Clinical Guidance

The low prevalence of PH2 does not allow genotype-phenotype correlations at the present time.

Source: GeneReviews — "Primary Hyperoxaluria Type 2"

Diagnostic Criteria

Suggestive Findings

Primary hyperoxaluria type 2 (PH2) should be suspected in individuals with the following clinical and laboratory features.

Clinical features

• Symptoms of nephrolithiasis (e.g., hematuria, renal colic, obstruction of the urinary tract)

• Frequent recurrent nephrolithiasis

• Nephrocalcinosis

• End-stage kidney disease with a history of nephrolithiasis

Laboratory features

Source: GeneReviews — "Primary Hyperoxaluria Type 2"

Differential Diagnosis

Primary hyperoxaluria type 1

(PH1) is the most common form of inherited hyperoxaluria, accounting for approximately 80% of cases. It is caused by a deficiency of the liver peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is absent, glyoxylate is converted to oxalate, which forms insoluble calcium salts that accumulate in the kidney and other organs. Individuals with PH1 are at risk for recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis/ urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), or ESKD with a history of kidney stones or oxalosis.

Source: GeneReviews — "Primary Hyperoxaluria Type 2"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with primary hyperoxaluria type 2 (PH2), the following evaluations, originally outlined for PH1, are recommended if they have not already been completed :

• Assessment of kidney function

• If moderate to advanced ESKD is present, assessment of systemic oxalate deposition in tissue and bone:

• Bone radiographs to look for radiodense metaphyseal bands followed by cystic rarefaction of bones

• Ophthalmic examination of the retina to look for oxalate crystals

• Evaluation of cardiac function by echocardiography and EKG

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Management follows general guidance for that of kidney stones: to relieve obstruction, and to manage symptoms of renal impairment as they arise.

Reduction of Calcium Oxalate Supersaturation

As with PH1, conservative therapy is applied with the aim of minimizing oxalate-related renal injury and preserving renal function. Treatment of persons with preserved renal function, reviewed by , essentially aims to improve oxalate solubility as follows:

• Adequate fluid intake (2.5 L/m2 surface area/day)

• Urinary inhibitors of calcium oxalate crystallization:

• Orthophosphate treatment (20-30 mg/kg body weight/day)

• Potassium citrate (0.1-0.15 g/kg body weight/day)

Dialysis

Because the plasma oxalate concentration begins to rise when the renal clearance is less than 40 mL/min/1.73 m2, early initiation of dial...

Source: GeneReviews — "Primary Hyperoxaluria Type 2"

Clinical Guidance

The following should be avoided:

• Dehydration

• Excessive ascorbate (i.e. vitamin C; 1000 mg/day)

• Foods rich in oxalate (chocolate, rhubarb, spinach, and star fruit in particular)

• High salt (sodium) diet should be discouraged.

• Excessive stone interventions with extracorporal shock wave lithotripsy

Source: GeneReviews — "Primary Hyperoxaluria Type 2"

Therapies Under Investigation

Oxalobacter formigenes treatment did not demonstrate significant effect in reducing oxalate via gut excretion in individuals with PH1 but continues to undergo clinical trials in individuals with hyperoxaluria and impaired kidney function . Other proposed trials include the use of inhibitors of glycolate oxidase (ALN-GO1) to reduce the amount of glyoxylate produced, although this treatment would be mainly relevant to treatment of individuals with PH1. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Primary Hyperoxaluria Type 2"

Surveillance Guidelines

Frequency of recommended screening can vary; however, as a guide, the following are recommended. Individuals with preserved renal function (i.e., measured or estimated GFR ≥60 mL/min/1.73 m2) require the following to evaluate/ensure treatment efficacy:

• Biannually. Assessment of renal function, urinalysis with measurements of urine oxalate excretion using 24-hour collection if easy to facilitate; or spot urine oxalate-to-creatinine ratio, and calcium oxalate saturation if available, blood pressure, and full blood count including hematocrit. The presence of blood in the urine may indicate stones, but protein in an early morning sample necessitates review of renal function as it may herald a decline in GRF.

• Biannually to annually. Renal imaging (ultrasound or CT examination) to assess kidney stone burden as appropriate. Note: Annual scans are appropriate if no stones or nephrocalcinosis are visualized.

Individuals with a GFR 60 mL/min/1.73 m2 should have the above evaluations performed quarterly, as well as the following testing annually to evaluate for involvement of other organ systems apart from the renal tract.

Source: GeneReviews — "Primary Hyperoxaluria Type 2"