Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome.

BACKGROUND: Macrophages in renal transplants have been shown to participate in antibody-mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival. METHODS: GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10-year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed. RESULTS: GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI < .5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10-year graft-survival, compared to > 80% with GMI ≤ 1.8. CONCLUSION: GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow-up and therapy.

High impact of rejection therapy on the incidence of post-transplant diabetes mellitus after kidney transplantation.

BACKGROUND: Although major risk factors for post-transplant diabetes (PTDM) after kidney transplantation have been identified, a systematic study on the impact of rejection and rejection therapy is missing so far. METHODS: Five hundred and twenty-six kidney transplant recipients transplanted in the years 2000-2007 were included. PTDM was defined according to WHO guidelines, and patients' data were compared with special attention to protocol and for cause biopsies and rejection therapies. Survival analyses were made for graft loss and patient death. RESULTS: 16.7% of all patients developed PTDM. Among common risk factors as higher age, body mass index (BMI), and others, the factor "acute cellular rejections" was comparably most relevant with a hazard ratio of 3.7. Consequently, antirejective treatment with steroid pulses and conversion to tacrolimus was the factor with the highest relative risk for the onset of PTDM (RR 3.5). PTDM itself had no impact on graft or patients' survival, but the decreased graft survival in PTDM patients was dominantly influenced by the higher frequency of acute cellular rejections, and patients' survival was reduced due to higher age. CONCLUSION: Based upon a higher rate of acute rejections (AR), the necessity of frequent antirejective treatments was more relevant for the induction of PTDM than age or BMI.

Recognition of intraglomerular histological features with deep learning in protocol transplant biopsies and their association with kidney function and prognosis.

Background: The Banff Classification may not adequately address protocol transplant biopsies categorized as normal in patients experiencing unexplained graft function deterioration. This study seeks to employ convolutional neural networks to automate the segmentation of glomerular cells and capillaries and assess their correlation with transplant function. Methods: A total of 215 patients were categorized into three groups. In the Training cohort, glomerular cells and capillaries from 37 patients were manually annotated to train the networks. The Test cohort (24 patients) compared manual annotations vs automated predictions, while the Application cohort (154 protocol transplant biopsies) examined predicted factors in relation to kidney function and prognosis. Results: In the Test cohort, the networks recognized histological structures with Precision, Recall, F-score and Intersection Over Union exceeding 0.92, 0.85, 0.89 and 0.74, respectively. Univariate analysis revealed associations between the estimated glomerular filtration rate (eGFR) at biopsy and relative endothelial area (r = 0.19, P = .027), endothelial cell density (r = 0.20, P = .017), mean parietal epithelial cell area (r = -0.38, P < .001), parietal epithelial cell density (r = 0.29, P < .001) and mesangial cell density (r = 0.22, P = .010). Multivariate analysis retained only endothelial cell density as associated with eGFR (Beta = 0.13, P = .040). Endothelial cell density (r = -0.22, P = .010) and mean podocyte area (r = 0.21, P = .016) were linked to proteinuria at biopsy. Over 44 ± 29 months, 25 patients (16%) reached the primary composite endpoint (dialysis initiation, or 30% eGFR sustained decline), with relative endothelial area, mean endothelial cell area and parietal epithelial cell density below medians linked to this endpoint [hazard ratios, respectively, of 2.63 (P = .048), 2.60 (P = .039) and 3.23 (P = .019)]. Conclusion: This study automated the measurement of intraglomerular cells and capillaries. Our results suggest that the precise segmentation of endothelial and epithelial cells may serve as a potential future marker for the risk of graft loss.

Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

Organ shortage represents one of the major limitations to the development of kidney transplantation. To increase the donor pool and to answer the ever increasing kidney request, physicians are recurring to marginal kidneys as kidneys from older donors, from hypertensive or diabetic donors and from non-heart beating donors. These kidneys are known to have frequently a worse outcome in the recipients. To date major problem is to evaluate such kidneys in order to use or to discard them before transplantation. The use of such kidneys create other relevant question as whether to use them as single or dual transplant and to allocate them fairly according transplant programs. The pre-transplant histological evaluation, the clinical evaluation of the donor or both the criteria joined has been used and according the time each criterion prevailed over the others. Aim of this review has been to examine the advantages and the drawbacks of any criterion and how they have changed with time. To date any criterion has several limitations and several authors have argued for the development of new guidelines in the field of the kidney evaluation for transplantation. Several authors argue that the use of omic technologies should improve the organ evaluation and studies are ongoing to evaluate these technologies either in the donor urine or in the biopsies taken before transplantation.