This week we discussed the CREDENCE trial published in the NEJM, on the effect of Canaglifozin on diabetic nephropathy. There was lots to discuss so it may be a long podcast.The article is available here.The NephJC summary can be read here, with links to the visual abstract, and the wrapup.Links from the show:Swapnil’s first post at AJKDblog on SGLT2i in 2014! SGLT-2 Inhibitors: Can They Prevent Diabetic Nephropathy?Lonnie Pyne’s brilliant tweetorial on proteinuria as a proposed end-point in CKD trials.Combined RAAS blockade (don’t do it)Combining ACEI and direct renin inhibitorsCombining ACEi and ARBWe repeatedly compare CREDENCE to IDNT by Ed Lewis and RENAAL by Barry BrennerYou will need to be familiar with EMPA-REG and CANVAS (links to summaries on NephJC)Why run-in periods are bad for clinical trials: Run-in Periods in Randomized TrialsImplications for the Application of Results in Clinical PracticeHispanics in the study: https://twitter.com/VladoPerkovic/status/1121078118029103105Lot of discussion on mechanisms: • The original description of phlorizin by Josef von Mering in 1800• Podocyte effects in JCI• Effect on Hyperfiltration by SGlT2i in humans• Emerging role of proximal tubule in CKD via GWAS studies• SGLT2i effect on Na/H exchangers in heart and kidney• SGLT2i interact with heart NHE1 (mouse model)• SGLT2i as the ‘betablockers’ of the kidney?Jordan Weinstein on the clinical scientists’ mechanism of SHGLT2i:https://twitter.com/drjjw/status/1121577808164159491Why subgroups should be interpreted very carefullyHost: Joel TopfDiscussants: Samira Farouk, Swapnil Hiremath, Jennie Lin and Matt Sparks.