PONE-D-20-22587

Acute and long-term kidney function after parathyroidectomy for primary hyperparathyroidism

PLOS ONE

Dear Dr. Belli,

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Itamar Ashkenazi

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Well written article regarding a large retrospective cohort of patients operated for PHPT showing in an important percentage various degrees of kidney dysfunction, mostly acutely, but some with long term persistance, suggesting that more cation should be invested in their renal follow-up.

Authors do not mention which was the time span of hyperparathyroidism before surgery.

It is also not clear how come so many patients were having MEN1, because he ratio is way above literature data. They should comment on that.

Table 1 – authors should underline significant changes compared to baseline at different time points (e.g. p values)

Table 2 – the information regarding p values needs to be simplified, e.g. * compared to AKI stage 1, # compared to AKI stage 2, $ compared to AKI stage 3. One sign – p < 0.05, two signs – p < 0.01, three signs – p < 0.001.

Patients with AKI type 3 had clearly higher PTH levels, but also lower 25OH-D3, authors should comment more in detail on that (they already commented in discussion)

Authors should make discussions more concentrated and more focused on the main message - that parathyroidectomized patients should be more attentively followed regarding kidney function. They should add separate comments on study limits - retrospective study, small control group, etc. - and conclusions - follow up of kidney function in this type of patients, the effect of surgery itself with decrease of PTH on kidney function, which may be important also in secondary hyperparathyroidism, the importance to revisit vitamin D repletion before surgery in PHPT.

Finally, English needs to be improved

Introduction

- after the acute episode: during the acute period

- patients who underwent parathyroidectomy

- during the first month after surgery

- patients operated for PHPT seem to present…. When compared to control thyroidectomized patients

Main text

- row 56 – Other authors found that, despite…..most patients recover

- row 86 – with a control group

- row 496 – PHPT

- row 549 – this difference disappeared however at 24 months

- row 559 the authors concluded that (without comma)

- row 607 – dysfunction, not disfunction

etc.

Reviewer #2: The aim of this retrospective study, was to investigate both the acute and chronic effects of parathyroidectomy on renal function and relate these to serum biochemistry before surgery in 494 patients with surgically proven PHPT, and to compare with control group.

The authors found that there is a significant acute impairment in renal function after parathyroidectomy for PHPT and almost half of patients meet the criteria for AKI. Significant eGFR recovery was observed during first month after surgery, but a small permanent reduction may occur.

Comments

1. The discussion is too long. Please condense it.

2. Please show serial changes in body weight over time.

3. You mentioned that permanent reduction in eGFR occurred in 60.7 % of the patients, after acute episode. Please reveal independent factors contributing to permanent reduction in eGFR by multivariate analysis.

4. Did you look at blood urea nitrogen (BUN) or uric acid (UA) and their serial changes?

5. Table 6 showed a significant difference in preoperative GFR between PHPT and control. This is a major limitation. Please describe this as a limitation of this study in the main text.

6. How do you feel about an association of acute kidney impairment after surgery with renal tubular damage? Or did you look at biomarkers of renal tubular damage, such as beta2 microglobulin or liver-type fatty acid protein?

Reviewer #3: I commend Belli and col for this interesting article which evaluates changes in renal function following parathyroidectomy for PHPT. The conclusion is interesting and may have important practical conséquences. One major strengths of the article is the long in hospital stay and ability to evaluate renal function several days after PHPT. As in most centers PHPT patients are currently operated on an outpatient basis the present study design would be difficult to reproduce.

I have several comments.

1. The authors have included PHPT for adenoma, hyperplasia, MEN1 and parathyroid cancer. Although all these patients have primary hypeparathytoidism these are different diseases with different mechanisms of PHPTand diffrent treatments...I think the article should focus only on patients with PHPT related to parathyroid adenoma which is the most usual cause of PHPT

2. I Don't see the utility of the control group. Thyroidectomy can result in ablation of one parathyroid gland without significant impact on the overall parathyroid function.

3. The result section is much too long. as a result it is quite difficult to read.I think that the chapters on relationships between eGFR and AKI, CKD and vit D should only be cited and presented in Tables. Tables and Figures should be counted separately and some should be published as suplementarry material because there are too many of them…

4. I think an uni/multivariate analysis would be helpful in identifying patients at risk of developping renal disfunction after parathyroidectomy for PHPT.

5. How many patients developped clinically relevant renal failure? How were they managed? Could the authors identify risk factors for such complication?

6. The discussion is much too long. the authors should stick to their results rather than discuss tertiary parathyroidism and chronic kidney disease....2 or three pages are enough in my opinion

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Acute and long-term kidney function after parathyroidectomy for primary hyperparathyroidism

PONE-D-20-22587R1

Dear Dr. Belli,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Itamar Ashkenazi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: (No Response)

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Well written article regarding a large retrospective cohort of patients operated for PHPT showing in an important percentage various degrees of kidney dysfunction, mostly acutely, but some with long term persistance, suggesting that more caution should be invested in their renal follow-up.

All advices were successfully tackled by the authors and improved paper quality. They detailed in discussions the suggestions made. Also, discussions stressed the importance of kidney function follow-up in these patients, as well as vitamin D measurement. The authors finely tuned their English language as adviced. The changes of tables 1 and 2 are satisfactory.

I believe that the paper in the actual form can be accepted for publication in PLOS One.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No