Volume 9 Issue 12, December 2013

Cystatin C continues to show its superiority over serum creatinine in predicting mortality among patients with chronic kidney disease (CKD). This superiority is, in part, due to the non-glomerular filtration rate (GFR) determinants of cystatin C associating with CKD risk factors and outcomes. The definition and classification of CKD should not exclusively equate cystatin C with GFR.

The disease manifestations and outcomes in lupus nephritis are exceptionally heterogeneous. In particular, some ethnic populations are disproportionately affected by the most severe forms of the disease. A new study exploring NF-κB dysregulation and its associated genetic variants might help explain the link between ancestry and outcomes in lupus nephritis.

In a recent study using transgenic mice with inducible podocyte-specific expression of tagged albumin, Tenten and colleagues report transtubular transport of albumin, possibly mediated by the neonatal Fc receptor. This study raises several questions about the physiological importance of this potential pathway and the implications for albuminuria in renal disease.

Skin carcinomas, triggered by ultraviolet light, commonly develop post-transplantation and are associated with substantial morbidity and mortality. A recent study in kidney transplant recipients has shown that some of these tumours arise from donor-derived cells. This phenomenon is interesting for the study of carcinogenesis, although its effect on clinical practice is unknown.

In contrast to earlier studies that showed a beneficial influence of rituximab on HLA antibody production after kidney transplantation, a recent report by Ashimine et al. questions such an effect. That previous studies included presensitized patients who are more prone to antibody development, might explain this controversy.

The potential roles for autoantibodies in renal transplantation are increasing, as illustrated by a recent report of polyreactive autoantibodies produced by B-cell clones from a kidney transplant recipient that can bind apoptotic cells and activate complement. Such autoantibodies have the potential to amplify microcirculation injury caused by alloantibody in antibody-mediated transplant rejection.

A recent publication by Bonthuis et al. shows a high prevalence of overweight or obesity in children with end-stage renal disease, particularly in renal transplant recipients. Underweight is more prevalent in infants than in other age groups. This study highlights the need to evaluate and implement interventional strategies in this patient population.

In a recent study, Lambie and colleagues suggest that systemic and local intraperitoneal inflammation, evidenced by elevated levels of interleukin-6, are independent processes and have different consequences for patients undergoing peritoneal dialysis. Prevention of inflammation in these patients will, therefore, require different therapeutic approaches.

Albuminuria is rapidly gaining recognition as a marker of the presence and of the progression of chronic kidney disease (CKD). In a new study, Naresh et al. attempt to define cut-off values for percentage change in urinary albumin:creatinine ratio that reflect changes in CKD status rather than random biological variation.

Acidosis affects sodium and potassium excretion, likely via the pH sensitivity of ion transporters. A recent paper shows that β-intercalated cells with deleted H⁺-ATPase release ATP into urine, which induces the production of prostaglandin E2 (PGE2). PGE2 then reduces sodium absorption in the principal cells of the cortical collecting tubule and increases potassium secretion.

New data suggest that among kidney transplant recipients, those whose serum contains donor-specific antibodies that bind C1q fare the worst. Although these findings are intriguing, several unanswered questions remain and changing practice to include a C1q binding assay as standard of care in kidney transplantation would be premature.

Two types of parietal podocyte were previously described in the Bowman capsule: one characterized by coexpression of podocyte and parietal epithelial cell markers, the other characterized by expression of podocyte markers only. New research demonstrates that these populations represent podocyte progenitors and ectopic podocytes—distinct cell types with different clinical implications.

The glomerular endothelium is the first part of the glomerular filtration barrier that provides a barrier to albumin. In this Review, Simon Satchell describes the evidence for a role of the glomerular endothelium, and particularly the endothelial surface layer, in albumin handling. He also discusses the roles of podocytes and glomerular endothelial cells in glomerular homeostasis, and the therapeutic potential of targeting the endothelial surface layer in glomerular and vascular diseases.

Orthostatic hypertension—a condition characterized by a hyper-reactive pressor response to orthostatic stress—is an emerging new risk factor for the development of hypertension, hypertensive target-organ damage and subsequent cardiovascular events. In this Review, Kazuomi Kario describes the diagnosis, epidemiology and pathophysiology of orthostatic hypertension and discusses its clinical implications.

After a period of ischaemia, organs can be further damaged by inflammatory responses and oxidative stress induced by restoring circulation. However, prior application of a non-lethal ischaemic episode can protect the organ before a larger ischaemic event, known as conditioning. This Review discusses the role of ischaemic conditioning in nephrology, to both protect the kidney and improve cardiovascular outcomes in chronic kidney disease.

As the prevalence of chronic kidney disease increases, new strategies to reverse or prevent tissue damage are under investigation. Here, Rabelink and Little describe progenitor cell populations that may have a key role in tissue repair and regeneration in the kidney. They also discuss the potential to harness the innate regenerative capacity of the kidney in the context of ongoing studies of mesenchymal stromal cell therapy.