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More than skin deep? Potential nicotinamide treatment applications in chronic kidney transplant recipients

机译:超过皮肤深处?潜在的烟酰胺治疗在慢性肾脏移植受者中的应用

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摘要

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.
机译:非黑色素瘤皮肤癌或皮肤癌,主要是鳞状细胞癌(SCC),是肾移植受者(KTR)中最常见的恶性肿瘤。在KTR中,鳞状细胞癌的风险显着升高,发生率是一般人群的45-250倍。与以前的非黑色素瘤皮肤癌相比,KTR中新出现的非黑色素瘤皮肤癌的发病率是具有相同临床病史的非KTR中报道的三倍。 SCC在KTR中的独特侵袭性增加了患者的发病率,这是因为需要治疗的新病变率很高,而且经常需要手术切除。口服烟酰胺在化学预防在KTR中发生的特别具有侵略性的非黑色素瘤皮肤癌中显示出希望。可以通过抑制沉默调节蛋白酶途径来赋予这种益处。烟酰胺同时发生的降磷作用也可能部分缓解这些患者中钙磷稳态的紊乱,这是死亡率和移植失败的公认危险因素。可以想象,一项烟酰胺预防KTR中非黑素瘤皮肤癌的3期试验(持续至少12个月)也可以纳入影像学和实验室措施,以评估烟酰胺对亚临床心血管疾病和慢性肾脏疾病风险及进展的影响。

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