The Role of Cystatin C and the CKD-EPICr-Cyst equation in evaluating Glomerular Filtration Rate in Kidney Transplant Donors

Case Report | DOI: https://doi.org/10.31579/2834-5142/054

The Role of Cystatin C and the CKD-EPICr-Cyst equation in evaluating Glomerular Filtration Rate in Kidney Transplant Donors

  • Morched Haddad *

Néphrologie, Transplantation, Alger, Algérie.

*Corresponding Author: Néphrologie, Transplantation, Alger, Algérie.

Citation: Morched Haddad (2023), The Role of Cystatin C and the CKD-EPICr-Cyst equation in evaluating Glomerular Filtration Rate in Kidney Transplant Donors, International Journal of Clinical Nephrology. 5(3); DOI:10.31579/2834-5142/054

Copyright: © 2023, Morched Haddad. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 04 May 2023 | Accepted: 26 May 2023 | Published: 08 June 2023

Keywords: kidney; urolithiasis; kidney stone disease ; glomerular filtration rate (gfr);chronic kidney disease (ckd); extracorporeal shock wave lithotripsy (eswl); ureteroscopy, percutaneous nephrolithotomy (pcnl); retrograde intra renal surgery (rirs) and min

Abstract

Introduction

The incidence of chronic kidneydisease has  increased markedly  in recent years, with these serious complications, especially in the terminal stage, requiring treatment with dialysis and kidney transplantation (1). The latter, made from a living donor, remains the ideal treatment for IRCT;  It offers a better quality of life for patients (2).  S he realization from a living donor is based on strict and well-defined selection criteria,   which concern both the donor and the recipient. One of the main criteria is the  evaluation of the glomerular filtration rate (GFR) before donation, this is done by different evaluation methods from one country to another: GFR measurement methods,  isotopic methods and  GFR estimation methods by specific equations (4,5).  In our country, the only transplant that is done is from a  living donor, hence the interest  of   a good evaluation of the donor (2,3). The eGFR is calculated by the MDRD and CKD-EPICr equations according to the habits of the transplant teams without having a clear idea of the superiority of one over the other. The objective  of our study is the evaluation of GFR in pre- and post-donation donors, using cystatin C and the equations CKDEPIcyst and CKDEPICr-cyst.

Cystatin C (cyst C) has been known since 1961. The two techniques for the determination of cystatin C are: immuno-nephelometry and immuno-turbidimetry. The sample can be stored for at least 48 hours at room temperature, 7 days at + 4 ° C and several months or even several years at - 80 C °. Several cycles (3-10) of freeze-thaw can be done. Blood is collected on either heparin or EDTA(6,7,8,9,10).

Recent guidelines from KDIGO 2012(11) suggest the use of cyst C to validate CKD in patients considered as such on the basis of a GFR < 60>

Problematic:

The eGFR before authorizing donation requires a rigorous assessment, to allow the donor to be selected safely. Recommendations suggest measuring GFR by reference methods or measuring by isotopic method. The unavailability of these techniques and the practical difficulty of their realization, have led to the development of other methods such as the online calculator. In our country, we use creatinine equations, but these equations are still insufficient. Lack of access to the above methods; which led us to use other equations based on the combination of creatinine and cystatin C. The objective of our study is the usefulness  of  hepatitis C in the evaluation of GFR by the mixed CKD-PPE equation in living donors before  donation and after kidney donation, to select the donor in the absence of reference measurement methods.

Materials and Methods:

Materials and Methods:

It is a  prospective follow-up, longitudinal,  descriptive and analytical, multicenter study involving three nephrology  teams . We recruited 55 couples (55 donors and 55 recipients), then we excluded 04 recipients because of their ages, note that: The sample size is calculated: n = P (1-P) X (Z/d) 2.P: prevalence: 1,025%. Z: 1.96 with an alfa risk of 5%. D: accuracy: 3%.n: 43.3. 

After rigorous interrogation and clinical examination. eGFR was calculated using equations (MDRD, CKD-EPICr, CKD-EPICyst and CKD-EPICr-cyst) using an online calculator   "06 GFR equations" before  donation, 3 months and 6 months after donation.

Results:

In our study (Table 01) we have 55 donors, among them 53.6% women, the average age is: 47.8±11.78 years, the average BMI is 25.56±2.94 kg/m² and donors are classified according to age with a Cut-off: 40 years:  

30 donors (representing 75% of donors over 40 years of age) have a BMI between 25-29.9 kg/m² donation they are overweight.

 3 donors out of 55 have a BMI >30 kg/m² considered obese, two of them are over 40 years old 

The different means of the eGFR calculated by the 04 equations (MDRD; CKDEPICr, CKDEPIcyst, CKDEPICr-cyst) which are: 103.67±28.2;101.15±18.77;99.58±21.25 and 98.07±19.53 respectively. By the ANOVA test: there is no significant difference between the means of GFR by the 04 equations before donation.52 donors out of 55 are normo tense and 03 hypertensive donors balanced under monotherapy without visceral impact, which represents 5.4% of all donors.

The mean cystatin C prior to donation was: 0.81±0.21mg/l (Table 01).  There is a significant difference between the pre-donation means of creatinine and cystatin C by sex, the hourshad  higher means of creatinine  and cystatin C  than women respectively: 7.13±1.91 and 8.52±1.70 with a P<0>

With regard to the eGFR averages calculated by the different equations: there is a highly significant difference between the age-specific eGFR averages for a cut-off: 40 years calculated by CKD-EPICr-cyst and CKD-EPIcyst, donors aged less than 40 years had higher averages compared to donors over 40 years of age with a P of 0.002. While the eGFR averages that are calculated by MDRD there is no significant difference. Also there is a significant difference between eGFR averages by sex,

Table 01:

Table No.:02

Which are calculated by CKD-EPICr-cyst and CKD-EPIcyst with a P of 0.03 and  0.004 respectively, while those calculated by MDRD and CKD-EPICr have no significant difference.18 candidates out of 55 donors representing 32.72% are excluded from donation by the MDRD equation according to the authorized donation threshold defined by the KDIGO 2017 recommendations.  the mixed CKDEPI equation made it possible to reclassify 08 candidates out of 18, they were recovered and accepted. It misranked 10 donors who represent 18.18%.  There is a strong relationship between the two equations with a highly significant P while the concordance with Kappa is equal to 0.4.These   10 donors were collected and did not definitively exclude themselves from donation because we cannot exclude a healthy donor candidate who has no uronephrological abnormalities on the basis of an estimated GFR figure. GFR calculation equations may underestimate or overestimate GFR. 04 out of 10 donors had an eGFR calculated by CKDEPI cyst >90 ml.mn.1.73m² beforedonation

Conclusion :

The determination of cystatin C and the use of mixed CKDEPIis essential for the proper assessment of GFR. This equation is able to assess GFR in  the closest way to actual GFR because it is based on two endogenous markers. It recovered 08 donors out of 18 who were rejected for donation by the MDRD without any nephrological biological or radiological abnormalities. The CKD-PPE Cr-cyst equation has proven its effectiveness in readjusting the GFR assessment by the MDRD equation for a donation threshold (Cut-off: 90 ml.mn.1.73m²). It acceptedmore donors than MDRD, with good quality graft and remaining kidney function in the donor

Collaborators:

 

Kidney transplant teams in 03 kidney transplant centers at 03 hospitals:

Nephrology department at their t,Pr RAYANE, and Mazari at the University Hospital of Nafisa Hamoud (Ex Parnet): nephrologists, general practitioners The vascular surgeons of the vascular surgery department of the EHS of Maouche Mohand Amokrane..The renal transplant team of the nephrology department of the Central Hospital of the Army headed by Professor BOULAHIA and all the medical and paramedical staff, as well as the urological surgeons and vascular surgeons at their head Pr GAACHI. Thekidney transplant team of the CHU Batna: at their head Pr BOUGROURA and Pr Missoum with the entire medical team: general practitioners and nephrologists.As well as the surgical team headed by Professor Chaouche, and Professor Ourlent.


 

                        

There is a correlation between the GFR calculated by MDRD and CKD mixed PPE (R=0, 6, P<0 R²=0.409)>

The concordance between the different equations of the calculation of GFR before donation in donors, calculated by the two equations MDRD and mixed ckdepi:

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

img

Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

img

Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

img

Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

img

Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

img

Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

img

Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

img

Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

img

Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

img

Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

img

Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

img

Luiz Sellmann