Reviews & Analysis

Low-molecular-weight heparins are replacing unfractionated heparin as the anticoagulant of choice for patients receiving hemodialysis. However, clotting can still be a problem during hemodialysis. This Review discusses the different anticoagulant options for these patients.

Clinical practice guidelines recommend target serum levels for phosphorus, calcium and parathyroid hormone in patients with chronic kidney disease. However, a recent meta-analysis has found that only levels of phosphorus seem to be associated with the risk of death in these patients.

This article reports the case of a 50-year-old man who had undergone kidney and pancreas transplantation and developed pancytopenia following treatment with azathioprine. A genotype test for thiopurineS-methyltransferase (TPMT) showed that the patient was homozygous for TPMT^*3A, which accounted for the susceptibility to azathioprine-related myelosuppression. The authors discuss the importance of TPMT testing and describe the tools available for monitoring for adverse effects from treatment.

Genome-wide association studies have advanced our understanding of the genetic basis for common renal diseases. The ability to establish these associations raises the question of whether these discoveries offer help to patients with (or at risk of) renal disease. Here, Drawz and Sedor describe recent discoveries in relation to the genetic associations underlying common kidney disease and related disorders, and discuss the issues and challenges of translating these data into the clinic.

This Review focuses on early detection of chronic kidney disease (CKD) and highlights its associations with cardiac disease and other comorbidities that contribute to poor outcomes. The authors describe the role of estimated glomerular filtration rate and albuminuria in identifying early CKD, examine the benefits of early CKD detection, and describe the limitations of current knowledge with respect to screening, early detection and treatment.

Genetic forms of steroid-resistant nephrotic syndrome are characterized by an unremitting clinical course, resistance to treatment and a favorable outcome after transplantation. The recognition of these diseases is essential, but difficult, owing to genetic and phenotypic heterogeneity. Such difficulties have led to the proposal of a systematic step-wise approach for mutational screening.

A recent study reports the expansion of the donor pool by using kidneys from donors after cardiac death with prolonged agonal time. The duration of the agonal period and hemodynamic instability do not influence kidney transplantation outcome, indicating that this approach is feasible and may help meet the need for donor kidneys for transplantation.

Hypertension is a major risk factor for the progression of chronic kidney disease (CKD) in adults and children, and existing evidence suggests that pharmacological intervention could slow the decline in renal function. In this Review, Wühl and Schaefer discuss the pathology of CKD progression, including the role of hypertension and proteinuria. The use of tight blood-pressure control to prevent progressive CKD and the various antihypertensive agents used in patients with CKD are also discussed.

Protein-energy wasting (PEW), manifested by low serum levels of albumin and weight loss, is common in patients with chronic kidney disease (CKD) and is a strong predictor of mortality. The authors of this Review discuss the evidence indicating that dietary interventions and nutritional support can mitigate PEW and improve outcomes in patients with CKD. They also describe how in-center meals and oral supplements during dialysis may improve survival and quality of life in this group of patients.

Inflammation is highly prevalent in patients with chronic kidney disease (CKD) and is associated with increased mortality and cardiovascular events. Besides reducing lipid levels, statins have anti-inflammatory effects that are modified by the presence of inflammation, making these agents especially effective in patients with CKD who show evidence of inflammation and raised levels of C-reactive protein. In this Review, Krane and Wanner provide an overview of statin studies in patients with CKD, and discuss how the results could influence clinical decision making.

Results of a clinical trial reported in the New England Journal of Medicine suggest that the use of recombinant tissue plasminogen activator as a lock solution improves catheter patency and reduces the risk of catheter-related infections. These effects have important clinical and economic ramifications. So why is tissue plasminogen activator not more widely used?

Including proteinuria in the NKF KDOQI staging system for chronic kidney disease will increase the accuracy of risk stratification, but will not improve the precision of glomerular filtration rate (GFR) estimation by prediction formulas. Using markers of glomerular filtration other than serum creatinine will hopefully enable implementation of novel formulas that more precisely estimate true GFR, especially in individuals with near-normal renal function.

Uncertainty exists over whether hemodialysis or peritoneal dialysis is the modality associated with better survival in patients with end-stage renal disease. Mehrotra and colleagues have shown that survival rates have improved more with peritoneal dialysis than with hemodialysis in more recent cohorts of US patients starting dialysis and that, overall, the two modalities have very similar 5-year mortality rates.

The consequences of fluid administration and the maintenance of fluid balance, despite their ubiquity in critical care, remain a topic of much debate among clinicians. Emerging evidence suggests that fluid administration and a positive fluid balance can be harmful in a number of conditions, including acute kidney injury.

Results from the ROADMAP trial have highlighted the discrepancy between the renoprotective effects of olmesartan treatment in patients with type 2 diabetes mellitus, and the observed increase in cardiovascular deaths. Several explanations for these results need to be considered, which may influence future clinical practice.

In response to data from trials showing an increase in clinical events with the use of erythropoiesis-stimulating agents (ESAs), Seliger et al. carried out an observational case–control study and have found that high doses of ESAs are associated with an increased risk of stroke.

In the CKiD study, extracellular fluid volume (ECV) was estimated from plasma iohexol curves in children with chronic kidney disease. A simple formula for ECV that uses weight and height data has now been derived. No relationship existed between weight-normalized ECV and hypertension, suggesting that volume overload does not underlie hypertension in this population.

Gene silencing using small interfering RNA (siRNA) molecules is a promising therapeutic strategy for renal diseases, but many practical challenges hinder their clinical application. The authors of this Review provide a comprehensive overview of the current status of siRNA-based therapies for glomerulonephritis, and discuss current and future delivery systems for these agents.

Reactivation of latent BK polyomavirus (BKV) infection is a major challenge in renal graft recipients and progression of BKV infection to BKV-associated nephropathy (BKVAN) leads to graft loss in up to 60% of affected patients. This Review discusses the available data on the diagnosis and monitoring of BKV infection and BKVAN, describes the known risk factors for BKV-related disease, and reviews current approaches to treatment and prevention of both BKV infection and BKVAN.

Extensive rhabdomyolysis is often lethal unless treated immediately, owing to hypovolemic shock, hyperkalemia, acidosis and myoglobinuric acute kidney injury. In patients with rhabdomyolysis caused by muscle crush syndrome, the use of early fluid resuscitation at the scene of injury has reduced mortality from ∼100% to <20% over the past 70 years. In this article, Better and Abassi discuss the lifesaving and limb-saving potential of early vigorous fluid resuscitation in patients with extensive traumatic and nontraumatic rhabdomyolysis.