2) This #accredited #tweetorial series on the foundations of #kidneydisease #DKD through the lens of #T2D is supported by an independent educational grant from the Boehringer Ingelheim/Lilly Alliance and is intended for healthcare providers.
— @CKD_ce (@ckd_ce) September 7, 2022
4a) Let’s start with a case. 53♂️ with new onset #T2D 2Y ago is referred for suspected #DKD in light of 3mos’ dipstick proteinuria. Meds include metformin/sitagliptin. BP 143/85. BMI 31. pic.twitter.com/TEw6ur55eY
— @CKD_ce (@ckd_ce) September 7, 2022
5) What is your diagnosis?
— @CKD_ce (@ckd_ce) September 7, 2022
A. Definite #DKD because pt has #T2D + #macroproteinuria + #hypertension
B. Suspected #DKD but #kidney biopsy should rule out #GN or #FSGS
C. #CKD. Unlikely #DKD because at that age #CKD is usually multifactorial
7) The global prevalences of both #CKD & #T2D are high & concomitance 🚫 necessarily imply causality when #CKD may be caused by e.g., #genetics, #ischemia, toxins, #autoimmunity or obstruction. In addition, example, obesity can be an upstream cause of both #CKD and of #T2D. pic.twitter.com/LfAQDmgu3l
— @CKD_ce (@ckd_ce) September 7, 2022
9) Wait: Researchers have spent billions 💲💶💴in research funds to understand #DKD, and companies spent billions 💲💶💴in private investments to develop cures for #DKD and the disease does not even exist?
— @CKD_ce (@ckd_ce) September 7, 2022
No, there are still pts with #DKD, e.g.: pic.twitter.com/ulsaNPQGTG
11a) From a clinical perspective, #CKD +/- #diabetes is preferred also because no #DKD-specific cures exist. All approved drugs target either #DM, #CKD, or both:
— @CKD_ce (@ckd_ce) September 7, 2022
12) Now, we better understand (and overcome) the previous hurdles for progress.
— @CKD_ce (@ckd_ce) September 7, 2022
Let`s have a look @ the decades of #DKD research concepts about #DKD pathophysiology from the different angles. pic.twitter.com/SP4VRQDI6J
14) Perspective of the #cellculture expert:
— @CKD_ce (@ckd_ce) September 7, 2022
👉 #glucocentric view
👉 static models of #kidney cell stress
👉 missing #hemodynamics, #pressures, #metabolism, #shearstress, and adaptive mechanismshttps://t.co/ZNK52snTTc pic.twitter.com/x7Hnxj2Rtt
15b) … but, an advantage of the pathologist’s perspective:
— @CKD_ce (@ckd_ce) September 7, 2022
👍#kidneybiopsy can identify alternative upstream causes of #CKD that may benefit from specific treatmentshttps://t.co/VDGuBQnJnx pic.twitter.com/1EKf7U1bLa
16b) 👉Missed #RAAS #SGLT2 & #MRA as key tx targets
— @CKD_ce (@ckd_ce) September 7, 2022
🔓https://t.co/R0fldciOKB pic.twitter.com/9FtaZ9SpuB
17b) … &
— @CKD_ce (@ckd_ce) September 7, 2022
👉APOL-1 gene variants (=podocyte weakness; see 🔓https://t.co/OgDWAH7GjO), suggesting that #DM promotes onset & progression of #CKD in #CKD-susceptible individuals, thus #diabetes = a RF for accelerated #CKD progression, esp when #CKD develops shortly after #DM onset
19) Thank you for coming back! You are learning from @hjanders_hans all about #CKD + #T2D while you earn 🆓CE/#CME! Hello to @kdjhaveri @KuppeChristoph @Tiff_Caza @AstridWeins @suz_allison @LinusButt @Renalpathsoc @JeanHouMD @ChristophWanne4 @mvaduganathan @KidneyPath
— @CKD_ce (@ckd_ce) September 8, 2022
21) Thus, with increasing age it becomes less and less likely that the origin of #CKD is a single disease. Thus in adults, targeting the unspecific mechanisms of #CKD progression and minimizing all RF for #CKD progression has become a management priority.https://t.co/go9sQEiT5u pic.twitter.com/aCDFGEsWrW
— @CKD_ce (@ckd_ce) September 8, 2022
23a) Learned from recent RCTs with unprecedented large effect sizes:#Diabetes accelerates onset & progression of #CKD via…
— @CKD_ce (@ckd_ce) September 8, 2022
👉forced ↑ #glucose reabsorption in the PT= ↑ metabolic PT stress = #hypoxia & #cytokine signaling & irreversible loss of PT cells
(cont)
24) An integrated view of mechanisms leading to the structural changes of #CKD that are all accelerated by the presence of persistent hyperglycemia (= #diabetes) is also shown here:
— @CKD_ce (@ckd_ce) September 8, 2022
See https://t.co/VDGuBQnJnx pic.twitter.com/y9bxk5Lz0E
26) These mechanisms apply to all forms of #CKD. #Diabetes is just one of many RF that create a dysbalance between #nephron no./capacity & metabolic demands of the body. https://t.co/rKcjhfjZxB pic.twitter.com/BpUHDwRp3a
— @CKD_ce (@ckd_ce) September 8, 2022
28a) What is the evidence for hemodynamic and metabolic nephron overload as key drivers of #CKD +/- #diabetes?
— @CKD_ce (@ckd_ce) September 8, 2022
👉Rodents with #diabetes: identical overload but capacity for adaption ↑↑↑ prevents progressive #CKD: Reducing overload is key in humans
(cont)
29a) How do #RAASi affect #nephron overload in #CKD +/- #diabetes?
— @CKD_ce (@ckd_ce) September 8, 2022
👉The #RAS is a key stress response pathway activated in #diabetes, #kidneydisease and #heartfailure
(cont)
30a) How do #SGLT2i affect #nephron overload in #CKD +/- #diabetes beyond #RAASi?
— @CKD_ce (@ckd_ce) September 8, 2022
👉Block Na+/glucose reabsorption in PT = less metabolic PT workload
(cont)
31) More insights from human #RCT about the pathophysiology of #CKD + #diabetes?
— @CKD_ce (@ckd_ce) September 8, 2022
👉Mineralocorticoid receptor signaling, another pleiotrophic stress pathway, has non-redundant contributions to #CKD + #diabetes
See 🔓https://t.co/hpuUIH51cM
(cont)
33a) Let me summarize:
— @CKD_ce (@ckd_ce) September 8, 2022
👉#DKD as a term should be used only for pts where #diabetes is the only or predominant cause of #CKD, which is rare in older adults with #T2D
👉Global epidemic & unmet need = #CKD + #diabetes
– Check @goKDIGO guidelines for tx of #diabetes in this setting
33c) Finally,
— @CKD_ce (@ckd_ce) September 8, 2022
👉#Inflammation and #fibrosis are downstream pathomechanism, whether targeting these beyond dual #RAASi/SGLT2i will have additional effects is possible but currently unknown
34b) Therapy: Dual #RAASi/SGLT2i, consider triple #CKD therapy by adding #MRA. The #SGLT2i could improve A1c, BMI, BP & reduce the risk of #hyperkalemia
— @CKD_ce (@ckd_ce) September 8, 2022
35) And that's it! YOU MADE IT! 0.5h CE/#CME credit. Go claim your certificate at https://t.co/z0JguZVyu9. I am @hjanders_hans and I invite you to FOLLOW @ckd_ce (and @cardiomet_ce) for more outstanding education and credit for 🇪🇺🇬🇧🇨🇦🇺🇸 clinicians!
— @CKD_ce (@ckd_ce) September 8, 2022