous reports, as more than 50% of our cohort experienced chronic kidney disease stage 2 (CKD2) or worse and almost one-quarter had reached CKD5 during follow-up, with a median renal survival of 43 years," Dr. Sander F. Garrelfs of Emma Children's Hospital, University of Amsterdam, told Reuters Health by email.

PH2, a subtype of primary hyperoxaluria, is caused by a deficiency of the enzyme glyoxylate reductase/hydroxypyruvate reductase encoded by GRHPR. Its manifestations seem to be milder than those of primary hyperoxaluria type 1.

Conservative treatment includes high fluid intake and calcium oxalate crystallization inhibitors, but liver transplantation is thought to be the only curative option.

Dr. Garrelfs and colleagues sought to describe the disease course of PH2 and to identify potential factors that could predict outcome in their study of 101 PH2 patients (46 females and 55 males) from 75 families.

Symptom onset occurred at a median age of 3.2 years, but the median age at time of diagnosis for index cases was nine years.

The main presenting features were urolithiasis (82.8%), nephrocalcinosis (35.1%) and recurrent urinary-tract infections (32.1%).

During a median duration of follow-up of 12.8 years (1,321 patient-years), 43 stone-forming patients required 144 urological procedures, and four patients required unilateral nephrectomy.

Eleven patients had progressed to CKD5 before the diagnosis was made, 22 (24.7%) reached CKD5 at a median age of 40.4 years, and 23 others had impaired renal function at follow-up, the researchers report in Kidney International, online September 3.

There were no significant associations between incident CKD5 and gender, diagnosis by family screening, age at first symptom, nephrolithiasis, or L-glycericaciduria.

All patients received conservative treatment consisting of hyperhydration and alkalinization of the urine with oral potassium citrate to inhibit calcium-oxalate-stone formation.

Ten patients with CKD5 received cadaveric kidney transplant at a median 1.6 years following onset of renal failure, and cumulative kidney allograft survival (censored for death) was 43% at one year and 29% at five years.

Seven of the 22 individuals with CKD5, all transplant recipients, died at ages ranging from 28 to 56 years.

"Accurate diagnosis (by at least two 24-hour urine analysis followed by genetic testing) and careful follow-up are required to initiate (conservative) treatment in an early stage, in order to attempt to ameliorate its poor outcome," Dr. Garrelfs said. "It is important that patients are managed by a nephrologist/urologist with knowledge of the disease and its treatment."

"It is important to note that patients with PH2 are indistinguishable from PH1 simply based on clinical characteristics," he said. "Our data shows that the diagnosis of PH2 is commonly overlooked for years and/or completely missed. We hope to increase the familiarity and awareness for PH2."

"The role of liver transplantation remains unclear although it is evident that renal transplantation alone does not cure the disease," the researchers note. "Future siRNA drug interventions targeting LDHA (the gene that encodes LDH, which converts glyoxylate to oxalate) may offer a novel approach in reducing oxalate production in PH2 and could thereby improve long-term prognosis."


Kidney Int 2019.