Wednesday, November 26, 2014

Sunday, November 23, 2014

Hyperkalemia meets their new K-busters


      Hyperkalemia is a challenge in CKD and ESRD patients. The treatment agents for this complication have been limited to bowel resins, diuretics and dialysis.  There has been some recent interest in novel agents as some evidence suggesting the efficacy of Kayexalate and side effects leading to colonic necrosis in some settings.



Three articles published this week (2 in NEJM and 1 in JAMA) give us trials of using novel K lowering agents in three different settings.
The first trial looked at patiromer use for hyperkalemia in CKD patients on RAAS inhibitors. The active moiety of patiromer for oral suspension is a nonabsorbed polymer that binds potassium in exchange for calcium in the distal colon leading to highest K excretion possible. Patiromer is a dry powder, primarily a spherical bead that is not absorbed and that binds potassium when mixed in small amounts of water. It exchanges potassium for calcium, which would be of some concern if the drug were absorbed. It appears, however, that the drug is not absorbed and that the amount of calcium absorbed is small. In A RCT with placebo, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%.

The second trial looked at zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia. ZS-9 is a compound with a crystalline structure that traps potassium  10 times as much potassium as kayexalate does. It is insoluble and remains in the intestine during transit. This was in a variety of diagnosis leading to hyperkalemia in over 700 patients. There was an initial phase and then a maintenance phase. Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of maintenance therapy per their conclusion

The third trial titled HARMONIZE was a phase 3, multicenter, randomized,
double-blind, placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia (serum potassium_5.1mEq/L) . Among outpatients with hyperkalemia, sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours; compared with placebo, all 3 doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days.

Two accompanying editorials are in NEJM and JAMA as well

Few questions still remain and are a concern:

Since all 3 trials were pharmaceutical company sponsored, placebo was used to compare the agents for efficacy. Why not kayexalate?- it works and it’s cheaper. The authors in one study did state that the agent was not compared to sodium or calcium polystyrene  since prospective studies are lacking in the later and also agents cause bowel necrosis.
But there are significant years of experience and pathophysiology that it works.  Side effects are part and parcel of every agent. The above agents had constipation as side effect, and some might have calcium and magnesium concerns if used long term given how they work. Also all three trials were very short term and long term trials are needed still.  FDA approval is also warranted before any use.
Nevertheless, the patients we have that have CKD and or heart failure and we really want them to be on ACEI, ARB or aldactone but cannot due to K related concerns and or require diuretics with them:- now we may have an alternative option for the situation. 



Tuesday, November 18, 2014

Pause to think about POISE


One of the largest AKI trials was presented at ASN Kidney week 2014 and just published in JAMA as well- POISE 2.  It was a trial to look at a preventive strategy for AKI in non cardiac surgery setting.   An international trial, with 88 centers, 22 countries, from 2011-2013 of over 6000 patients was done to see if ASA or clonidine given prior to surgery prevented AKI post surgery.  Not to my surprise, a mong patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. In addition, the ASA group had more risk of bleeding and the clonidine arm had more risk of hypotension. 

The logic behind using this strategy doesn’t make sense to me.  There are few trials in the surgical literature that might have prompted this trial.


The funding was provided by the CIHR, Spanish ministry of health and few other funding pharm agencies.  A multi international trial of AKI that might be one of the largest to date is an amazing ordeal but the concept seemed less likely to have worked.  A drug that causes bleeding and another one that causes hypotension is more likely to cause harm then benefit.  Ischemic re conditioning or sonogram might have been an interesting approach.  

Sunday, November 9, 2014

ASN Nephrology Fellow's Events 2014

Welcome reception: Nov 12th: 6-7PM
Marriott Downtown, Grand Ballroom, Salon H

Fellows In Training Bowl( Mystery Case Debate): Nov 14th 2-3PM
Convention Center, Room  119A

Fellows In Training Bowl( Jeopardy game Nephrology Challenge): Nov 14th 3-4PM
Convention Center, Room  119A

Meet the Experts Session Nov 15th  9:30AM - 10:30AM( Meeting the ASN Award Winners)
Convention Center, Hall D

Fellows Forum Nov 15th 10:30-11:30AM
Convention Center, Room 203

Fellows Poster Discussion Section Nov 15th 2-3PM
Convention Center, Room 112

Sunday, November 2, 2014

ASN 2014 Abstracts

ASN abstracts 2014 are now online and available for review.
Posters on demand will also have online posters for viewing soon as well.

For those interested in Social media and education in nephrology, few special sessions being held this year


1. Tweets, likes and Blogs: How to use social media for your patients and your benefit.Nov 13, 1030-12:30PM

2.Boost your teaching skills to become a contemporary nephrology educator. Nov 14, 2-4PM
3. Case Based Debates ( Fellows in training bowl)- Mystery case competition Nov 14, 2-3PM
4. Nephrology fellows jeopardy- Nov 14, 3-4PM

Saturday, November 1, 2014

IS CKD-MBD a syndrome?


 


Is it a syndrome? An article in NDT addresses this entity as a possible syndrome in CKD
When one looks at nephrotic syndrome or metabolic syndrome, those entities usually fulfill the criteria for calling it a “syndrome” as most patients would fit that criteria and prognosis and treatment would be resulted.  In CKD-MBD, this article argues against it being a potential syndrome in CKD but perhaps might be.  CKD-MBD represents a synopsis of three closely related disease conditions: laboratory abnormalities indicative of disturbed bone and mineral metabolism; renal osteodystrophy summarizing the variety of bone lesion subtypes occurring in CKD; cardiovascular disease representing accelerated arteriosclerosis, left ventricular hypertrophy and a variety of additional pathologies in the vasculature and the heart in patients with CKD.
But do all patients with CKD have all the bone parameters abnormal; and if they do, what is the CVD risk and prognosis?  But it’s worth some thought of this potentially being a syndrome.

Have a look at the full paper.

http://m.ndt.oxfordjournals.org/content/29/10/1815.full.pdf
A workshop is being held in Europe to further define this


Sunday, October 19, 2014

C-KIN( Cancer and Kidney International Network)

C-KIN | Cancer and the Kidney International Network

The first ever international society specifically for onconephrology has been created.
It's called the C-KIN( Caner and Kidney International Network).
Check out the their twitter feed at https://twitter.com/CKINnews and their annual conference schedule and abstract details as well. C-KIN aims at improving patient care through better knowledge, education and awareness on cancer and the kidney related issues and research.


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