Submited on: 21 Sep 2017 12:27:22 AM GMT
Published on: 25 Sep 2017 09:30:38 AM GMT
 
Possible NKCC2 Gain of Function Mutation - Review
Posted by Mr. Aaron Hunter on 02 Nov 2017 02:46:34 AM GMT Reviewed by Interested Peers

  • What are the main claims of the paper and how important are they?

    They believe they found the first naturally occurring gain of function mutation in NKCC2, which if true if quite important due to being able to classify this in newer patients.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    It proposes a novel claim.


  • Are the claims properly placed in the context of the previous literature?

    Yes, the cited literature contains what they are taking from it. The paper is very well cited for all its information.


  • Do the results support the claims? If not, what other evidence is required?

    The results seem to support the claims, but there could always be further testing to determine what's going on. They could've done a multitude of extra tests on the patients to determine another cause, for her cyclic edema, that could just as easily be treated with furosemide as well.


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    This was a patient case study so this doesn't apply.


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    The methodology was valid and very well done. They used proper techniques and listed the materials used for these techniques. A step by step procedure wasn't listed but the methods steps could easily be looked up online to effectively reproduce the study.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    I am not an expert on this topic so I can't say exactly what additional experiments would help improve the paper, but doing varying experiments to rule other causes of cyclic edema would help strengthen their case. Doing this would make it an excellent paper but it was already a very nicely done study.


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    I wouldn't call it an outstanding paper, but it is quite a good one. The paper was very well written with only one punctuation error, that I found. Doing a few more common tests on the patient to rule out other causes of her cyclic edema would have made it an outstanding paper.


  • Other Comments:

    Overall, I really enjoyed reading this paper and did not expect to find something like this to review today.

  • Competing interests:
    .
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    I am currently a pharmacy student who has studied edema and its treatment/causes along with taking numerous biochemistry and genetics courses relating to this topic.

  • How to cite:  Hunter A .Possible NKCC2 Gain of Function Mutation - Review[Review of the article 'A Gain of Function NKCC2 Mutation in a Patient with Chronic Cyclic Edema ' by Kurtz I].WebmedCentral 2017;8(11):WMCRW003386
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Convincing in vitro, less convincing in vivo
Posted by Dr. Reto Krapf on 25 Sep 2017 02:09:35 PM GMT Reviewed by Author Invited Reviewers

  • What are the main claims of the paper and how important are they?

    The authors present convincing in vitro data using state of the art methodology. The data provide strong evidence for a gain of function mutation of the thick ascending limb Na/K/2Cl cotransporter. This is to the authors and mine knoweldge the first description in a human subject


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    The report is novel.


  • Are the claims properly placed in the context of the previous literature?

    Yes. The selection of the cited literature is adequate and the discussion is well written


  • Do the results support the claims? If not, what other evidence is required?

    The in vitro evidence for a gain of function is quite convincing. I am far less sure about the human data and the claim that this mutation is responsible for the "cyclic edema" observed in this case:

    First, 24 h urine data in a patient apparently under her self selected regular diet, reflect primarily dietary intake. The renin/aldo levels (were they determined with the patient lying, sitting or standing") would be compatible with slight volume expansion at that single time point, however, an increase in NKCC2 activity would not be expected to result in chronicly low 24h urinary NaCl, Ca and mg excretion rates. It would be interesting to study this patient under metabolic diet conditions going from low to high dietary NaCl intake and tracking the effects on urinary excretion rates (including fractional exretion rates), blood pressure and renin/aldo levels. The *furosemide" test described by the authors should contain infos on dosage, administration route etc. This metabolic study would also allow tracking of the blood pressure effect. I did not find any blood pressure value in the paper! Was the patient hypertensive? How do the authors explain the cyclicity? Any clues that this young lady migh be bulimic?


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    Not applicable


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    See my comments under "do the results support the claim", but could not go furhter due to space limit. I do not think that the authors have proven that the mutation is functionally severe enough to explain the clinical observation.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    see above


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    This paper is very interesting, with a diligent metabolic workup it might become outstanding.


  • Other Comments:

    No

  • Competing interests:
    .
  • Invited by the author to review this article? :
    Yes
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    I am an academic nephrology with longstanding Research experience in electrolyte and acid-base regulation.

  • How to cite:  Krapf R .Convincing in vitro, less convincing in vivo[Review of the article 'A Gain of Function NKCC2 Mutation in a Patient with Chronic Cyclic Edema ' by Kurtz I].WebmedCentral 2017;8(9):WMCRW003365
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