Nephrogenic diabetes insipidus in a geriatric patient affected by SARS-CoV-2: complexity of a diagnosis, complexity of a virus

  1. Maria Ada Corich
  2. Michele Niero
  3. Lucia Corich
  4. Elisabetta Ferretti
  5. Paolo De Colle
  6. Stella Bernardi
  7. Giuliano Ceschia
  8. Gianfranco Sanson
  9. Michela Zanetti

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Abstract

Background. Coronavirus Disease-19 (COVID-19) has an important impact on the kidney through direct and indirect damage mechanisms. Most previous studies have highlighted lesions caused by this virus in the early segments of the nephron. However, due to the antigenic characteristics of the virus with almost ubiquitous receptors, and the molecular release it triggers, the distal segments of the nephron could also be affected. Methods. A 71 years old man with a respiratory failure in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pneumonia presented the typical symptoms of diabetes insipidus after about 20 days of hospitalization. The water deprivation test led to the diagnosis of nephrogenic diabetes insipidus. The etiological study was complex particularly because due to the patient’s previous lithium therapy. Results. The sequence of pathognomonic events typical of diabetes insipidus associated with anamnestic, clinical and laboratory evidences supported strongly the diagnosis of nephrogenic diabetes insipidus due to SARS-CoV-2, rather than to other etiologies. Conclusions. The collecting duct could represent a target for SARS-CoV-2 infection, directly or indirectly as a result of lesions of upstream portions of the nephron which would cascade into the distal segment. Other molecules, besides angiotensin 2 converting enzyme, might be involved in facilitating the viral aggression. The complexity of the geriatric patient shows the importance of a comprehensive approach which integrates a careful monitoring of clinical signs and symptoms,  laboratory and instrumental tests. This is especially important in the context of SARS-CoV-2 infection and in the management of its unexpected complications.

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  1. Access Microbiology

    I am pleased to tell you that your article has now been accepted for publication in Access Microbiology. The work presented is clear and the arguments well formed. The manuscript is well written and contributes to the literature. Thank you for addressing all reviewers comments satisfactorily and in a timely manner.

  2. Version published to 10.1099/acmi.0.000598.v3 on Access Microbiology
  3. Version published to 10.1099/acmi.0.000598.v4 on Access Microbiology
  4. Access Microbiology

    Thank you for submitting your revised manuscript for publication in Access Microbiology. After reviewing the manuscript, I'm happy that most of the reviewer's comments have been addressed. However, some minor changes are needed to include: 1. The numbered points should be discussed in complete sentences / paragraphs (lines 195-198, 202-217, 259-265, 270-284) 2. The abstract can be improved. The background should not be describing what you have done in this study, this should be in the results or conclusion. The background should give a brief overview of the topic so far. The abstract should provide a concise summary of your research, highlighting the key contributions and innovations you have made.

  5. Version published to 10.1099/acmi.0.000598.v2 on Access Microbiology
  6. Access Microbiology

    Thank you for submitting your manuscript for publication in Access Microbiology. It has been examined by expert reviewers who have concluded that the work is of potential interest to the readership of Access Microbiology. However, based on the comments received, it is clear that a major revision of this manuscript will be required before a decision can be made on its publication. I will be pleased to consider a revised manuscript along with a document including a point by point response to each of the reviewers comments. Your revised manuscript may be returned to one or more of the original reviewers, along with your itemised response to the reviewers’ comments.

  7. Access Microbiology

    Comments to Author

    Dear Authors, I have carefully reviewed your work and would like to provide you with some feedback and suggestions for improvement. 1. The abstract of your paper can be improved to better emphasize the novelty of your study. The abstract should provide a concise summary of your research, highlighting the key contributions and innovations you have made. Consider revising the abstract to clearly articulate the unique aspects and significance of your work, attracting readers' attention and motivating them to explore your paper further. 2. Some of the references cited in the manuscript are quite old. I recommend replacing them with more recent studies available in the literature. This will ensure that your work is aligned with the latest advancements in the relevant research field. 3. I have identified some language, grammar, and punctuation errors that require attention and correction. I kindly request your cooperation in refining these aspects to ensure that the clarity and rigor of the manuscript aligns with the high standards of the journal. Best regards.

    Please rate the quality of the presentation and structure of the manuscript

    Good

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

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  8. Access Microbiology

    Comments to Author

    The case discusses nephrogenic diabetes insipidus as a result of COVID-19 pneumonia. Interesting findings have been presented and the phenomenon has not been widely reported. The case has been presented well but a few revisions have to be made for more coherence. 1. The case discusses nephrogenic diabetes insipidus as a result of COVID-19 pneumonia. 2. The case has been presented well. But a few details need to be specified: -For how long was lithium discontinued? -The d-dimer was elevated, was a ventilation perfusion scan performed at any point? -Did the patient need ECMO at any point? -What benefit was observed after performing the water deprivation test? -How was the patient at follow-up? 3. Line 29 should be rephrased. Remove numbers from diagnostic criteria in lines 75-77 Line 79" for the first time" is redundant, please delete Line 78 "differential diagnosis", the sentence previously just mentions 1 diagnosis. Better to rephrase as "the diagnosis" was confirmed by... Line 160 change "most reported" to commonly reported "Every clinical and laboratory result was reviewed by a fellow endocrinologist who has definitely confirmed the diagnosis of nephrogenic diabetes insipidus", please rephrase this sentence to endocrinology was consulted. Additionally, what did endocrinology recommend in terms of management. I would suggest discussing the numbered points in complete sentences, with the paragraph to start by "The etiology of this finding seems multifactorial". The same pattern should be followed in conclusion and the conclusion should suggest points for investigation in future. 4. There is not enough discussion to suggest hypothesis 4. induction of dysfunctions in renal microcirculation, due to the prothrombotic state linked to the COVID-19 disease, as demonstrated by the finding of fibrin deposits in the glomerular loops. Reference 25 should be discussed a bit more to compare with the fact that the patient is still susceptible to the damage given 8 years benchmark has not passed yet. It is important to know if the patient had a VTE/PE/DVT at any point because of the features in Goo YJ, et al. Venous thromboembolism and severe hypernatremia in a patient with lithium-induced nephrogenic diabetes insipidus and acute kidney injury: a case report. Ann Palliat Med. 2022 Aug;11(8):2756-2760. doi: 10.21037/apm-21-2025. Additionally, Goo et al. also discusses about how lithium impacts arginine system which should be mentioned to support the lithium hypothesis given how recent literature now groups NDI and CDI as arginine disorders. Please include Dupuis et al. in your discussion that reports another case of NDI. https://pubmed.ncbi.nlm.nih.gov/35310519/.

    Please rate the quality of the presentation and structure of the manuscript

    Good

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  9. Version published to 10.1099/acmi.0.000598.v1 on Access Microbiology