Reviews & Analysis

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.

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.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterized by inflammation of blood vessels, which can lead to severe organ and tissue damage. Previously considered life-threatening, they are now treated using remission induction and maintenance therapies. This article outlines the current treatment regimens, reviews clinical trial data, and discusses new developments in the treatment of ANCA-associated vasculitides.

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.

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.

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.

A recent study developed a formula predicting hard outcomes of rhabdomyolysis (dialysis and death). Based on a rigid analytical approach, an eight factor score was elaborated with acceptable prognostic value, but clinical usefulness at this time seems limited. Perhaps the most promising application is for triage.

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 a meta-analysis of randomized trials, de Borst and colleagues report that vitamin D therapy reduces proteinuria and might also slow the progression of chronic kidney disease. In light of the limited options for renoprotective therapy, we evaluate whether this evidence for vitamin D treatment justifies a large, definitive trial.

Changes in bone quality and quantity are associated with an increased risk of fracture in patients with chronic kidney disease–mineral and bone disorder (CKD–MBD). Here, methods used to assess bone quality abnormalities across different hierarchical levels are outlined, as well as the results, such as abnormalities in structural parameters and bone material or mechanical properties, which are linked to an increased risk of fracture. Such assessment will improve our understanding of CKD–MBD and aid therapeutic development.

Co-inhibitory and co-stimulatory signals that are expressed upon T-cell-activation influence both autoreactive and alloreactive T-cell responses. Here, the authors describe the functional importance of T-cell co-stimulatory molecules in transplantation, tolerance and autoimmunity, and how therapeutic blockade of these pathways might be harnessed to manipulate the immune response to prevent or attenuate pathological immune responses.

Patients with chronic kidney disease (CKD) have a high risk of bone fracture and low bone mineral density, which resembles osteoporosis. However, the mineral and bone disorder associated with CKD (CKD–MBD) is more complex than osteoporosis and the same treatments might not be appropriate in these patients. In this Review, Susan Ott discusses therapies for osteoporosis, and the evidence for their use in patients with CKD–MBD.

Two trials of low-glucose-containing peritoneal dialysis regimen in patients with diabetes mellitus show that although this strategy improved glycaemic control, it was associated with increased risk of serious adverse events and mortality. These studies suggest caution is needed when evaluating effectiveness using surrogate measures and awareness of confounding factors is important.

Renal biopsy is the gold standard for detection of rejection in kidney transplant recipients, but is not considered until evidence of renal dysfunction is apparent. Now, Suthanthiran and colleagues suggest that mRNA levels in urinary cells from these patients might be diagnostic and prognostic of acute cellular rejection.