Table 1 Consensus statements on the management of patients with or suspected to have PH
Statement number | Statement | Grading |
|---|---|---|
Genetics | ||
1 | We recommend genetic testing of each patient with high clinical and/or biochemical suspicion of PH | A (strong recommendation) |
2 | We recommend offering genetic counselling to patients with PH and their families | A (strong recommendation) |
Diagnostics | ||
3 | We recommend assessing urinary oxalate excretion, along with creatinine, by 24 h urine collection | A (strong recommendation) |
4 | We suggest that spot urine collections may be used in place of 24 h urine collections where clinically necessary, provided that oxalate assessment is expressed as the oxalate-to-creatinine ratio | C (moderate recommendation) |
5 | We recommend at least two positive urine assessments (urine oxalate higher than the upper reference limit) to establish hyperoxaluria | B (strong recommendation) |
6 | Acidification of urine samples for oxalate assessment can be done in the laboratory within 24 h, provided the sample is kept at 4 °C after collection | B (moderate recommendation) |
7 | We recommend using age-related reference values in interpreting urinary oxalate-to-creatinine ratios | B (strong recommendation) |
8 | We suggest including assessment of urinary calcium oxalate crystal volume, if available, in the diagnostic work-up of PHa | D (weak recommendation) |
9 | We suggest measuring PH urine metabolites (glycolate, l-glycerate, HOG, DHG) in patients with hyperoxaluria | B (moderate recommendation) |
10 | We recommend confirming a diagnosis of PH1 by genetic testing in situations in which increased urinary glycolate is found in the presence of hyperoxaluria, noting that normal values of urinary glycolate do not exclude PH1 | A (strong recommendation) |
11 | We recommend confirming a diagnosis of PH2 by genetic testing in situations in which increased urinary l-glycerate is found in the presence of hyperoxaluria | A (strong recommendation) |
12 | We recommend confirming a diagnosis of PH3 by genetic testing in situations in which increased HOG and DHG are found in the presence of hyperoxaluria, noting that normal values of urinary HOG do not exclude a diagnosis of PH3 | A (strong recommendation) |
13 | We recommend measuring plasma oxalate levels only in patients with CKD stage 4 or higher | A (strong recommendation) |
14 | We recommend interpreting plasma oxalate levels on the basis of reference values, taking the impact of kidney failure into account | B (strong recommendation) |
Conservative treatment | ||
15 | We recommend prompt initiation of conservative therapy in all patients with suspected PH | B (strong recommendation) |
16 | We recommend starting hyperhydration (3.5–4 l/day in adults; 2–3 l/m2 BSA in children, to be consumed throughout 24 h), in all patients with suspected PH and preserved kidney function | A–B (strong recommendation) |
17 | We recommend monitoring hyperhydration on the basis of urinary markers; the frequency of monitoring is dependent on disease severity | B (moderate recommendation) |
18 | We recommend oral administration of potassium citrate (0.1–0.15 g/kg) in patients with preserved kidney function | C (moderate recommendation) |
19 | We recommend that patients with PH receive a balanced diet, avoiding only foods that contain extremely high levels of oxalate | D (weak recommendation) |
20 | We recommend testing pyridoxine responsiveness in all patients with PH1 and titrating its dose based on urinary oxalate excretion | A (strong recommendation) |
Dialysis treatment | ||
21 | We suggest considering kidney replacement therapy before kidney failure has developed in patients with PH1 who are at high risk of systemic oxalosis due to high plasma oxalate values or those already suffering from comorbidities | X (moderate recommendation) |
22 | In situations of no access or response to oxalate-lowering therapies, we recommend intensified haemodialysis, which is dose titrated to the clinical condition and plasma oxalate levels, and in accordance with the tolerance levels of the patient and family | X (strong recommendation) |
23 | We recommend using a high-flux haemodialyser (>1 m² capillary surface per 1 m2 BSA) with maximal blood flow (>150–200 cm3/min/m2 BSA) when performing haemodialysis | C (moderate recommendation) |
24 | We recommend personalizing the dialysis regimen based on clinical observations of oxalosis and plasma oxalate values, aiming to keep plasma oxalate values in the range of values for patients with kidney failure without PH | X (strong recommendation) |
Transplantation | ||
25 | Liver transplantation for PH should always be performed with complete removal of the native liver | A (strong recommendation) |
26 | The strategy for either sequentially or simultaneously performed liver and kidney transplantation should be decided based on the clinical situation and the preference of the local surgeon | B (moderate recommendation) |
27 | We recommend that liver transplantation is combined with kidney transplantation in patients with PH1 and advanced disease (eGFR <30 ml/min/1.73 m2) who do not respond to pyridoxine and have no access to RNAi therapy | X (strong recommendation) |
28 | Liver transplantation may be suggested in patients with PH2 and advanced disease (eGFR <30 ml/min/1.73 m2) | C (moderate recommendation) |
29 | Isolated kidney transplantation should be considered in patients with PH1 and stage 5D CKD who are homozygous for pyridoxine-responsive mutations | B (strong recommendation) |
30 | We recommend monitoring urinary and plasma oxalate levels at least every 6 months after liver transplantation until normal values (that is, below the upper limit of normal), are obtained on at least three occasions | C (moderate recommendation) |
31 | We recommend monitoring urinary and plasma oxalate levels at least every 6 months after kidney transplantation for patients receiving pyridoxine or/and RNAi therapy until levels normalize, and thereafter at least once per year | C (weak recommendation) |
Urology | ||
32 | We recommend following the EAU guidelines for surgical management | X (strong recommendation) |
33 | We suggest PCNL and ureteroscopy instead of ESWL as intervention to remove stones in PH | C (moderate recommendation) |
34 | We recommend following the EAU guidelines on imaging | X (moderate recommendation) |
35 | We suggest that patients with PH should have lifelong imaging follow-up | B (strong recommendation) |
36 | We suggest that patients with PH should have annual imaging follow-up | D (weak recommendation) |
Infantile oxalosis | ||
37 | Infantile oxalosis is defined as stage 5D CKD due to PH before the age of 1 year | X (strong recommendation) |
38 | We suggest performing bone X-rays only in case of bone symptoms | C (moderate recommendation) |
39 | We recommend performing eye examination at time of diagnosis and to repeat as indicated | B (strong recommendation) |
40 | We recommend performing cardiac ultrasound at time of diagnosis and to repeat at least yearly | C (moderate recommendation) |
RNAi therapy | ||
41 | We suggest that the benefit of RNAi therapy should always be weighed against its potential long-term risks in patients with PH1 | X (strong recommendation) |
42 | We recommend treatment with RNAi therapy under the following conditions: 1. PH1 is genetically established in patients of any age AND 2. patients are biochemically unresponsive to pyridoxine OR have a mutation consistent with pyridoxine unresponsiveness AND 3. urine oxalate excretion is >1.5 times the upper reference limit AND 4. patients demonstrate a clinical phenotype of PH1, characterized by active stone disease AND/OR nephrocalcinosis AND/OR renal impairment | B (strong recommendation) |
43 | We recommend treatment with RNAi therapy under the following conditions: 1. PH1 is genetically established in patients of any age with a mutation consistent with pyridoxine unresponsiveness and eGFR <30 ml/min/1.73 m2 OR 2. patients are suspected to have PH1 based on findings of elevated plasma oxalate and plasma glycolate levels with stage 5D CKD, but are awaiting genetic confirmation | B (strong recommendation) |
44 | We suggest treatment with RNAi therapy under the following conditions: 1. PH1 is genetically established in patients of any age AND 2. partial pyridoxine responsiveness has been biochemically established up to urinary oxalate remaining >1.5 times the upper reference limit of normal AND 3. patients demonstrate a clinical phenotype of PH1, characterized by active stone disease AND/OR nephrocalcinosis AND/OR renal impairment | B (moderate recommendation) |
45 | We suggest treatment with RNAi therapy under the following conditions: 1. PH1 is genetically established AND 2. pyridoxine unresponsiveness is biochemically established OR patients have a mutation consistent with pyridoxine unresponsiveness AND 3. urine oxalate excretion is >1.5 times the upper reference limit AND 4. patients have no ongoing clinical disease | C (weak recommendation) |
46 | If RNAi therapy is not available, we suggest testing other medications that are currently under investigation (for example, stiripentol). | D (weak recommendation) |
47 | We do not recommend administering RNAi therapies to patients with PH who are pyridoxine-responsive and have normalization of urinary oxalate excretion | C (moderate recommendation) |
48 | We suggest that continuation of RNAi and other specific new therapies should be based on annual re-evaluation of biochemical and clinical efficacy | X (strong recommendation) |
