Ethnicity and Renal Replacement Therapy

There are significant ethnic variations in the incidence of kidney disease. White European populations appear to be uniquely protected compared to increased incidences of end-stage renal disease in indigenous and migrant ethnic minority populations. This increase is partly explained by a high prevalence of diabetic nephropathy, but there is also an increased susceptibility to a range of other renal diseases. The relative contributions of genetic, environmental and fetal environmental factors to this susceptibility are not yet well understood. Strategies for early detection and management of chronic kidney disease to delay progression are particularly critical in countries where access to renal replacement therapy (RRT) is restricted. In developed countries with wide availability of RRT, resources to provide dialysis will need to be increased in regions with substantial minority populations. There is apparently counterintuitive evidence that survival on dialysis is increased in many minority populations. Access to renal transplantation, both from deceased and living donors, is also restricted in many minority populations, and graft survival is often inferior. Analysis of the explanations for these differences is complex because of the many confounding factors (for example cultural, social and economic) which typically cosegregate with ethnicity. Nevertheless, reduction of the varied and substantial inequities faced by ethnic minority populations with kidney disease is an important responsibility for the renal community

Should Immunosuppressive Therapy Be Used in Slowly Progressive IgA Nephropathy?

Commentary on Rauen T, Eitner F, Fitzner C, et al; for the STOP-IgAN Investigators. Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med. 2015;373(23):2225-2236

Is progression of IgA nephropathy conditioned by genes regulating atherosclerotic damage?

Progress has been slow in identifying genetic factors that influence either susceptibility to IgA nephropathy (IgAN) or its progression to end-stage renal disease (ESRD) [1]. Studies of both familial and sporadic IgAN strongly point to clinical and genetic heterogeneity in the entity we presently call IgAN. The human IgAN phenotype does not exhibit classic Mendelian inheritance patterns, but is better considered using the paradigm for genetically complex human autoimmune diseases, for which multiple loci have been identified by family-based genetic studies. In these complex diseases many different types of genetic variations contribute to the final phenotype. Among the many potential mechanisms involved, interest has recently been focused on specific single-nucleotide polymorphism (SNP) alleles that alter the transcriptional activity of genes involved in the pathogenesis. Recently, it has been said that 30–50% of human genes with coding SNPs can present allelic variation in gene expression [2]

The pathogenic role of IgA1 0-linked glycosyation in the pathogenesis of IgA nephropathy

The pathogenic role of IgA1 0-linked glycosyation in the pathogenesis of IgA nephropath

Immune complex formation in IgA nephropathy: a case of the ‘right’ antibodies in the ‘wrong’ place at the ‘wrong’ time?

One of the most striking findings in IgAN is an increase in the circulating levels of poorly galactosylated IgA1 O-glycoforms (Figure 1B). This has been observed in patient populations from North America, Europe and Asia, using a variety of techniques [1–3]. Importantly, two studies of IgA1 eluted from isolated glomeruli have shown that mesangial IgA is enriched with poorly galactosylated IgA1 O-glycoforms, strongly implicating the composition of IgA1 hinge region glycans in the mechanism of IgA1 deposition [4,5]. Novak and colleagues have also reported that these poorly galactosylated IgA1 O-glycoforms are predominantly found in circulating high molecular weight IgA-IC in IgAN [6]

Is sialylation of IgA the agent provocateur of IgA nephropathy?

In IgA nephropathy (IgAN), the mechanisms responsible for deposition of IgA1 in the glomerular mesangium, and subsequent initiation of glomerular injury in some patients, remain unclear. Much research evidence now demonstrates that the O-glycosylation of IgA1 is abnormal in IgAN, and that this is potentially pathogenic. However, the exact nature of the O-glycoyslation abnormality, and the metabolic processes resulting in its production, are not well understood. Progress in this field has partly been limited by the lack of a suitable animal model, because the IgA of laboratory animals is not O-glycosylated. In this paper, Suzuki and colleagues have established B cell lines from patients with IgAN that produce IgA1 with abnormal O-glycosylation. This has allowed them to show that abnormal IgA1 carries an increased proportion of O-glycans terminating in sialic acid rather than the normal galactose units (Figure 1), and that this is associated with increased mRNA expression and activity of the sialylating enzyme ST6GalNAcII, and decreased expression and activity of the galactosylating enzyme C1GalT1. These findings contribute new insights to the study of defective IgA1 O-galactosylation and mark a significant step forward in the field of IgAN research

P10 interview .wps

post IDE implementation patient interview no 1

PFG3

pre IDE implementation patient focus group no

S4 interview

post IDE implementation staff interview no