Remuzzi Score Research Articles

Quantifying measurement uncertainty in renal transplant biopsy assessment.

Renal transplant biopsies provide insights into graft health and support decision making. The current evidence on links between biopsy scores and transplant outcomes suggests there may be numerous factors affecting biopsy scores. Here we adopt measurement science approach to investigate the sources of uncertainty in biopsy assessment and suggest techniques to improve its robustness. Histological assessments, Remuzzi scores, biopsy processing and clinical variables are obtained from 144 repeat biopsies originating from 16 deceased-donor kidneys. We conducted sensitivity analysis to find the morphometric features with highest discriminating power and studied the dependencies of these features on biopsy and stain type. The analysis results formed a basis for recommendations on reducing the assessment variability. Most morphometric variables are influenced by the biopsy and stain types. The variables with the highest discriminatory power are sclerotic glomeruli counts, healthy glomeruli counts per unit area, percentages of interstitial fibrosis and tubular atrophy as well as diameter and lumen of the worst artery. A revised glomeruli adequacy score is proposed to improve the robustness of the glomeruli statistics, whereby a minimum of 104 µm2 of cortex tissue is recommended to keep type 1 and type 2 error probabilities below 0.15 and 0.2. The findings are transferable to several biopsy scoring systems. We hope that this work will help practitioners to understand the sources of statistical uncertainty and improve the utility of renal biopsy.

Prediction of allograft function in pre-transplant kidneys using sound touch elastography (STE): an ex vivo study

BackgroundThe purpose of the study was to evaluate renal quality and predict posttransplant graft function using ex vivo sound touch elastography (STE).MethodsIn this prospective study, 106 donor kidneys underwent ex vivo STE examination and biopsy from March 2022 to August 2023. The mean stiffness of the superficial cortex (STEsc), deep cortex (STEdc), and medulla (STEme) was obtained and synthesized into one index (STE) through the factor analysis method. Additionally, 100 recipients were followed up for 6 months. A random forest algorithm was employed to explore significant predictive factors associated with the Remuzzi score and allograft function. The performance of parameters was evaluated by using the area under the receiver operating characteristic curve (AUC).ResultsSTE had AUC values of 0.803 for diagnosing low Remuzzi and 0.943 for diagnosing high Remuzzi. Meanwhile, STE had an AUC of 0.723 for diagnosing moderate to severe ATI. Random forest algorithm identified STE and Remuzzi score as significant predictors for 6-month renal function. The AUC for STE in predicting postoperative allograft function was 0.717, which was comparable with that of the Remuzzi score (AUC = 0.756). Nevertheless, the specificity of STE was significantly higher than that of Remuzzi (0.913 vs 0.652, p < 0.001). Given these promising results, donor kidneys can be transplanted directly without the need for biopsy when STE ≤ 11.741.ConclusionsThe assessment of kidney quality using ex vivo STE demonstrated significant predictive value for the Remuzzi score and allograft function, which could help avoid unnecessary biopsy.Critical relevance statementPre-transplant kidney quality measured with ex vivo STE can be used to assess donor kidney quality and avoid unnecessary biopsy.Key PointsSTE has significant value for diagnosing low Remuzzi and high Remuzzi scores.STE achieved good performance in predicting posttransplant allograft function.Assessment of kidney quality using ex vivo STE could avoid unnecessary biopsies.Graphical

#856 Performance of ex vivo confocal microscopy in the assessment of Remuzzi score in preimplantation biopsies

Abstract Background and Aims Confocal microscopy (CM) is a technique that generates digital images from fresh tissue samples with resolution comparable to that obtained with conventional stains. These images are digitally stained with Hematoxylin/Eosin-like. The clear advantage of this technique with respect to conventional staining is the speed in obtaining results which is of great importance in the donation process, as well as their digitalization. The aims of the present study were two: 1) to assess reproducibility for CM between two nephropathologist in preimplantation biopsies and 2) to describe the correlation between gold standard for preimplantation biopsies in our institution performed in frozen block and CM. Method Donor biopsies were reviewed according to Remuzzi score (RS) by on-call pathologist for frozen block and two nephropathologist for CM, blinded to the original frozen block report. The intraclass correlation coefficient (ICC) for every variable in RS was calculated for the two nephropathologists. Later, concordance between the techniques was evaluated by the κ index. Results We included 50 preimplantation biopsies between January and October 2023. Median donor age was 74 years (IQR 62-77.3), 56% were male, 74% had arterial hypertension and 24% had diabetes mellitus. Number of glomeruli were 23 (IQR 14.25-30.25). ICC was excellent for glomerulosclerosis (0.755) and total RS (0.787) and good for interstitial fibrosis (0.536), while fair for tubular atrophy (0.412) and poor for vascular narrowing (0.14). There was excellent agreement between frozen block and CM for interstitial fibrosis (κ 0.898) and global RS (κ 0.898) and substantial for glomerulosclerosis (κ 0.694) while it failed to moderate for vascular narrowing (κ 0.522) and fair for tubular atrophy (κ 0.37). Conclusion CM proved to have reproducibility between nephropathologists and comparability to our gold standard technique in evaluating preimplantation biopsies. The ease of acquisition of CM images suggests that it may be useful for rapid evaluation of graft histology.

Predictive value of donor kidney quality assessment and risk quantification scores on 5-year outcomes of deceased donor kidney transplantation.

Due to the excess demand for deceased donor kidneys, risk quantification scores were developed to help with kidney allocation. The kidney donor risk index (KDRI) is used in the US kidney allocation system. We currently use expanded criteria (UNOS) and Remuzzi scoring for allocation of deceased donor kidneys and the utility of KDRI in our cohort is unknown. We aim to evaluate the association of KDRI with relation to 5year graft and patient survival. Retrospective cohort study of 225 adults who received a deceased donor kidney transplant between 1 Nov 2005 and 30 June 2014. Patients were followed up for 5years or until graft-loss or death. Implant biopsies of donor kidneys were done and the Remuzzi score was calculated. The median age was 48 (IQR 42, 52.5) years and 50.7% were male. KDRI-USA, KDRI-THAI, and KDRI-AUST were found to have no correlation with 5year graft survival. Donor characteristics which define an expanded criteria donor kidney, not associated with 5year graft survival are age (p = 0.58), terminal creatinine (p = 0.71) and history of hypertension (p = 0.35). Donor cerebrovascular accident (CVA) as a cause of death (p = 0.02) and Remuzzi score were associated with graft survival at 5years, with 75.8% with Remuzzi score ≤ 3 vs 24.2% with Remuzzi score of > 3 achieving 5year graft survival (p = 0.001). The association of KDRI with graft and patient survival was not demonstrated in our cohort. Histological assessment of the transplant kidney remains the best method of predicting long-term survival during donor selection.

Canadian Anatomic Kidney Score: Quantitative Macroscopic Assessment of Donor Kidney Quality for Transplantation.

The Canadian Anatomic Kidney Score (CAKS) is a novel 6-point grading system that standardizes the gross description of a donor kidney across 3 components-vessels, anatomy, and sticky fat. We hypothesized that the CAKS predicts allograft functional outcomes and provides additional information to the Kidney Donor Profile Index (KDPI) and histologic assessment of the donor kidney. Single-center cohort of 145 patients who underwent renal transplantation with CAKS analysis between 2018 and 2021. CAKS was prospectively determined before transplantation. Preimplantation core biopsies were assessed according to the Remuzzi score (RS). The primary outcome was 1-y allograft function represented by an estimated glomerular filtration rate (eGFR). Linear regression without adjustment for KDPI or RS showed a significant association between the CAKS and 1-y eGFR (-8.7 mL/min/1.73 m2 per point increase in CAKS; 95% CI, -13.0 to -4.4; P < 0.001). Most of that association was attributed to the vessel component (-12.1; -19.4 to -4.8; P = 0.002). Adjustment for KDPI and RS attenuated the relationship between 1-y function and CAKS (-4.6; -9.5 to 0.3; P = 0.065) and vessel component (-7.4; -15.2 to 0.5; P = 0.068). Anatomic assessment of donor kidneys at the time of transplantation associates with allograft function at 1 y. Vascular assessment appears to make the dominant contribution.

Assessment of renal quality with quantitative contrast-enhanced ultrasound (CEUS) for differentiating kidney histopathology before procurement.

Purpose: This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement. Methods: This prospective study included 74 donors and 148 recipients of kidneys. 119 kidneys underwent quantitative analysis. Before organ procurement, potential kidney donors underwent CEUS, though organ procurement involved a zero-point puncture biopsy. CEUS parameters of the renal cortex and medulla were evaluated, including rise time (RT), time to peak (TTP), the area under the curve (AUC), wash-in slope (WIS), peak intensity (PI), and mean transit time (MTT). Donors' kidneys were classified based on their pathological. Additionally, short-term clinical indicators of renal recipients were collected and analyzed to determine whether the patients had delayed recovery of renal allograft function. Results: This experiment included 148 cases of kidney information, divided into two groups based on the Remuzzi score of the kidneys. However, 29 kidneys were excluded from the quantitative analysis due to loss or low quality of CEUS images. Comparing the time-intensity curve (TIC) of renal cortical region of interest (ROI), we found that the group with lower pathological scores exhibited higher PI (P=0.002), AUC(P=0.003), and WIS (P=0.009). TIC comparison results for renal medulla ROI revealed that the group with lower pathological scores had higher PI (P=0.010), AUC (P=0.023), and WIS (P=0.024). Conclusions: This study highlighted the potential of CEUS as a non-invasive, safe, and real-time examination method that correlates with the Remuzzi score and renal pathology. Therefore, it can be used as a prospective preoperative non-invasive evaluation method for the donor's kidney.

PD31-05 THE CANADIAN ANATOMIC KIDNEY SCORE: QUANTITATIVE MACROSCOPIC ASSESSMENT VERSUS HISTOLOGICAL GRADING IN PRE-TRANSPLANT EVALUATION OF DONOR KIDNEYS

You have accessJournal of UrologyCME1 Apr 2023PD31-05 THE CANADIAN ANATOMIC KIDNEY SCORE: QUANTITATIVE MACROSCOPIC ASSESSMENT VERSUS HISTOLOGICAL GRADING IN PRE-TRANSPLANT EVALUATION OF DONOR KIDNEYS Jirong Lu, Juliano Offerni, Danny Matti, Haider Abed, Pavel Roshanov, Alp Sener, and Patrick Luke Jirong LuJirong Lu More articles by this author , Juliano OfferniJuliano Offerni More articles by this author , Danny MattiDanny Matti More articles by this author , Haider AbedHaider Abed More articles by this author , Pavel RoshanovPavel Roshanov More articles by this author , Alp SenerAlp Sener More articles by this author , and Patrick LukePatrick Luke More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003324.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Canadian Anatomic Kidney Score (CAKS) is a novel grading system that provides a framework for macroscopic description of the donor kidney that can standardize communication between clinicians on the quality of the graft. We hypothesize that the CAKS score can independently predict graft outcomes and correlates with KDPI and histologic assessment. METHODS: Between 2018-2020, donor kidneys were prospectively evaluated using CAKS by assessing the macroscopic appearance of the kidney. CAKS uses set criteria to evaluate the arterial vessel, parenchymal anatomy (presence of cysts and scars), sticky fat, and fibrosis (up to 2 points each for a maximum of 8). Renal implantation core biopsy was performed and histologically graded by Remuzzi score (RS). Neither CAKS nor RS was used to determine donor utility. Pre-operative donor score was also obtained using KDPI. Graft outcomes were prospectively tracked with graft failure defined by graft loss or GFR<30 at one year. RESULTS: 174 patients were analysed. There was a poor correlation between CAKS and RS (r2=0.03). CAKS correlated better with KDPI (r2=0.22) than RS with KDPI (r2=0.06). On logistic regression analysis, both CAKS (OR 1.48, p=0.029) and RS (OR 1.55, p=0.010) independently predicted for graft failure. On subset analysis, vascular features were the strongest predictors of graft failure for both CAKS (OR 2.26, p=0.22) and RS (OR 2.39, p=0.054). CONCLUSIONS: The novel CAKS can be used to predict graft outcomes and correlates well with KDPI scores. We seek to evaluate the replicability of CAKS in other centres and potentially develop composite scores to better predict donor graft function in the future. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e902 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jirong Lu More articles by this author Juliano Offerni More articles by this author Danny Matti More articles by this author Haider Abed More articles by this author Pavel Roshanov More articles by this author Alp Sener More articles by this author Patrick Luke More articles by this author Expand All Advertisement PDF downloadLoading ...

APSH-OP-4: HISTOLOGICAL MEASURES OF STRUCTURAL KIDNEY DAMAGE ARE ASSOCIATED WITH SHORTENING OF KIDNEY TELOMERE LENGTH

Objective: Telomeres shorten with each cell division and serve as markers of cell senescence. The rate of telomere attrition varies across tissues within the same individual. Telomere attrition and dysfunction has been associated with various disease states. Studies have shown that leukocyte telomere length (LTL) may be predictive of telomere length in other tissues of the body. Several histological changes occur in the kidney before functional impairment becomes evident. It is unclear if telomeres are associated with these early changes. We sought to (i) investigate whether LTL is a proxy of kidney telomere length (KTL), and (ii) estimate the extent to which both measures of biological ageing associate with histological markers of kidney damage. Design and Methods: Study group consisted of 200 participants (Female 38% and Male 62%) from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study. Participants had no personal history of primary nephropathy and were eligible for unilateral elective nephrectomy because of sporadic non-invasive renal cancer. Kidney tissue samples were collected from the healthy (unaffected by cancer) pole immediately after nephrectomy and fixed in 10% formalin, then embedded in paraffin blocks. The extent of kidney histological damage was assessed using a semi-quantitative method of kidney slide evaluation. LTL and KTL were quantified using quantitative polymerase chain reaction. Results: There was a significant negative correlation between KTL and age (r = -0.287, P &lt; 0.001). The correlation between LTL and age showed directionally consistent, but non-significant pattern (r = -0.135, P = 0.063). Unadjusted and adjusted analysis showed insignificant association between LTL and KTL (r = 0.042, P = 0.575). However, both KTL and LTL correlated with tubular atrophy (r = -0.28, -0.16; P &lt; 0.001, 0.05, respectively). Each increased unit of both KTL and LTL also associated with a decrease of 61.3% and 47.4%, respectively in likelihood of developing tubular atrophy (Table 1). Shorter KTL was associated with increased odds of developing interstitial fibrosis, interstitial inflammation, and Bowmans capsule thickening (Table 1). KTL also associated with percentage of Bowmans capsule thickening (β = -0.214, P = 0.027), percentage of sclerosed glomeruli (β = -0.227, P = 0.017), and Remuzzi score (β = -0.280, P = 0.001). In contrast, LTL did not show an association with any other kidney histology variables, except with tubular atrophy in adjusted analysis. Conclusions: LTL shows only a weak association with tubular atrophy and KTL is a much more accurate measure of histologically confirmed structural kidney damage than LTL. LTL cannot be used as a proxy of KTL or the extent of kidney damage.

Multi-photon microscopy for the evaluation of interstitial fibrosis in extended criteria donor kidneys: A proof-of-concept study.

To evaluate the initial use of label-free second harmonic generation (SHG) imaging with two-photon excitation (2PE) auto-fluorescence in multiphoton microscopy (MPM) for the quantification of collagen/fibrosis on preimplantation biopsies of extended criteria donors (ECD). Twenty preimplantation core biopsies were extracted from 10 donor kidney samples, of which originated from seven donors. Kidney Donor Profile Index (KDPI) and Remuzzi scores of biopsies were calculated. Collagen parameters measured included quantification by the Collagen Area Ratio in Total Tissue (CART) and qualitative measurements by Collagen Reticulation Index (CRI). Biopsies classified with>85% KDPI scores had significantly higher CART (p=.011) and lower CRI values (p=.025) than biopsies with ≤ 85% KDPI scores. Increase in CRI values correlated significantly with rise in recipient creatinine levels 1-year post-transplant (p=.027; 95% CI: 4.635-66.797). MPM is an evolving technology that enables the quantification of the amount (CART) and quality (CRI) of collagen deposition in unstained preimplantation biopsies of donor kidneys stratified by KDPI scores. This initial evaluation found significant differences in both parameters between donor kidneys with more or less than 85% KDPI.

Impact of pre-transplant biopsy on 5-year outcomes of expanded criteria donor kidney transplantation.

Compared to Standard Criteria Donors (SCD), Expanded Criteria Donor (ECD) kidneys are associated with poorer outcomes, although pre-transplant biopsy may mitigate risks. This study assessed 5-year outcomes of deceased-donor kidney transplant recipients, comparing recipients of ECD allografts evaluated histologically to recipients of SCD and ECD kidneys assessed clinically. This is a single-centre retrospective study. From November 2005 to December 2009 (Era 1), donors were assessed clinically for suitability for kidney donation. From December 2009 to October 2017 (Era 2), kidneys from ECDs and diabetics underwent pre-transplant biopsy and were allocated based on Remuzzi score. Outcomes of Era 1 and 2 recipients were compared. ECD kidney transplantation increased from 30.4% to 40.0% from Era 1 to 2. Univariable Cox regression, stratified by transplant era, found that 5-year graft loss was highest with Era 1 ECD (HR 2.5, 95% CI 1.1-5.5, P = .027) while graft loss for Era 2 ECD recipients was similar to SCD recipients. There was no difference in 5-year recipient survival. Amongst Era 1 ECD recipients, 51.2% experienced rejection compared to 30.8-41.5% for other subgroups. Five-year eGFR was higher with Era 2 ECD at 48.4 (33.3-60.7) ml/min/1.73 m2 compared to 42.2 (35.8-57.3) ml/min/1.73 m2 for Era 1 ECD. However, these differences were not statistically significant. Introduction of pre-transplant biopsy assessment may be associated with improved outcomes of ECD kidney recipients such that they are now comparable to SCD kidney recipients, with benefits persisting over 5 years.

P1727DECEASED DONOR KIDNEY CHARACTERISTICS AND IMPACT ON 10-YEAR GRAFT SURVIVAL - A LONG-TERM OBSERVATIONAL STUDY

Abstract Background and Aims The long waiting list for deceased donor kidney transplantation has prompted the use of Expanded Criteria Donors (ECD) though it is possibly associated with worse graft function and outcomes than Standard Criteria Donors (SCD). Our centre had also implemented a protocol kidney biopsy at implantation from 2005 to 2009. The aim of this study was to evaluate the impact of donor factors and donor kidney histology on 10-year graft outcomes. Method A retrospective analysis was performed on 108 kidney transplant recipients who underwent a protocol biopsy at implantation from November 2005 to November 2009. The biopsy sample was evaluated for glomerulosclerosis, tubular atrophy, interstitial fibrosis and arteriolar narrowing and scored according to Remuzzi et al., N Engl J Med. 2006;354(4):343 (Remuzzi score). Donor factors evaluated were donor age, hypertension, diabetes mellitus, and terminal serum creatinine. The 10-year graft survival and estimated glomerular filtration rate (eGFR) was the main outcome of interest. Results The deceased donors included 58% males, 85% Chinese, with a median age of 49 (IQR 12) years. There were 13% diabetics, 51% hypertensive donors and the median terminal creatinine was 95 umol/L. The recipients were 51% male, 79% Chinese, with a median age of 47 (IQR 11) years at transplant. The time interval to transplant was 9.2 (IQR 3.0) years and the overall 10-year graft survival was 67.6%. Remuzzi score of ≤3 was associated with better 10-year graft survival compared with Remuzzi score of &amp;gt;3 (76.6% versus 45.2%, P =0.02). 10-year graft survival for SCD and ECD was not statistically different (71.6% versus 58.8%, P=0.187). A multivariate analysis was performed which included donor status (ECD vs SCD), Remuzzi score (&amp;gt;3 vs ≤3), donor age (≥60 or &amp;lt;60 years), donor hypertension, donor diabetes mellitus and terminal serum creatinine (≥133 umol/L versus &amp;lt;133 umol/L). Only Remuzzi score correlated with a better 10-year graft survival rate (P=0.020). All other factors did not correlate with 10-year graft survival. Amongst the 73 ten-year graft survivors, the median eGFR at year 10 was 47.5 (IQR 20.3) ml/min if the Remuzzi Score was ≤3 while the eGFR was 39.7 (IQR 33.0) ml/min if Remuzzi score was &amp;gt;3. However, this difference was not statistically significant (P=0.570). The 10-year eGFR was 45.8 (IQR 22.2) for SCD kidney recipients vs 49.5 (IQR 25.6) for ECD kidney recipients. Paradoxically, the median eGFR was higher with the ECD cohort but this was not statistically significant (P=0.443). Conclusion An implantation Remuzzi score of more than 3 is associated with poorer long-term graft survival as compared to other donor factors evaluated on 10-year graft survival or eGFR. Where possible, assessment of the kidney histology should be included as part of the kidney selection and allocation process in order to determine long term outcomes.

P0729AKARDI: A NEW PREDICTIVE MODEL FOR RENAL DECAY AFTER NEPHRECTOMY

Abstract Background and Aims Radical Nephrectomy is usually associated to the risk of future development of a mild to severe chronic kidney disease stage especially for those patients who already present early stages of CKD (e.g CKD class II and IIIa). Any insight on this topic could influence the clinical decision about the surgery. But how can we know for sure the magnitude of the renal function’s decay? In this preliminary work, our aim was to identify a new model able to predict at time surgery the renal function’s variation at 1 year from the operation Method We collected prospectively clinical data of a group of consecutive 114 patients who underwent radical nephrectomy (RN) for the presence of a benign or malignant renal mass. We estimated Glomerular Filtration Rate (eGFR) with MDRD formula. We considered the following clinical varibles: AKI onset (according to RIFLE criteria), age, gender, presence of blood hypertension, diabetes type II and BMI. Moreover, to investigate a possible correlation between renal basal histology and renal functional decay, renal biopsies were performed on each on the healthy part of the removed kidney &amp;gt; 3cm far from tumor. A pathological evaluation using a chronicity score (Remuzzi Score) was subsequently carried out evaluating damage on four parameters: (a) glomerular global sclerosis, (b) tubular atrophy, (c) interstitial fibrosis and (d) arterial narrowing. Statistical analysis were performed using generalized linear model (GLM), Kruskal-Wallis test and chi-square test. Multivariate analysis were applied using stepwise regressions method in order to select the best fitting model. Statistically significant correlations were considered for p-value&amp;lt;0.05. Results At t0, 21% of the patients had an eGFR&amp;gt;90ml/min/1.73m2, 45% between 60 and 90, 23% between 30 and 45, and 11% under 45. Median observed decay after 12 months was 32.8% (IQR= 17.9%:41.9%).Taking in account the eGFR decay’s percentage there was a strong correlation with AKI onset (decay increased by 22.4%, CI= 14%:30.8%, p&amp;lt;0.0001), with Diabetes ( decay increased by 13%, CI= 2%: 24.5%, p=0.02) and with the CKD stages at t0 (p=0.0007). Considering the histology, a significative negative correlation was found with the presence of arterial narrowing (-14%, CI=-23%:-6%, p&amp;lt;0.01) even though the whole chronicity score did not correlate (p=0.5). No significative correlations were found between the decay of eGFR and other variables such as age, gender or comorbidities. The multivariate analysis by stepwise regression, including all the significative variables from the univariate analysis, proposed as best model to predict the decay the use of AKI onset (14%, CI=6%:22%, p=0.001), arterial narrowing (-13%, CI=-22%:-5%, p=0.001) and diabetes (p=0.14) as variables. Conclusion A precise and reliable prediction of renal function decrease after RN represents a cornerstone for urologist and nephrologist in order to create a personalized medical approach and management.In our cohort of study, CKD stage I and II patients displayed a huge decrease of eGFR in respect to CKD stages III-IV over time. One possible biological explanation can be that the healthy kidney of the patients affected by moderate and severe CKD starts working with a compensatory mechanism before the entire removal of the kidney with cancer so that the surgical acute nephron loss does not represent a shock in comparison to healthy patients with an eGFR &amp;gt;90 ml/min. Our preliminary study identified a new clinical and pathological panel of variables able to predict at time zero the magnitude of eGFR decay after 1 year from surgical operation. Further studies are needed in order to validate and improve this model.

Comprehensive assessment of deceased donor kidneys with clinical characteristics, pre-implant biopsy histopathology and hypothermic mechanical perfusion parameters is highly predictive of delayed graft function

Background Due to the current high demand for transplant tissue, an increasing proportion of kidney donors are considered extended criteria donors, which results in a higher incidence of delayed graft function (DGF) in organ recipients. Therefore, it is important to fully investigate the risk factors of DGF, and establish a prediction system to assess donor kidney quality before transplantation. Methods A total of 333 donation after cardiac death kidney transplant recipients were included in this retrospective study. Both univariate and multivariate analyses were used to analyze the risk factors of DGF occurrence. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of variables on DGF posttransplant. Results The donor clinical scores, kidney histopathologic Remuzzi scores and hypothermic mechanical perfusion (HMP) parameters (flow and resistance index) were all correlated. 46 recipients developed DGF postoperatively, with an incidence of 13.8% (46/333). Multivariate logistic regression analysis of the kidney transplants revealed that the independent risk factors of DGF occurrence post-transplantation included donor score (OR = 1.12, 95% CI 1.06–1.19, p < 0.001), Remuzzi score (OR = 1.21, 95% CI 1.02–1.43, p = 0.029) and acute tubular injury (ATI) score (OR = 4.72, 95% CI 2.32–9.60, p < 0.001). Prediction of DGF with ROC curve showed that the area under the curve was increased to 0.89 when all variables (donor score, Remuzzi score, ATI score and HMP resistance index) were considered together. Conclusions Combination of donor clinical information, kidney pre-implant histopathology and HMP parameters provide a more accurate prediction of DGF occurrence post-transplantation than any of the measures alone.

Pre-implantation kidney biopsy: value of the expertise in determining histological score and comparison with the whole organ on a series of discarded kidneys.

Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist's expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys. 46 discarded kidneys were identified with their corresponding biopsies. The biopsies were reviewed by three general and two specialist pathologists, blinded to the original report, according to Remuzzi score. The intraclass correlation coefficient (ICC) was calculated for both groups. Discarded kidneys were scored according to Remuzzi score by a single specialist pathologist. Biopsies and organs were compared by Wilcoxon signed rank test. Weighted κ coefficients between biopsy and organ scores were also calculated. Specialist pathologists achieved higher values of ICC, reaching excellent or good agreement in most of the parameters, while general pathologists values were mainly fair or good. On whole organs, scores were consistently lower than biopsies, with a significant difference in most of the parameters. Weighted κ coefficient was slight or fair for most of the parameters. Our data suggests that the creation of a pool of specialist pathologists would improve organ utilization. Moreover, biopsies are not representative of the whole organ. As the Remuzzi score on biopsy is a major reasons for discard, a quota of transplantable kidneys may be erroneously discarded. Refinement in Remuzzi cut-offs based on expert reporting and recognition of sampling error of biopsies in correlation with clinical outcome data should be undertaken.

Pre-Transplant Histological Assessment Provides a Useful Predictor of Subsequent Kidney Allograft Function

Introduction Organ shortage is a major challenge in transplantation. In view of this problem, organs from marginal donors are increasingly being considered for transplantation. In kidney transplantation, histological assessment of deceased donor kidneys with the Remuzzi score (RS) has proven to be effective at predicting renal allograft survival but requires further validation. Addenbrookes Hospital in Cambridge, UK, has used RSs to determine suitability of deceased donor kidneys from older donors and those with multiple co-morbidities, for single or dual transplantation. From 2010, kidneys with a RS of 1-3 were deemed suitable for single kidney transplantation, and in 2014 this was extended to include kidneys with a RS of 4. We sought to assess the efficacy of the RS to predict kidney transplant outcomes and to confirm that single kidneys transplanted with RS of 4 had reasonable outcomes. Methods All recipients of single deceased donor kidney transplants performed at Addenbrookes hospital, Cambridge, with available pre-transplant RSs, between 2010 and 2016 were identified. Transplant outcomes (death censored graft survival and 1 year eGFR) were analysed. Results In total, 495 single deceased donor kidneys with RSs were identified. Of these 40.2% were from donation after brain stem death donors (DBD), and 59.8% were from donation after circulatory death donors (DCD). The breakdown of the RS of these kidneys are shown in figure 1. The 1 year eGFR and graft survivals according to their RS are shown in Table 1. 1 year death censored graft survival was not negatively impacted by higher pre-donation RS (p=0.54). However, graft function at 1 year was significantly worse with a RS ≥ 5, median eGFR 41.9 ml/min (95% CI 34.3-49.5) versus 52.3 ml/min (95% CI 49.8-54.7) with a score <5 (p=0.02) (figure 2). Increasing RS conferred reductions in 1 year eGFR (r=-0.356, p<0.01). Discussion This single centre, retrospective observational study demonstrates that the RS is effective in predicting deceased donor renal allograft function at one year. The data also shows that selected kidneys with a RS>5 have reasonable transplant outcomes. These results highlight the need for additional indicators to improve prediction of post-transplant renal function. We developed a model to highlight if any of the individual parameters were more predictive of 1 year eGFR in this cohort, but they were not. However this was with a small cohort and we are collecting additional data to better power this analysis. Furthermore we are currently looking biomarkers which may be predictive of functional outcomes, using transcriptomics on these biopsy samples.

Application of Nonlinear Optical Microscopic Imaging Technology for Quality Assessment of Donor Kidneys

BackgroundNonlinear optical microscopic (NLOM) imaging technique shows its high resolution imaging features in histocytology. The purpose of this study was to investigate NLOM imaging technique as a useful tool for a donor kidney quality assessment. Materials and MethodsEighty-three pretransplant kidney biopsies from adult donors were analyzed retrospectively. Each specimen was paraffin-embedded and sectioned into 2 consecutive 5-μm thick sections. One section was stained with Masson trichrome, and the other was left unstained for NLOM imaging using second harmonic generation combined with two-photon excited fluorescence (SHG/TPEF). The pretransplant kidney quality was assessed by an experienced pathologist using the Remuzzi scoring system, which characterizes renal tissue morphology into 4 aspects: tubular atrophy, interstitial fibrosis, glomerulosclerosis, and vascular injury. The K coefficient was used to measure the consistency of the Remuzzi scores between conventional Masson trichrome stained images and SHG/TPEF images. ResultsNLOM imaging technology can capture high-resolution tissue images from unstained renal tissue, is easy to operate, and shortens time-consuming histological processing procedures. No significant differences (P > .05) were found between the Remuzzi scores of the SHG/TPEF images and the Masson trichrome stained images. The high κ coefficients (0.804–0.895) showed a good consistency between these 2 techniques. ConclusionThe NLOM technique is suitable for renal tissue imaging and could potentially be used for routine pretransplant kidney evaluation in clinical settings.

It is the time to rethink the criteria to define transplantable kidneys. Should we combine histological and clinical evaluation?

In this issue of Transplantation International, Sanchez-Escudero et al [1] report the results obtained from a prospective single centre study enrolling 485 consecutive transplant recipients receiving a kidney with a Remuzzi score (RS) [2] of Pre Transplant Donor Biopsies (PTDB) lower or equal to 4. Then retrospectively, the authors compared their organ allocation policy based on RS with kidney donor profile index (KDPI) [3] and evaluated the discard rate between KDPI and PTDB and five years graft and patients survival. Their data support the hypothesis that PTDB could support the acceptance of kidneys with the highest KDPI. This article is protected by copyright. All rights reserved.

Histopathological evaluation of pretransplant donor biopsies in expanded criteria donors with high kidney donor profile index: a retrospective observational cohort study

There is no consensus on the allocation of renal transplants from expanded criteria donors (ECD). The Kidney Donor Profile Index (KDPI) is used without the need for pretransplant donor biopsies (PTDB). We explored whether PTDB based on Remuzzi Score (RS) allows identification of those marginal kidneys in the highest calculated KDPI risk group (>91%) that appropriate for single transplantation. A retrospective study was conducted of 485 consecutive kidneys procured from a single center and transplanted if the RS was ≤4. We compared 5-year kidney and patients survival between KDPI groups and between RS <4 or =4 in the highest KDPI group. The median KDPI (interquartile range) was 71 (66-76) for KDPI <80% (n=77), 86 (81-90) for KDPI 81-90% (n=82), and 97 (94-100) for KDPI >91% (n=205). Patient survival at 5years was 85.7%, 85.3%, and 76.09% (P=0.058) and death-censored graft survival was 84.4%, 86.5%, 73.6% (P=0.015), respectively for each KDPI group. In >91% calculated KDPI group, there were no differences in graft survival depending on the RS (<4 vs. =4) (P=0.714). The implementation of PTDB based on RS used for allocation of organs with the highest KDPI range could support to the acceptance of suitable organs for single transplantation with good patient and graft survival rate.

Pre-implantation analysis of kidney biopsies from expanded criteria donors: testing the accuracy of frozen section technique and the adequacy of their assessment by on-call pathologists.

Pre-implantation renal biopsies of expanded criteria donors are one of the criteria used for allocation decisions, but there are concerns about the impact of the interobserver variability and the technique to be used. The aim was (i) to compare the original report performed by on-call pathologists using frozen sections (FS) to a retrospective analysis carried out by a trained pathologist using the same frozen section, and (ii) to compare the same FS to subsequently obtained paraffin sections (PS) by the same pathologist. A total of 92 biopsies, 78 from transplanted and 14 from nontransplanted cases, were analyzed. Agreement between observers using the same FS was weaker than the correlation between FS and PS in all the examined parameters (Kendall's Tau b for the Remuzzi score 0.104 vs. 0.306). According to the Remuzzi score, the revised FS analysis would have resulted in a higher rate of organ discard (n=19) than PS (n=14) and the original report (n=6). However, kidneys that would have been discarded according to the retrospective analysis showed adequate outcomes in terms of graft survival and function. Accordingly, the impact of interobserver and technique-related variability can be minimized by the use of a relatively low threshold (RS≤4) for organ acceptance.

Successful Transplantation of Kidneys From Elderly Circulatory Death Donors by Using Microscopic and Macroscopic Characteristics to Guide Single or Dual Implantation

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.