Wednesday, December 25, 2013

Top nephrology-related stories of 2013

The votes are in! Hard to believe that another year has come and gone. RFN has presented the top 10 stories as voted by the readers of RFN since 2010. 2013 proved to be another interesting year. This years list is almost completely dominated by clinical trials. Basic science was snubbed this year (unlike other years). New this year was the active participation of the nephrology blogosphere in promoting different stories. Eleven different people posting on six different blogs and discussed why some of the stories were worthy of the top 10 list this year. These bloggers included Joel, Christos and Ed El Sayed over at PBFluids. Myself and Edgar at eAJKD. Adrian at Red Beans. Kenar at Nephron Power. Pascale at WhizBANG. Andrew, Paul and Gearoid here on RFN. This was a lot of fun and a great learning opportunity. Going into greater detail and hearing about different perspectives about how each of these stories might impact the field of nephrology was nice. This year set a record in voting at 155. Thanks to all who took the time to vote. As always this is not by any means a comprehensive list. If you have additions, feel free to add your story below as a comment. Now lets get to it...

First, a review of the top stories for the last several years can be found below.
Top stories of 2010
Top stories of 2011
Top stories of 2012

Hold up, stop the press, we have a last minute addition..
Honorable Mention- The much awaited hypertension guidelines (JNC 8 aka JNC late) was finally published in JAMA. I guess it is fitting that JNC 8 was published AFTER the year-end poll. The recommendations were a vast simplification to the JNC 7 report. In a nutshell, the JNC 8 committee recommended to treat blood pressure to 150/90 (JNC 7- 140/90) in patients greater than 60 yrs old and 140/90 (JNC 7- 130/80) for everyone else including patients with CKD, diabetes and those less than 60 years old. The new guidelines also recommend black patients take either a thiazide diuretic or a calcium channel blocker (CCB) as initial Rx. They recommended non-black patients to take thiazides, ACEi, ARB or CCB. Patients with CKD should be on ACEi or ARB. JNC 8 will still be fair game for next years top nephrology-related story.

10. Controversial cholesterol guideline published by AHA/ACC (14%)- Coming in at number 10 is the new cholesterol guidelines published in JACC by the AHA/ACC. There was much debate about the calculator that accompanied these guidelines as many felt that it was flawed and over-estimated the risk of cardiovascular disease. This over-estimation (75-150%) would place many more people on statins that would not be warranted. Joel over at PBFluids has a nice discussion about this. For a review on treating cholesterol in patients with kidney disease check out Andrew's post at RFN.

9. A novel potassium binder ZS-9 presented at ASN (14%)- This was a big surprise for just about everyone at ASN this year. However, the study is not published yet. The medical community is sorely in need of a better potassium binder for treating hyperkalemia. This is a frequently encountered problem with life threatening implications. Sodium polystyrene sulphonate (kayexalate) has been put through the ringer as of late. Many have been calling into question its effectiveness and potential risks (bowel necrosis). For another view on SPS check out Joel at PBFluids. The company ZS Pharma presented results from a phase II clinical trial and demonstrated that ZS-9 was capable of lowering potassium with minimal side effects. This could be a huge breakthrough and a much needed drug to treat a common medical condition. This is a well-deserved top story of the year in my opinion.

8. APOL1 risk alleles linked to CKD progression in AASK and CRIC cohorts presented at ASN and published in NEJM (15%)- The story of APOL1 risk alleles continues to gain traction in the medical literature. This year at ASN the story deepened with a study by Parsa et al. I discussed this on eAJKD. The authors showed that having 2 APOL1 risk alleles was associated with faster decline of kidney function in both the AASK and CRIC cohorts. The original APOL1 study published in Science was the #4 RFN top story of 2010. This is an exciting avenue of investigation as a target for APOL1 could have huge ramifications in treating kidney disease. However, this could be a long way off.

7. JASN paper by DeSilva et al showing that Fistula First perhaps not best for Elderly CKD patients (16%)- Coming in at number 7 is a very interesting paper from DeSilva et al in JASN. The Fistula First campaign has largely been seen as effective in decreasing the number of patients initiating dialysis with either a catheter or a graft. However, the benefit of performing dialysis with a fistula over a graft might not be apparent until several years. Is is possible that the survival benefit of a fistula over a graft is lost in the elderly? This group showed that in patients over 80 years old mortality did not differ between patients with a fistula versus a graft. Furthermore, they show that patients receiving a fistula were much more likely to require a catheter at some point as compared to a graft. An accompanied editorial states that we should shift our focus from a "fistula first" to a "patient first" approach. A one size fits all approach to medicine can be dangerous. This is an important study and worthy of the top 10 list.

6. Tolvaptan fails to gain approval from FDA for ADPKD (18%)- Number 6 is #TeamTolvaptan. Joel pushed for this story to be the number one story of the year over at PBFluids. Patients with CKD and in particular ADPKD have few pharmacological weapons to combat the relentless decline of renal function. The results of the TEMPO3:4 trial was the number 1 story of last year and the nephrology community was hopeful tolvaptan would gain FDA approval for ADPKD this year.  However, this was not the case as the FDA focused on liver toxicity and lack of hard outcomes (no ESRD outcomes only change in cyst size and slope of creatinine). I hope we see the tolvaptan story making the number 1 story of 2014 with approval from the FDA. We will see.

5. Abatacept in B7-1 Postivie Proteinuric Kidney Disease presented at ASN and published in NEJM (22%)- This was a small case series published in NEJM of abatacept (fusion protein composed of the Fc region of IgG1 fused to CTLA-4 inhibiting B7-1 binding) in patients with FSGS. Five patients with FSGS underwent immunostaining for B7-1 and showed positivity. These patients were subsequently treated with abatacept. All had either a partial or a complete remission. The thought is that B7-1 activation leads to podocyte dysfunction and abnormal motility through its interaction with beta-1-integrin. Paul discussed the utility of abatacept in FSGS, Lupus Nephritis and Diabetic Nephropathy on RFN. I hope a large trial will be underway soon as these are encouraging results.

4. RAVE Trial showing Rituximab as effective as conventional immunosuppression as induction agent in ANCA vasculitis reported in NEJM (25%)- The use of rituximab has continued to gain popularity treating a variety of autoimmune-related diseases. The difficulty in treating ANCA vasculitis is that the toxicity of the meds can sometimes be worse than the disease itself. Enter the RAVE trial. This was a randomized trial originally published in 2010 and demonstrated non-inferiority of rituximab as compared to oral cyclophosphamide for remission of severe ANCA associated vasculitis at 6 months. The follow-up to RAVE was reported in NEJM and discussed by Paul at RFN in December. In the RAVE trial the experimental group received rituximab and those who had remission only recieve placebo therafter. Whereas the comparison group received continued immunosuppression with cyclophosphamide followed by azathioprine (conventional group). Overall results showed that the rituximab group was non-inferior to the conventional group at 18 months. Rituximab was also superior to conventional immunosuppression in relapsing patients over the first 12 months. Interestingly and surprisingly, adverse events were similar between the two groups. These are encouraging results and adds to the armamentarium of drugs for ANCA vasculitis.

3. JASN paper by Maduell et al showing Online Hemodiafiltration reduces mortality compared to standard HD (27%)- Online hemodiafiltration continues to gain traction in Europe but its use the US has been slow to catch up. Online hemodiafiltration is a technique that involves the addition of convective clearance (hemofiltration) to the diffusive clearance of hemodialysis. This gives better middle molecule clearance of uremic toxins. Maduell et al reported in JASN this year a multicenter, open-label, randomized controlled trial with 906 patients on HD with either hemodialysis versus online-hemodiafiltration. After 2-years the online hemodiafiltration group had a 30% reduction in mortality (P=0.01). Paul at RFN reviews the evidence for why online hemodiafltration has gained momentum in Europe. Lets hope the big dialysis groups catch on and start offering this therapy to patients on hemodialysis. 

2. NEPHRON-D trial presented at ASN and published in NEJM (27%)- Number 2 is the NEPHRON-D trial. Edgar covered this at eAJKD and Ed Al Sayed at PBFluids. This trial effectively put the nail in the coffin of combined ACEi/ARB therapy for diabetic nephropathy. In short the trial was stopped early due to adverse events such as  hyperkalemia and acute renal failure, but still didn't show a difference in CKD progression or death. Even though this was a negative trial it answered an important question about the use of combination therapy and appears that readers agree as it is the number 2 story of the year.

1. CORAL trial for Renal Artery Stenosis presented at AHA and published in NEJM (33%)- Coming in at number 1 is the CORAL trial. This was presented at AHA Scientific Sessions and published in NEJM. As with combo ACEi/ARB therapy this is another nail in the coffin for this time stenting renal arteries in hypertension associated with renal artery stenosis. The CORAL trial was a large trial of 947 patients with renal artery stenosis. There was no difference in any of the outcomes most notably death, MI, stroke, progression of CKD or need for RRT. Jonathan has a nice discussion about this trial at RFN. There still could be a small subset of patients who might benefit from stenting (e.g. flash pulm edema). However, this could be the end of routine stenting in renal artery stenosis.

Again, quite a busy and exciting year in the world of nephrology in 2013. Thanks to all of the contributors and readers for keeping the site fun, interesting and educational.

Thanks for supporting RFN and happy holidays. Can't wait to see what 2014 has in store!

1 comment:

Matt Sparks said...

Here are the stories that didn't make the top 10

11. Results from the HDPAL Study- 13%
12. BEACON bardoxalone trial- 12%
13. Nature Medicine Paper by Trudu et al linking UMOD to NKCC2- 12%
14. JCI paper by Humphreys et al showing KIM-1 causes kidney injury- 11%
15. Retrospective study in CJASN by Muriithi et al showing urine eosinophils perform poorly in AIN- 9%
16. HIV Organ Policy Equity (HOPE) Act approved by US Congress- 5%
17. FDA tells 23andMe to stop marketing genomic services- 4%
18. Nature Medicine paper by Rowe et al showing cysts in ADPKD utilize aerobic glycolysis and open new targets for therapy- 3%

Others that were not in the poll
-Long-term risk for kidney donors in KI by Mjoen et al
-The voluntary recall and abandonment of peginesatide