Reviews & Analysis

Prospective cohort studies have shown that anaemia is an independent predictor of adverse outcomes in patients with chronic kidney disease. However, randomized controlled trials of the use of erythropoiesis-stimulating agents to correct moderate anaemia in this patient group have failed to show clinical benefit, and indicate that such treatment may even be harmful. Here, Patrick Parfrey discusses possible explanations for these seemingly contradictory results.

Emerging evidence suggests that 15–20% of patients who do not fulfill current consensus criteria for AKI have acute tubular damage, which is associated with adverse outcomes. Haase et al. argue that the spectrum of AKI should be extended to incorporate subclinical forms of the disorder diagnosed on the basis of biomarkers of tubular damage.

Fibroblast growth factor 23 (FGF23) is a hormone involved in bone and mineral metabolism. Increased FGF23 levels are associated with poor clinical outcomes in patients with kidney disease and could represent a novel biomarker and therapeutic target. In this article, Komaba and Fukagawa provide an overview of the physiological role of FGF23 and discuss the Klotho-dependent and Klotho-independent effects of FGF23 in disease.

Klotho deficiency is now considered an early event in acute kidney injury (AKI), and a pathogenic factor that contributes to kidney damage. Here, the authors discuss why this renal-derived protein is a highly promising candidate as both an early biomarker and therapeutic agent for AKI.

The Declaration of Istanbul on Organ Trafficking and Transplant Tourism was formulated at an international meeting held in 2008 with the aim of promoting the welfare of living organ donors in the context of improved global organ transplantation practice. In this Perspectives article, Danovitch and Al-Mousawi provide an update on this endeavor, specifically discussing promulgation of the Declaration, how it has been put into action and legislative changes that have since come into effect.

The slowly progressing nature of chronic kidney disease makes the design of clinical trials with hard end points extremely challenging. One way of establishing a drug's effectiveness is by demonstrating an effect on a surrogate end point. In this Perspectives article, the authors describe data supporting proteinuria as a valuable predictor of renal survival and argue that it should be used as a surrogate marker of renal disease progression in renal clinical trials.

In this Perspectives article, Aliza Thompson from the FDA's Division of Cardiovascular and Renal Products argues that existing data do not support the adoption of proteinuria as a general-purpose surrogate end point for establishing a drug's effectiveness in treating chronic kidney disease. She suggests, however, that it may be reasonable to use changes in proteinuria as a basis for the accelerated approval of a drug if certain conditions are met.

Revascularization alone might be sufficient to restore kidney function and regenerate the structure of the diseased kidney. In this Perspectives article, David Long, Jill Norman and Leon Fine provide an overview of how revascularization might be achieved using vascular growth factors or adoptive transfer of endothelial progenitor cells. The authors also describe how therapeutic strategies targeting the microvasculature could be enhanced in the future.

Lupus nephritis is a complication of systemic lupus erythematosus, a heterogeneous autoimmune syndrome that involves multiple pathogenetic pathways. Here, Adriana Migliorini and Hans-Joachim Anders summarize accumulating data from the fields of genetics, clinical science, transcriptomics and basic immunology which indicate that antiviral immunity is involved in the pathogenesis of lupus nephritis. The authors also discuss the potential implications for innovative therapeutic strategies.