Systemic inflammation early after kidney transplantation is associated with long-term graft loss: a cohort study.

Background: Early graft loss following kidney transplantation is mainly a result of acute rejection or surgical complications, while long-term kidney allograft loss is more complex. We examined the association between systemic inflammation early after kidney transplantation and long-term graft loss, as well as correlations between systemic inflammation scores and inflammatory findings in biopsies 6 weeks and 1 year after kidney transplantation. Methods: We measured 21 inflammatory biomarkers 10 weeks after transplantation in 699 patients who were transplanted between 2009 and 2012 at Oslo University Hospital, Rikshospitalet, Norway. Low-grade inflammation was assessed with predefined inflammation scores based on specific biomarkers: one overall inflammation score and five pathway-specific scores. Surveillance or indication biopsies were performed in all patients 6 weeks after transplantation. The scores were tested in Cox regression models. Results: Median follow-up time was 9.1 years (interquartile range 7.6-10.7 years). During the study period, there were 84 (12.2%) death-censored graft losses. The overall inflammation score was associated with long-term kidney graft loss both when assessed as a continuous variable (hazard ratio 1.03, 95% CI 1.01-1.06, P = 0.005) and as a categorical variable (4th quartile: hazard ratio 3.19, 95% CI 1.43-7.10, P = 0.005). In the pathway-specific analyses, fibrogenesis activity and vascular inflammation stood out. The vascular inflammation score was associated with inflammation in biopsies 6 weeks and 1 year after transplantation, while the fibrinogenesis score was associated with interstitial fibrosis and tubular atrophy. Conclusion: In conclusion, a systemic inflammatory environment early after kidney transplantation was associated with biopsy-confirmed kidney graft pathology and long-term kidney graft loss. The systemic vascular inflammation score correlated with inflammatory findings in biopsies 6 weeks and 1 year after transplantation.

Estimated glomerular filtration rate in stable older kidney transplant recipients-are present algorithms valid? A national cross-sectional cohort study.

Several equations have been developed for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD), but none were developed based on data from elderly kidney transplant recipients (KTR). The primary aim of this study was to evaluate different creatinine-based equations in stable elderly KTR. A national cross-sectional study was performed using data from 263 consecutive kidney transplant recipients 60 years or older who performed a routine GFR measurement one year after engraftment. GFR was measured by iohexol clearance calculation based on two samples. eGFR was calculated from a range of different creatinine-based equations using information obtained at the time of GFR measurement. Bias, precision, and accuracy were evaluated for each equation. All equations apart from Nankivell had accuracy (P30) > 80%. The BIS1, FAS, LMRCR , and Cockcroft & Gault equations in recipients older than 70 years and the FAS, LMRCR , and MDRD in recipients 60-69 years old had nonsignificant bias. The CKD-EPI had significant bias in both groups. If one should choose a single equation for follow-up of individual CKD progression in all recipients ≥ 60 years, the FAS or LMRCR equations are probably the best alternatives.

Inflammatory and related biomarkers are associated with post-transplant diabetes mellitus in kidney recipients: a retrospective study.

In this study, we investigate the association between selected inflammatory-related biomarkers and post-transplant hyperglycemia in kidney transplant recipients. This retrospective analysis comprises 852 patients receiving a kidney transplant at the Norwegian national transplant center between 2007 and 2012, all having a normal oral glucose tolerance test (OGTT) before transplantation. A diagnostic OGTT was performed 10 weeks post-transplant to examine the association between inflammation-related biomarkers and two-hour plasma glucose (2HPG) by multivariable linear regression models adjusting for BMI, age, graft function, fasting insulin levels, dosage of prednisolone, and concentration of calcineurin inhibitors. Six of 20 biomarkers were significantly associated with 2HPG in multivariate analyses showing strong associations with soluble tumor necrosis factor type 1 (P = 0.027), Pentraxin 3 (P = 0.019), macrophage migration inhibitory factor (P = 0.024), and endothelial protein C receptor (P = 0.001). These associated markers reflect several distinct but also overlapping pathways including activation of tumor necrosis factor, macrophages, and endothelial cells. The multinomial logistic regression model showed a clear association between the inflammatory biomarkers and post-transplant diabetes mellitus (PTDM). The association between a range of inflammation markers and PTDM suggests that these markers may be target for future studies on pathogenesis and perhaps also treatment of PTDM.