Guideline sources The following summarized guidelines for the evaluation and management of hyperoxaluria are prepared by our editorial team based on guidelines from the European Hyperoxaluria Consortium (OxalEurope/ERKNet 2023), the Canadian Urological Association (CUA 2022), the European Association of Urology (EAU 2021), the American Society of Anesthesiologists (ASA/ACE/OS/AACE/ASMBS/OMA 2020), the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2020), the American College of Endocrinology (ACE/AACE 2016), the American Urological Association (AUA 2014), and the American Association for the Study of Liver Diseases (AASLD 2014). 1 2 3 4 5 6 7 8 Guidelines 1. Screening and diagnosis Indications for testing: obtain metabolic testing including urinary oxalate assessment (with one or two 24-hour urine collections obtained on a random diet) in patients with recurrent https://web.pathway.md/diseases/recURu9iv10sfKMhE 1/5 6/24/23, 12:45 PM Hyperoxaluria Pathway nephrolithiasis, or in high-risk or interested patients with a first episode of nephrolithiasis. B 2. Diagnostic investigations Urine oxalate studies: assess urinary oxalate excretion, along with creatinine, by 24-hour urine collection. B Consider obtaining spot urine collections instead of 24-hour urine collections, where clinically necessary, provided that oxalate assessment is expressed as the oxalate-to- creatinine ratio. B Show 4 more Plasma oxalate levels: measure plasma oxalate levels only in patients with CKD stage 4. B Interpret plasma oxalate levels on the basis of reference values, taking the impact of kidney failure into account. B Genetic testing: obtain genetic testing in all patients with high clinical and/or biochemical suspicion of primary hyperoxaluria. B Show 2 more 3. Medical management RNA interference therapy: consider weighing the benefit of RNA interference therapy against its potential long-term risks in patients with primary hyperoxaluria type 1. C Show 7 more 4. Nonpharmacologic interventions Dietary oxalate restriction: As per ERKNet 2023 guidelines: Initiate conservative therapy promptly in all patients with suspected primary hyperoxaluria. B Offer a balanced diet in patients with primary hyperoxaluria, avoiding only foods containing extremely high levels of oxalate. B As per CUA 2022 guidelines, advise minimization of high-oxalate foods in patients with hyperoxaluria. Consider offering a diet high in fiber, fruits, and vegetables as a protective measure against stone formation. B As per EAU 2021 guidelines, advise oxalate restriction for the prevention of kidney stone formation in patients with hyperoxaluria. Advise reducing dietary fat and oxalate in patients with enteric hyperoxaluria. B Fluid intake: Initiate hyperhydration (3.5-4 L/day in adult and 2-3 L/m BSA in pediatric patients, consumed throughout 24 hours) in all patients with suspected primary hyperoxaluria and preserved kidney function. B https://web.pathway.md/diseases/recURu9iv10sfKMhE 2/5 6/24/23, 12:45 PM Hyperoxaluria Pathway Monitor hyperhydration based on urinary markers at a frequency depending on disease severity. B Pyridoxine supplementation: As per CUA 2022 guidelines, consider initiating pyridoxine supplementation to lower urinary oxalate levels in patients with hyperoxaluria, if dietary modification has been unsuccessful. C As per EAU 2021 guidelines, initiate pyridoxine for the prevention of kidney stone formation in patients with primary hyperoxaluria. A Potassium supplementation: initiate oral supplementation of potassium citrate (0.1-0.15 g/kg) in patients with preserved kidney function. B 5. Therapeutic procedures Kidney stone removal: consider performing percutaneous nephrolithotomy or ureteroscopy rather than external shock wave lithotripsy for stone removal in patients with primary hyperoxaluria. C Dialysis: consider performing kidney replacement therapy before kidney failure has developed in patients with primary hyperoxaluria type 1 at high risk of systemic oxalosis because of the high plasma oxalate values or patients already having comorbidities. C Show 3 more 6. Surgical interventions Kidney transplantation: As per ERKNet 2023 guidelines, decide on performing either sequential or simultaneous liver and kidney transplantation based on the clinical situation and the preference of the local surgeon. B Show 3 more As per KDIGO 2020 guidelines, consider performing combined or sequential liver-kidney transplantation in eligible patients with primary hyperoxaluria type 1. C Show 2 more As per AASLD 2014 guidelines, consider performing combined liver and kidney transplantation in patients with primary hyperoxaluria and end-stage renal disease not responding to medical therapy. B Liver transplantation: As per ERKNet 2023 guidelines, perform liver transplantation with complete removal of the native liver in patients with primary hyperoxaluria. B Show 4 more As per AASLD 2014 guidelines, consider performing preemptive liver transplantation (before the development of advanced renal disease) or combined liver and kidney transplantation in the https://web.pathway.md/diseases/recURu9iv10sfKMhE 3/5 6/24/23, 12:45 PM Hyperoxaluria Pathway setting of end-stage renal disease in patients with primary hyperoxaluria not responding to medical therapy. B 7. Specific circumstances Patients with infantile oxalosis: define infantile oxalosis as stage 5D CKD due to primary hyperoxaluria before the age of 1 year. B Show 3 more Patients with enteric hyperoxaluria: As per CUA 2022 guidelines, offer elemental calcium or calcium citrate taken with meals to bind with dietary oxalate and reduce its intestinal absorption in patients with enteric hyperoxaluria. B As per EAU 2021 guidelines, offer alkaline citrates and calcium supplements for the prevention of kidney stones in patients with enteric hyperoxaluria. Advise reducing dietary fat and oxalate intake. B As per AACE 2020 guidelines, advise avoiding dehydration, B adopting a low-oxalate meal plan, B and offer oral calcium B and potassium citrate therapy B for the management of oxalosis and calcium oxalate stones occurred after bariatric surgery. Consider offering probiotics containing Oxalobacter formigenes to improve renal oxalate excretion and improve supersaturation levels. B Patients with hyperuricosuria: initiate allopurinol in patients with recurrent calcium oxalate stones with hyperuricosuria and normal urinary calcium. B 8. Preventative measures Medications to avoid: As per CUA 2022 guidelines, do not use vitamin C supplementation of > 1,000 mg/day because of the associated risk of hyperoxaluria and nephrolithiasis. D As per AACE 2016 guidelines, do not use orlistat in patients with, or at risk of, oxalate nephropathy. D 9. Follow-up and surveillance Assessment of treatment response: Assess pyridoxine responsiveness in all patients with primary hyperoxaluria type 1 and titrate its dose based on urinary oxalate excretion. B Consider continuing RNA interference therapy and other specific new therapies based on annual re-evaluation of biochemical and clinical efficacy. C Imaging surveillance: consider obtaining lifelong imaging surveillance in patients with primary hyperoxaluria. C https://web.pathway.md/diseases/recURu9iv10sfKMhE 4/5 6/24/23, 12:45 PM Hyperoxaluria Pathway References 1. Jaap W Groothoff, Ella Metry, Lisa Deesker et al. Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. Nat Rev Nephrol. 2023 Jan 5. Open 2. C T rk, A. Neisius, A. Pet k et al. EAU Guidelines on Urolithiasis. EAU Guidelines. 2021 Mar. Open 3. Pearle MS, Goldfarb DS, Assimos DG et al. Medical management of kidney stones: AUA guideline. J Urol. 2014 Aug;192 2 316 24. Open 4. Naeem Bhojani, Jennifer Bjazevic, Brendan Wallace et al. Update 2022 Canadian Urological Association guideline: Evaluation and medical management of the kidney stone patient. Can Urol Assoc J. 2022 Mar 11. Open 5. Paul Martin, Andrea DiMartini, Sandy Feng et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014 Mar;59 3 1144 65. Open 6. W Timothy Garvey, Jeffrey I Mechanick, Elise M Brett et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract. 2016 Jul;22 Suppl 3 1 203. Open 7. Jeffrey I Mechanick, Caroline Apovian, Stacy Brethauer et al. Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures 2019 Update: Cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Obesity Silver Spring). 2020 Apr;28 4 O1 O58. Open 8. Steven J Chadban, Curie Ahn, David A Axelrod et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020 Apr;104 4S1 Suppl 1 S11 S103. Open https://web.pathway.md/diseases/recURu9iv10sfKMhE 5/5