Normal reference values for glomerular filtration rate: what do we really know?

In nephrology, chronic kidney disease is defined by both proteinuria and measurement of glomerular filtration rate (GFR). This article focuses on GFR and different ways to define its normal reference values. In this context, we compare two perspectives: first the reference values defined by measuring GFR in normal individuals (the 'classical way') and secondly a fixed cut-off value at 60 mL/min/1.73 m(2) according to the associated mortality risk (the 'prognostic way'). Following the classical way, we can assert that normal GFR values are largely over 60 mL/min/1.73 m(2) in healthy subjects, at least before the age of 70 years. However, we know that GFR physiologically decreases with age, and in adults older than 70 years, values below 60 mL/min/1.73 m(2) could be considered normal. Following the 'prognostic way', the fixed cut-off of 60 mL/min/1.73 m(2) has been retained in the K-DIGO guidelines. However, we challenge this concept and the fact that the variable 'age' is poorly taken into account in these data. There is an obvious discrepancy between the reference values defined either by the 'classical way' or by the 'prognostic way' which we think could be largely reduced, if age was better taken into consideration in these definitions

MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program.

Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP