Eugenia Sola

Long-Term Improvement of Deceased Donor Renal Allograft Survival Since 1996: A Single Transplant Center Study

Background. The rate of acute rejection (AR) has decreased significantly, but whether this is associated with improvement in long-term graft survival is controversial. Methods. We analyzed 1445 consecutive adult deceased donor kidney transplant recipients from 1985 to 2005, over two periods (1985–1995 vs. 1996–2005) to compare long-term graft survival. Results. The second period was associated with older donors and recipients and a reduction in AR. A significant increase of 10.1 months at 11 years was seen in death-censored graft survival in 1996 to 2005. For this posttransplant time, graft half-life was 10.8 years in 1985 to 1995, while at this point in the second period 62% of recipients had a functioning graft. The yearly increase in serum creatinine was less pronounced in the latter period (0.05 mg/dL vs. 0.02 mg/dL, P<0.01). No difference was found in patient survival. Cox analysis showed that donor age (HR 1.02, P<0.001), AR (HR 1.72, P<0.001), panel-reactive antibody at transplantation (HR 1.01, P<0.001), and serum creatinine at 1 year (HR 2.01, P<0.001) had a negative impact on graft outcome. By contrast, the use of mycophenolate mofetil was associated with a 24% reduction in graft loss rate (HR 0.76, P<0.05). Conclusion. Long-term graft survival and renal function have improved in renal transplant recipients since 1996.

Decrease in the percentage of peripheral blood CXCR3highCD4+ lymphocytes after renal transplantation.

INTRODUCTION Previous studies suggest that infiltration into the graft of active T cells following kidney transplantation depends on the expression of chemokines and their interaction with their T-cell receptors. However, little is known about the natural history of the expression of these molecules during the early post-transplantation phase. AIM To evaluate the percentage of CXCR3highCD4+ and CCR4highCD4+ cells, as markers of the Th1 and Th2 populations, in peripheral blood from uremic patients before transplantation and six months after maintaining an acceptable kidney graft function. MATERIAL AND METHODS Flow cytometry was used to measure CXCR3highCD4+ and CCR4highCD4+ cells from 44 consecutive patients who received a kidney transplant at our center. Measurements were made at the time of transplantation and six months later. RESULTS There was a significant reduction after transplantation in the CXCR3highCD4+/CCR4highCD4+ balance (10.68±20.28 vs. 2.01±3.15, p=0.001). Separate analysis of each subset showed a significant reduction after transplantation in CXCR3highCD4+ (2.37±2.75 vs. 1.49±2.66, p=0.010) but no difference in CCR4highCD4+ (0.83±1.01 vs. 1.01±1.12, p=0.812). CONCLUSION Prior to kidney transplantation uremic patients have an immunologic activation with Th1 polarization (studied by analyzing the CXCR3highCD4+ and CCR4highCD4+ populations) that falls after transplantation. This can be monitored with the CXCR3highCD4+ lymphocyte subset. This may help understand the pathologic mechanisms intervening in immunologic dysfunction of kidney grafts.

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.

Increase in CD8+CD158a+ T Cells in Kidney Graft Blood is Associated with Better Renal Function

BACKGROUND Studies of liver and heart transplant patients have shown a gradual reconstruction of the CD8 KIR2D+ T cell subpopulations, measured in peripheral blood (PB), associated with better graft acceptance. The kinetics of these populations in kidney transplants, however, is still poorly understood, especially given the lack of studies of blood samples from the kidney graft. MATERIAL AND METHODS Flow cytometry was used to measure CD8+CD158a/b/e T cells in 69 kidney transplant patients who had stable renal function during follow-up. Measurements were made at 3, 6, and 12 months post-transplantation in graft capillary blood extracted by fine needle aspiration puncture (FNAP) and in PB. RESULTS No progressive increase was found in the PB subpopulations. However, the CD8+CD158a+ subsets increased significantly at 12 months in the graft blood versus the PB samples (3.91±4.59 vs. 2.84±4.71; p=0.021). The ratio of the percentage of CD8+CD158a+ cells in graft blood compared to PB at 12 months was associated with better renal function in those patients with a ratio ≥3 (66.6±14.53 vs. 55.7±21.6; p=0.032). CONCLUSIONS An increased ratio of CD8+CD158a+ cells, measured by flow cytometry, between graft blood and PB was associated with improved renal function.

Kidney Donor Profile Index: The Impact on Graft Survival in Deceased Donor Kidney Transplant Recipients

Introduction The Kidney Donor Profile Index (KDPI) (a scoring system based on 10 donor factors) is usually used in USA as a screening tool for donor quality and has been shown to be predictive of both short and long term graft survival. However, whether this clinical tool has accuracy predictive value in other population is undetermined. Objective To evaluate the association between KDPI and graft survival in Southern European deceased donor kidney transplant recipients (DKT). Methods A longitudinal, retrospective cohort study, where were included 733 DKT performed in our center (Regional University Hospital, Málaga, Spain) during 1999-2012. KDPI was calculated in all deceased donors. Results Recipient´s mean age was 49,9±13,8 ys. and 61,1% were male. Mean dialysis time was 38±35 months. 85% was the first transplant. Donor´s mean age was 49,4±17,3 years, and hypertension and diabetes was present in 31,7% and 12%, respectively. Stroke was the cause of donor death in 61%. There was no deceased after cardiac-death. Cold ischemia time (CIT) was 15,3±4,5 h. and 41% of patients had delayed graft function. The most commonly used immunosuppressive treatment was steroids, MMF and Tacrolimus (88%). Induction therapy (46,4% antiCD25, 14,4% thymoglobuline) was administered in 61% of patients. A total of 150 patients (17.1%) lost the graft during follow-up (96±58 months) and the leading cause of loss was death with functioning graft. Median KDPI was 63 (IQR 34-86). Patients were divided into 2 categories: KDPI ⩽80 (502 patients) and KDPI>80 (231 patients). Donors with KDPI>80 were older (65±7 vs 41±14 years; p<0.001), and had more hypertension (63% vs 16%; p<0.001) and diabetes (26,3% vs 5,4%; p<0.001). The patients who received a kidney with KDPI >80 also were older (60±8 vs 45±13 years; p<0.001) and had a higher proportion of diabetics (14,4% vs 6,9%; p=0.001). There were no differences in CIT (15,6±4,2 vs 15,2±4,6; p=0.3). Overall graft survival at first, 5th and 10th years was significantly lower in patients with KDPI>80 vs ⩽80, ( 88%, 74%, 52% vs 91%, 83%, 70%, respectively; p<0.001), as well as patient death-censored graft survival (91%, 83%, 71% vs 93%, 87%,80%; respectively, p=0.03; Figure). This difference was not significant in the recipients over 60 years. In multivariate cox regression analysis, a KDPI value (⩽ o > 80) was significantly associated with graft failure (HR 1.9; 95% IC 1.1-3.3; p=0.009). Conclusions A KDPI value >80 represents an important risk factor for graft loss in our kidney transplant population, with an increased of risk of 1.7 times. These differences are not significant in patients older than 60 years, so these grafts could be viable for this specific population.

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.