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World J Transplant. Dec 24, 2016; 6(4): 658-664
Published online Dec 24, 2016. doi: 10.5500/wjt.v6.i4.658
More than skin deep? Potential nicotinamide treatment applications in chronic kidney transplant recipients
Andrew G Bostom, Basma Merhi, Joanna Walker, Leslie Robinson-Bostom
Andrew G Bostom, Division of Hypertension and Kidney Diseases, Department of Medicine, Rhode Island Hospital, Providence, RI 02903, United States
Basma Merhi, Division of Hypertension and Kidney Diseases, Department of Medicine, Rhode Island Hospital and Organ Transplantation, Providence, RI 02903, United States
Joanna Walker, Leslie Robinson-Bostom, Department of Dermatology, Rhode Island Hospital, Providence, RI 02903, United States
Author contributions: Bostom AG did the preponderance of the writing, and prepared Figures 2 and 3; Merhi B reviewed all the descriptive data provided, and made editorial suggestions; Walker J reviewed the dermatological data presented, and made editorial suggestions; Robinson-Bostom L provided Figure 1, reviewed the dermatological data presented, and made editorial suggestions.
Conflict-of-interest statement: There are no conflicts of interest for any of the authors.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrew G Bostom, MD, MS, Associate Professor of Medicine, Research Physician, Division of Hypertension and Kidney Diseases, Department of Medicine, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, United States. abostom@cox.net
Telephone: +1-401-4446844 Fax: +1-401-6494061
Received: July 11, 2016
Peer-review started: July 11, 2016
First decision: September 26, 2016
Revised: October 3, 2016
Accepted: November 1, 2016
Article in press: November 1, 2016
Published online: December 24, 2016
Processing time: 156 Days and 8.9 Hours
Abstract

Non-melanoma cutaneous carcinomas, or skin cancers, predominantly squamous cell carcinomas (SCCs), are the most common malignancies occurring in kidney transplant recipients (KTRs). Squamous cell carcinoma risk is dramatically elevated in KTRs, occurring at rates of up 45-250 times those reported in general populations. New non-melanoma skin cancers in KTRs with a prior non-melanoma skin cancer also develop at 3-times the rate reported in non-KTRs with the same clinical history. The unique aggressiveness of SCCs in KTRs increases patient morbidity, due to the high rate of new lesions requiring treatment, frequently surgical excision. Oral nicotinamide shows promise in the chemoprevention of the especially aggressive non-melanoma skin cancers which occur in KTRs. This benefit might be conferred via its inhibition of sirtuin enzymatic pathways. Nicotinamide’s concurrent hypophosphatemic effect may also partially ameliorate the disturbed calcium-phosphorus homeostasis in these patients-a putative risk factor for mortality, and graft failure. Conceivably, a phase 3 trial of nicotinamide for the prevention of non-melanoma skin cancers in KTRs, lasting at least 12-mo, could also incorporate imaging and laboratory measures which assess nicotinamide’s impact on subclinical cardiovascular and chronic kidney disease risk, and progression.

Keywords: Kidney transplantation; Skin neoplasms; Niacinamide; Phosphorus

Core tip: Our unique review describes promising evidence that oral nicotinamide may have dual therapeutic clinical applications in chronic kidney transplant recipients (KTRs). First, nicotinamide, via its inhibition of sirtuin-mediated enzymatic pathways, may reduce the rate of KTR non-melanoma skin cancers. Second, nicotinamide’s hypophosphatemic effect could lower the rate of cardiorenal outcomes in KTRs. These hypothesized benefits warrant further study in randomized, placebo-controlled trials of nicotinamide treatment with both intermediate, and eventually, hard clinical outcomes.