Review Articles in 2010

Accelerated atherosclerosis is common in patients with chronic kidney disease (CKD). The association between CKD and atherosclerosis is in part driven by the downregulated synthesis of high-density lipoprotein (HDL) and an impairment of HDL antioxidant and anti-inflammatory activity. In this Review, Vaziri and colleagues discuss the mechanisms by which CKD adversely affects HDL level, activity and ability to mediate reverse lipid transport, and describe the mechanisms by which HDL dysregulation predisposes patients to atherosclerosis and CKD progression.

Aldosterone is a steroid hormone that is mainly recognized for its action on sodium reabsorption in the distal nephron of the kidney. In addition, however, aldosterone exerts other effects on the kidney, blood vessels and the heart, which can have pathophysiological consequences. In this Review, Briet and Schiffrin discuss the mechanisms of aldosterone-induced kidney and cardiovascular injury. The role of mineralocorticoid receptor antagonists in preventing the progression of chronic kidney disease and in the treatment of patients at high risk of cardiovascular events is also described.

Finding a suitable donor kidney for renal transplant candidates who are allosensitized to human leukocyte antigen (HLA) can be challenging. In this Review, Gloor and Stegall discuss currently available strategies for screening and desensitization and new techniques that are under development. Treatments that target donor-specific antibodies have shown some success in reversing acute antibody-mediated rejection, a common complication in antibody-incompatible kidney transplantation. New treatments, such as anti-C5 antibody-mediated complement blockade and proteasome inhibitor-mediated plasma cell depletion, are promising therapeutic avenues.

A wide range of erythropoiesis-stimulating agents to stimulate red blood cell production are currently in clinical use, but advances in our understanding of erythropoiesis have provided an ever-increasing array of potential therapeutic targets. Here, Robert Foley describes the desirable properties of erythropoiesis-stimulating agents and discusses various novel agents currently under assessment for the treatment of anemia in patients with chronic kidney disease. Such agents include proteins and peptides that activate erythropoietin receptors, non-protein agents, and strategies with targets other than erythropoietin receptors.

Phosphate is critical for the maintenance of skeletal integrity, is a necessary component of important biomolecules, and is essential for cellular metabolism. Mechanisms of phosphate regulation in the kidney—the most critical organ for maintaining short-term serum phosphate concentrations—are incompletely understood. This Review describes how the identification of genetic alterations in Mendelian disorders of hypophosphatemia and hyperphosphatemia has led to the isolation of novel genes and the identification of new roles for existing proteins in the control of renal phosphate handling.

Toll-like receptors (TLRs) have a key role in the regulation of innate immunity by mediating signal transduction pathways that modulate the expression of proinflammatory cytokines and chemokines. This Review discusses the potential role of TLRs in the pathogenesis of renal conditions such as acute kidney injury, acute glomerulonephritis, and renal transplant rejection. The authors also describe studies that have used pharmacological inhibition of TLR signaling to modify the response to proinflammatory stimuli.

Autosomal dominant polycystic kidney disease (ADPKD) is a common nephropathy caused by mutations in eitherPKD1 or PKD2. Molecular analyses are increasingly used for the diagnosis of this disease and are particularly helpful when imaging studies are equivocal and a definite diagnosis is required. In this Review, Harris and Rossetti discuss the role of molecular diagnostics in ADPKD and describe the different approaches that are used. Genetic complexities that require consideration when using molecular diagnostics in ADPKD are also described.

A number of new promising agents for the prevention of acute and chronic transplant rejection have been or are being developed. In this Review, Antoine Durrbach and colleagues discuss agents that interfere with antibody-mediated rejection and those that deplete allogenic T cells or inhibit T-cell activation. The capacity of these agents to prevent acute rejection is also described.

Elderly hospitalized patients are at high risk of developing acute kidney injury (AKI). In this Review, Alexandra Chronopoulos and colleagues discuss the reasons for the increased risk of AKI in this patient group, including age-related changes in the kidney, systemic vasculature, and immunological system, as well as frequent comorbidities and high exposure to iatrogenic insults such as medications, radiocontrast agents, and surgery. The difficulties of treating AKI in older individuals are also described, and the importance of early diagnosis is emphasized.

The defining characteristic of autosomal dominant polycystic kidney disease is the progressive formation and enlargement of large numbers of renal cysts, which in most patients eventually leads to end-stage renal disease. In this Review, Bae and Grantham examine the evidence that supports a prognostic role for imaging-based measurements of volume and rate of enlargement of cysts and of whole kidneys for patients with autosomal dominant polycystic kidney disease.

Of the aquaporins found in humans, seven are known to be expressed in the kidneys. In this Review, Noda et al. discuss evidence from clinical and animal studies regarding the localization, physiological function and mechanism of regulation of these water channels in renal cells. The authors also describe the pathological conditions associated with dysfunctional aquaporins with particular attention dedicated to the water channel aquaporin-2 and to nephrogenic diabetes insipidus, a condition associated with dysfunctional aquaporin-2.

Narrowing of the renal artery reduces renal perfusion and can lead to hypertension, renal dysfunction and/or pulmonary edema. In this Review, Plouin and Bax discuss the diagnosis and management of the two most common types of renal artery stenosis: atherosclerotic renal artery stenosis and fibromuscular renal artery dysplasia. The authors also describe recent data from randomized, controlled trials of patients with atherosclerotic renal artery stenosis.