Histological Findings and T2 Relaxation Time in Canine Menisci of Elderly Dogs-An Ex Vivo Study in Stifle Joints.

Osteoarthritis is a chronic disease that often affects the canine stifle joint. Due to their biomechanical function, the menisci in the canine stifle play an important role in osteoarthritis. They compensate for the incongruence in the joint and distribute and minimize compressive loads, protecting the hyaline articular cartilage from damage. Meniscal degeneration favors the development and progression of stifle joint osteoarthritis. Qualitative magnetic resonance imaging (MRI) is the current golden standard for detecting meniscal changes, but it has limitations in detecting early signs of meniscal degeneration. A quantitative MRI offers new options for detecting early structural changes. T2 mapping can especially visualize structural changes such as altered collagen structures and water content, as well as deviations in proteoglycan content. This study evaluated T2 mapping and performed a histological scoring of menisci in elderly dogs that had no or only low radiographic osteoarthritis grades. A total of 16 stifles from 8 older dogs of different sex and breed underwent ex vivo magnet resonance imaging, including a T2 mapping pulse sequence with multiple echoes. A histological analysis of corresponding menisci was performed using a modified scoring system. The mean T2 relaxation time was 18.2 ms and the mean histological score was 4.25. Descriptive statistics did not reveal a correlation between T2 relaxation time and histological score. Ex vivo T2 mapping of canine menisci did not demonstrate histological changes, suggesting that early meniscal degeneration can be present in the absence of radiological signs of osteoarthritis, including no significant changes in T2 relaxation time.

A Semi-quantitative Scoring System for Green Histopathological Evaluation of Large Animal Models of Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) is a life-threatening, high mortality pulmonary condition characterized by acute lung injury (ALI) resulting in diffuse alveolar damage. Despite progress regarding the understanding of ARDS pathophysiology, there are presently no effective pharmacotherapies. Due to the complexity and multiorgan involvement typically associated with ARDS, animal models remain the most commonly used research tool for investigating potential new therapies. Experimental models of ALI/ARDS use different methods of injury to acutely induce lung damage in both small and large animals. These models have historically played an important role in the development of new clinical interventions, such as fluid therapy and the use of supportive mechanical ventilation (MV). However, failures in recent clinical trials have highlighted the potential inadequacy of small animal models due to major anatomical and physiological differences, as well as technical challenges associated with the use of clinical co-interventions [e.g., MV and extracorporeal membrane oxygenation (ECMO)]. Thus, there is a need for larger animal models of ALI/ARDS, to allow the incorporation of clinically relevant measurements and co-interventions, hopefully leading to improved rates of clinical translation. However, one of the main challenges in using large animal models of preclinical research is that fewer species-specific experimental tools and metrics are available for evaluating the extent of lung injury, as compared to rodent models. One of the most relevant indicators of ALI in all animal models is evidence of histological tissue damage, and while histological scoring systems exist for small animal models, these cannot frequently be readily applied to large animal models. Histological injury in these models differs due to the type and severity of the injury being modeled. Additionally, the incorporation of other clinical support devices such as MV and ECMO in large animal models can lead to further lung damage and appearance of features absent in the small animal models. Therefore, semi-quantitative histological scoring systems designed to evaluate tissue-level injury in large animal models of ALI/ARDS are needed. Here we describe a semi-quantitative scoring system to evaluate histological injury using a previously established porcine model of ALI via intratracheal and intravascular lipopolysaccharide (LPS) administration. Additionally, and owing to the higher number of samples generated from large animal models, we worked to implement a more sustainable and greener histopathological workflow throughout the entire process.

Long-Term Outcomes of Kidney Transplants from Older/Marginal Donors: A Cohort Study.

INTRODUCTION: To safely expand the donor pool, we introduced a strategy of biopsy-guided selection and allocation to single or dual transplantation of kidneys from donors >60 years old or with hypertension, diabetes, and/or proteinuria (older/marginal donors). Here, we evaluated the long-term performance of this approach in everyday clinical practice. METHODS: In this single-center cohort study, we compared outcomes of 98 patients who received one or two biopsy-evaluated grafts from older/marginal donors ("recipients") and 198 patients who received nonhistologically assessed single graft from ideal donors ("reference-recipients") from October 2004 to December 2015 at the Bergamo Transplant Center (Italy). RESULTS: Older/marginal donors and their recipients were 27.9 and 19.3 years older than ideal donors and their reference-recipients, respectively. KDPI/KDRI and donor serum creatinine were higher and cold ischemia time longer in the recipient group. During a median follow-up of 51.9 (interquartile range 23.1-88.6) months, 11.2% of recipients died, 7.1% lost their graft, and 16.3% had biopsy-proven acute rejection (BPAR) versus 3.5, 7.6, and 17.7%, respectively, of reference-recipients. Overall death-censored graft failure (rate ratio 0.78 [95% CI 0.33-2.08]), 5-year death-censored graft survival (94.3% [87.8-100.0] vs. 94.2% [90.5-98.0]), BPAR incidence (rate ratio 0.87 [0.49-1.62]), and yearly measured glomerular filtration rate decline (1.18 ± 3.27 vs. 0.68 ± 2.42 mL/min/1.73 m2, p = 0.37) were similar between recipients and reference-recipients, respectively. CONCLUSIONS: Biopsy-guided selection and allocation of kidneys from older/marginal donors can safely increase transplant activity in clinical practice without affecting long-term outcomes. This may help manage the growing gap between organ demand and supply without affecting long-term recipient and graft outcomes.

Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis.

BACKGROUND AND AIMS: Elevated fecal calprotectin (FC) levels have been reported to correlate with histological activity in patients with ulcerative colitis (UC). However, the accuracy of FC for evaluating histological activity of UC remains to be determined. The aim of this study was to determine the accuracy of FC for evaluating histological activity of UC, based on updated definitions. METHODS: Related studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Adult participants diagnosed with UC were included when sufficient data could be extracted to calculate the accuracy of FC for evaluating histological activity. The primary outcome was histological response, and the secondary outcome was histological remission, defined according to a recently updated position paper of European Crohn's and Colitis Organization. Statistics were pooled using bivariate mixed-effects models. The area under the curve was estimated by summary receiver-operating characteristic curves. RESULTS: Nine studies were included, from which 1039 patients were included for the analysis of histological response and 591 patients for histological remission. For the evaluation of histological response, the pooled sensitivity, specificity, and the area under the curve were 0.69 [95% confidence interval (CI): 0.52-0.82], 0.77 (95% CI: 0.63-0.87), and 0.80 (95% CI: 0.76-0.83), respectively. For the evaluation of histological remission, the corresponding estimates were 0.76 (95% CI: 0.71-0.81), 0.71 (95% CI: 0.62-0.78), and 0.79 (95% CI: 0.75-0.82), respectively. FC had a higher accuracy in studies using Nancy Index. For histological response, the cut-off values of FC ranged from 50 to 172 µg/g, and the sensitivity was higher in studies with FC cut-off values >100 µg/g (0.77 versus 0.65). CONCLUSION: FC is a valuable biomarker for assessing histological activity in patients with UC. A cut-off value of 100-200 µg/g is more appropriate to spare patients from an unnecessary endoscopy and biopsy.

Histological distribution pattern of hemosiderin deposition on the chorionic plate and fetal membrane of diffuse chorioamniotic hemosiderosis related to chronic abruption oligohydramnios sequence.

INTRODUCTION: Chronic abruption oligohydramnios sequence (CAOS) is histologically characterized by diffuse chorioamniotic hemosiderosis (DCH). However, the criteria for the histological evaluation of the extent of CAOS-related hemosiderin deposition (HD) of the membranes and the difference in HD between the chorionic plate (CP) and fetal membrane (FM) are not well studied. This case control study compared the degree and distribution pattern of HD on CP and FM to present the histological features of DCH and the criteria for histological evaluation. METHODS: From the medical records of Kyoto University Hospital (2010-2019), we selected 20 CAOS cases that were clinically diagnosed by Elliot's criteria. Twenty non-CAOS cases matched to the CAOS group by gestational age were selected as controls. We compared the clinical data and pathological features in the two groups. We performed iron staining in all the cases and analyzed HD in CP and FM according to the histological score (H-Score: 0-12), which was determined as the density (0-3) multiplied by the extent of staining (0-4). RESULTS: HD was found in 100% (20/20) of CAOS and 15% (3/20) of control cases. In both the FM and CP, CAOS cases showed a significantly higher HS than control cases (CAOS, HS = 4-12; Control, HS = 0-1, p < 0.0001). Three CAOS patients presented HD alone in the CP. The HS of the CP was significantly higher than that of the FM (p = 0.0003). DISCUSSION: CAOS presented DCH with HS ≥ 4. This study showed that the CP might be more suitable for evaluating DCH than the FM.

Preimplantation Histological Score Associates with 6-Month GFR in Recipients of Perfused, Older Kidney Grafts: Results from a Pilot Study.

BACKGROUND: Biopsy-guided selection of older kidneys safely expands the organ pool, and pretransplant perfusion improves the preservation of these fragile organs. Herein, we studied morphofunctional variables associated with graft outcomes in perfused, histologically evaluated older kidneys. METHODS: This single-center prospective cohort pilot study evaluated the relationships between preimplantation histologic scores and renal perfusion parameters during hypothermic, pulsatile, machine perfusion (MP) and assessed whether these morphofunctional parameters associated with GFR (iohexol plasma clearance) at 6 months after transplantation in 20 consecutive consenting recipients of a biopsy-guided single or dual kidney transplant from >60-year-old deceased donors. RESULTS: The donor and recipient age was 70.4 ± 6.5 and 63.6 ± 7.9 years (p = 0.005), respectively. The kidney donor profile index (KDPI) was 93.3 ± 8.4% (>80% in 19 cases), histologic score 4.4 ± 1.4, and median (IQR) cold ischemia time 19.8 (17.8-22.8 h; >24 h in 5 cases). The 6-month GFR was 41.2 (34.9-55.7) mL/min. Vascular resistances positively correlated with global histologic score (p = 0.018) at MP start and then decreased from 0.88 ± 0.43 to 0.36 ± 0.13 mm Hg/mL/min (p < 0.001) in parallel with a three-fold renal flow increase from 24.0 ± 14.7 to 74.7 ± 31.8 mL/min (p < 0.001). Consistently, vascular resistance reductions positively correlated with global histologic score (p = 0.009, r = -0.429). Unlike KDPI or vascular resistances, histologic score was independently associated with 6-month GFR (beta standardized coefficient: -0.894, p = 0.005). CONCLUSIONS: MP safely improves graft perfusion, particularly in kidneys with severe histologic changes that would not be considered for transplantation because of high KDPI. The preimplantation histologic score associates with the functional recovery of older kidneys even in the context of a standardized program of pulsatile perfusion.

Deep learning enables the automation of grading histological tissue engineered cartilage images for quality control standardization.

OBJECTIVE: To automate the grading of histological images of engineered cartilage tissues using deep learning. METHODS: Cartilaginous tissues were engineered from various cell sources. Safranin O and fast green stained histological images of the tissues were graded for chondrogenic quality according to the Modified Bern Score, which ranks images on a scale from zero to six according to the intensity of staining and cell morphology. The whole images were tiled, and the tiles were graded by two experts and grouped into four categories with the following grades: 0, 1-2, 3-4, and 5-6. Deep learning was used to train models to classify images into these histological score groups. Finally, the tile grades per donor were averaged. The root mean square errors (RMSEs) were calculated between each user and the model. RESULTS: Transfer learning using a pretrained DenseNet model was selected. The RMSEs of the model predictions and 95% confidence intervals were 0.49 (0.37, 0.61) and 0.78 (0.57, 0.99) for each user, which was in the same range as the inter-user RMSE of 0.71 (0.51, 0.93). CONCLUSION: Using supervised deep learning, we could automate the scoring of histological images of engineered cartilage and achieve results with errors comparable to inter-user error. Thus, the model could enable the automation and standardization of assessments currently used for experimental studies as well as release criteria that ensure the quality of manufactured clinical grafts and compliance with regulatory requirements.

Animal models of osteoarthritis: characterization of a model induced by Mono-Iodo-Acetate injected in rabbits.

Knee Osteoarthritis is a considerable public health concern, both in terms of life quality and treatment financial impacts. To investigate this disease, animal models are deemed a promising alternative. In fact, although a perfect model is generally farfetched, the creation of models that simulate human disease as accurately as possible remains an important research stake. This study aims to highlight the usefulness of the model induced by injected Mono-Iodo-Acetate and to standardize it for the rabbit species. Osteoarthritis was induced by an infra-patellar injection of 0.2 ml of an MIA solution in the left knee of 24 female New Zealand rabbits. The right knee served as a control by receiving an injection of physiological serum. The rabbits were divided into 4 groups of 6 individuals each according to the dose of MIA received per knee. All rabbits were euthanized 30 days after the injection. After sacrifice, the knees were carefully dissected and macroscopic and microscopic scores of cartilage, meniscal and synovial lesions were attributed to each group. Our study followed the laboratory animal care and management guideline published in 2017 by the Canadian Council of Animal Care. The control knees of all rabbits showed no macroscopic or microscopic lesions. The macroscopic lesions: osteophytes, meniscal lesions, fibrillation and erosion of the cartilage and microscopic lesions: disorganization of the chondrocytes, decrease in proteoglycans and synovial inflammation clinically diagnosed in human pathology were all detected and were similarly reproducible among the knees of the same group. Through this work, we highlighted the merits of the arthritis model induced by MIA, namely its simulation of several aspects of human pathology. Further advantages are low cost, speed, reproducibility. This model notably avoids delicate and risky surgical operations.

Morphological Evaluation of Wound Healing Events in the Excisional Wound Healing Model in Rats.

Skin wound healing is a complex process involving different events such as blood coagulation, inflammation, new blood vessels formation, and extracellular matrix deposition. These events can be observed by using histology techniques. However, the lack of the standardization of such parameters impacts on the reproducibility of results. Here, we describe a protocol to perform macroscopic and microscopic analyses of the events that occur during skin wound healing using the experimental model of excisional wounds in rats.

Histological and reference system for the analysis of mouse intervertebral disc.

A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorized into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. "Normal NP" exhibited a highly cellularized cell mass that decreased with natural ageing and in disc degeneration. "Normal AF" consisted of distinct concentric lamellar structures, which was disrupted in severe degeneration. NP/AF clefts indicated more severe changes. Consistent scores were obtained between experienced and new users. Altogether, our scoring system effectively differentiated IVD changes in various strains of wild-type and genetically modified mice and in induced models of IVD degeneration, and is applicable from the post-natal stage to the aged mouse. This scoring tool and reference resource addresses a pressing need in the field for studying IVD changes and cross-study comparisons in mice, and facilitates a means to normalize mouse IVD assessment between different laboratories. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:233-243, 2018.

Lung tissue remodelling in MCT-induced pulmonary hypertension: a proposal for a novel scoring system and changes in extracellular matrix and fibrosis associated gene expression.

Pulmonary hypertension (PH) is associated with vasoconstriction and remodelling. We studied lung tissue remodelling in a rat model of PH with special focus on histology and extracellular matrix (ECM) remodelling. After induction of PH by monocrotaline, lung tissue was analysed histologically, by gene expression analysis and immunofluorescence labelling of ED-A domain containing fibronectin (ED-A+ Fn), B domain containing tenascin-C (B+ Tn-C) as well as alpha-smooth muscle actin (α-SMA). Serum concentrations of ED-A+ Fn were determined by ELISA. Systolic right ventricular pressure (RVPsys) values were significantly elevated in PH (n = 18; 75 ± 26.4 mmHg) compared to controls (n = 10; 29 ± 19.3 mmHg; p = 0.015). The histological sum-score was significantly increased in PH (8.0 ± 2.2) compared to controls (2.5 ± 1.6; p < 0.001). Gene expression analysis revealed relevant induction of several key genes of extracellular matrix remodelling. Increased protein deposition of ED-A+ Fn but not of B+ Tn-C and α-SMA in lung tissue was found in PH (2.88 ± 3.19 area%) compared to controls (1.32 ± 0.16 area%; p = 0.030). Serum levels of ED-A+ Fn were significantly higher in PH (p = 0.007) positively correlating with RVPsys (r = 0.618, p = 0.019). We here present a novel histological scoring system to assess lung tissue remodelling in PH. Gene expression analysis revealed induction of candidate genes involved in collagen matrix turnover, fibrosis and vascular remodelling. The stable increased tissue deposition of ED-A+ Fn in PH as well as its dynamics in serum suggests a role as a promising novel biomarker and potential therapeutic target.

Modelo de instilación intra-traqueal de jugo gástrico en la rata: curso temporal de las alteraciones histológicas / Intra-tracheal instillation of gastric juice in the rat: time course of histological changes

Introduction: Aspiration of gastric content is associated with a wide range of clinical conditions (acute lung injury, severe interstitial pneumonia or bronchiolitis obliterans following lung transplantation). Objective: To study the course of histological alterations in a model of intra-tracheal instillation of gastric juice in rats. Methods: Anesthetized rats were euthanized at different times: 4, 12 and 24 hours and 4 and 7 days after intratacheal (IT) instillation of gastric juice. Animals that were not intervened served as controls. The right inferior lobe was studied (H-E) and a histological injury score was given according to a recently published score system. Results: Between 4-24 h an inflammatory-hemorragic pattern with bronchiol-centric distribution was characterized by a large proportion of neutrophils in both alveoli and interstitium, alveolarfluid accumulation, proteinaceous material andfew hyaline membranes. Between 4 and 7 days, mononuclear cells were more prevalent, the hemorrhagic component disappeared, the percentage of abnormal bronchioles was significantly reduced and there was organization of the alveolar infiltrate, with Masson bodies, granulomas and giant cells associated with gastric juice particles. Conclusions: In rats, IT instillation of gastric juice induces diffuse alveolar damage that evolves towards an early granulomatous interstitial pneumonia along with lax fibrous tissue. Knowledge of the temporary course of the pulmonary responses helps to the understanding of the consequences of the several clinical conditions that favor gastric content aspiration.

Introducción: La aspiración de contenido gástrico se asocia con diversas condiciones clínicas (daño pulmonar agudo, neumonía intersticial severa o bronquiolitis obliterante post-trasplante). Objetivo: Estudiar el curso de las alteraciones histológicas en un modelo de instilación intra-traqueal (IT)de jugo gástrico en ratas. Métodos: Ratas anestesiadas recibieron vía ITjugo gástrico de un pool obtenido previamente. Los animales fueron sacrificados a las: 4, 12 y 24 h y 4 y 7 días post-instilación. Animales sin intervención sirvieron como controles. El lóbulo inferior derecho fue estudiado (H-E) para la asignación de un puntaje de daño histológico de acuerdo a un sistema de puntuación recientemente publicado. Resultados: Entre 4-24 h se observó un patrón inflamatorio-hemorrágico de distribución bronquíolo-céntrica, con predominio de neutrófilos intersticiales y alveolares, edema, material proteináceo alveolar y escasas membranas hialinas. Entre los 4 y 7 días, se observó predominio mononuclear y desaparición del componente hemorrágico, se redujo significativamente el porcentaje de bronquíolos afectados y se observó organización del infiltrado inflamatorio, con cuerpos de Masson, granulomas y células gigantes asociadas a partículas del jugo gástrico. Conclusiones: En ratas, la instilación IT de jugo gástrico induce daño alveolar difuso que progresa hacia una neumonía intersticial granulo-matosa temprana con tejido fibroso laxo. El conocimiento del curso de la respuesta pulmonar en este modelo, contribuye a comprender las posibles consecuencias de las condiciones clínicas que favorecen la aspiración de contenido gástrico.

Psoriasis treatment: faster and long-standing results after bathing in geothermal seawater. A randomized trial of three UVB phototherapy regimens.

BACKGROUND: The combination of seawater baths and narrowband ultraviolet B (NB-UVB) is a known treatment for psoriasis. This study evaluates two treatment regimens that combine bathing in geothermal seawater and NB-UVB therapy in comparison with NB-UVB monotherapy. METHODS: Sixty-eight psoriasis patients were randomly assigned to outpatient bathing in geothermal seawater combined with NB-UVB therapy three times a week, intensive daily treatment involving bathing in geothermal seawater combined with NB-UVB therapy, or NB-UVB therapy alone three times a week; treatment period was 6 weeks. Disease severity [Psoriasis Area Severity Index (PASI) and Lattice System Physician's Global Assessment scores], quality of life (Dermatology Life Quality Index) and histological changes were evaluated before, during and after treatment. The primary end point was the proportion of patients who achieved PASI 75 at 6 weeks. RESULTS: At 6 weeks, the percentage of patients who achieved PASI 75 and PASI 90 was significantly greater for both regimens, bathing in geothermal seawater three times a week (68.1% and 18.2%, respectively) and intensive treatment with geothermal seawater (73.1% and 42.3%, respectively) than for NB-UVB monotherapy (16.7% and 0%, respectively) (P < 0.05 in all comparisons). Clinical improvement was paralleled by improvement in quality of life and histological score and a reduction in NB-UVB doses. CONCLUSION: Bathing in geothermal seawater combined with NB-UVB therapy in psoriasis induces faster clinical and histological improvement, produces longer remission time and permits lower NB-UVB doses than UVB therapy alone.

Effects of intra-arterial octreotide on pancreatic texture: a randomized controlled trial.

BACKGROUND AND AIMS: Octreotide is suggested to harden the pancreas, thus facilitating the construction of a pancreatic anastomosis and lowering the risk of postoperative fistula. We tested the hypothesis that intra-arterial application of octreotide in the gastroduodenal artery during pancreatectomy may increase pancreatic hardness. MATERIAL AND METHODS: A single-center, prospective, double-blinded, randomized controlled trial with parallel assignment was conducted. Patients planned for a pancreatoduodenectomy or a total pancreatectomy, who had a palpatory and durometer proven (<40 Shore units) soft pancreas, were assigned to receive intraoperatively either 5 mL 500µg octreotide or 5 mL 0.9% saline solution as a bolus injection in the gastroduodenal artery. Pancreatic hardness was measured before, early, and late after intervention. The investigator performing the durometer measurements and pathologist were masked to group assignment. The primary outcome was increased pancreatic hardness. Analysis was by intention to treat. This trial is registered at http://www.clinicaltrials.gov (ID NCT01400100). RESULTS: A total of 12 patients received octreotide and 13 received saline solution. Pancreatic hardness marginally increased in the octreotide group: 0.67 ± 2.3 Shore units, whereas it decreased in the control group: -2.15 ± 2.7 Shore units. The difference was statistically significant, p = 0.029 (95% confidence interval = -4.87 to -0.77). Histology did not find any correlate for this clinically irrelevant hardening effect. CONCLUSIONS: A single bolus application of octreotide did not deliver a clinically relevant increase in pancreatic hardness. Future studies on the hardening effect of octreotide should employ repeated or continuous preoperative administration of this drug.

Impact of the pre-transplant histological score on 3-year graft outcomes of kidneys from marginal donors: a single-centre study.

BACKGROUND: The reliability of kidney biopsy as the sole means for assessing kidneys from extended-criteria donors (ECDs) to be allocated to single or dual transplantation is still a matter of debate. METHODS: We compared retrospectively 3 years graft survival and renal function in 44 recipients of a single kidney graft from a marginal donor with good renal function and a Karpinski histological score of ≤ 3 and 56 recipients of a single transplant with a Karpinski score of 4 or 5. The donors' and recipients' characteristics were compared by means of Wilcoxon's rank-sum test and Fisher's exact test, and survival was analysed using the log-rank test and Cox regression survival analysis. RESULTS: The donors with the worse histological scores were slightly younger (68.0 ± 4.74 versus 71.3 ± 4.6 years, P < 0.01) and had a higher glomerular filtration rate (85.8 ± 28.2 versus 76.3 ± 26.53 mL/min, P = 0.013), but there was no difference in serum creatinine levels (0.83 ± 0.24 versus 0.85 ± 0.30 mg/dL, P = 0.381). Three years after transplantation, there was no difference between the two groups in terms of recipient serum creatinine levels (1.94 ± 0.69 versus 1.74 ± 0.49 mg/dL, P = 0.134), estimated glomerular filtration rate (eGFR, 45.6 ± 21.1 versus 51.7 ± 22.0 mL/min, P = 0.331) or the rates of graft loss (27.3 versus 35.7%, P = 0.47), delayed graft function or acute rejection. CONCLUSIONS: In our experience, provided the donor has a normal renal function, a difference in the pre-transplant histological score of kidneys from marginal cadaveric donors do not have a significant influence on the outcome 3 years after transplantation. Our findings might represent a basis for designing a randomized controlled trial of using a higher histological score threshold for the DKT allocation of grafts from ECDs with a normal renal function.