Reviews & Analysis

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.

Prospective cohort studies have shown that anaemia is an independent predictor of adverse outcomes in patients with chronic kidney disease. However, randomized controlled trials of the use of erythropoiesis-stimulating agents to correct moderate anaemia in this patient group have failed to show clinical benefit, and indicate that such treatment may even be harmful. Here, Patrick Parfrey discusses possible explanations for these seemingly contradictory results.

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.

Oral phosphate binder therapy is considered a 'tower of strength' in the ever-expanding armamentarium of drugs used to treat abnormal mineral metabolism in patients with chronic kidney disease (CKD) and use of these agents early in the course of CKD is gaining much interest. Recent data from a randomized controlled study by Block et al. challenge this strategy, raise doubts about its safety and indicate the need for additional studies of hard end points.

A recently published study suggests that sirolimus is an attractive treatment option for the prevention of secondary skin cancer in kidney transplant recipients. However, before we think about switching all patients with a previous skin cancer (or with any other malignancy) to sirolimus, we should have a closer look at the data.

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.

The new KDIGO anaemia guidelines represent a bold, sensible, and patient-centred approach to anaemia management in patients with chronic kidney disease. Recommendations regarding haemoglobin targets, blood transfusions, and erythropoiesis-stimulating agent therapy are provided, and individualizing the management of anaemia is emphasized.

Cell hypertrophy is the only mechanism by which podocytes can cope with increased functional demands, whereas other glomerular cells can adapt by cell proliferation. In the setting of systemically stimulated glomerular growth, a 'mismatch' of inadequate podocyte hypertrophy and overall glomerular growth may lead to podocyte loss and development of focal segmental glomerulosclerosis.

Several management guidelines for lupus nephritis have been published this year. All of the guidelines provide clear and consistent recommendations, but although evidence-based, many of the recommendations are not supported by high-quality clinical data. The guidelines reveal these evidence gaps and are thus an important roadmap for future lupus nephritis clinical research.

Emerging evidence suggests that 15–20% of patients who do not fulfill current consensus criteria for AKI have acute tubular damage, which is associated with adverse outcomes. Haase et al. argue that the spectrum of AKI should be extended to incorporate subclinical forms of the disorder diagnosed on the basis of biomarkers of tubular damage.

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.

German health-care providers should be applauded for their heroic efforts in facing the 2011 Escherichia coli O104:H4 outbreak. However, a unique opportunity was missed to compare the efficacy of antibiotics, plasma therapy and eculizumab therapy in a randomized study, and the open questions concerning the optimal treatment of severe Shiga-toxin-associated haemolytic uraemic syndrome remained unanswered.

Current dogma suggests that fluid overload—when associated with acute kidney injury (AKI)—is an independent risk factor for death. Although the volume status of the patient is important, there are other predictors of morbidity, mortality and the need for renal replacement therapy in patients with AKI.

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.

For more than 20 years, Doppler ultrasound has been a valuable noninvasive imaging tool in the evaluation of several forms of kidney disease. Modifying the typical parameters used in clinical practice as shown in a study by Grün et al. may lead to a more kidney-specific Doppler value.

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.