Review Articles in 2012

Blockade of the renin-angiotensin-aldosterone system (RAAS) is a standard treatment for patients with chronic kidney disease (CKD). Intensive strategies with single-agent or dual-agent RAAS blockade have been used to reduce proteinuria and blood pressure in these patients. This Review discusses strategies for improving the long-term outcomes of patients with CKD treated with RAAS blockade, focusing on the effects of combined low-dietary sodium intake and RAAS-blockade on the risk of renal and cardiovascular outcomes.

Heart failure and renal dysfunction frequently coexist. The term cardiorenal syndrome (CRS) is frequently used to describe this scenario, but the definition of CRS has been a matter of debate and has evolved over time. Here, the authors review the concept of CRS and its evolution and classification, and describe current and future targets for the clinical management of CRS. In addition, they propose a new classification system with seven distinct categories.

In the past few years, basic research and epidemiological studies have provided a wealth of new data on renal prognosis following acute kidney injury (AKI) and the potential association of AKI with incident chronic kidney disease (CKD), progression of CKD, and incident end-stage renal disease. The authors of this Review describe these findings and discuss the possible mechanisms by which AKI might lead to CKD or CKD progression.

The development of blockers of the renin–angiotensin–aldosterone system (RAAS) has led to the identification of new RAAS components that might contribute to the effectiveness and/or adverse effects of these drugs. Here, the authors describe the roles of the prorenin receptor, type 2 angiotensin II receptors, angiotensin 1–7 and aldosterone–angiotensin II interactions and discuss the potential of modulators of these components to enhance RAAS blockade with potentially beneficial effects in patients with cardiovascular and renal diseases.

Alport syndrome is a rare disease caused by mutations in the genes encoding collagen type IV. The underlying disease mechanisms are unknown, but disrupted formation of glomerular basement membranes is thought to have a key role in pathogenesis. In this Review, the authors describe the diagnosis of Alport syndrome, current understanding of underlying pathogenetic mechanisms and treatment of this disease.

Hyponatraemia—the most common serum electrolyte disorder—is an important marker of the severity and prognosis of a number of diseases. In this Review, Schrier et al. discuss the effect of hyponatraemia in different patient groups, including those with pneumonia, heart failure, cirrhosis, and the elderly population. The authors discuss the need for prospective studies to examine whether correcting hyponatraemia can improve outcomes or whether hyponatraemia is just a marker of severe disease.

Chronic kidney disease (CKD) is an important public health issue that is strongly associated with adverse outcomes. Evaluation of existing therapies, development of new interventions, and timely patient counselling requires accurate prediction models that estimate individual-level risk. Here, Grams and Coresh outline the fundamentals of risk prediction, including considerations pertinent to CKD, common methodological shortcomings in risk prediction studies, and metrics often used to assess the performance of risk prediction models.

Resistant hypertension is defined as failure to reach goal blood pressure in patients who are compliant with maximal doses of three antihypertensive drugs, one of which is a diuretic. Despite improvements in controlling blood pressure in the past decade, studies show the prevalence of resistant hypertension is increasing. In this Review, the authors define resistant hypertension and discuss current data on its prevalence, associated comorbidities and prognostic implications.

Flares of systemic lupus erythematosus are broadly defined as an increase in disease activity requiring an intensification of therapy. A renal flare is indicated by an increase in proteinuria and/or serum creatinine concentration, abnormal urine sediment or a reduction in creatinine clearance rate as a result of active disease. In this Review the authors examine current definitions of renal flares and describe developments in the diagnosis and treatment of renal flares.

As the world population continues to age, the number of elderly patients with chronic kidney disease who require a kidney transplant is increasing. In this Review, the effects of aging on the adaptive and innate immune systems are discussed, with a focus on the implications of age-related changes in the immune system on kidney transplantation and immunosuppression in elderly patients.

In this Review, Finkelstein and colleagues discuss the effects of end-stage renal disease (ESRD) and therapy on the health-related quality of life (HRQOL) of patients. They suggest that monitoring HRQOL—using standardized tools that incorporate assessment of patient-reported outcomes—should form part of the routine care of patients with ESRD, and emphasize the importance of developing strategies to improve the HRQOL of these patients.

Water used for dialysis can be contaminated by many chemical and microbiological factors that are potentially harmful to patients on haemodialysis. The quality of dialysis water has improved over the years, and in this Review the authors describe the evolution of the current standards for the provision of water quality. In addition, they outline new developments, with a particular focus on haemodialysis in the home.

Mineralocorticoid-receptor antagonists (MRAs) effectively reduce blood pressure and albuminuria in patients with chronic kidney disease who experience aldosterone breakthrough. Use of MRAs is limited, however, by the occurrence of hyperkalaemia, which frequently develops in patients with impaired kidney function, and/or diabetes. This Review discusses potential approaches to identify patients who are particularly prone to developing hyperkalaemia with MRA therapy and describes currently available and promising strategies to prevent and control hyperkalaemia in patients with CKD.

Improved understanding of the role of complement in the pathogenesis of a number of glomerular diseases has led to progress in disease classification and treatment. In this Review, Bomback and Appel re-examine the previous classification schemes for membranoproliferative glomerulonephritis (MPGN) and discuss the role of complement in the various MPGN lesions including the C3 glomerulopathies. In addition, they discuss the pathogenesis, diagnosis, treatment, and prognosis of the C3 glomerulopathies.

Much progress has been made in understanding the processes underlying antibody-mediated rejection (AMR) of transplanted organs. In this Review, the authors discuss the role of the complement system in acute and chronic AMR, with specific emphasis on renal transplantation, and describe studies demonstrating that blockade of terminal complement activation can prevent AMR in sensitized renal transplant recipients.

Here, Zuber et al., on behalf of the French Study Group for aHUS/C3G, discuss the role of eculizumab in the treatment of atypical haemolytic uraemic syndrome (aHUS). They review data from case reports and preliminary data from prospective trials, present their opinions, and describe issues that require further study. In addition, they discuss the potential use of eculizumab in C3 glomerulopathies.

Shiga toxin-producingEscherichia coli-associated haemolytic uraemic syndrome (STEC-HUS) is associated with renal and neurological injury. This Review summarizes the pathophysiology and clinical presentation of STEC-HUS and its acute and long-term effects on the kidney and central nervous system. The authors also describe the experience of a single centre that was affected by the STEC-HUS outbreak in Germany in 2011.

Atypical haemolytic uraemic syndrome (HUS), Shiga toxin-producingEscherichia coli-associated HUS and thrombotic thrombocytopaenic purpura are diseases characterized by microvascular thrombosis, with subsequent dysfunction of affected organs. In this Review, the authors discuss data indicating that complement dysregulation is a common pathogenetic effector of all three diseases, and describe the emerging evidence indicating that targeting complement may effectively treat these disease entities.

Acute metabolic acidosis is common in seriously ill patients, and is associated with increased morbidity and mortality. Rapid recognition of this acid–base disorder and provision of effective therapy are, therefore, essential. This Review summarizes current approaches to the treatment of acute metabolic acidosis, highlights the evidence for and against base therapy, and discusses the potential benefits of newer targeted therapies.

Hypertension is a leading cause of morbidity and mortality and the kidney has a pivotal role in this condition by regulating arterial blood pressure. In this Review, Wadei and Textor provide examples of the regulatory mechanisms that are involved in controlling blood pressure and discuss how disorders that affect the kidney contribute to hypertension.