A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.

We report 3 cases of renal toxicity associated with use of the antiviral agent tenofovir. Renal failure, proximal tubular dysfunction, and nephrogenic diabetes insipidus were observed, and, in 2 cases, renal biopsy revealed severe tubular necrosis with characteristic nuclear changes. Patients receiving tenofovir must be monitored closely for early signs of tubulopathy (glycosuria, acidosis, mild increase in the plasma creatinine level, and proteinuria).

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BackgroundOrodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders.MethodsWe designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption.ResultsWe discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases.ConclusionsWe have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease.Trial registration numbersNCT01746121 and NCT02397824.