Juana Alonso-Titos

Survival in Southern European patients waitlisted for kidney transplant after graft failure: A competing risk analysis

Background Whether patients waitlisted for a second transplant after failure of a previous kidney graft have higher mortality than transplant-näive waitlisted patients is uncertain. Methods We assessed the relationship between a failed transplant and mortality in 3851 adult KT candidates, listed between 1984–2012, using a competing risk analysis in the total population and in a propensity score-matched cohort. Mortality was also modeled by inverse probability weighting (IPTW) competing risk regression. Results At waitlist entry 225 (5.8%) patients had experienced transplant failure. All-cause mortality was higher in the post-graft failure group (16% vs. 11%; P = 0.033). Most deaths occurred within three years after listing. Cardiovascular disease was the leading cause of death (25.3%), followed by infections (19.3%). Multivariate competing risk regression showed that prior transplant failure was associated with a 1.5-fold increased risk of mortality (95% confidence interval [CI], 1.01–2.2). After propensity score matching (1:5), the competing risk regression model revealed a subhazard ratio (SHR) of 1.6 (95% CI, 1.01–2.5). A similar mortality risk was observed after the IPTW analysis (SHR, 1.7; 95% CI, 1.1–2.6). Conclusions Previous transplant failure is associated with increased mortality among KT candidates after relisting. This information is important in daily clinical practice when assessing relisted patients for a retransplant.

Mortality in Elderly Waiting-List Patients Versus Age-Matched Kidney Transplant Recipients: Where is the Risk?

The number of elderly patients on the waiting list (WL) for kidney transplantation (KT) has risen significantly in recent years. Because KT offers a better survival than dialysis therapy, even in the elderly, candidates for KT should be selected carefully, particularly in older waitlisted patients. Identification of risk factors for death in WL patients and prediction of both perioperative risk and long-term post-transplant mortality are crucial for the proper allocation of organs and the clinical management of these patients in order to decrease mortality, both while on the WL and after KT. In this review, we examine the clinical results in studies concerning: a) risk factors for mortality in WL patients and KT recipients; 2) the benefits and risks of performing KT in the elderly, comparing survival between patients on the WL and KT recipients; and 3) clinical tools that should be used to assess the perioperative risk of mortality and predict long-term post-transplant survival. The acknowledgment of these concerns could contribute to better management of high-risk patients and prophylactic interventions to prolong survival in this particular population, provided a higher mortality is assumed.

Effect of Steroid Withdrawal on the Appearance of De Novo Donor-Specific HLA Antibodies in Kidney Transplant Recipients: A Prospective, Randomized, Controlled, Parallel Group Study. Preliminary Results

Introduction Steroids represent one of the mainstays of immunosuppression after kidney transplant (KT). Steroid withdrawal reduces metabolic and cardiovascular complications, but whether it increases the risk of acute rejection and the generation of donor-specific anti-HLA antibodies (DSA) is currently undetermined. Materials and Methods In a controlled clinical trial (NCT02284464), a total of 176 KT patients with low immunological risk were recruited to randomly receive either conventional triple immunosuppression: steroids, TAC and MMF versus steroid withdrawal at the third post-KT month. We compared the incidence of de novo DSA, determined by Luminex Mixed and Luminex Single Antigen (One Lambda®), and its impact on graft histology in patients with steroid withdrawal at the 3 post-KT month (after a protocol biopsy) versus patients who continue to receive conventional triple immunosuppression. Results So far, 68 patients have been randomized (34 per group), with no significant differences in the clinical and demographic characteristics between the groups. The intermediate analysis in those patients who had completed one year of follow-up (n=28) showed no significant differences in the formation of DSA (0% vs. 0%), nor was there rejection in those patients in whom prednisone was withdrawn after randomization. Patients with triple therapy showed a trend toward better renal function compared to those without steroids at the first post-KT year (1.29±0.25 vs. 1.56±0.42 mg/dL, P=0.088). HbA1c levels were similar between both group at the first post-KT year (5.79±0.59 vs. 5.68±0.81%, P=0.734). Conclusion The preliminary results show that steroid withdrawal at the 3 month post-KT seems safe when assessing the appearance of rejection and formation of DSA compared to the patients who continued to receive conventional triple immunosuppression. Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional–FEDER, RETICS (REDINREN RD12/0021/0015, RD16/0009/0006, RD16/0009/0003, RD16/0009/0030, RD16/0009/0031).

Analysis of CCR4high CD4+ in Kidney Graft Blood After Steroid Withdrawal: A Prospective, Randomized, Controlled, Parallel Group Study. Preliminary Results

Introduction Steroids represent a mainstay of immunosuppression after kidney transplant. The infiltration into the graft of active T cells following KT depends on the expression of chemokines and their interaction with their T-cell receptors. However, the natural history of the expression of these molecules in patients who undergo steroid withdrawal after transplant is unknown. Materials and Methods In a controlled clinical trial (NCT02284464), a total of 176 KT patients with low immunological risk were recruited to randomly receive either conventional triple immunosuppression: steroids, TAC and MMF (Group A) versus steroid withdrawal at the 3 post-KT month (Group B). We compared the evolution of CCR4highCD4+ and CXCR3highCD4+ lymphocyte subpopulations in graft blood (GB) extracted by fine needle aspiration puncture determined by flow cytometry in patients after steroid withdrawal at the 3 month post-KT versus patients who continue to receive conventional triple immunosuppression. Measurements were made at 3 (baseline) and 6 months post-KT in GB and in peripheral blood (PB). Results So far, 68 patients have been randomized (34 in each group). There were no significant differences in the clinical and demographic characteristics between the groups at baseline. The first analysis (at 3 months) in those patients who had completed 6 months of follow-up (Group A: n=13; Group B: n=15) showed a significant increase in the CCR4highCD4 subpopulations in GB versus PB in both groups. However, at six months a significant increase in GB versus PB was only seen in Group A. There were no significant differences in the CXCR3highCD4+ lymphocyte subpopulation at the third or sixth month between GB and PB in either group (Table). Table. No title available. Conclusion These preliminary results could suggest a possible effect of prednisone that would favor the recruitment of CCR4highCD4+ cells into the renal graft. Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional–FEDER, RETICS (REDINREN RD12/0021/0015, RD16/0009/0006).

C3 glomerulonephritis associated with monoclonal gammopathy of renal significance: case report

BackgroundMorbidity associated with monoclonal gammopathy of renal significance is high due to the severe renal lesions and the associated systemic alterations. Accordingly, early diagnosis is fundamental, as is stopping the clonal production of immunoglobulins using specific chemotherapy.Case presentationA 75-year-old man with chronic renal disease of unknown origin since 2010 experienced rapid worsening of renal function over a period of 6 mos. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance. Kidney biopsy showed the presence of C3 glomerulonephritis, with exclusive deposits of C3 visible on immunofluorescence and a membranoproliferative pattern on light microscopy. Skin biopsy showed endothelial deposition of complement. Given both the renal and cutaneous involvement the patient was considered to have monoclonal gammopathy of renal significance. We considered an underlying pathogenic mechanism for the renal alteration secondary to activation of the alternative complement pathway by the anomalous immunoglobulin. Despite treatment with plasmapheresis, bortezomib and steroids, advanced chronic kidney disease developed.ConclusionsThe possible underlying cause of the monoclonal gammopathy of renal significance suggests that monoclonal gammopathy should be considered in adult patients with membranoproliferative glomerulonephritis.

Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link

Abstract Kidney transplant (KT) is the treatment of choice for most patients with chronic kidney disease, but this has a high cardiovascular mortality due to traditional and nontraditional risk factors, including vascular calcification. Inflammation could precede the appearance of artery wall lesions, leading to arteriosclerosis and clinical and subclinical atherosclerosis in these patients. Additionally, mineral metabolism disorders and activation of the renin‐angiotensin system could contribute to this vascular damage. Thus, understanding the vascular lesions that occur in KT recipients and the pathogenic mechanisms involved in their development could be crucial to optimize the therapeutic management and outcomes in survival of this population. This review focuses on the following issues: (1) epidemiological data framing the problem; (2) atheromatosis in KT patients: subclinical and clinical atheromatosis, involving ischemic heart disease, congestive heart failure, stroke and peripheral vascular disease; (3) arteriosclerosis and vascular calcifications; and (4) potential pathogenic mechanisms and their therapeutic targets.