ABSTRACT:Transplantation-associated thrombotic microangiopathy (TA-TMA) is relatively rare and requires immediate intervention to avoid irreversible organ damage or death; however, consensus regarding the treatment approach is lacking. Atypical haemolytic uraemic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative complement pathway resulting in TMA. aHUS is histologically similar to TA-TMA; approximately 60% of TA-TMA patients have complement dysregulation. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal membrane-attack complex formation and TMA progression. Eculizumab has been successfully used to treat aHUS posttransplant. We present two cases of kidney TA-TMA due to unknown causes, suspected antibody-mediated rejection, or calcineurin inhibitor (CNI)-related toxicity that developed on day 1 or 2 post-kidney transplantation. Low platelet count and haemoglobin level with red cell fragments were detected. Despite steroid pulse, plasma exchange (PE), and intravenous immunoglobulin therapy, TA-TMA did not improve; therefore, eculizumab was administered despite no genetic testing. Laboratory data, including renal function, improved immediately. TA-TMA treatment primarily involves PE initiation or CNI discontinuation; eculizumab can be used to safely treat TA-TMA and then be ceased in the short term. Therefore, eculizumab administration might be beneficial for kidney TA-TMA as early as the diagnosis of refractory to PE.
Hem-o-lok clips have been widely used in laparoscopic or robot-assisted surgery. We report a case of an incidentally discovered Hem-o-lok migration into the bladder after laparoscopic radical prostatectomy. The patient was a 75-year-old man with localized prostate cancer who underwent laparoscopic radical prostatectomy in July 2009. At 3 postoperative years, follow-up ultrasonography revealed a small round mass in the bladder. No lower urinary tract symptoms were reported, and urinalysis results had never indicated hematuria or pyuria. Cystoscopy revealed a Hem-o-lok clip in the bladder, near the vesicourethral anastomotic site. We could not remove it with forceps in the outpatient clinic, so we performed the procedure again under general anesthesia and successfully removed the Hem-o-lok clip. To our knowledge, this is the first report of an asymptomatic Hem-o-lok migration into the bladder.
Summary Regulatory T cells (Tregs) play a significant role in immune tolerance. Since Treg function deeply depends on Interleukin‐2 signaling, calcineurin inhibitors could affect their suppressive potentials, whereas mammalian target of rapamycin (mTOR) inhibitors may have less impact, as mTOR signaling is not fundamental to Treg proliferation. We previously reported a novel mixed hematopoietic chimerism induction regimen that promotes Treg proliferation by stimulating invariant natural killer T cells under CD40 blockade. Here, we use a mouse model to show the impact of tacrolimus (TAC) or everolimus (EVL) on the establishment of chimerism and Treg proliferation in the regimen. In the immunosuppressive drug‐dosing phase, peripheral blood chimerism was comparably enhanced by both TAC and EVL. After dosing was discontinued, TAC‐treated mice showed gradual graft rejection, whereas EVL‐treated mice sustained long‐term robust chimerism. Tregs of TAC‐treated mice showed lower expression of both Ki67 and cytotoxic T lymphocyte antigen‐4 (CTLA‐4), and lower suppressive activity in vitro than those of EVL‐treated mice, indicating that TAC negatively impacted the regimen by interfering with Treg proliferation and activation. Our results suggest that the usage of calcineurin inhibitors should be avoided if utilizing the regimen to induce Tregs in vivo for the establishment of mixed hematopoietic chimerism.
Abbreviations & Acronyms ABMR = antibody-mediated rejection AS = arteriosclerosis CNI = calcineurin inhibitor DSA = donor-specific antibody eGFR = estimated glomerular filtration rate IgA = immunoglobulin A PSM = propensity score matching PTA = post-transplant anemia PTDM = post-transplant diabetes mellitus PTLD = post-transplant lymphoproliferative disease TAC = tacrolimus TCMR = T-cell-mediated rejection Objectives: To compare the long-term outcome and complications of living-kidney grafts with arteriosclerosis to those without abnormal findings diagnosed using pretransplant graft biopsy, and to assess the impact of the arteriosclerosis in livingdonor kidneys. Methods: The influence of arteriosclerosis in pretransplant biopsy on long-term outcomes and complications was evaluated in both unmatched (n = 1351, without arteriosclerosis n = 788 vs with arteriosclerosis n = 563) and propensity score-matched cohorts (n = 984, without arteriosclerosis n = 492 vs with arteriosclerosis n = 492) of adults who underwent living-kidney transplant. Results: In both the unmatched and matched cohort, there was no significant difference in patient and death-censored graft survival at 10 years between the without arteriosclerosis and with arteriosclerosis groups. The with arteriosclerosis group had a higher incidence rate of overall rejection than did the without arteriosclerosis group in both the unmatched (P = 0.026) and matched (P = 0.060) cohorts. The with arteriosclerosis group had significantly higher chronic antibody-mediated rejection than did the without arteriosclerosis group (P = 0.006) in the unmatched cohort. The with arteriosclerosis group had a significantly lower estimated glomerular filtration rate in recipients, but there was no significant difference after matching. The incidence rates of calcineurin inhibitor nephrotoxicity and post-transplant anemia were significantly higher in the with arteriosclerosis group than in the without arteriosclerosis group in both the unmatched and matched cohorts. Long-term postoperative kidney function of living donors was lower in the with arteriosclerosis group. Conclusions: Kidney graft with arteriosclerosis might affect the incidence of rejection, complications and postoperative kidney function of donors. Long-term careful observation is required for both the recipients who received grafts with arteriosclerosis and the donors who had kidneys with arteriosclerosis.
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