Effect of sirolimus on carotid atherosclerosis in kidney transplant recipients: data derived from a prospective randomized controlled trial

Silva, Andre L; Fusco, D.; Nga, Hong Si; Takase, Henrique Mochida; Bravin, Ariane Moyses; Contti, Mariana Moraes; Valiatti, Mariana Farina; Andrade, Luís Gustavo Modelli de

doi:10.1093/ckj/sfy041

Cited by 11 publications

(11 citation statements)

References 28 publications

(36 reference statements)

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“…Total cholesterol level was moderately increased but within normal range after 1-year treatment. Although sirolimus may cause dyslipidemia, recent studies suggest that sirolimus may prevent atherosclerosis, decrease adiposity, and improve metabolism (47,48). There were no events of edema, headaches, and joint pains related to the use of sirolimus.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Sirolimus for Blue Rubber Bleb Nevus Syndrome: A Prospective Study

et al. 2021

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INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic venous malformation (VM) disease. The characteristic gastrointestinal (GI) bleeding from multiple VM lesions causes severe chronic anemia which renders most patients depend on lifelong blood transfusion and frequent endoscopic treatment with dismayed outcomes. Although recent case reports suggest that oral sirolimus (rapamycin) is effective, a comprehensive evaluation of its efficacy and safety is in need. METHODS: A prospective study was conducted for both pediatric and adult BRBNS patients with administration of sirolimus at the dose of 1.0 mg/m2 to maintain a trough concentration of 3–10 ng/mL. Laboratory tests including complete blood count, biochemical profile, D-dimer, and whole-body magnetic resonance imaging were performed at baseline and 3, 6, and 12 months after treatment. Clinical indicators such as hemoglobin level, lesion size, and transfusion need were evaluated. Adverse effects were recorded regularly. RESULTS: A total of 11 patients (4 males and 7 females) with median age of 14 (range, 5–49) years were recruited. The average lesion size was reduced by 7.4% (P < 0.001), 9.3% (P < 0.001), and 13.0% (P < 0.05) at 3, 6, and 12 months of sirolimus treatment, respectively. Hemoglobin increased significantly after 6- and 12-month treatment (P = 0.006 and 0.019, respectively). Only 1 patient received blood transfusion once during the study. Patients' quality of life and coagulation function were improved. Grade 1–2 adverse effects including oral ulcers (81.8%), acne (27.3%), transient elevation of liver enzymes (18.2%), and hair loss (9.1%) were observed. DISCUSSION: Sirolimus reduces the size of VMs, alleviates GI bleeding, and eliminates transfusion dependence of patients with BRBNS. The drug-related adverse effects are mild and mostly self-limited. These findings support sirolimus as a first-line treatment for GI and cutaneous VMs of BRBNS (see Visual abstract, Supplementary Digital Content, http://links.lww.com/AJG/B819).

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Sirolimus for Blue Rubber Bleb Nevus Syndrome: A Prospective Study

et al. 2021

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“…54 In some adult studies, IMT values decreased after late KTx. 33 As reference values derived from cross-sectional data 34 suggest a continuous rise of IMT with age, it might be conceivable that stabilizing IMT in pediatric patients allows them to get back within normal limits of IMT later in life. Hence, it remains to be shown to what extent a mere stabilization of IMT impacts hard CV outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Serum phosphorous, 28 bicarbonate, 29 serum albumin, 30 and C-reactive protein 31 were only assessed during dialysis. Kidney function 32 and immunosuppressive medication 33 were only incorporated into the separate models for late and preemptive KTx, whereas time on dialysis (dialysis vintage) was only included for late KTx. 23 Most of our cohort was treated with calcineurin inhibitors (CNIs; Table S1, SDC , http://links.lww.com/TP/C938), which are known to dose dependently influence other CV risk factors.…”

Section: Methodsmentioning

confidence: 99%

Long-term Effects of Kidney Transplantation Compared With Dialysis on Intima–media Thickness in Children—Results From the 4C-T Study

Grabitz,

Sugianto,

Doyon

et al. 2024

Transplantation

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Background. Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima–media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events. Methods. We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study. Results. A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P = 0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate. Conclusions. IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid–base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk.

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“…Rapamycin (sirolimus) and its analog (everolimus) attenuate atherosclerosis in mice [ 21 ] and rabbits [ 22 ]. According to a prospective randomized controlled trial, rapamycin (sirolimus) decreased carotid atherosclerosis in humans [ 23 ].…”

Section: Atherosclerosismentioning

confidence: 99%

Are menopause, aging and prostate cancer diseases?

Blagosklonny

2022

Aging

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Prostate cancerProstate cancer is an age-related disease. Every man would be diagnosed with prostate cancer, except that most men do not live long enough, dying from other age-related diseases. The frequency of prostate cancer detected by autopsy is 30-fold higher than mortality from prostate cancer so that "more men die with prostate cancer than because of it" [1]. Among men aged 70-79, a tumor is found by autopsy in 36% of Caucasians and 51% of African-Americans [1,2]. The older the man, the higher frequency of autopsy-detected prostate cancer. The frequency of high-grade prostate cancer doubles every ten years [1].Puberty is critical for susceptibility to prostate cancer later in life [3]. Older age at sexual maturation is linked to a decreased risk of prostate cancer later [4,5]. Thus, prostate cancer is partially quasi-programmed (it will be discussed later) in puberty and would develop almost in everyone, if other causes of death did not exist. Prostate enlargement or BPHBenign prostatic hyperplasia (BPH) is the most common age-related disease in men. An enlarged prostate can block the urethra, leading to an inability to urinate and kidney damage and, if left untreated, to death. Benign prostatic hyperplasia can be detectable by the age of 30. Between 30 and 50 the prostate grows in size, with a doubling time of 4.5 years. Between 51 and 70 years old, the doubling time is around 10 years [6]. Thus, the prostate is enlarged in every aging man, and therefore it is a "normal" disease, occurring in everyone, often asymptomatic.Early in puberty, the prostate doubles in size, and its secretory function is increased to produce prostate fluid. During puberty, the prostate reaches the required size and function, but it continues to grow without purpose, becoming eventually hypertrophic, hyperplasic and hyper functional. The disease is quasiprogrammed, a continuation of the developmental growth and reproductive program that was not switched off upon its completion. Quasi-programs are purely harmful and unintended by nature, but they are a continuation (or a byproduct) of essential programs, so natural selection is powerless to eliminate them. (Note: The force of natural selection is negligible late in life, so selection is very weak against quasiprograms. Natural selection is maximally strong for growth and reproductive programs, and quasiprograms are by-products).

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Effect of sirolimus on carotid atherosclerosis in kidney transplant recipients: data derived from a prospective randomized controlled trial

Cited by 11 publications

References 28 publications

Efficacy and Safety of Sirolimus for Blue Rubber Bleb Nevus Syndrome: A Prospective Study

Efficacy and Safety of Sirolimus for Blue Rubber Bleb Nevus Syndrome: A Prospective Study

Long-term Effects of Kidney Transplantation Compared With Dialysis on Intima–media Thickness in Children—Results From the 4C-T Study

Are menopause, aging and prostate cancer diseases?

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