Rosanna Coppo

A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy

The Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m2 and median (interquartile range) proteinuria of 1.2 (0.7-2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in one fourth or more of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.

Beyond the Differences in Tonsillectomy in IgA Nephropathy: From Rationale To Indications in Patients

In the special symposiums on IgA nephropathy (IgAN) (Symposium 3, IgAN Basic; Symposium 4, IgAN Clinical/KDIGO) at the last Asian Pacific Congress of Nephrology (APCN) 2014 in Tokyo, discussion by expert nephrologists from Asian and Western countries revealed how actual clinical practices in IgAN, including timing of renal biopsy and choices of treatments, are different, despite evidence-based guidelines. In particular, indication for tonsillectomy with or without steroid pulse therapy for IgAN patients is markedly different between Asian and European-American practices. The tonsillectomy is considered to be old-fashioned in Western countries, while it is still widely accepted in Asian countries such as Japan and China. The present chapter discusses rationale of tonsillectomy, with up-to-date understanding of IgAN pathogenesis, and summarizes the actual difference in the IgAN practice with respect to tonsillectomy with or without steroid pulse therapy, such as clinical stages at the intervention, based on some key papers from Asian and Western countries. In addition, we attempt to identify the medical and social causes behind these differences.

Pregnancy and oxidative stress

Pre-eclampsia is a relatively common complication of pregnancy, interesting about a 3% of the pregnancies. Its pathogenesis has been not yet completely clarified. However, a maternal endothelial dysfunction, particularly at the placenta level, seem to be the key factor in the development of this disease that clinically involves many organs such as kidney, brain and liver, characterized by hypertension, proteinuria and oedema. Recent works suggest a pathogenetic role of an altered expression of placental anti-angiogenic factors with consequent modifications in the redox state resulting in an oxidative stress. The effects to these anti-angiogenic factors results in a systemic endothelial dysfunction with hypertension, proteinuria, and the other systemic manifestations, such as encelophalopathy. Here, we will describe the most recent insights into the pathophysiology of preeclampsia attempting to provide a unifying hypothesis to reconcile the abnormalities at the feto-placental level and the clinical features of the maternal syndrome and provide a rationale for potential future prophylactic and therapeutic interventions for this pregnancy complication.