Reviews & Analysis

The past year was marked by several excellent studies that represent important therapeutic advances in kidney transplantation or that further our understanding of the genetic basis of chronic allograft dysfunction, clinical tolerance and outcomes of kidney transplantation.

Infection is one of the most common causes of morbidity, mortality and hospitalization in patients undergoing dialysis. This Review focuses on the epidemiology and characteristics of access-related infections—bloodstream infections in hemodialysis and peritonitis in peritoneal dialysis—as well as access-unrelated infections, such as viral hepatitis and respiratory infection.

Urolithiasis is a common disorder that has several metabolic risk factors, most notably hypercalciuria. Genetic variants associated with urolithiasis have been identified from linkage and candidate gene studies, as well as from the first genome-wide association study of this condition, highlighting the role of several proteins in disease development and progression. In this Review, Monico and Milliner summarize the findings from studies that have advanced the understanding of the genetic basis of urolithiasis.

Diuretics are commonly used in the treatment of patients with chronic kidney disease. However, many questions remain regarding this practice, such as how best to combine diuretics and whether loop diuretics can be used in patients on hemodialysis. In this Review, Dominic Sica addresses these and other important questions surrounding the use of diuretics in patients with renal disease.

More than 1.4 million patients are on renal replacement therapy worldwide. Mortality in patients with end-stage renal disease (ESRD) is as high as that seen in some types of metastatic cancer, and premature cardiovascular disease is the major killer in ESRD. Several publications in 2011 addressed how interventions can modify cardiovascular risk factors and improve outcomes.

Research into genetic susceptibilities for proteinuric glomerular diseases has uncovered key pathogenic contributions from inheritable defects in podocytes. However, much less is known about environmental factors that may initiate or propagate podocyte injury. Seminal reports in 2011 provided new mechanistic insights into how this may occur.

Understanding the complex interactions between the various pathways disrupted in polycystic kidney and liver disease is essential to identify and optimize therapies for these disorders. Studies published in the past year have demonstrated a functional interaction between the main proteins implicated in these diseases and identified novel therapeutic approaches.

Non-communicable diseases (NCDs) are taking center stage in global health policy. Intensive lobbying by the International Society of Nephrology has gained recognition for chronic kidney disease (CKD) as a major NCD. Continuing advocacy is needed for the health risk of CKD to be understood and opportunities for prevention and treatment grasped.

In 2011, studies of chronic kidney disease (CKD) were published in abundance. The articles selected here represent the growing appreciation of the importance of CKD as a modifier of outcomes, breakthroughs in understanding the pathobiology and genetics of specific conditions, and clinical trials of treatment strategies that offer hope to patients with CKD.

Identification of effective therapies for nephrotic syndrome is challenging. The pituitary adrenocorticotropic hormone (ACTH) has been shown to be renoprotective in patients with proteinuric neuropathies, but its mechanism of action is unknown. In this Perspectives, Runjun Gong provides an overview of the biophysiology of ACTH, the effects of ACTH on proteinuric renal diseases and the mechanisms likely to be involved in its therapeutic activity. The potential therapeutic role of ACTH for nephrotic glomerulopathies is also discussed.

Genome-wide association studies (GWASs) have led to the identification of genes underlying renal traits such as glomerular filtration rate, and improved our understanding of the pathogenesis of chronic kidney disease. In this Review, O'Seaghdha and Fox discuss how GWASs have revolutionized genetic research, using several large-scale studies as examples, and explain how the knowledge derived from these studies can be applied to improve our understanding of the pathogenesis of kidney disease and to identify novel therapeutic targets.

For predicting complications related to chronic kidney disease, endogenous filtration markers such as cystatin C and creatinine perform as well, if not better, than measured glomerular filtration rate (GFR). Measured GFR by clearance of an inert exogenous marker may still be the gold standard measure of GFR, but determining GFR may not answer the right clinical question.

A recent study has reviewed records of patients on thrice-weekly hemodialysis and shown that serious and fatal complications—including overall and cardiac mortality, as well as hospitalization for cardiovascular reasons—are more frequent on the last day of the long interdialytic interval than on other days.

New-onset diabetes mellitus after kidney transplantation (NODAT) is associated with increased morbidity and mortality, as well as poor quality of life. NODAT is likely to become more common in the transplantation setting as patient and graft survival improves. In this Review, Sharif and Baboolal provide specific guidance on diabetes mellitus-related complications in patients who have had renal transplantation.

General severity of illness scores lack high predictive accuracy for mortality in patients with acute kidney injury (AKI). Using the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network database, Demirjian et al. identified 21 independent predictors of mortality and developed an accurate scoring system for outcomes in patients with AKI requiring renal replacement therapy.

The podocyte is a key target of injury in a number of renal diseases. Although some current therapies—including glucocorticosteroids and calcineurin inhibitors—have potent effects on the podocyte, their effects are nonspecific and lead to unwanted systemic adverse effects. In this Review, Peter Mathieson describes how advances in our understanding of podocyte biology has enabled the identification of potential therapeutic targets that may be able to prevent or limit podocyte injury and/or promote podocyte repair or regeneration.

Several studies have indicated that an intensive continuous renal replacement therapy (CRRT) dose has no benefit over a standard CRRT dose. However, treatment-related factors may have influenced these findings. In this article, Macedo et al. discuss the assumption that delivered dialysis dose is equivalent to the effluent volume and highlight the importance of assessing filter efficacy and dose parameters in patients receiving CRRT.

Biomarkers have the potential to refine prognosis, improve risk stratification and guide therapy in patients on hemodialysis. The authors of this Review discuss the validation and potential use of biomarkers, including markers of chronic kidney disease-related mineral and bone disorders, markers of protein–energy wasting and inflammation, and markers of cardiovascular disease, in patients on hemodialysis. The authors also describe how proteomics can be used to identify and study new biomarkers.

Patients with acute kidney injury (AKI) complicating multiple myeloma often have poor outcomes. In this Review, Hutchison et al. discuss the pathogenic role of monoclonal free light chains in inducing proximal tubular damage and cast nephropathy in patients with multiple myeloma. The authors also provide an update on the diagnostic approaches to patients with AKI complicating multiple myeloma.

An understanding of the intricacies of cytoskeletal dynamics and regulation in podocytes is essential to facilitate investigation and treatment of patients with glomerular disease. This Review outlines the most recent concepts and advances in podocyte biology, and discusses how an improved understanding of the podocyte cytoskeleton is starting to shape advances in delineating the pathogenesis of common glomerular diseases.