Articles in 2016

A new study reports an independent association between albuminuria and skin capillary rarefaction in a population-based cohort. These findings suggest that as well as reflecting injury to the glomeruli — a highly specialized microvascular bed — albuminuria might be a surrogate marker of systemic microvascular and endothelial dysfunction.

Antibodies against several podocyte antigens have evolved as markers of diagnosis, disease activity, and prognosis in membranous nephropathy, but their pathogenic role remains debated. Detailed work-up of two cases of primary and secondary membranous nephropathy now supports the concept that thrombospondin type-1 domain-containing 7A autoantibodies are pathogenic.

Time-averaged proteinuria (TAP) is thought to be the most reliable predictor of outcomes in IgA nephropathy (IgAN). New data suggest that corticosteroids reduce TAP and presumably improve outcomes in IgAN, but increase the risk of adverse effects. Whether TAP is a good surrogate end point for clinical trials remains unclear.

The incidence of obesity-related glomerulopathy (ORG) — a distinct entity featuring proteinuria, glomerulomegaly, progressive glomerulosclerosis and renal functional decline — is increasing in parallel with the obesity epidemic. Here, Vivette D'Agati and colleagues review the pathology, clinical features, treatment and pathogenesis of ORG.

The 0by25 Global Snapshot sheds light on the recognition, management and outcomes of acute kidney injury (AKI) in countries worldwide stratified by gross national income. These novel epidemiological data open new horizons for preventing death from AKI particularly in developing countries.

Neutrophils are crucial regulators of the innate immune response and act as a first line of defence against invading microorganisms. To target microorganisms, neutrophils release extracellular structures called neutrophil extracellular traps (NETs), which externalize key autoantigens. In this Review, Gupta and Kaplan explore the contribution of neutrophils and NETs to the pathophysiology of systemic autoimmune disorders that can affect the kidneys, and discuss neutrophils as novel therapeutic targets for these diseases.

The functions of the complement system are diverse and extend beyond its role in host defence; complement activation is now known to contribute to numerous immunological, inflammatory and age-related conditions, including kidney disorders. Here, John Lambris and colleagues discuss the key activating, regulatory, and effector mechanisms of the complement system. They highlight important crosstalk connections with other regulatory systems, and, with a focus on kidney disease and transplantation, describe the involvement of complement in clinical conditions as well as promising therapeutic approaches.

The heterogeneity of pathomechanisms leading to systemic lupus erythematosus (SLE) might contribute to between-patient variations in treatment response. A new, longitudinal transcriptome analysis has identified molecularly distinct subgroups of SLE that correlate with disease activity; use of such disease classifiers might facilitate the development of stratified treatment recommendations.

The calcium-sensing receptor (CaSR) can detect small changes in serum calcium levels and feeds back to modulate parathyroid hormone secretion to elicit appropriate biological responses in different tissues. In this Review, Daniela Riccardi and Giovanna Valenti describe the localization of the CaSR within the nephron and outline its differential functions in different nephron segments. They outline how modulation of the CaSR by pharmacologic approaches could be used in the therapeutic management of disorders such as hyperparathyroidism or hypercalciuric disorders.