The MEST score provides earlier risk prediction in lgA nephropathy

Abstract

The Oxford Classification of IgA nephropathy (IgAN) includes the following four histologic components: mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S) and interstitial fibrosis/tubular atrophy (T). These combine to form the MEST score and are independently associated with renal outcome. Current prediction and risk stratification in IgAN requires clinical data over 2 years of follow-up. Using modern prediction tools, we examined whether combining MEST with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than current best methods that use 2 years of follow-up data. We used a cohort of 901 adults with IgAN from the Oxford derivation and North American validation studies and the VALIGA study followed for a median of 5.6 years to analyze the primary outcome (50% decrease in eGFR or ESRD) using Cox regression models. Covariates of clinical data at biopsy (eGFR, proteinuria, MAP) with or without MEST, and then 2-year clinical data alone (2-year average of proteinuria/MAP, eGFR at biopsy) were considered. There was significant improvement in prediction by adding MEST to clinical data at biopsy. The combination predicted the outcome as well as the 2-year clinical data alone, with comparable calibration curves. This effect did not change in subgroups treated or not with RAS blockade or immunosuppression. Thus, combining the MEST score with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than our current best methods.

IgA Nephropathy

“…Pooled cohorts from the European Validation Study of the Oxford Classification of IgA Nephropathy (VALIGA) and North American cohorts indicate rates ESRD or halving of eGFR of 27% at 10 years (7). There are regional differences in the progression of disease, however these are difficult to ascertain given lead-time biases introduced by variation in biopsy practice.…”

Serum Matrix Metalloproteinase-7 Level is Associated with Fibrosis and Renal Survival in Patients with IgA Nephropathy

“…Allow for previous reports of heightened renal MMP-7 expression in renal fibrosis and the significance of kidney fibrosis implicated in the pathogenesis of IgAN [25, 26], we hypothesized that the intrarenal fibrosis signature could be detected noninvasively by quantification of MMP-7 level in circulation and, it might serve as a noninvasive prognostic biomarker in IgAN. Since MMP-7 expression is little investigated in IgAN by now, in this study, we examined the association of serum MMP-7 level and histopathological change, as well as the renal progression of IgAN in a cohort of biopsy proven patients.…”

IgA Nephropathy: A European Perspective in the Corticosteroid Treatment

“…The presence of M1 was a histological marker predicting benefits of steroid therapy [16]. In 261 young subjects aged < 23 years enrolled in VALIGA, the presence of M1 was a significant risk for survival from the combined end point and for high time-averaged proteinuria during the subsequent follow-up [17].…”

“…Ten years after the end of the treatment, the renal survival was significantly better in children previously treated with corticosteroids/immunosuppressors [19]. In Europe, the present tendency is to consider the presence of M1 as a possible marker of the need of corticosteroid therapy particularly in children and young subjects even with mild proteinuria, as suggested also from the collaborative study which pooled data from VALIGA, Chinese, Japanese, and North American cohorts [16]. This study proved that the presence of M1 was a significant risk factor for progression even in patients with proteinuria < 1 g/day at renal biopsy, which showed a decline similar to that of patients with persistent time-averaged proteinuria of 1–2 g/day for 2 years, hence fully eligible for corticosteroid treatment according to KDIGO 2012 [20].…”

“…The STOP-IgAN trial provided a negative answer, but a personalized approach may be proposed: no when proteinuria 0.75–1.5 g/day and negative MEST scores [16]; yes when IgAN is in progression with rapid loss of GFR or when crescents are present in > 25% of glo­meruli (C1) [24]; probably yes when risk factors are present, with persistent proteinuria > 1 g/day [8] or when proteinuria < 1 g/day with M1 or E1 or S1 with podocytopathy [22]. …”