Tripterygium wilfordii Hook F is effective in the prevention of acute kidney transplant rejection and improves long-term graft survival rates,

Abstract Background: This study investigated the impact of posttransplantation de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection.Methods: This retrospective cohort study included 121 patients who received kidney transplants from deceased donors with negative complement-dependent cytotoxicity crossmatch. Based on the presence of dnDSAs, recipients were divided into dnDSA+ (n=31) and dnDSA− (n=90) groups. We evaluated the occurrence of rejection and long-term graft survival in the recipients along with pathologic changes in transplanted kidneys.Results: DnDSAs were identified in 31/121 (25.6%) patients, who had lower graft survival rates than patients without dnDSAs (P=0.007). There was no difference in graft survival rate between patients with high (≥4000) and low (<4000) DSA mean fluorescence intensity (P=0.669). The presence of dnDSA in serum was associated with a higher incidence of antigen- and T-cell–mediated rejection (P<0.0001). DnDSA+ and dnDSA− groups differed in terms of Banff score for arterial fibrointimal and arteriolar hyaline thickening (P<0.05).Conclusion: DnDSAs are associated with decreased long-term graft survival and increased rate of rejection, which is often accompanied by microcirculatory inflammation and positive C4d staining.

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Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates

Nature Communications ◽

10.1038/s41467-021-21517-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zongliang Chang ◽

Weibing Qin ◽

Huili Zheng ◽

Kathleen Schegg ◽

Lu Han ◽

...

Keyword(s):

Chinese Herb ◽

Tripterygium Wilfordii ◽

Tripterygium Wilfordii Hook F ◽

Male Contraceptive ◽

Serum Biochemical ◽

Tripterygium Wilfordii Hook ◽

Biochemical Analyses ◽

Oral Doses ◽

Contraceptive Agent

AbstractThere are no non-hormonal male contraceptives currently on the market despite decades of efforts toward the development of “male pills”. Here, we report that triptonide, a natural compound purified from the Chinese herb Tripterygium Wilfordii Hook F displays reversible male contraceptive effects in both mice and monkeys. Single daily oral doses of triptonide induces deformed sperm with minimal or no forward motility (close to 100% penetrance) and consequently male infertility in 3–4 and 5–6 weeks in mice and cynomolgus monkeys, respectively. Male fertility is regained in ~4–6 weeks after cessation of triptonide intake in both species. Either short- or long-term triptonide treatment causes no discernable systematic toxic side effects based on histological examination of vital organs in mice and hematological and serum biochemical analyses in monkeys. Triptonide appears to target junction plakoglobin and disrupts its interactions with SPEM1 during spermiogenesis. Our data further prove that targeting late spermiogenesis represents an effective strategy for developing non-hormonal male contraceptives.

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Comparing the Effect of rATG Dosing on Long-Term Outcomes in Young (40-59) and Elderly (≥60) Kidney Transplant Recipients

10.21203/rs.3.rs-271219/v1 ◽

2021 ◽

Author(s):

Iman Bajjoka ◽

Salvatore Serra ◽

Jade Mourad ◽

Catherine Crombez ◽

Mohamed Safwan ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Survival ◽

Patient Survival ◽

Statistical Tests ◽

Survival Rates ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Long Term Outcomes ◽

Long Term Outcome

Abstract BackgroundAs the number of elderly kidney transplant recipients increases, long-term outcome differences between this population and younger kidney transplant recipients are not well documented. The purpose of the study is to evaluate the effect of rATG dosing on long-term outcomes between elderly and young kidney transplant recipients.MethodsA single-center retrospective analysis of medical records of 688 first-time kidney transplant recipients (KTR) from 2003 to 2014 on a regimen of mycophenolate mofetil, tacrolimus, and steroids was performed. During the 11-year period there were no immunosuppresion protocol changes. Baseline characteristics, first biopsy-proven acute rejection (BPAR), estimated glomerular filtration rates (eGFR), graft survival, and patient survival at discharge and annually up to 5 years post-transplant were analyzed. Various statistical tests including Chi-square test, two-sample t-test, and Mann-Whitney U test were used to compare data obtained from this study.ResultsThe study population was divided into two cohorts: elderly (E-KTR) (≥60 years; n=277) and younger (Y-KTR) (40-59 years; n=411). E-KTR received more expanded criteria donor kidneys (p<0.001) and older donor kidneys (p<0.001). Y-KTR experienced more BPAR in incidence (p<0.001) than E-KTR, however, the severity of BPAR was similar. A difference in eGFR was observed at discharge, where Y-KTR had better eGFR rates than E-KTR (p<0.05). At 5-years, a trend was observed indicating that E-KTR have better eGFR rates than Y-KTR. Despite similar long-term graft survival, patient survival was significantly lower among the elderly patients (p<0.01). An indication for higher mortality rates in E-KTR is due to rATG dosing for which we found that mortality increased with patients who received high rATG doses in comparison to low doses (p<0.05).ConclusionE-KTR had lower patient survival rates yet similar graft survival rates when compared to Y-KTR. Lower survival rates in E-KTR was associated with higher rATG dosing. Larger validation studies need to be performed to assess the benefit of using less harmful immunosuppressants to improve long-term outcomes for E-KTR.

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