
- Updated June 2011
- Added CKD data
- included the two RCTs of allopurinol on CKD progression (both positive)
- 121 slides
- Keynote is 96mb, PDF 59mb
- You can do it in an hour, really, you can
- Here is a handout with miniatures of the slides (pdf, 3.8 mb)
I’m giving grand rounds on Tuesday on SGLT2 inhibitors and I’m trying to come up with a list of therapies that lower CV death in diabetes.
Here is my list:
Drugs that have run the FDA CV disease gauntlet and that are non-inferior to standard of care:
I’m sure I’m missing some. There must be a statin trial of diabetics. Right?
Swapnil was first with the statin answer:
Cites 7-9 from https://t.co/nlIqGSAso3 seem to be statin in DM RCTs pic.twitter.com/KVwu0aKC2A
— Swapnil Hiremath @hswapnil@bsky.social (@hswapnil) December 3, 2017
And Edgar came up with a great visual from a review paper:
Completed and ongoing CV outcome trials in Type 2 Diabetes #Nephpearls
https://t.co/Ez2eNLUrlR pic.twitter.com/y09I8B8JQU
— Edgar V. Lerma
(@edgarvlermamd) December 3, 2017
And Szymon came up with the Steno trial. I can’t believe I forgot about that one.
Multifactorial intervention in DM2 https://t.co/Xyd9f7Bwg4 STENO-2 Trial pic.twitter.com/QImGBS0Srx
— Szymon Brzósko (@brzoskos) December 3, 2017
Robert Leversee had some questions regarding my presentation on diabetic nephropathy. You can see his concerns in the comments after the post. he was specifically concerned about this slide.
Robert felt it minimized the GFR gains found with bardoxolone. What is not clear from the deck is that 56 weeks, represents the GFR one month after stopping the drug. In the lecture, I pointed out that patients that were on bardoxolone all had a higher GFR than at baseline, while patients randomized to placebo had a lower GFR.
The reason I included the slide showing the 56 week data was my concern that bardoxolone may be pulling a creatinine slight of hand. My personal concern is that the changes in GFR are due to simple hemodynamic changes like were seen with amlodipine in AASK.
AASK was a trial of hypertension therapy in African Americans with a renal end-point rather than a cardiovascular end-point that are more common in hypertension trials. The trial is a two by three design with two blood pressure targets (MAP 102-107 vs <92) and three blood pressure medications (amlodipine, ramipril, metoprolol).
The data is difficult to interpret because the amlodipine caused an acute hemodynamic-related bump in the GFR, but after 12 months the loss of GFR in the amlodipine group was faster than with ramipril. The study designers designated co-primary end points, a total change in GFR and a chronic change in GFR that ignored the initial 3 months.
Ramipril was superior to amlodipine in the chronic phase but not in the total change in GFR. Though this ambiguity was not represented in the conclusions of the trial:
I am a believer in Richard Johnson’s theory regarding fructose uric acid and hypertension/CKD. So I love it when I see another study adding to the foundation. This from Diabetes Care. The investigators looked at 1500 patients with diabetes and normal renal function and no proteinuria. Over 5 years they tracked who developed CKD (either GFR<60 or proteinuria):
During a 5-year follow-up period, 194 (13.4%) patients developed incident CKD. The cumulative incidence of CKD was significantly greater in patients with hyperuricemia than in those without hyperuricemia (29.5 vs. 11.4%, P < 0.001). In univariate logistic regression analysis, the presence of hyperuricemia roughly doubled the risk of developing CKD.
The curse of treating chronic kidney disease is that one is always treating patients to the numbers:
I walk into a patient’s encounter today and he is reading Twitter on his iPhone 4. We exchanged Twitter handles and began discussing his diabetic nephropathy.
I ask how his blood sugars have been and he fires up Glucose Buddy and proceeds to show me all of his blood sugar reading since March of 2010. Then he e-mails me the data.
When we discuss blood pressure, he fires up the iPhone again and shows me iBP. When he sends me his home blood pressure readings I get the choice of receiving them as text, html or CSV. Awesome.
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Glucose Buddy for the iPhone |
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iBP for the iPhone |
Here’s is what the e-mail output looks like:
Dixon et al. Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med (2009) vol. 360 (21) pp. 2191-201 (PDF)
Randomized placebo controlled double blind trial of patients on hemodialysis or to start hemodialysis in the next 6 months with a new AVG.
Primary outcome was loss of primary unassisted graft patency. thrombosis, 50% stenosis. Patients underwent regular site monitoring and referred for angiography if qB was less than 600 or less than 1000 and a greater than 25% reduction of qB.
Power analysis required 1054 patients.
results: 321 randomized to Aggrenox
328 assigned to placebo
No difference in bleeding or cardiovascular events.
Take home message: modest benefit from expensive drug in underpowered but well designed and executed study.
Brunelli et al. Thiazolidinedione use is associated with better survival in hemodialysis patients with non-insulin dependent diabetes. Kidney Int (2009) vol. 75 (9) pp. 961-8 (pdf)
Thiazolidinediones (TZDs)
This study is a retrospective analysis of hemodialysis patients in the ArMORR cohort.
ArMORR is a cohort of incident dialysis patients at FMC units. The total cohort includes 10,044 patients.
This analysis restricted to patients with diabetes surviving at least 30 days on dialysis.
Patients on pioglitazone (Actos) or rosiglitazone (Avandia) were placed in the TZD group. Primary outcome was time to death from any cause. Maximum follow-up was one year.
Results: 5,290 patientss were eligible for inclusion.
9.6% were treated with a TZD
Improved survival was seen among patients on TZDs, especially patients not also on insulin. Interestingly the survival benefit came from a reduction of non-CV end-points.
This morning I woke to find this in my in-box:
Hi nephron!
Your presentation Diabetic Nephropathy is currently being showcased on the ‘Health & Medicine’ page by our editorial team.
It’s likely to be there for the next 16-20 hours…
Cheers,
– the SlideShare team
And here it is:
Here is the actual lecture. I would recommend going to the SlideShare website and downloading the lecture as it looks a lot better in PowerPoint than in the online presentation. You will need to establish a SlideShare account to download the presentation.