Early renal function trajectories, cytomegalovirus serostatus and long-term graft outcomes in kidney transplant recipients

Abstract

Background Improved recognition of factors influencing graft survival has led to better short-term kidney transplant outcomes. However, efforts to prevent long-term graft decline and improve graft survival have seen more modest improvements. The adoption of electronic health records has enabled better recording and identification of donor-recipient factors through the use of modern statistical techniques. We have previously shown in a prevalent renal transplant population that episodes of rapid deterioration are associated with graft loss. Methods Estimated glomerular filtration rates (eGFR) between 3 and 27 months after transplantation were collected from 310 kidney transplant recipients. We utilised a Bayesian approach to estimate the most likely eGFR trajectory as a smooth curve from an average of 10,000 Monte Carlo samples. The probability of having an episode of rapid deterioration (decline greater than 5 ml/min/1.73 m2 per year in any 1-month period) was calculated. Graft loss and mortality data was collected over a median follow-up period of 8 years. Factors associated with having an episode of rapid deterioration and associations with long-term graft loss were explored. Results In multivariable Cox Proportional Hazard analysis, a probability greater than 0.8 of rapid deterioration was associated with long-term death-censored graft loss (Hazard ratio 2.17; 95% Confidence intervals [CI] 1.04–4.55). In separate multivariable logistic regression models, cytomegalovirus (CMV) serostatus donor positive to recipient positive (Odds ratio [OR] 3.82; 95%CI 1.63–8.97), CMV donor positive (OR 2.06; 95%CI 1.15–3.68), and CMV recipient positive (OR 2.03; 95%CI 1.14–3.60) were associated with having a greater than 0.8 probability of an episode of rapid deterioration. Conclusions Early episodes of rapid deterioration are associated with long-term death-censored graft loss and are associated with cytomegalovirus seropositivity. Further study is required to better manage these potentially modifiable risks factors and improve long-term graft survival.

Stratification of Kidney Transplant Recipients Into Five Subgroups Based on Temporal Disease Trajectories

“…28 Additionally, studies have investigated eGFR trajectories and their clinical implications but for patients with chronic kidney disease and not kidney transplantation recipients. [49][50][51] The majority of previous clinical research aim to improve short-term kidney transplantation outcomes and graft survival 23,28,29,[52][53][54] ; in complement we here focus on long-term outcomes as individualized risk of comorbidities, complications and patient survival. Disease progression and complications can be challenging to predict, hence stratifying patients into more fine-grained, homogenous subgroups that show higher risk of certain progression paths is 1 step toward an increased level of personalized medicine in this domain.…”

Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach

“…Therefore, the MC method includes mathematical models and numeric simulations that can ultimately provide the prediction of potential long-term outcomes after Tx, based on the derived regression equation. Monte Carlo simulation repeatedly simulates the model, each time drawing a different random set of values (inputs) from the sampling distribution of the model parameters in order to produce distributions of possible outcome values (outputs) [10,11].…”

Immunosenescence: an unexplored role in glomerulonephritis

“…85 High viral loads of CMV and serostatus were associated with a faster decline of kidney graft function. [86][87][88] In KTR, CMV infection was associated with an incremental increase in CD28 null T cells, with a very high expression of CX3CR1 and NKG2D in CD27 null T cells. 13 Their concentration in lymph nodes remained low suggesting directed recruitment.…”

“…The not‐uncommon presence of CMV (antigen/DNA) in especially the renal graft cortex was associated with intimal thickening of small arterioles on KTR protocol biopsies 85 . High viral loads of CMV and serostatus were associated with a faster decline of kidney graft function 86–88 . In KTR, CMV infection was associated with an incremental increase in CD28 null T cells, with a very high expression of CX3CR1 and NKG2D in CD27 null T cells 13 .…”