Thread by @ckd_ce

1) Welcome to a new #accredited #tweetorial on the #goKDIGO guidance regarding evaluation and management of focal segmental glomerulosclerosis (#FSGS)--one of the most common causes of primary glomerular disease in adults. Leading us through this material is @edgarvlermamd.

2) Dr. Lerma is core faculty at both @ckd_ce & @cardiomet_CE and is an expert #nephrologist and #educator. This tweetorial is accredited for 0.5h CE/#CME for #physicians #nurses #NPs #PAs #pharmacists. Please follow along!

3) This educational program is supported by grants from Travere, Bayer, & Otsuka, and is intended for healthcare providers. Faculty disclosures can be found at ckd-ce.com/disclosures/. Past programs, still available for CE/#CME credit, are at ckd-ce.com.

4) So let's look at Focal Segmental Glomerulosclerosis (#FSGS) 2012 -> 2021 in the evolving @goKDIGO guidance.
pubmed.ncbi.nlm.nih.gov/34556256/

5) Patients with FSGS typically present with #proteinuria or #nephrotic syndrome & diagnosis must be confirmed by renal biopsy showing characteristic histopath lesions. FSGS may be primary (~25% genetic) or secondary, but nearly half progress to #ESRD.
accessmedicine.mhmedical.com/book.aspx?book…

6) Pathologically, #FSGS may be further classified into collapsing, cellular, tip lesion, or perihilar variant forms.
pubmed.ncbi.nlm.nih.gov/25447132/

7) There are prognostic implications of that pathologic classification. Non-nephrotic proteinuria, whether intrinsic or medically induced, is associated with better renal outcomes.
pubmed.ncbi.nlm.nih.gov/16518352/

8) The terms “primary” and “idiopathic” FSGS have too often been used interchangeably, leading to a great deal of confusion around FSGS nomenclature. The @goKDIGO Work Group stepped in and suggests eliminating the use of “idiopathic” to describe any type of FSGS . . .

9) . . . endorsing instead these types & definitions for FSGS going forward: primary, genetic, secondary, and FSGS--undetermined cause.
pubmed.ncbi.nlm.nih.gov/34556256/

10) Further clarification in the #FSGS space includes standard definitions for remission, relapse, resistance, & treatment dependence for FSGS
pubmed.ncbi.nlm.nih.gov/34556256/

11) There is standard guidance for differentiating between Primary FSGS vs Secondary FSGS, again based on histopathology of the renal biopsy specimen. The first branch point is the presence or absence of nephrotic syndrome.
pubmed.ncbi.nlm.nih.gov/34556256/

12) Further, adults with #FSGS who do NOT have nephrotic syndrome should be evaluated for a secondary cause
pubmed.ncbi.nlm.nih.gov/34556256/

13) Genetic abnormalities associated with FSGS include a number of mutations in genes that encode for proteins expressed mostly in #podocytes & their slit diaphragm, & also . . .

14) . . . in other components of the glomerular filtration barrier such as the glomerular basement membrane (#GBM) & the fenestrated endothelial layer.
accessmedicine.mhmedical.com/book.aspx?book…

15) So let's look at a case: 30M with nephrotic syndrome, kidney biopsy shows FSGS. Serum creat is 1.9mg/dL. HIV and hepatitis B&C are neg. No known fam history of nephrotic syndrome, FSGS, or CKD. What factors should guide a recommendation re genetic testing?

16) Mark your response and return TOMORROW for the correct answer, more education on #FSGS, and your link to FREE CE/#CME! #nephtwitter @nephondemand @IgAN_JBarratt @ChristosArgyrop @CKJsocial @ERAkidney @kidneypathology @Vikas_R_D @Renalpathsoc

17) Welcome back! I am @edgarvlermamd & we are talking the latest and greatest on #FSGS, guided by our friends at @goKDIGO. You have found the ONLY source for #accredited serialized #tweetorials in the #CKD space. Follow this thread for your CE/#CME credit from @academiccme.

18) Yesterday's poll? Wait--did you vote?? If not, scroll up to tweet # 15 and TAKE A STAND before going forward!

19) The correct answer is D. In adults with #FSGS & no family history of disease, genetic testing may be considered as part of the FSGS recurrence post-transplant risk assessment. Specifically causative genetic polymorphisms confer a lower risk for FSGS recurrence.

20) Genetic testing has been incorporated in many research studies that support discovery of disease mechanisms, novel therapeutic targets, and phenotype/ genotype associations.
accessmedicine.mhmedical.com/book.aspx?book…

21) Genetic testing may be beneficial for selected patients with #FSGS who should be referred to specialized centers with such expertise
🔓pubmed.ncbi.nlm.nih.gov/34556256/

22) Before we go to specific treatment of FSGS, let us look at “General Management Principles for Patients with Glomerular Diseases”
🔓pubmed.ncbi.nlm.nih.gov/34556256/

23) Re #bloodpressure mgt in glomerular disease, while target SBP in most adult pts is <120mmHg using standardized office BP measurement, this has not been validated in GN. In practicality, shoot for SBP 120-130 in most pts with glomerular diseases.
🔓pubmed.ncbi.nlm.nih.gov/33637192/

24) So . . . now on to treatment of #FSGS: see
🔓pubmed.ncbi.nlm.nih.gov/34556256/.
#Immunosuppression should not be used in adults with FSGS of undetermined cause (FSGS-UC), or in those with secondary FSGS.

25) Per pubmed.ncbi.nlm.nih.gov/34556256/, initial treatment of primary FSGS--with glucocorticoids-- is shown below. Initial high-dose glucocorticoids should be continued until complete remission is achieved, or as tolerated by patients up to a maximum of 16 weeks, whichever is earlier.

26) Adults with primary #FSGS who respond to glucocorticoid treatment should receive glucocorticoids for ≥6 months. In adults with relative contraindications or intolerance to glucocorticoids, alternative immunosuppression with CNIs should be considered as initial therapy.

27) For more guidance on treatment of steroid-resistant FSGS, see pubmed.ncbi.nlm.nih.gov/34556256/ for @goKDIGO guidance:

28) So what does the future hold for FSGS therapies?

29) Context demands a basic understanding of the pathophysiological role of endothelin in chronic kidney disease (#CKD) development
🔓pubmed.ncbi.nlm.nih.gov/24805108/

30) And then you can put 👀on data: in DUET: A Phase 2 study, patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of #sparsentan versus #irbesartan. Sparsentan was safe and well tolerated.
🔓pubmed.ncbi.nlm.nih.gov/30361325/

31) 🔓at jasn.asnjournals.org/content/29/11/…

32) Take a look also at the DUPLEX Study, and ongoing Phase 3 characterization of the long-term antiproteinuric efficacy &nephroprotective potential of dual ETA and AT1 receptor blockade with #sparsentan, compared to irbesentan, in patients with FSGS:
🔓pubmed.ncbi.nlm.nih.gov/32274453/

33) That's what's coming--but there are existing data on patients with FSGS and #CKD, with a drug that's already approved. Do you recall the study?

34) Mark your answer and return tomorrow. You'll get the correct answer and a link to grab your FREE CE/#CME! COME BACK! Nods to @drbstewart @NatRevNeph @VelezNephHepato @acssjr @Sglt2inhibitorL @SantosGallegoMD @drricardocorrea @AliceYYCheng #FSGS