Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

Abstract

Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up. SectionsUnanswered questions and research agenda Conclusions

A Policy Call to Address Rare Kidney Disease in Health Care Plans

“…With today's limited therapeutic resources, some may question the usefulness of an early diagnosis, but it will still allow a number of appropriate lifestyle measures and BP control. Early action will gain importance because the number of specific therapies will increase, as has already been demonstrated in selected diseases (e.g., cystinosis 17 and primary hyperoxaluria 18 ).…”

“…Early action will gain importance because the number of specific therapies will increase, as has already been demonstrated in selected diseases ( e.g. , cystinosis 17 and primary hyperoxaluria 18 ).…”

Combined liver‐kidney transplantation in pediatric patients

“…64 CLKT is now recommended in PH1 and advanced kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m 2 ) who shows no response to pyridoxine therapy where RNAi therapy is not accessible. 64 In cases where chronic dialysis becomes a necessity, the severity of systemic oxalosis escalates, making sqLKT a viable therapeutic option. After LT, it is imperative to employ rigorous kidney replacement therapy to mitigate the accumulation of systemically deposited oxalate in anticipation of the KT.…”

“…Patients with PH1 present with kidney stones or nephrocalcinosis early in life with mean age of 5.6 years and transplant was required in mean age of 16.5 years 63 . According to the clinical practice recommendations from the European Rare Kidney Disease Reference Network and OxalEurope, hyperhydration (2–3 L/m 2 ) throughout 24 hours is recommended in patients with preserved kidney function 64 . Moreover, since in some cases of PH1 pyridoxine is effective in lowering urinary oxalate excretion, it is recommended as supplementation (5–20 mg/kg/day) in PH1 group with monitoring of the response.…”

How to Monitor Hydration Status and Urine Dilution in Patients with Nephrolithiasis

“…For cystine stone former patients, this daily urine volume should even be above 3L per day [ 42 ]. Patients with primary hyperoxaluria and preserved kidney function are advised to have hyperhydration, corresponding to 3.5–4 L/d in adults and 2–3 L/m 2 body surface area in children to be consumed over 24 h [ 43 ].…”