Histologic Classification of IgA Nephropathy: Past, Present, and Future.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Since its description in 1968, a number of histologic descriptions and classification systems have emerged, the most recent of which is the Oxford Classification of IgAN. We present a historical panorama of histologic classifications of IgAN and discuss the most recent developments, updates, and future challenges of the Oxford Classification of IgAN.

Treatment of IgA Nephropathy: Evolution Over Half a Century.

Fifty years into the original description of IgA nephropathy, there is still no specific therapy for this condition and general measures including blood pressure control with blockers of the renin-angiotensin-aldosterone system and salt restriction remain the cornerstone to slow disease progression. Although the paucity in treatment advances could be related to the disease's complex pathogenesis, which requires multiple hits, heterogeneity as reflected by diverse ethnic differences, and genetic predisposition and histopathologic variations, many nonspecific and immunomodulatory agents have been tested with variable degrees of success and tribulations. Here, we review the evolution of these different therapeutic approaches over time that culminated in the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Glomerulonephritis that presently is being updated, and provide an appraisal of recent data on various forms of immunosuppressive agents. Finally, we discuss the theoretical basis of ongoing and upcoming clinical trials that are more pathway- or cell-type-specific as knowledge in disease mechanisms advances.

IgA nephropathy: progress before and since Berger.

Immunoglobulin A nephropathy (IgAN) is linked inextricably to the name Jean Berger, the Parisian pathologist who published the first description of IgAN in 1968. We reflect on the significance of Berger's first report and consider 40 years of progress in our understanding of IgAN since it was published. We also look back to the days before Berger, when IgAN could not have been identified (because there were no techniques for detecting IgA deposits), classification of glomerulonephritis was even more contentious and confusing than it is today, and it is likely that the literature describing focal glomerulonephritis contained many of the cases we would now identify as IgAN.

3rd College of Physicians' lecture--translational research: From bench to bedside and from bedside to bench; incorporating a clinical research journey in IgA nephritis (1976 to 2006).

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.

Hipotiroidismo autoinmune asociado a nefropatía por IgA

La nefropatía por IgA, cuya incidencia en la población pediátrica oscila entre 1.5 y 56.21 según reportes publicados en el sur de Europa, Australia y Japón, se reporta como primera causa de glomerulonefritis primaria en niños. La nefropatía por IgA puede ser primaria o secundaria, se diagnostica por demostración de IgA predominantemente mesangial o IgA codominante en el glomérulo sin evidencia de lupus eritematoso. La mayoría de los pacientes presenta hematuria macroscópica y el pronóstico depende de los marcadores genéticos y la severidad de la lesión histológica renal. A continuación presentamos el reporte de un caso de una paciente con evidencia de hipotiroidismo primario autoinmune y nefropatía por IgA.