Banff Histopathological Consensus Criteria for Preimplantation Kidney Biopsies.

The Banff working group on preimplantation biopsy was established to develop consensus criteria (best practice guidelines) for the interpretation of preimplantation kidney biopsies. Digitally scanned slides were used (i) to evaluate interobserver variability of histopathologic findings, comparing frozen sections with formalin-fixed, paraffin-embedded tissue of wedge and needle core biopsies, and (ii) to correlate consensus histopathologic findings with graft outcome in a cohort of biopsies from international medical centers. Intraclass correlations (ICCs) and univariable and multivariable statistical analyses were performed. Good to fair reproducibility was observed in semiquantitative scores for percentage of glomerulosclerosis, arterial intimal fibrosis and interstitial fibrosis on frozen wedge biopsies. Evaluation of frozen wedge and core biopsies was comparable for number of glomeruli, but needle biopsies showed worse ICCs for glomerulosclerosis, interstitial fibrosis and tubular atrophy. A consensus evaluation form is provided to help standardize the reporting of histopathologic lesions in donor biopsies. It should be recognized that histologic parameters may not correlate with graft outcome in studies based on organs deemed to be acceptable after careful clinical assessment. Significant limitations remain in the assessment of implantation biopsies.

Clinicopathological Features of Cardiac Glycolipid Storage Disease in an Adult Pug.

A 12-year-old neutered male pug suffered cardiac arrest and died under general anaesthesia during diagnostic imaging for evaluation of exercise intolerance and respiratory crisis. Histopathological evaluation revealed two types of storage material, glycolipid and lipopigment, having differential distributions in multiple organs. The heart was most strikingly affected and other less affected tissues included the liver, brain, kidneys and skin. Cardiomyocytes were swollen with extensive sarcoplasmic vacuolation together with coalescing areas of myocardial fibrosis. Transmission electron microscopy revealed irregular myelin-like structures and complex concentric lamellar bodies dominating the sarcoplasm and displacing myofibrils. These findings were consistent with a lysosomal storage disease (LSD) as the cause of cardiac disease and death. The unique clinical presentation, histomorphology and ultrastructural features of the material suggested a glycolipid storage disease most closely resembling Anderson-Fabry (Fabry) disease in man. Fabry disease is a LSD that can present in later life and is characterized by loss of α-galactosidase A function and, often, accumulation of glycosphingolipids in tissues including the heart, kidneys, vascular endothelium and smooth muscle.

The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology.

The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i-IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell-mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus-based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next-generation clinical trials.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

An uncommon glomerular disease in an HIV patient: value of renal biopsy and review of the literature.

Renal disease is not uncommon in those infected with HIV. The most common manifestation of HIV in the kidney is HIV-associated nephropathy (HIVAN). Other HIV- and non-HIV-related causes have been described in the literature. Immunotactoid glomerulonephritis (ITG) is a rare disorder found in 0.06% of renal biopsies characterized by organized tubular immune complex deposits, observed more often in Caucasians. ITG tends to occur in an older age group and in some patients has been associated with a hemopoietic malignancy. In this report, we describe a case of ITG occurring in an HIV-positive, hepatitis C (HCV)- and hepatitis B (HBV)-negative female, who presented with microscopic hematuria and proteinuria. A percutaneous kidney biopsy showed diffuse membranous glomerulopathy, with mild mesangial proliferation and segmental sclerosing lesions containing mainly IgG, Kappa- and C3-positive deposits. Electron microscopy revealed diffuse subepithelial tubular deposits diagnostic of ITG. Out of 5 reported HIV-positive cases and ITG in the literature, 3 were HCV+, 2 were Caucasian and 3 were African-American (AA) without detectable hematologic malignancy. We report another case of ITG in an HCV- and HBV-negative, AA female.

Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups.

The 10th Banff Conference on Allograft Pathology was held in Banff, Canada from August 9 to 14, 2009. A total of 263 transplant clinicians, pathologists, surgeons, immunologists and researchers discussed several aspects of solid organ transplants with a special focus on antibody mediated graft injury. The willingness of the Banff process to adapt continuously in response to new research and improve potential weaknesses, led to the implementation of six working groups on the following areas: isolated v-lesion, fibrosis scoring, glomerular lesions, molecular pathology, polyomavirus nephropathy and quality assurance. Banff working groups will conduct multicenter trials to evaluate the clinical relevance, practical feasibility and reproducibility of potential changes to the Banff classification. There were also sessions on quality improvement in biopsy reading and utilization of virtual microscopy for maintaining competence in transplant biopsy interpretation. In addition, compelling molecular research data led to the discussion of incorporation of omics-technologies and discovery of new tissue markers with the goal of combining histopathology and molecular parameters within the Banff working classification in the near future.

Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution.

BACKGROUND: Gemcitabine is used in a variety of advanced malignancies. Hemolytic uremic syndrome has been reported as a side effect. METHODS: we reviewed medical records of 29 patients with gemcitabine nephrotoxicity. RESULTS: The median cumulative dose of gemcitabine was 22 g/m2 (4 - 81) given over 7.5 months (2 - 34). Prior chemotherapy with mitomycin had been given to 9 patients, and in 4 the hemolytic uremic syndrome was particularly severe and appeared shortly after gemcitabine initiation. All patients had renal insufficiency. Microhematuria and proteinuria were present in 27 patients and red blood cell casts were seen in 8. Renal biopsies in 4 patients showed thrombotic microangiopathy. Worsening or new-onset hypertension was seen in 26 patients. Edema, shortness of breath and congestive heart failure were present in 21, 15 and 7 patients, respectively. All had anemia, thrombocytopenia and elevated serum lactate dehydrogenase. Haptoglobin was low in 23 of the 26 patients who had it measured. Schistocytes were present in 21 of the 24 patients who had blood smear reviewed. Gemcitabine was discontinued once hemolytic uremic syndrome was recognized. Full or partial recovery of renal function occurred in 19 patients. 7 patients progressed to end-stage renal disease and 3 patients developed chronic renal failure. CONCLUSIONS: Gemcitabine nephrotoxicity presents as new-onset renal disease with associated hypertension, thrombocytopenia and microangiopathic hemolytic anemia. Prior chemotherapy with mitomycin, especially when given in close proximity, may be synergistic. A high index of suspicion is essential to make an early diagnosis. Stopping gemcitabine improves the outcome.

Cyclooxygenase-2 expression in the developing human kidney.

Cyclooxygenase (COX) exists in two related but unique isoforms, COX-1 and COX-2, and is suggested to have specific functions in different segments of the nephron. COX-2 knockout mice develop fatal nephropathy, which implies that this isoform is important during nephrogenesis. The histologic changes seen in the COX-2 knockout mice are similar to those observed in the kidneys of human fetuses exposed to non-steroidal anti-inflammatory drugs (NSAIDs) in the third trimester of pregnancy. However, only minimal amounts of COX-2 mRNA or protein have been reported in the adult human kidney. We hypothesized that expression of COX-2 is significant in the fetal human kidney and that it is involved in the development of the nephron. To characterize the presence of COX-2 in the human fetal kidney, we used immunohistochemistry to evaluate its expression in 23 fetal kidneys ranging between 15 and 23 weeks of gestational age. Strong expression of COX-2 was localized primarily in the macula densa and the thick ascending limb of the loop of Henle, and in rare glomerular podocytes and vascular endothelial cells. There was a progressive decrease in COX-2 immunoreactivity from the most immature nephrons adjacent to the metanephric regions to the well-developed nephrons in the middle to inner cortex. In contrast to the adult human kidney, this temporal and spatial expression of COX-2 in the fetal kidney suggests that this enzyme may be involved in nephrogenesis, and its inhibition by NSAIDs during the third trimester may be responsible for fetal renal syndromes.

Maternal cocaine abuse and fetal renal arteries: a morphometric study.

The purpose of the present study was to evaluate the pathological findings and perform morphometric analysis of the renal arteries of fetuses exposed to cocaine in utero. The control group consisted of 22 stillborn fetuses of unknown etiology whose mothers' urine was negative for cocaine or any other vasoactive substances. The study group comprised 29 stillborn fetuses whose mothers' urine was positive only for cocaine on the day of admission. Sections of fetal kidneys (4 microm), stained with hematoxylin and eosin and periodic acid-Schiff reagent, were examined under light microscopy (x40) to identify interlobular arteries. Morphometric analysis of these arteries was performed using a self-assembled system with a touch-sensitive screen as an interactive peripheral. Their inner and outer circumferences were measured by outlining them on the screen with a stylus. The radius (r) was calculated from the measurement of the circumference (2.pi.r). The difference of the radii of the outer and inner circumferences was the thickness of the arterial wall. The interlobular arterial thickness was significantly greater (P<0.001) in the cocaine-exposed group (mean 15.46+/-5.8 microm, 2SD) compared with the normal (mean 9.03+/-3.96 microm, 2SD). There was a significantly (P<0.001) positive relation with advancing gestational ages in both groups. The circumferences of the lumen of the arteries showed a significant (P<0.05) relation with advancing gestational ages in the normal group only. In the cocaine-exposed group, the arterial lumen circumference (mean 167.88+/-17.58 microm, 2SD) was significantly (P<0.001) smaller than in the normal group (mean 227.73+/-6.82 microm, 2SD). Thus, maternal cocaine abuse is associated with thickening of the interlobular arterial wall of the fetal kidney and narrowing of the lumen.

Placental vessel morphometry in growth retardation and increased resistance of the umbilical artery Doppler flow.

OBJECTIVES: To study the tertiary-stem villi vessel lumen and wall thickness of placenta in pregnancy complicated with placental insufficiency and intrauterine growth retardation (IUGR), its correlation with the umbilical artery Doppler flow study, and compare with normal and non-IUGR pregnancies. METHODS: Placentas from 45 deliveries (between 28 and 38 weeks) were collected for morphometric study of the tertiary-stem villi vessels. Each pregnancy had clinical suspicion of IUGR and was confirmed by serial ultrasound biometry, HC/AC ratio, and had abnormal umbilical artery Doppler velocimetry (RI). Each placenta was weighed after trimming of the membrane and the cord. Sections of the placenta (4 micron) were stained with hematoxylin and eosin and periodic acid-Schiff reagents. Tertiary-stem villi vessels were identified under a microscope (x40) and morphometric study was performed. Inner and outer circumferences (2.pi.r) were measured, radii (r) were calculated, and vessel wall thickness was determined (outer r - inner r). These findings were compared with the findings from 78 placentas from normal pregnancies (between 28-40 weeks) and 27 placentas from pregnancies with medical complications without IUGR (non-IUGR) and with normal Doppler velocimetry (between 33 and 38 weeks). RESULTS: Weight of placentas were significantly (P < 0.005) lower in IUGR than the normal and non-IUGR groups. The vessel wall thickness was significantly (P < 0.0001) increased in IUGR group (mean 21.17 +/- 3.16 micron [SD]) compared to normal and non-IUGR groups (mean 13.19 +/- 1.66 micron). With advancing gestational age, the thicknesses of vessel walls in all groups were significantly (P < 0.001) decreased. There was significant (P < 0.001) decrease in lumen circumference in the IUGR group (mean 173 +/- 31 micron) compared to normal and non-IUGR groups (mean 69 +/- 23 micron). Significant (P < 0.001) correlation was observed between the thickness of a vessel wall and the increase in Doppler RI. CONCLUSIONS: Pregnancies with growth retardation are associated with smaller placentas, increase in the thickness of tertiary-stem villi vessel wall, and decrease in lumen circumference. These changes are associated with an increase in the resistance index of the umbilical artery Doppler flow velocimetry.

Renal manifestations of concurrent systemic lupus erythematosus and HIV infection.

Autoimmune phenomena are common in human immunodeficiency virus (HIV) infection, yet systemic lupus erythematosus (SLE) and HIV infection rarely are seen concurrently in the same patient. Many of the cases of combined HIV infection and SLE reported in the literature are patients with SLE before HIV infection and who did not undergo renal biopsy at a time when both processes were present. We report the clinical manifestations and renal biopsy findings in four subjects with concurrent HIV infection and SLE and compare them with the seven previously reported cases in the literature. Taken together, most patients were black (91%) and male (73%), and approximately half (55%) were children with perinatal HIV infection. These demographics differ markedly from those of idiopathic SLE, a disease that predominantly affects female adults. Renal presentations included proteinuria and hypocomplementemia, frequently with hematuria and renal insufficiency. Renal biopsy findings in 10 cases included all classes of lupus nephritis (class IIb in two cases, class III in one case, class IV in three cases, class V in three cases, class III and V in one case), two of which also displayed overlapping features of HIV-associated nephropathy (HIVAN). One case had isolated findings of HIVAN. This cohort provides a unique population in which to study interacting pathomechanisms between HIV infection and SLE.