A Clinicopathologic Study of Thrombotic Microangiopathy in IgA Nephropathy

Abstract

Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44627 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or ,20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes.

Oxford-MEST classification in IgAnephropathy patinets: A report from Iran

“…Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension (46). Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA.…”

Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group

“…These studies are typically described as validation studies, although none prospectively studied new cohorts; nevertheless they provide valuable corroborative evidence. Sixteen such studies [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , including cohorts from Europe, North America, and East Asia were meta-analysed in a report published in 2013 21 . Lately, more studies have been published including cohorts from Iran, Europe, Japan and Korea [22][23][24][25][26][27][28] .…”

“…Patients whose biopsies were scored E1 were more likely to receive immunosuppressive therapy, most frequently corticosteroids, and patients with E lesions had an improved outcome if treated with corticosteroids. The two studies in which no patients received corticosteroid/cytotoxic therapy both reported that E1 was independently associated with more rapid loss of renal function and worse renal survival 8,27 . This is consistent with the reversibility of E following immunosuppression in a study reporting repeat renal biopsies after treatment 29 .…”

Current Understanding of the Role of Complement in IgA Nephropathy

“…49 Also, another small study identified no mutation of CFH, CFI, and Membrane Cofactor Protein genes in 11 patients with IgAN presenting with severe thrombotic microangiopathy. 50 Clearly, larger-scale sequencing efforts will Figure 2. C3 proteolytic cascade.…”