Reviews & Analysis

Disordered mineral metabolism is linked to the increased risk of total and cardiovascular morbidity and mortality seen in patients with chronic kidney disease. In this Review, Goldsmith and Cunningham describe the association between patient outcomes and mineral biomarkers such as phosphate, calcium, parathyroid hormone and vitamin D, and explore how current therapies can be used to probe these relationships and how future trials could be designed to establish their significance.

Population-based genetic studies initially identifiedMYH9as a major susceptibility locus for diabetes-unrelated kidney diseases in persons of West African ancestry, but further research found more strongly associated mutations in the neighboring APOL1 gene. This Review describes how evolutionary selection pressure of an infectious pathogen in West Africa favored the spread of APOL1 variants that protect against a lethal form of African sleeping sickness but are associated with an increased risk of kidney disease. The authors discuss lessons that can be learned for future population genetics research.

Inflammation has a key role in the pathogenesis and progression of diabetic nephropathy; however, the pathways, ligands and receptors involved in this condition are complex and only partially understood. The authors of this Review discuss the molecular networks that are implicated in the development of diabetic nephropathy and describe how these pathways function in health and disease, as well as their importance in the identification and development of potential therapeutics.

A recent article exposes the ongoing industry of transplant tourism in China, where foreign patients can receive vendor organs recovered from executed prisoners. Concerning data reveal the long-term complications of kidney transplant tourism, particularly the increased risk of malignancy. These findings relay an important message to transplant communities and physicians worldwide.

Restriction of dietary phosphorus has long been established as a cornerstone for the treatment of hyperphosphatemia in patients on dialysis. However, the study by Lynch et al. published in the Clinical Journal of the American Society of Nephrology reports that prescribed dietary phosphorus restriction is not associated with improved survival among patients undergoing hemodialysis.

Arterial calcification is highly prevalent in patients with chronic kidney disease, and is a process associated with cardiovascular morbidity and mortality. Calcium phosphate deposits may be found in the intima, the media, or both. Whether determination of the precise location of calcification is possible and whether this distinction is clinically useful remains a matter of debate.

In light of recent proposed changes to the deceased donor allocation policy in the USA, considerable interest has arisen in the development of assessment tools to grade donor organ quality. Kahu and colleagues have suggested a new donor risk score that incorporates 10 distinct donor characteristics, correlating their presence with baseline histologic findings and graft outcomes.

Attempts to achieve pharmacological suppression of the renin–angiotensin–aldosterone system (RAAS) fall short of complete success, owing to the existence of accessory enzyme pathways. In this article, the therapeutic targets and limitations of RAAS inhibition are discussed, and the use of combination therapy and the direct renin inhibitor, aliskiren, are described.

Information technology is being increasingly used in medicine to improve patient care and safety. Computerized physician order entry and clinical decision support systems have been shown to reduce the rate of adverse drug events, which are a frequent cause of morbidity and mortality and are of increased likelihood in patients with renal impairment. The authors of this Review discuss the benefits and limitations of computerized support systems and outline features that can be refined to encourage the implementation of these tools.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is a marker of renal dysfunction progression, vascular complications and death. Levels of ADMA and levels of its isomer symmetric dimethylarginine (SDMA) are elevated in patients with kidney disease. In this Review, Schwedhelm and Böger provide an overview of the roles of both dimethylarginines in renal, cerebrovascular and cardiovascular disease, and discuss how the biological function of ADMA and SDMA could be targeted to treat renal disease in the future.

A recent observational study from the UK raises questions over the control of mineral metabolism parameters to within target levels defined by the KDOQI clinical practice guidelines. Data from this study highlight the need for a randomized controlled trial to determine whether optimal management of bone mineral metabolism actually provides any survival benefit.

Individuals with HIV disease frequently experience kidney dysfunction, which is accompanied by an increased risk of cardiovascular disease and death. Choi et al. have found that albuminuria and an estimated glomerular filtration rate of <60 ml/min/1.73 m², estimated using serum cystatin C level, accounted for 17% of the population-attributable 5-year mortality risk in a cohort of patients with HIV infection.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is a common cause of acute kidney injury in the elderly. This patient group is particularly susceptible to disease-related morbidity and mortality, and to adverse effects of induction immunosuppression. A new study adds to the debate on the most appropriate way to treat this vulnerable group of patients.

Melamine has been used in industry to adulterate human and animal foodstuffs owing to its high nitrogen content, which gives misleading results in assays that measure protein content in food. Ingestion of melamine can result in kidney stones, renal failure and, occasionally, death. The authors of this Review discuss the epidemiological, clinical, pathological, and toxicological observations that have been linked to melamine alone and in combination with cyanuric acid.

Micro (mi)RNAs are short, noncoding nucleotides that target and regulate messenger RNA at the post-transcriptional level. In this Review, Lorenzen and colleagues discuss the generation and function of miRNAs as well as their role in chronic kidney diseases such as diabetic nephropathy and hypertensive kidney disease. The potential of miRNA therapeutics for kidney diseases will also be discussed.

Central venous catheters used for hemodialysis continue to be associated with high rates of bloodstream infections. In this article, Michiel Betjes reviews the evidence showing that such infections can be prevented by meticulous catheter care and discusses how improved management protocols could help to reduce the incidence of catheter-related infections, even in the absence of topical antimicrobial agents and/or lock solutions.

Sepsis is the most common and severe cause of morbidity and mortality among critically ill patients. Acute kidney injury (AKI) can complicate sepsis, with a linear relationship between the severity of kidney damage and patient prognosis. In this Review, the authors describe currently available interventions for sepsis-related AKI. In addition, they discuss preventive methods, pharmacological support and extracorporeal blood purification for septic AKI.

Acute kidney injury (AKI) is often overlooked in hospitalized patients, despite a strong association with poor clinical outcomes. In this Review, Ricci et al. discuss the advantages and limitations of the RIFLE and AKIN consensus definitions for AKI. The authors also consider the integration of novel biomarkers into these definitions to aid early diagnosis and prediction of the prognosis of AKI.

Ischemia is the most common cause of acute kidney injury (AKI) in hospitalized patients. The authors of this Review describe the morphological and functional responses of kidney cells to ischemic injury. They also outline the characteristics of patients who are at highest risk of developing ischemic AKI and discuss therapeutic strategies for the prevention and management of this condition.

March 10, 2011 will mark the 6^th World Kidney Day, an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. World Kidney Day aims to raise awareness among both the general public and government health officials about the dangers of kidney disease, especially chronic kidney disease.