IgA nephropathy (IgAN) is an unpredictable beast, and identifying patients who will go on to develop progressive disease can be challenging. The classic predictors of progression, namely heavy proteinuria, CKD, glomerular sclerosis and tubulointerstitial fibrosis, are themselves just markers of advanced disease. There is a real need for better early histopathologic predictors of renal prognosis.
One promising prospect is glomerular density (GD), i.e. the number of nonsclerotic glomeruli per mm2, which was the focus of this recent study from Japan. The investigators performed a retrospective analysis of almost 100 IgAN cases with preserved renal function at the time of biopsy (average GFR 90 ml/min). Interestingly, they found that the GD varied hugely between patients, from 1 to 8 glomeruli per mm2. In multivariate analysis, only GD, and the presence of a cellular/fibrocellular crescent, were found to be significant predictors of progression. Patients with a low GD experienced more rapid decline in renal function, and this enhanced risk for progression was increased if a cellular/fibrocellular crescent was also present. Interestingly, the classic predictors of progression listed above did not predict prognosis, presumably due to the early stage of disease.
Of course, these findings will need to be replicated in other ethnic groups. Nonetheless, when a case of IgAN next appears at your biopsy conference, you should pipe up “what’s the GD?”. Just try not to look too smug when you do it.
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