2) This #accredited #tweetorial series on #ADPKD and emerging therapies is supported by an independent educational grant from Otsuka Pharmaceuticals and is intended for healthcare providers. YOU CAN EARN 0.75 HOUR 🆓CE/#CME CREDIT WITH THIS PROGRAM!#MedEd #FOAMed @MedTweetorials
— @CKD_ce (@ckd_ce) March 22, 2023
4) #ADPKD is a genetic disorder characterized by the development of fluid-filled cysts in the kidneys. These cysts can lead to kidney enlargement, progressive loss of kidney function, and other complications. #ADPKD #KidneyDisease #GeneticDisorders pic.twitter.com/WWgMgSbAqd
— @CKD_ce (@ckd_ce) March 22, 2023
5b) The polycystin proteins are involved in a wide range of cellular mechanisms, including cell-cell and cell-matrix interactions, fluid flow sensing, and intracellular signaling pathways. #ADPKD #Genetics #PolycystinProteins
— @CKD_ce (@ckd_ce) March 22, 2023
6a) So what is the THIRD most common cause of autosomal dominant polycystic kidney disease (#ADPKD)?
— @CKD_ce (@ckd_ce) March 22, 2023
A: Mutations in the #PKD2 gene
B. Mutations in the #DNAJB11 gene
C. Monoallelic mutations in the #IFT140 gene
D. Mutations in the #GANAB gene
7a) #Genetic testing is important in individuals with suspected or diagnosed #PKD as accurate diagnosis is critical in understanding disease progression and potential treatment options #PKD #GeneticTesting @ecorneclegall @AlexchangMD pic.twitter.com/WRJtjQfJAl
— @CKD_ce (@ckd_ce) March 22, 2023
7c) A rare variant was identified in a cystic gene in 180/235 (76.6%) of ADPKD patients, with the most common genes implicated PKD1 (127) and PKD2 (34) and then IFT140 (7), PKHD1 (3), GANAB (4), HNF1B (2), ALG8 (1), ALG9 (1), IFT140+PKHD1 (1). pic.twitter.com/3UfSN2QJyg
— @CKD_ce (@ckd_ce) March 22, 2023
8b) What is the definition of #risk of rapid progression in #ADPKD?
— @CKD_ce (@ckd_ce) March 22, 2023
A. Diagnosis at early age
B. Risk of reaching kidney failure by age 62
C. Rapid decline of GFR over weeks to months
D. Other (please add in comment)
9a) This morning, a 35-year-old male with #ADPKD and #CKD stage 2 presented to your clinic. He reports a family history of early onset end-stage kidney failure (#ESKF) before age 50, has a truncating mutation in the #PKD1 gene and Mayo Imaging Class 1E.
— @CKD_ce (@ckd_ce) March 22, 2023
9c) You tell him:
— @CKD_ce (@ckd_ce) March 22, 2023
A: Start the “basic optimized ADPKD management”
B: Start Vasopressin-receptor antagonist, tolvaptan
C: If not a candidate or ready to start a vaptan, consider enrolling in a clinical trial
D: All of the above
10a) Your patient asks you about the underlying what is the driving force that causes his kidneys to become relentlessly cystic:
— @CKD_ce (@ckd_ce) March 22, 2023
A) Aberrant cell proliferation
B) Aberrant fluid secretion
C) Inflammation and fibrosis
D) All of the above
11a) #cAMP signaling plays a central role by stimulating cystic epithelial cell proliferation and fluid secretion. #Vasopressin actin on V2 receptor is the main hormonal regulator of cAMP in collecting duct cells.
— @CKD_ce (@ckd_ce) March 22, 2023
11c) Vaptans inhibit cAMP signaling by acting on the vasopressin 2 receptor (V2R) in the kidney, reducing fluid secretion and cyst growth in ADPKD. #ADPKD #Vaptans #cAMP pic.twitter.com/tNdovoh4vM
— @CKD_ce (@ckd_ce) March 22, 2023
11e) The #TEMPO 3:4 trial showed that tolvaptan treatment over 3 years decreased total kidney growth and the rate of decline in GFR in high-risk #ADPKD patients. The #REPRISE trial showed similar benefits in patients with late-stage ADPKD. #ADPKD #Tolvaptan #ClinicalTrials pic.twitter.com/HqihFIfguW
— @CKD_ce (@ckd_ce) March 22, 2023
12b) #Refer to my previous tweetorial on identifying rapid progression in #ADPKD, still available for 🆓CE/#CME, at https://t.co/GCce6vQOkO
— @CKD_ce (@ckd_ce) March 22, 2023
12d) So your patient asks you, if I start tolvaptan, how much do I expect to slow my disease process?
— @CKD_ce (@ckd_ce) March 22, 2023
A. Every 4 yrs of tx delays onset of ESRD by 1 yr
B. 1.3 ml/min gain for every year of treatment
C. Predicted 3.1-year delay of ESRD over 13.7 yrs of tx
D. All of the above
12f) Your patient would like to learn how to get tolvaptan prescribed and what are the side effects. You tell him (cont):
— @CKD_ce (@ckd_ce) March 22, 2023
12h) Answer is D. For full details, please refer to the practical guide for treatment of Rapidly progressive ADPKD with tolvaptan. https://t.co/YausSkqDFx pic.twitter.com/GaL7XQyeto
— @CKD_ce (@ckd_ce) March 22, 2023
13b) There was no effect between prescribed (high) water intake and ad libitum on changes on #GFR slope or #TKV growth. However, only 52% achieved target Uosm. Water prescription remains beneficial in my opinion when limited therapeutic options are available in #ADPKD. pic.twitter.com/o2KQE15YoS
— @CKD_ce (@ckd_ce) March 22, 2023
15) Take a breath & return here TOMORROW; we’ll review recent clinical trials on #ADPKD management. @AlanYuNeph @ndahl48 @PKDfoundation @dr_nikhilshah @shubharthikar @Elektra @kidneydoc101 @NephRodby @edgarvlermamd @nephondemand @NephPhD @FLAVIAZH @dguerrot @KorstUwe @kkalra_22
— @CKD_ce (@ckd_ce) March 22, 2023
17a) Clinical studies investigating #somatostatin analogues in #ADPKD patients have reported conflicting results. The #ALADIN trial showed that octreotide LAR reduced total kidney volume (TKV) growth after 1 year but not at 3 years. #ADPKD #Somatostatin #ALADIN pic.twitter.com/MzUHeIFxN3
— @CKD_ce (@ckd_ce) March 23, 2023
17c) However, patients treated with octreotide LAR progressed less frequently to a composite endpoint of doubling of serum creatinine or ESKD compared to placebo. #ADPKD #Somatostatin #ALADIN2
— @CKD_ce (@ckd_ce) March 23, 2023
18b) The #LIPS study also investigated #lanreotide but publication of the results is still awaited. #ADPKD #Somatostatin #Lanreotide #DIPAK1 #LIPS
— @CKD_ce (@ckd_ce) March 23, 2023
20a) The #mTOR pathway has been implicated in the pathogenesis of ADPKD, and drugs that target this pathway, such as everolimus and sirolimus, have been investigated as potential treatments for the disease. #ADPKD #mTOR #Everolimus #Sirolimus pic.twitter.com/lRZHTpC7RT
— @CKD_ce (@ckd_ce) March 23, 2023
20c) Mucositis and diarrhea were among the most commonly reported side effects, which led to dose reductions and interruptions that compromised the drugs' effectiveness. #ADPKD #mTOR #Everolimus #Sirolimus #ClinicalTrials pic.twitter.com/5Z9FAWvZW9
— @CKD_ce (@ckd_ce) March 23, 2023
20e) New drugs that can effectively inhibit the mTOR pathway without causing severe side effects may hold promise for slowing disease progression and improving outcomes for ADPKD patients. #ADPKD #mTOR #DrugDevelopment #FutureResearch
— @CKD_ce (@ckd_ce) March 23, 2023
21b) #Bardoxolone, a potent activator of Nrf2, has been found to have renoprotective effects in #DKD. It was assoc'd w/ an increased eGFR compared to placebo, but also an ⬆️in urinary albumin to creatinine ratio (#UACR) which may indicate drug-induced glomerular hyperfiltration. pic.twitter.com/Q4Js3YO69H
— @CKD_ce (@ckd_ce) March 23, 2023
22a) Metabolic reprogramming in ADPKD, inc a shift to glycolysis & excess ATP production, contributes to cyst formation. Drugs 🎯 metabolic pathways, eg metformin & AMPK activators, show promise in preclinical studies & are in clinical trials. #ADPKD #metabolicReprogramming pic.twitter.com/qqiPtU1min
— @CKD_ce (@ckd_ce) March 23, 2023
22c) However, the results of animal studies have been inconsistent, and the timing and duration of treatment as well as the method of metformin administration may contribute to this.
— @CKD_ce (@ckd_ce) March 23, 2023
22e) A new Ph 3 study, #IMPEDE_PKD, will investigate efficacy of metformin in ADPKD patients with CKD stages 2-3A & a risk of rapid disease progression. The study will include 1164 patients with a treatment duration of 24 months, with the primary endpoint being change in eGFR. pic.twitter.com/fnllmr3NW4
— @CKD_ce (@ckd_ce) March 23, 2023
24a) #CFTR regulates transepithelial chloride secretion and influences cystogenesis in #ADPKD. CFTR inhibitors, such as VX-809, have shown promising results in reducing cyst growth and preserving renal function in preclinical models.
— @CKD_ce (@ckd_ce) March 23, 2023
25a) #Anti_micro_RNAs or micro RNA inhibitors are a promising new class of drugs for #ADPKD. They inhibit the binding of miRNAs to target mRNA, ➡️⬆️ expression of encoded proteins. Multiple miRNAs are abnormally expressed in ADPKD; #miR-17 is a key driver of disease progression. pic.twitter.com/MjxVheGwZF
— @CKD_ce (@ckd_ce) March 23, 2023
25c) Recently, a dose-escalating phase 1b study was started to assess the short-term safety and tolerability of RGLS8429. pic.twitter.com/LaeXPhd0U0
— @CKD_ce (@ckd_ce) March 23, 2023
27) And that's it! You made it! You just earned 0.75 hour of🆓CE/#CME. Go claim it at https://t.co/tfadcevLW7 and please FOLLOW @ckd_ce (and @cardiomet_ce!) for more education by the world's leading authorities! I am @fouadchebib and I thank you for joining us!
— @CKD_ce (@ckd_ce) March 23, 2023