Primary IgA nephropathy with low histologic grade and disease progression: is there a "point of no return"?

Histologic low-grade chronic renal lesions in 144 adults with primary immunoglobulin A (IgA) nephropathy were correlated with clinical parameters of disease progression over a median follow-up of 93 months. Using chronicity-based histologic grading, 50, 59, and 35 patients were glomerular grade (GG) 1a, GG1b, and GG2; 83 and 61 patients were tubulointerstitial grade (TIG) 1 and TIG2; and 25 patients had hyaline arteriolosclerosis. On follow-up, GG and TIG were predictive of disease progression by impairment of renal function, development of hypertension, and significant proteinuria (>1 g/d). Hyaline arteriolosclerosis correlated only with the development of hypertension. Histologic lesions GG1a or TIG1 predicted a significant low risk for disease progression compared with other renal lesions, regardless of the renal manifestation at the time of biopsy. Combined GG1a, TIG1, and isolated hematuria at the time of biopsy enhanced the sensitivity to determine early IgA nephropathy and to define a nonearly cohort with a higher risk of disease progression appropriate for recruitment into clinical therapeutic trials within realistic time frames. The significant risk of progression in other low-grade lesions, such as GG1b or TIG2, suggests that the point of no return in IgA nephropathy may occur much earlier than perceived and that delayed biopsy in these patients no longer may be justified.