Transplant nephrectomy: what are the surgical risks?

Whether or not to remove a failed renal graft has been the subject of much debate. One reason for a cautious approach to graft removal is its high morbidity and mortality rates. We analyzed the morbidity, mortality, and risk factors of transplant nephrectomy at our center. We included 157 cases of transplant nephrectomy in 143 patients, performed between January 2000 and May 2012 at the Academic Medical Center, Amsterdam. Patient data were collected retrospectively. A total of 32 surgical complications occurred after transplant nephrectomy (20%) and 16 patients needed surgical re-intervention (10%). Hemorrhage and infection are the most frequent causes of surgical complications (14%). The mortality rate was 3.2%. There were no significant differences in characteristics and timing of transplant nephrectomy between the group with surgical complications and the group without. A total of 59 re-transplantations were performed in 57 patients (38%). Transplant nephrectomy is associated with high morbidity and mortality rates. We found no significant risk factors for surgical complications following transplant nephrectomy and no significant association between timing of transplant nephrectomy and surgical complications. Steps to reduce these complications need further investigatio

B cells in cluster or in a scattered pattern do not correlate with clinical outcome of renal allograft rejection

BACKGROUND: The role of CD20+ B cells in renal allograft rejection has been reappreciated. Importantly, recent studies suggest a relation between CD20+ B cell aggregates and poorer clinical outcome. In the present study, we attempted to confirm these early reports in a tightly controlled patient population and to differentiate between scattered infiltrates and clusters of B cells. METHODS: Fifty-four biopsies from renal transplant recipients with acute rejection were immunostained for CD20, CD3, and C4d. All patients received similar immunosuppressive therapy. Response to therapy was defined as a decrease in serum creatinine level within 2 weeks to 125% or less of the value before the clinically diagnosed episode of allograft rejection. Late clinical outcome was defined in creatinine clearance between 8 and 12 months after the episode of acute rejection or in graft failure. RESULTS AND CONCLUSION: A significant correlation was observed between interstitial infiltrates of CD20+ cells and CD3+ cells (r=0.720, P <0.001) suggesting that if B-cell infiltrates are present during rejection, they occur with T-cell infiltrates in a concurrent fashion. In contrast to previous reports, no relation was found between the number of CD20+ cells, in aggregates or in a scattered interstitial pattern, and response to conventional therapy. Remarkably, CD3+T cell aggregates did predict a favorable renal outcom

Everolimus-treated renal transplant recipients have a more robust CMV-specific CD8+ T-cell response compared with cyclosporine- or mycophenolate-treated patients

In renal transplant recipients, mammalian target of rapamycin (mTOR) inhibitors have been reported to protect against cytomegalovirus (CMV) disease. Here, we questioned whether mTOR inhibitors specifically influence human CMV-induced T-cell responses. We studied renal transplant recipients treated with prednisolone, cyclosporine A (CsA), and mycophenolate sodium (MPS) for the first 6 months after transplantation followed by double therapy consisting of prednisolone/everolimus, which is an mTOR inhibitor (P/EVL; n=10), prednisolone/CsA (P/CsA; n=7), or prednisolone/MPS (P/MPS; n=9). All patients were CMV-IgG positive before transplantation. CMV reactivation was detectable in the first 6 months after transplantation and not thereafter. None of the patients included in this study suffered from CMV disease. Both CD27CD8 and CD27CD28CD4 effector-type T-cell counts, known to be associated with CMV infection, were measured before transplantation and at 6 and 24 months after transplantation. Additionally, we determined both number and function of CMV-specific CD8 T cells at these time points. The number of total CD8 T cells, CD27CD8 T cells, and CD28CD4 T cells increased significantly after switch to therapy with P/EVL but not after switch to P/CsA or P/MPS. Specifically, CMV-specific CD8 T-cell counts significantly increased after switch to therapy with P/EVL. Furthermore, the mTOR inhibitor sirolimus strongly inhibited alloresponses in vitro, whereas it did not affect CMV-specific responses. We observed a significant increase in (CMV-specific) effector-type CD8 and CD4 T-cell counts in everolimus-treated patients. These findings may at least in part explain the reported low incidence of CMV-related pathology in everolimus-treated patient

CXCR5+CD4+ follicular helper T cells accumulate in resting human lymph nodes and have superior B cell helper activity

Although many relevant immune reactions are initiated in the lymph nodes, this compartment has not been systematically studied in humans. Analyses have been performed on immune cells derived from tonsils, but as this tissue is most often inflamed, generalization of these data is difficult. Here, we analyzed the phenotype and function of the human CD4(+) T-cell subsets and lineages in paired resting lymph node and peripheral blood samples. Naive, central memory cells and effector memory cells as well as Th1, Th2, Th17 and Treg cells were equally represented in both compartments. On the other hand, cytotoxic CD4(+) T cells were strikingly absent in the lymph nodes. CXCR5(+)CD4(+) T cells, representing putative follicular Th (Tfh) cells were over-represented in lymph nodes and expressed higher levels of Tfh markers than their peripheral blood counterparts. Compared with the circulating pool, lymph-node-derived CXCR5(+)CD4(+) T cells were superior in providing help to B cells. Thus, functionally competent Tfh cells accumulate in resting human lymph nodes, providing a swift induction of naive and memory antibody responses upon antigenic challeng

Maintenance immunosuppressive therapy with everolimus preserves humoral immune responses

While the guidelines for vaccination in renal transplant recipients recommend the use of pneumococcal polysaccharide (PPS) and tetanus toxoid (TT), their efficacy in immunocompromised renal transplant recipients is not known. Here we tested the effect of everolimus on immune responses after vaccination by measuring the capacity of 36 stable renal transplant recipients to mount cellular and humoral responses after vaccination. Twelve patients in each treatment arm received immunosuppressive therapy consisting of prednisolone (P) plus cyclosporine (CsA), mycophenolate sodium (MPA), or everolimus. Patients were vaccinated with the T-cell-dependent antigens immunocyanin and TT, and the T-cell-independent PPS. Treatment with CsA partially inhibited and MPA completely abolished the capacity to mount a primary humoral response, whereas everolimus left this largely intact. Recall responses were inhibited by MPA only. All drug combinations inhibited cellular responses against TT. In patients treated with MPA, B-cell numbers were severely reduced. Thus, combined with P, treatment with MPA completely disturbed primary and secondary humoral responses. Everolimus or CsA allowed the boosting of T-cell-dependent and -independent secondary humoral responses. Treatment with everolimus allowed a primary response. Kidney International (2010) 78, 934-940; doi:10.1038/ki.2010.269; published online 11 August 201

The 1-year decline in estimated glomerular filtration rate (eGFR) after radical nephrectomy in patients with renal masses and matched living kidney donors is the same

To determine short-term differences in renal function evolution between patients with renal cell carcinoma (RCC) submitted to radical nephrectomy (RN) and living kidney donors matched for age and gender. To assess the role of co-morbidity as a risk factor for developing an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) . In this retrospective study patients undergoing Radical Nefrectomy (RN) between January 2000 and February 2011 for suspicion of localised RCC were matched by age and gender to living kidney donors. Renal function was compared between the groups using the Modification in Diet and Renal Disease (MDRD) equation at 1 year after RN. Charlson co-morbidity score, incidence of hypertension, diabetes and cardiovascular disease were compared and assessed as predictors for developing an eGFR of <60 mL/min/1.73 m(2) . In all, 196 patients were included, 98 in each group. The mean age was respectively 60.6 (RCC group) and 59.1 years (donors). The 1-year postoperative mean eGFR (available in 89 patients with RCC and 87 donors) was similar, at a mean (sd) of 56.7 (16.4) mL/min/1.73 m(2) in patients with RCC and 56.2 (9.8) mL/min/1.73 m(2) in donors (P = 0.83). In patients with RCC the incidence and severity of co-morbidities was significantly higher. A preoperative eGFR of 60-89 mL/min/1.73 m(2) was the only independent risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2) (odds ratio 4.4, confidence interval 2.1-9.5, P < 0.001, 95% confidence interval). In our cohorts with advanced age the 1-year follow-up eGFR was similar in both groups. Despite increased co-morbidity in the RCC group there was no increased decline in renal function. Only reduced preoperative eGFR could be identified as risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2

Interleukin-17 positive cells accumulate in renal allografts during acute rejection and are independent predictors of worse graft outcome

Interleukin-17 (IL-17) plays an important role in the regulation of cellular and humoral immune responses. Recent studies suggest a role for IL-17 in transplantation. Our study investigated whether quantifying IL-17(+) cells in renal transplant biopsies during acute rejection could have additional prognostic value for better stratifying patients at risk for nonresponsiveness to anti-rejection therapy and future graft dysfunction. Forty-nine renal biopsies with acute rejection were double immunostained and quantitatively analyzed for IL-17 and CD3 (IL-17(+) T-lymphocytes), tryptase (IL-17(+) mast cells) or CD15 (IL-17(+) neutrophils). Total IL-17(+) cell count correlated with total percentage of inflamed biopsy and estimated GFR during rejection. Most IL-17(+) cells were mast cells and neutrophils. We could hardly find any IL-17(+) T-lymphocytes. IL-17(+) mast cells correlated with interstitial fibrosis/tubular atrophy (IF/TA). None of the IL-17(+) cell counts had an additional prognostic value for response to anti-rejection treatment. Multivariate analysis correcting for C4d positivity and time from transplantation to biopsy showed that total IL-17(+) cell count independently predicts graft dysfunction at the last follow-up, which was validated in an independent cohort of 48 renal biopsies with acute rejection. We conclude that intragraft IL-17(+) cell count during acute allograft rejection could have an additional value for predicting late graft dysfunctio