News & Views in 2014

Schreiber et al. have identified an unexpected immunoregulatory role of reactive oxygen species in antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis. Here, we discuss these findings in view of other pathways with well-known immunostimulatory roles in kidney disease that have recently been shown to have additional immunosuppressive effects.

The role of the innate immune system in mediating allograft rejection is unclear. A new study demonstrates for the first time the ability of allografts to stimulate the differentiation of monocytes into inflammatory dendritic cells, which produce IL-12 and stimulate T cells, leading to graft rejection.

A new study has addressed a key question in autosomal dominant polycystic kidney disease (ADPKD): can we predict renal outcome at an early disease stage? Indeed, this information is useful for any patient with ADPKD. Moreover, while targeted therapies continue to emerge, optimal selection of patients for clinical trials remains a challenge.

Despite an explosion in understanding of the disease process, the rates of patients with autosomal dominant polycystic kidney disease starting renal replacement therapy show no signs of slowing. Indeed, rates among people aged ≥70 years have increased, reflecting a greater propensity to offer renal replacement therapy to this age group.

A new study has advanced our understanding of iron management in chronic kidney disease (CKD) by comparing oral iron to high-dose and low-dose intravenous ferric carboxymaltose (FCM) in patients with predialysis CKD. Intravenous FCM treatment to achieve a higher serum ferritin target improved patient haemoglobin levels and reduced initiation of other anaemia treatments.

A new study suggests that use of unadjusted dosages of β-lactam antibiotics could reduce the risk of inadequate serum concentrations during continuous renal replacement therapy. However, risk of overdose compounds the problem. Therapeutic drug monitoring, pharmacokinetic modelling and dose simulation might provide opportunities to improve dose precision and patient outcomes.

New research indicates that intact soluble urokinase plasminogen activator receptor (suPAR) does not induce albuminuria in mice. These data corroborate the most recent clinical findings, showing that intact suPAR is not the plasma permeability factor responsible for recurrence of focal segmental glomerulosclerosis after renal transplantation.

Childhood-onset chronic kidney disease is the result of congenital anomalies of the kidneys and urinary tract in approximately two-thirds of all patients. An area of intense research in recent years, however, is the potential impact of maternal obesity on renal ontogenesis or postnatal renal function in the offspring.

Acute or chronic antibody-mediated rejection (ABMR) of kidney allografts is currently diagnosed by the presence of donor-specific alloantibodies and distinct pathological findings in biopsy samples. A new study highlights the potential of molecular diagnostics incorporated into standard criteria for acute ABMR to help identify patients at risk of graft loss.

The International Society of Nephrology–Advisory Committee of Clinical Trials and Studies aims to ensure access to timely and unbiased expert advice for all investigators, and to facilitate the development and execution of clinical trials within a highly ethical framework. The initiative will foster high-quality, cost-effective research in a sustainable network.

Pre-existing HLA antibodies negatively impact long-term graft survival and might be a major risk factor for the formation of new HLA antibodies. Whether conversion of transplant recipients from calcineurin inhibitors to mammalian target of rapamycin inhibitors increases the risk of allosensitization remains to be determined.

A reduction of salt intake to <5 g sodium chloride per day is generally advised for patients with chronic kidney disease. However, hard evidence to support this recommendation is lacking. New data from Fan et al. suggest that very strict sodium limits might be harmful in patients with renal disease.

Kidney transplant recipients who also receive a partial liver allograft have better long-term outcomes than those who receive a kidney alone, despite the more-complex surgery. Understanding how the liver exerts these beneficial effects might enable their exploitation in the future.

Secondary analysis of the FAVORIT data in kidney transplant recipients showed that systolic blood pressure ≥140 mmHg and diastolic blood pressure <70 mmHg at trial entry were associated with increased risks of cardiovascular disease over a mean of 4 years. Whether these blood pressure values are associated with mortality is unclear.

Two recent trials have highlighted that our strategies to restore tissue perfusion early and decrease mortality in patients with sepsis are varied and evidence for an effective therapy to reduce the incidence of kidney injury is lacking. However, newly reported data suggest an overall improved standard of care for patients.

The authors of a new study suggest that the proinflammatory state of acute rejection combined with the use of T-cell-depleting antibody therapy might explain the increased risk of cancer after kidney transplantation. However, their findings do not fully support this conclusion; use of T-cell-depleting antibodies alone is likely to increase cancer risk.

Blood-oxygen-level-dependent MRI enables noninvasive assessment of renal deoxyhaemoglobin levels and, therefore, hypoxia. As decreased tissue oxygenation might contribute to acute and chronic kidney disease (CKD), this tool has been examined in patients with CKD. Indeed, the benefits of renin–angiotensin–aldosterone system inhibitors might be partly conferred by increased oxygenation.

Well-controlled oral anticoagulation lowers the risk of ischaemic stroke in patients with atrial fibrillation; however, conflicting evidence exists on its benefits and risks in patients with end-stage renal disease. Shah and colleagues examined this question in a large cohort of patients on dialysis who were diagnosed with atrial fibrillation.

Immunosuppressive drugs commonly used in transplantation and autoimmune diseases are unfortunately associated with increased cancer incidence. Now, a new study reports a direct relationship between the number of regulatory T cells in the blood and the risk of developing invasive skin cancer in kidney transplant recipients.

Anti-CD20 therapy is increasingly being used in the treatment of various patterns of nephrotic syndrome in adults and children. However, its use is still based largely on observational studies and expert opinion. Well-designed randomized controlled trials are urgently needed to define the role of this expensive therapy.