Pathologic Classification of Renal Disorders

The promulgation of classification schema have always been a central interest of pathologists, as their framework reflects current understanding of the disease process and satisfies the basic human need to perceive order in the universe. In recent years, renal pathologists have devoted renewed attention to projects of this sort, providing ample opportunity for discussion and debate. The increasing use of the web for validation studies has also facilitated this trend. Classifications that are morphologically based must always answer the challenge of clinical relevance – do their distinctions carry therapeutic and/or prognostic significance? As such, they are an iterative process, requiring constant validation through correlation with clinical data.  Such data is only variably available. This year, for the first time at the ASN, the Renal Pathology Society sponsored a “Consensus Meeting:  Updates on Investigator Initiated Histological Classification Schemes on Renal Diseases”. Gathering in the pre-dawn hours, a remarkably large and enthusiastic audience was treated to a synopsis of current major systems and their challenges, presented by nephropathologists involved in their creation and moderated by Drs Volker Nickeleit (RPS President) & Ingeborg Bajema. A recording of this session together with the slides will be posted on the RPS website (http://www.renalpathsoc.org/) in the members section. What follows is a listing of speakers, classifications and a few selected remarks/observations regarding each system.

Diabetic Nephropathy: Jan Bruijn
(See Cohen Tervaert et al JASN)

A major challenge remains the ability to discriminate and reproducibility of the distinction between mild and moderate mesangial expansion (Class IIa vs. Class IIb). The clinical significance of this distinction is unclear. Classes may progress with duration of disease. Recent work suggests that the interstitial lesions are more predictive of progression than the glomerular lesions. Parenthetically, this observation is relevant for ALL systems, and underscores the significance of assessing chronicity in all biopsies.

C3 Glomerulopathy: Terry Cook
(See Pickering et al KI)

There were many sessions at the ASN devoted to this relatively new disease process, defined as glomerular pathology characterized by C3 accumulation with absent or scant immunoglobulin deposition. It contains two main entities C3 glomerulonephritis and dense deposit disease (DDD), both of which have variable lesions by light microscopy. Their distinction, often based on electron microscopy, may not be as straightforward or as clinically important as once thought. In depth studies to optimize work up of complement disorders (genetic and serologic) are greatly necessary. How to best define sub-groups for clinical trials remains unclear.

IgA Glomerulonephritis/Nephropathy: Ian Roberts
(See Roberts et al KI)

This is now the system with the largest number of clinical validation studies. However, it is important to recall that the classification is entirely based on correlation with a subset of IgA patients who had > 0.5 grams proteinuria, an eGFR > 60, and > 12 months follow-up (excluding the most rapidly progressive forms).  Some of the studies have emphasized the difference between central and local pathologic scoring. Possible modifications will be discussed at the 1^st Oxford Conference on IgA Nephropathy in June 2014.

ANCA-Associated Glomerulonephritis: Ingeborg Bajema
(See Bajema)

Validation studies have consistently and unsurprisingly confirmed that the prognosis is best for focal class and worst for sclerotic class. Results for the other two classes, crescentic and mixed, have been, also as expected, mixed. Some of this may relate to difficulties in definition. For example, it is not always clear when a crescent is cellular as opposed to fibro-cellular. The mixed group, which suffers an “identity crisis”, may be better defined in the future by subdivision based on degree of acute vs. chronic injury.

Focal and Segmental Glomerulosclerosis: Vivette D’Agati
(See D’Agati et al)

It is important to recall that the working proposal of the Columbia Pathologic Classification of FSGS was intended to be used in parallel with an etiologic classification. The consensus that the collapsing variant is the most clinically distinctive is stronger than that of the nature of the lesional cells involved. While data making the case that they represent parietal epithelial cells was presented, holdouts for the podocyte persist. Further study of the cellular lesion (the rarest) is needed, and consideration must be given to a stricter definition of the tip lesion. Nevertheless, the morphologic distinctions do correlate with clinical expressions.

Lupus Nephritis: Surya Seshan
(See Weening et al)

Both nephrologists and nephropathologists want to get rid of the distinction between segmental and global lesions in Class IV. While the current system defines segmental as involving less than half of the tuft, subglobal involvement may be a better approach (e.g., Schwartz’s “Q-lesion”). The activity and chronicity indices continue to guide therapy and greater emphasis needs to be put on tubular, interstitial, and vascular lesions in lupus. Indeed, the condition of the tubulointerstitial compartment continues to best correlate with both current and future renal function, an important point to remember in the often glomerulocentric world of nephropathology.

Post written by Dr. Isaac E. Stillman, eAJKD Contributor and AJKD Kidney Biopsy Teaching Case Advisory Board member.

Check out all of the eAJKD coverage of ASN’s Kidney Week 2013!