scholarly journals Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yehui Chen ◽  
Zhi Zhang ◽  
Yun Lin ◽  
Huaxin Lin ◽  
Miaoyuan Li ◽  
...  

Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged.

2017 ◽  
Vol 18 (4) ◽  
pp. 381-392 ◽  
Author(s):  
Qinxia Xu ◽  
Xiaoyan Qiu ◽  
Zheng Jiao ◽  
Ming Zhang ◽  
Jianping Chen ◽  
...  

2019 ◽  
Vol 8 (4) ◽  
pp. 453 ◽  
Author(s):  
Manuela Yepes-Calderón ◽  
Camilo Sotomayor ◽  
António Gomes-Neto ◽  
Rijk Gans ◽  
Stefan Berger ◽  
...  

New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92–3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6–6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36–0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.


2019 ◽  
Vol 35 (9) ◽  
pp. 1577-1584
Author(s):  
Jean-Baptiste de Freminville ◽  
Louis-Marie Vernier ◽  
Jérome Roumy ◽  
Frédéric Patat ◽  
Philippe Gatault ◽  
...  

Abstract Background Renal resistive index (RI) predicts mortality in renal transplant recipients, but we do not know whether this is true in diabetic patients. The objective of this study was to analyse the long-term predictive value of RI for death with a functioning graft (DWFG) in renal transplant recipients with or without pre-transplant diabetes. Methods We conducted a retrospective study in 1800 renal transplant recipients between 1985 and 2017 who were followed for up to 30 years (total observation period: 14 202 patient years). Donor and recipient characteristics at time of transplantation and at 3 months were reviewed. The long-term predictive value of RI for DWFG and the age–RI and arterial pressure–RI relationships were assessed. Results A total of 284/1800 (15.7%) patients had diabetes mellitus before transplantation. RI was &lt;0.75 in 1327/1800 patients (73.7%). High RI was associated with a higher risk of DWFG in non-diabetic patients [hazard ratio (HR) = 3.39, 95% confidence interval 2.50–4.61; P &lt; 0.001], but not in patients with pre-transplant diabetes (HR = 1.25, 0.70–2.19; P = 0.39), even after multiple adjustments. There was no interaction between diabetes and age. In contrast, there was an interaction between RI and pulse pressure. Conclusion Our study indicates that RI is not a predictor of DWFG in diabetic renal transplant recipients, in contrast to non-diabetic recipients. These findings could be due to a different age–RI or pulse pressure–RI relationship.


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