Contribution of donor T-lymphocytes to graft immunogenicity

We used genetically T-lymphopenic rats as donors to probe the contribution of T-lymphocytes to graft immunogenicity. Graft survival (GS) of lymphopenic donors was significantly increased as compared to normal donors (median (M) = 17 days vs M = 7d, n = 10). To confirm this observation, we reconstituted 7 lymphopenic rats before organ retrieval with $10 sp7-10 sp8$ purified T-lymphocytes. GS was significantly shorter than with lymphopenic donors (M = 7d, n = 7 vs M = 17d, n = 10). Conversely, we treated 6 normal donors with R7.3 (mouse anti-rat TCR $alpha/ beta$) monoclonal antibody (mab). GS was significantly increased as compared to normal donors (M = 23d, n = 6 vs M = 7d, n = 10). These experiments demonstrate that grafts of T-lymphopenic donors have a longer survival time. This advantage is lost after reconstitution with normal T-lymphocytes. GS is similarly prolonged after treatment of normal donors with anti-T-lymphocytes mab. Thus, donor T-lymphocytes contribute to the graft immunogenicity in this model

Influence of immunosuppression on seroconversion against SARS-CoV-2 in two kidney transplant recipients.

Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of coronavirus disease 2019 (COVID-19) in the United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID-19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS-CoV-2 infection monitored by both RT-PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti-SARS-CoV-2 antibodies

Influence of immunosuppression on seroconversion against SARS-CoV-2 in two kidney transplant recipients.

Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of coronavirus disease 2019 (COVID-19) in the United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID-19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS-CoV-2 infection monitored by both RT-PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti-SARS-CoV-2 antibodies

Glomerular Function, Structure, and Number in Renal Allografts from Older Deceased Donors

The 5-yr survival rate of renal allografts is significantly lower for grafts from older deceased donors than from younger deceased donors. For evaluation of the potential contribution of renal senescence in this shortened graft survival, glomerular function and structure were analyzed in allografts from deceased donors older than 55 yr (“aging”) or younger than 40 yr (“youthful”). Aging donors had a significantly higher prevalence of sclerotic glomeruli (P < 0.002), and their nonsclerotic glomeruli tended to be larger, had a larger filtration surface area (P = 0.02), and had a higher single-nephron ultrafiltration coefficient (Kf; P = 0.07), suggesting a compensatory response to functional loss of glomeruli. After serum creatinine reached a stable nadir in the transplant recipients, GFR and its hemodynamic determinants were evaluated and the whole allograft Kf was computed. Compared with the allografts from youthful donors, allografts from aging donors exhibited a 32% lower GFR, which was exclusively attributable to a 45% reduction in allograft Kf (both P < 0.001). In addition, the number of functioning glomeruli per allograft was profoundly lower in grafts from aging donors than from youthful donors (3.6 ± 2.1 × 105 versus 8.5 ± 3.4 × 105; P < 0.01), and this could not be explained by the relatively modest 17% prevalence of global glomerulosclerosis in the aging group. The marked reduction in overall glomerular number in many aging donors may lead to a “remnant kidney” phenomenon, potentially explaining the shorter mean survival of these allografts

Influence of immunosuppression on seroconversion against SARS‐CoV‐2 in two kidney transplant recipients

Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of coronavirus disease 2019 (COVID-19) in the United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID-19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS-CoV-2 infection monitored by both RT-PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti-SARS-CoV-2 antibodies

SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients

BackgroundMorbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease.MethodsWe performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available.ResultsThere were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak.ConclusionsBamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19

Imprecision of Creatinine-Based GFR Estimates in Uninephric Kidney Donors

Background and objectives: To ensure long-term safety of living kidney donors, it is now recommended that they be followed for at least 2 years after donation and that serum creatinine levels be monitored. Such levels are often subjected by clinical laboratories to estimating equations and are reported as estimated GFR (eGFR). The accuracy of such equations in uninephric living donors has yet to be validated. This is especially important in older living donors, who often have senescence-related depression of GFR