2) Our expert author is Cathy Quinlan MD @KidneyCathy, an academic paediatric nephrologist with a career focus on #GeneticKidneyDisease aiming to end #kidneyfailure in childhood. She works @MCRI_for_kids @RCHMelbourne @UniMelbMDHS🇦🇺 pic.twitter.com/P8POxAoTQx
— @CKD_ce (@ckd_ce) February 28, 2023
4) Did you know that #ADPKD, one of the most common genetic kidney diseases, impacts children? For the vast majority of kids, it is a relatively benign condition, so management can be overlooked. Buckle up for a #tweetorial on the course and management of #ADPKD in childhood. pic.twitter.com/jUjttQjO7a
— @CKD_ce (@ckd_ce) February 28, 2023
5b)
— @CKD_ce (@ckd_ce) February 28, 2023
1⃣ Improved understanding of its inheritance ➡️ more referrals of at-risk kids
2⃣ More frequent use of abdominal #imaging in the workup of common childhood conditions ➡️incidental detection of #cysts
3⃣ Widespread use of #prenatal #ultrasound ➡️ earlier detection of cysts
6b) PC1 & PC2 are multispan membrane proteins that form a heterodimeric complex thru interaction of the coiled-coil motifs in their carboxy-terminal tails; they are thought to play a role in the regulation of cell division & the formation of cilia.
— @CKD_ce (@ckd_ce) February 28, 2023
See https://t.co/GLF4zxpVfY pic.twitter.com/wc1DzZriRc
8a) #IFT140 is a core component of the intraflagellar transport complex A, involved in retrograde ciliary trafficking. Biallelic variants are associated with #nephronophthisis.
— @CKD_ce (@ckd_ce) February 28, 2023
8c) The same group showed that gene correction rescued the phenotype.
— @CKD_ce (@ckd_ce) February 28, 2023
See 🔓 https://t.co/JjItf8fkYP
10) #GANAB encodes the #glucosidase IIa subunit. GANAB-null kidney cells have depletion of mature #polycystin-1. Monoallelic variants in GANAB are associated with mild #PKD and variable #polycystic #liverdisease.
— @CKD_ce (@ckd_ce) February 28, 2023
See 🔓 https://t.co/q3eRkxV9wl
11b) Monoallelic variants in #DNAJB11 are associated with a milder #ADPKD phenotype, including small #kidney #cysts, non-enlarged kidneys, chronic interstitial fibrosis similar to #ADTKD, and liver cysts. pic.twitter.com/vwH8cWWIRn
— @CKD_ce (@ckd_ce) February 28, 2023
13) Children with @ADPKD are a neglected group who have only recently been included in guidelines. ADPKD in childhood represents an opportunity to act early, educate, & set up positive relationships w/healthcare professionals that will travel with the child through to adulthood. pic.twitter.com/uoRzpXMWzB
— @CKD_ce (@ckd_ce) February 28, 2023
15a) The “second hit” hypothesis suggests that disease progression in #ADPKD is due to 2 events: pic.twitter.com/rWduQZrCvi
— @CKD_ce (@ckd_ce) February 28, 2023
16) Knowing that kids with #ADPKD can have symptoms in childhood – how do we manage them? Several recent guidelines mention children, including @goKDIGO @cariguidelines @PKD_Int and #NEOCYST
— @CKD_ce (@ckd_ce) February 28, 2023
17b) Diagnosis confirmation or exclusion criteria based on ultrasound excludes children <15yo.
— @CKD_ce (@ckd_ce) February 28, 2023
Over 15yo, ≥3 cysts = confirmation @goKDIGO pic.twitter.com/y4JV6QMm4t
19) Incidence of kidney #cysts in childhood is low & multiple cysts ➡️⬆️high suspicion for cystic #KidneyDisease. Parents should be counselled that a negative USS can still be associated with #ADPKD, particularly with milder genotypes such as #PKD2. https://t.co/JG7gXmgRHV
— @CKD_ce (@ckd_ce) February 28, 2023
21) The @cariguidelines:
— @CKD_ce (@ckd_ce) February 28, 2023
🧬 At-risk children should be referred to genetic counselling to discuss testing
👉Screening is defined as #bloodpressure measurement +/- ultrasound
See https://t.co/EkE1KQm5lB pic.twitter.com/M1b9EotEmY
22b) (cont)
— @CKD_ce (@ckd_ce) February 28, 2023
🧬Offering genetic counselling to all children and families
🩺Monitoring for other complications including liver cysts and cardiovascular disease
🛋️ Provision of psychosocial support
23b)
— @CKD_ce (@ckd_ce) February 28, 2023
👉For asx at-risk children, ongoing surveillance or immediate diagnostic screening are 🟰 valid clinical approaches.
👉#Cyst on USS in at-risk child is highly suggestive of #ADPKD but negative scan can’t rule out ADPKD
23d) … progressive disease (increasing cyst number or kidney volume) ➕ negative #FamHx
— @CKD_ce (@ckd_ce) February 28, 2023
💊Vasopressin antagonists to be considered in selected children only
👉1+ #cysts on USS in an at-risk child is highly suggestive of #ADPKD, but a negative scan cannot r/o ADPKD in childhood.
24a) Whew! Drinking from the 🔥hose!
— @CKD_ce (@ckd_ce) February 28, 2023
So, what is considered to be the current gold standard for #ADPKD diagnosis in childhood?
25) WELCOME BACK! You are learning about #ADPKD in #childhood from expert author @KidneyCathy 🇦🇺 while you earn 🆓CE/#CME. Take a moment RIGHT NOW and if you don't follow @ckd_ce already, CLICK THAT BUTTON! pic.twitter.com/OQMX3Us4D6
— @CKD_ce (@ckd_ce) March 1, 2023
27a) Registry data are clearly needed to address knowledge gaps; @ADPedKD is 🔭 the unknowns by enrolling patients in a global database, recording demographics, genetics, #FamHx, renal & extra-renal features, medications, & current therapies.
— @CKD_ce (@ckd_ce) March 1, 2023
See 🔓https://t.co/n3R1MzfJpt pic.twitter.com/KOQ1FDLUje
28) The management of #ADPKD in adults has been changed by the #vasopressin V2 receptor antagonist #tolvaptan which slowed the ⬆️in total kidney volume (a measure of #cystogenesis) in the original #TEMPO trial.
— @CKD_ce (@ckd_ce) March 1, 2023
See 🔓 https://t.co/cOzihQdUJn
30) The #REPRISE trial then showed a slowing of decline in kidney function in selected patients with advanced #cystic #KidneyDisease. Could this be applied to children?
— @CKD_ce (@ckd_ce) March 1, 2023
See 🔓 https://t.co/qC7l8SNqw9 pic.twitter.com/Rs0fiAkDlD
32a) Mekahli & colleagues randomised 66 teenagers (12-17yo) & 25 children (4-11yo) w/ #eGFR >60 to #tolvaptan or placebo, showing good tolerability (similar discontinuation between drug & placebo)
— @CKD_ce (@ckd_ce) March 1, 2023
See 🔓 https://t.co/niBizifjQi. pic.twitter.com/Zo7dMqpgJ5
32c) But did it work? Impossible to say since a 1-year study was too short to know – the 2-year open label extension might provide more information. https://t.co/ZxOK93XF6g
— @CKD_ce (@ckd_ce) March 1, 2023
33b)
— @CKD_ce (@ckd_ce) March 1, 2023
👉Children are at risk of sx #ADPKD so they should be under the care of a #physician: pediatric nephrologist, pediatrician or GP depending on the #healthcare setting
33d)
— @CKD_ce (@ckd_ce) March 1, 2023
👉The presence of one or more cysts in an at-risk child is highly suspicious, but a negative ultrasound scan does not equal a negative test, and the child should continue to be considered at risk.
See https://t.co/VIQkSebMtc
33f)
— @CKD_ce (@ckd_ce) March 1, 2023
👉Children with #ADPKD are at risk of #HTN. They should have regular #BP measurements – every 1-3 years, depending on the healthcare setting. See 🔓https://t.co/hGYpexiKjD
33h)
— @CKD_ce (@ckd_ce) March 1, 2023
👉 Children with #ADPKD are at risk of #CKD. They should have urinalysis for #albuminuria or #proteinuria every 1-3 years with measurement of creatinine if positive. pic.twitter.com/erxwclcEIV
33j)
— @CKD_ce (@ckd_ce) March 1, 2023
👉Psychosocial family support should be provided pic.twitter.com/PhSC3YjFhF
34) Finally, register your patients with @ADPedKD at https://t.co/wL2sT8r9VH !
— @CKD_ce (@ckd_ce) March 1, 2023
36) You got this. It’s c, although studies are currently underway that may support starting treatment earlier. For now, just be 😀! You just earned 0.75h 🆓CE/#CME. Claim your certificate NOW at https://t.co/U1ZPLiFUTl. I am @KidneyCathy and I 🙏you for joining! Hurry back! pic.twitter.com/ECYyseKjHl
— @CKD_ce (@ckd_ce) March 1, 2023