Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies.

Allograft histology 1 year posttransplant is an independent correlate to long-term death-censored graft survival. We assessed prognostic implications of changes in histology first 2 years posttransplant in 938 first kidney recipients, transplanted 1999-2010, followed for 93.4 ± 37.7 months. Compared to implantation biopsies, histology changed posttransplant showing at 1 year that 72.6% of grafts had minor abnormalities (favorable histology), 20.2% unfavorable histology, and 7.2% glomerulonephritis. Compared to favorable, graft survival was reduced in recipients with unfavorable histology (hazards ratio [HR] = 4.79 [3.27-7.00], p < 0.0001) or glomerulonephritis (HR = 5.91 [3.17-11.0], p < 0.0001). Compared to unfavorable, in grafts with favorable histology, failure was most commonly due to death (42% vs. 70%, p < 0.0001) and less commonly due to alloimmune causes (27% vs. 10%, p < 0.0001). In 80% of cases, favorable histology persisted at 2 years. However, de novo 2-year unfavorable histology (15.3%) or glomerulonephritis (4.7%) related to reduced survival. The proportion of favorable grafts increased during this period (odds ratio = 0.920 [0.871-0.972], p = 0.003, per year) related to fewer DGF, rejections, polyoma-associated nephropathy (PVAN), and better function. Graft survival also improved (HR = 0.718 [0.550-0.937], p = 0.015) related to better histology and function. Evolution of graft histologic early posttransplant relate to long-term survival. Avoiding risk factors associated with unfavorable histology relates to improved histology and graft survival.

Kidney allograft survival after acute rejection, the value of follow-up biopsies.

Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss.

Cardiac troponin T before and after kidney transplantation: determinants and implications for posttransplant survival.

Pretransplant cardiac troponin T(cTnT(pre) ) is a significant predictor of survival postkidney transplantation. We assessed correlates of cTnT levels pre- and posttransplantation and their relationship with recipient survival. A total of 1206 adult recipients of kidney grafts between 2000 and 2010 were included. Pretransplant cTnT was elevated (≥0.01 ng/mL) in 56.4%. Higher cTnT(pre) was associated with increased risk of posttransplant death/cardiac events independent of cardiovascular risk factors. Elevated cTnT(pre) declined rapidly posttransplant and was normal in 75% of recipients at 3 weeks and 88.6% at 1 year. Elevated posttransplant cTnT was associated with reduced patient survival (cTnT(3wks) : HR = 5.575, CI 3.207-9.692, p < 0.0001; cTnT(1year) : 3.664, 2.129-6.305, p < 0.0001) independent of age, diabetes, pretransplant dialysis, heart disease and allograft function. Negative/positive predictive values for high cTnT(3wks) were 91.4%/50% respectively. Normalization of cTnT posttransplant was associated with reduced risk. Variables related to elevated cTnT posttransplant included pretransplant diabetes, older age, time on dialysis, high cTnT(pre) and lower graft function. Patients with delayed graft function and those with GFR < 30 mL/min at 3 weeks were more likely to have an elevated cTnT(3wks) and remained at high risk. When allografts restore sufficient kidney function cTnT normalizes and patient survival improves. Lack of normalization of cTnT posttransplant identifies a group of individuals with high risk of death/cardiac events.