Histologic classification of glomerular diseases: clinicopathologic correlations, limitations exposed by validation studies, and suggestions for modification

The value of classification systems applied to the examination of renal biopsies is based on several factors: first, on the ability to provide efficient communication between pathologists and between pathologists and clinicians; second, on the possibility to implement diagnostic information with prognostic indication. Even more important, the practical value of a classification is proved by the ability of providing elements that guide therapeutic decisions and can be used in the follow-up of the patient. With these aims, new histologic classification systems have been proposed in the last decade for lupus nephritis and IgA nephropathy under the leadership of the Renal Pathology Society and the International Society of Nephrology. These classifications have gained a significant level of worldwide acceptance and have been the subject of multiple single-center and multicenter validation studies, which have underpinned their clinical benefits and limitations and served to highlight remaining questions and difficulties of interpretation of the biopsy sample. More recently, a classification system has also been proposed for ANCA-associated crescentic glomerulonephritis (ANCA-GN), although the validation process for this is still in an early stage. In this review, we examine in some detail the ISN/RPS classification for lupus nephritis and the Oxford classification for IgA nephropathy, with emphasis on clinicopathologic correlations, their value for and evolving impact on clinical studies and clinical practice, and their significant limitations in this regard as exposed by validation studies. We also suggest possible ways by which these classifications might be modified to make them more applicable to clinical practice. Finally, we more briefly discuss the newly proposed classification for ANCA-GN.