2) They will be discussing Primary #Hyperoxaluria Type 1, with a #pediatric focus.#nephtwitter #FOAMed #MedTwitter @MedTweetorials #ThisIsISN pic.twitter.com/BH8iGl2OMp
— @CKD_ce (@ckd_ce) June 1, 2023
4a) Primary hyperoxalurias (#PH) are rare inborn errors of glyoxylate metabolism leading to the overproduction of #oxalate (Ox)
— @CKD_ce (@ckd_ce) June 1, 2023
Ox is typically excreted in urine, but is poorly soluble
5) Epidemiology#PH1 is a RARE disease
— @CKD_ce (@ckd_ce) June 1, 2023
✅Estimated prevalence –> 1 to 3 cases per 1 million population
✅incidence –> ~ 1 case per 120,000 live births per year in Europe
✅Cause of 1 to 2% of cases of pediatric #ESKD
7a) So which genetic mutation is linked to #PH1?
— @CKD_ce (@ckd_ce) June 1, 2023
8) *⃣ More than >190 variants of #AGXT have been identified.
— @CKD_ce (@ckd_ce) June 1, 2023
Gly170Arg 👉30%
c.33dupC 👉11%
💡The only known aspect of #PH1 with a strong genotype–phenotype relationship is response to #pyridoxine . . . this is seen in patients with #Gly170Arg and #Phe152Ile mutations
10) In #PH1:
— @CKD_ce (@ckd_ce) June 1, 2023
*⃣ Urine Ox excretion is 🔼> 1 mmol/1.73 m2 per day
👉Urine #CaOx supersaturation ➡️ kidney stones, and/or #nephrocalcinosis
*⃣ As the #GFR falls < 30 to 40 mL/min per 1.73 m2, plasma Ox levels 🔼 because of low urinary excretion.
This is 2nd phase of injury 📈
12) Median age dx~ 5 years (Range <1 to > 50)
— @CKD_ce (@ckd_ce) June 1, 2023
5 presentations:
*⃣ Infantile oxalosis, 26%
*⃣ Child w/recurrent stones & rapid 🔽in renal function, 30%
*⃣ Adult w/occasional stones, 30%
*⃣ Recurrence post #kidneytransplant, 10%
*⃣ Asx family screening
🔓 https://t.co/x6Bep0C3ax pic.twitter.com/ZtwgWhLT5n
14) When to clinically suspect #PH?
— @CKD_ce (@ckd_ce) June 1, 2023
*⃣ Recurrent Ca kidney stones esp in a patient with Ox crystals in the urine sediment, normal urinary calcium, uric acid excretion
*⃣ Pure #CaOx monohydrate kidney stones (#whewellite 👇)
*⃣ #Nephrocalcinosis, esp if associated with 🔽 #eGFR pic.twitter.com/GPRfcNeAhW
16) Metabolic testing (1)
— @CKD_ce (@ckd_ce) June 1, 2023
🔼 Urinary Ox excretion
✳️24 h Urinary excretion > 1 mmol/1.73 m2/d
✳️⬆️ urinary oxalate:Cr ratio (age adjusted)
🔼Plasma oxalate levels
✳️Useful only when eGFR < 30-45ml/min
✳️No clear cut off
✳️> 50 μmol/liter is suggestive
18) Genetic tests
— @CKD_ce (@ckd_ce) June 1, 2023
🧬Whole-gene sequencing (high clinical index of suspicion)
🧬Next-generation sequencing
🧬Targeted mutation analysis screens for the most common variants
20) Medical Management
— @CKD_ce (@ckd_ce) June 1, 2023
🎯reduce urinary #CaOx saturation ➡️ ⬇️ rate of loss of GFR
✳️⬆️ fluid intake to ~3L/d, may require gastrostomy in 👶
✳️Dietary oxalate restriction (may not be very effective)
🎯Inhibition of CaOx precipitation – urinary alkalinisation (K or Na citrate)
22) Specific management of #PH1#Lumasiran –
— @CKD_ce (@ckd_ce) June 1, 2023
A small interfering RNA (#siRNA) agent, targets glycolate oxidase (GO).
Inhibition of GO→ Reduced Glyoxylate ➡️ ⬇️ Ox
🔓 https://t.co/An1KndWAvD pic.twitter.com/GBDLXpnqds
24) Answer: B
— @CKD_ce (@ckd_ce) June 1, 2023
➕Ox generation ~ 4–7 mmol/1.73m2/d
➖Ox clearance
*⃣ on HD ~120 mL/min
*⃣ on PD ~7 mL/min
⚖️Removal via conventional HD/PD is 1–2 mmol/1.73m2/d ➡️uncontrolled tissue accretion
Combination of overnight #PD and intermittent daily #HD ➡️ ⬆️the overall clearance
26) Based on promising results with #siRNAs, it may be possible to slow #CKD progression & systemic oxalosis or even prevent oxalosis if the diagnosis is made early enough.
— @CKD_ce (@ckd_ce) June 1, 2023
🔓 https://t.co/ViJUYpas9s pic.twitter.com/cKPIxeLxDD
27b) ✳️Pre-emptive KTx at #CKD Stage 3b ➡️avoid the complications of systemic oxalosis (per @ERAkidney)
— @CKD_ce (@ckd_ce) June 1, 2023
🔓 https://t.co/x6Bep0C3ax pic.twitter.com/SXKyMSmOtO
29) Do we need to continue med management post CLKT?
— @CKD_ce (@ckd_ce) June 1, 2023
Yes!
*⃣ Duration depends on amount of Ox tissue stores
*⃣ Discontinued when urine Ox excretion normalises
*⃣ B/L nephrectomy at time of KTx ⬇️Ox stores
👉No place for routine #HD (may be needed if severe systemic oxalosis)
30) And CONGRATULATIONS! You just earned 0.5hr 🆓CE/#CME! Claim your certificate now at https://t.co/6dbSgGh7Av. Please FOLLOW us for more #nephtwitter #MedEd! @ISNkidneycare and our authors @Dilushiwijay & @acssjr thank you for joining us!
— @CKD_ce (@ckd_ce) June 1, 2023