Antibody-mediated rejection with the presence of glomerular crescents in a pediatric kidney transplant recipient: A case report.

Glomerular crescents in kidney transplantation are indicative of severe glomerular injury and constitute a hallmark of RPGN. Their concurrence with ABMR has been rarely described only in adult patients. We report a case of 10-year-old boy with compound heterozygous Fin-major Finnish-type congenital nephrotic syndrome, who had received a deceased-donor kidney transplant 5 years before onset of acute kidney injury and nephrotic range proteinuria without hematuria. Kidney allograft biopsy illustrated 6 glomeruli with global sclerosis and 6 with remarkable circumferential or segmental cellular crescents. Negative glomerular immunofluorescence for immune-complex deposits and the absence of serum ANCA eliminated the presence of immune-mediated and ANCA-positive pauci-immune crescentic glomerulonephritis. Diagnosis of ABMR was based on the high levels of HLA class II DSA and the histological evidence of glomerulitis, peritubular capillaritis, and acute tubular injury with positive linear peritubular capillary C4d staining. The patient despite plasmapheresis and enhanced immunosuppressive treatment progressed to end-stage renal disease. We conclude that glomerular crescents may represent a finding of AMBR and possibly a marker of poor allograft prognosis in pediatric patients.

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients.

AIMS: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. METHODS AND RESULTS: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15-85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112-376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. CONCLUSIONS: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

Phenotypic characterization of a novel HO-1 depletion model in the rat.

Although the protective role of HO-1 induction in various forms of kidney disease is well established, mechanisms other than heme catabolism to biliverdin, bilirubin and carbon monoxide have recently been identified. Unraveling these mechanisms requires the generation of appropriate animal models. The present study describes the generation of a HO-1 deficient Hmox1 -/- rat model and characterizes its renal and extrarenal phenotype. Hmox1 -/- rats had growth retardation and splenomegaly compared to their Hmox1 +/+ littermates. Focal segmental glomerulosclerosis-type lesions and interstitial inflammatory infiltrates were prominent morphologic findings and were associated with increased blood urea nitrogen, serum creatinine and albuminuria. There was no increase in iron deposition in glomeruli, tubules or interstitium. Iron deposition in spleen and liver was reduced. Electron microscopic examination of glomeruli revealed edematous podocytes with scant areas of foot process effacement but otherwise well preserved processes and slit-diaphragms. Of the filtration barrier proteins examined, ß-catenin expression was markedly reduced both in glomeruli and extrarenal tissues. Since the rat is the preferred laboratory animal in experimental physiology and pathophysiology, the rat model of HO-1 deficiency may provide a novel tool for investigation of the role of this enzyme in renal function and disease.

Towards a tailored lymphadenectomy for gastric cancer based on the correlation between the primary tumor location and the first lymphatic drain basin: Preliminary data.

PURPOSE: The contradictory long-term results following D2 lymphadenectomy have revealed the necessity for a more tailored lymphadenectomy in cases of gastric cancer. Among the patients who had undergone a modified D2 lymphadenectomy for gastric cancer, we further analyzed the subgroup in which histologically and immunohistochemically solitary lymph node metastases were detected. Classifying the primary tumors as towards to the lesser and towards to the grater curvature, we propose possible routes of lymphatic spread and possible clinical implications. METHOD: Between January 2007 and December 2016, 212 patients suffering from gastric adenocarcinoma underwent a modified D2 lymphadenectomy. Solitary lymph node metastases were detected by histology in 14 patients (7 skip metastases) and by immunohistochemistry in an additional 10 patients (5 skip micrometastases). RESULTS: The incidence of the histologically detected solitary lymph node metastases was 6.6% for the whole cohort, increasing to 11.3% with the use of immunohistochemistry. The incidence of the histologically detected skip solitary lymph node metastases was 3.3% for the whole cohort, increasing to 5.7% with the use of immunohistochemistry. Tumors of the lower and middle third of the stomach were equally drained both to the level I and II lymph node stations. However, tumors towards the lesser curvature were mainly drained in the level II lymph node stations (12 out of 19; 63%), while tumors towards the greater curvature were all drained in the level I lymph node stations (5 out of 5; 100%). CONCLUSION: Primary gastric tumors towards the lesser curvature should be treated by a modified D2 lymphadenctomy. However, for tumors towards the greater curvature, a D1(+) lymphadenectomy always including the no. 7 & 9 lymph node stations complex, might be enough.

Kidney transplantation outcomes from expanded criteria donors, standard criteria donors or living donors older than 60 years.

OBJECTIVES: To evaluate outcomes in kidney allograft recipients from donors with expanded criteria (ECD) versus standard criteria (SCD) or living donors (LD) >60 years. METHODS: We studied all patients who received a kidney between 2005 and 2011, focusing in recipients of kidneys from deceased ECD, SCD and LD >60 years. ECD was any deceased donor >60 years or >50 years with two of the following: hypertension (HTN), stroke as the cause of death, or serum creatinine >1.5 mg/dL. We recorded characteristics of the transplant procedure, patient, graft survival and renal function 1 year after transplantation and at the end of follow-up. RESULTS: Six-hundred and five patients were transplanted between 2005 and 2011 in our department. There were 142 (25.1%) transplantations from ECD, 192 (33.98%) from SCD and 96 (16.99%) from LDs older than 60 years. In a mean follow-up time of 36.4 months, graft survival rates were similar for all groups. Calculated GFR was found statistically different between the ECD and SCD groups, but still satisfactory at first year, and at end of follow-up time. Comparison of the patients, who received transplants from ECD, even older than 70 years, and those from LD >60 years revealed equivalent renal function in short and long term. CONCLUSIONS: Utilization of marginal kidneys effectively doubled our deceased transplant volume in the period 2005-2011. Patients' and graft survival were shown similar at the end of follow-up for all groups. Renal outcomes were shown equivalent between the ECD and LD >60 years groups, and although significantly lower between the ECD and the SCD group, were still very satisfactory.

Understanding the complement-mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies.

An enhanced understanding of the role of complement in the pathogenesis of membranoproliferative glomerulonephritis has led to reclassification of the latter into immunoglobulin-mediated and non-immunoglobulin-mediated disease. The new classification schema resulted in improved diagnostic clinical algorithms, while it brought into light again the diseases, which are characterized by the presence of glomerular deposits, composed predominantly by C3, in the absence of significant amounts of immunoglobulins in renal biopsy, namely, C3 glomerulopathies (dense deposit disease and C3 glomerulonephritis). Despite the lack of randomized controlled trials following the advances in the understanding of the pathogenetic pathways involved in membranoproliferative glomerulonephritis, it is important that the new mechanistic approach has opened new roads for the exploration and discovery of targeted therapies.

Giant liposarcoma of the back with 4 types of histopathology: a case report.

The incidence of soft tissue tumours, both malignant and benign, is very common. However, the coexistence of 4 types of histopathology is rare and the aim of this article is to present one treated in our Department. An 87-year-old Greek man was treated in our Department for a huge tumour on his back, under local anaesthesia. The pathology report of the specimen referred 4 types of neoplasia. This case represents this incidence in a giant liposarcoma of the back.

Routine modified D2 lymphadenectomy performance in pT1-T2N0 gastric cancer.

AIM: To evaluate routine modified D2 lymphadenectomy in gastric cancer, based on immunohistochemically detected skip micrometastases in level II lymph nodes. METHODS: Among 95 gastric cancer patients who were routinely submitted to curative modified D2 lymphadenectomy, from January 2004 to December 2008, 32 were classified as pN0. All level I lymph nodes of these 32 patients were submitted to immunohistochemistry for micrometastases detection. Patients in whom micrometastases were detected in the level I lymph node stations (n = 4) were excluded from further analysis. The level II lymph nodes of the remaining 28 patients were studied immunohistochemically for micrometastases detection and constitute the material of the present study. RESULTS: Skip micrometastases in the level II lymph nodes were detected in 14% (4 out of 28) of the patients. The incidence was further increased to 17% (4 out of 24) in the subgroup of T1-2 gastric cancer patients. All micrometastases were detected in the No. 7 lymph node station. Thus, the disease was upstaged from stage IA to IB in one patient and from stage IB to II in three patients. CONCLUSION: In gastric cancer, true R0 resection may not be achieved without modified D2 lymphadenectomy. Until D2+/D3 lymphadenectomy becomes standard, modified D2 lymphadenectomy should be performed routinely.