Reviews & Analysis

Elevated levels of fibrobast growth factor 23 (FGF-23) are associated with cardiovascular and all-cause mortality in patients with kidney disease. A secondary analysis of the EVOLVE trial reports that cinacalcet-induced reductions in FGF-23 were associated with a reduced risk of cardiovascular events in patients with secondary hyperparathyroidism on dialysis.

The constitutive uptake and degradation of filtered albumin by the proximal tubule has resulted in this process being relegated a passive player in albuminuria. Real-time intravital imaging of the rat kidney now describes a new paradigm in which the proximal tubule dynamically increases or decreases albumin uptake following changes in plasma albumin levels.

Human adult stem or progenitor cell organoid cultures have been established for multiple organs and have proved valuable in the basic study of pathophysiology as well as in clinical applications. Such an organoid culture system has not yet, however, been developed for the kidney. Here the authors describe the development and application of the available adult stem or progenitor cell organoid cultures, the challenges and feasibility of developing such a system for the kidney, and the potential kidney-specific applications of organoids.

The association between hypertension and chronic kidney disease is cyclic and complex. In this Review, Townsend and Taler discuss the underlying mechanisms of this association and emphasize the importance of achieving and maintaining adequate blood pressure control in renal disease. They outline the necessity of accurate blood pressure monitoring, the value of drug and non-drug therapies, and assess the current blood pressure targets recommended by different guidelines for patients with chronic kidney disease.

Maintaining steroid-free remission in children with idiopathic nephrotic syndrome is an important goal of therapy. A new trial provides evidence that mycophenolate mofetil can be added to the list of effective steroid-sparing agents. The majority of participants relapsed, however, highlighting an unmet need for more effective treatment modalities.

A new study reports that state-level policies have had little effect on rates of organ donation in the USA, highlighting the limited ability of scattered initiatives to have a national effect. Regardless of their impact on donation rate, a need exists for policies that make donation financially neutral for donors.

Chronic kidney disease is associated with an increased risk of cardiovascular disease that often exceeds risk of progression to end-stage renal disease. A meta-analysis has shown that the addition of glomerular filtration rate and albuminuria to traditional risk factors for cardiovascular outcomes improves the discrimination of cardiovascular risk prediction models.

Urinary tract infections (UTIs), including pyelonephritis, are among the most common and serious infections encountered by nephrologists. Emerging evidence suggests a fundamental role for the innate immune system in protecting the urothelium from bacterial challenge. This Review provides an overview of UTI pathogenesis in the upper and lower urinary tract. The authors describe the role of intercalated cells and the innate immune response in preventing UTI, focusing on the role of antimicrobial peptides in maintaining urinary tract sterility.

Cardiac surgery often requires the use of cardiopulmonary bypass, which can cause an inflammatory cascade that results in acute kidney injury (AKI). A recent post hoc analysis of a placebo-controlled, randomized trial suggests that intraoperative steroids might lower the risk of renal replacement therapy for AKI after cardiac surgery.

IgG4-related disease can affect any organ system, including the kidney. Renal involvement is an indication for prompt treatment, owing to an increased risk of chronic kidney disease. In this Review, Frank Cortazar and John Stone provide an overview of systemic IgG4-related disease before describing in detail the renal manifestations of IgG4-related tubulointerstitial nephritis and membranous glomerulonephropathy secondary to IgG4-related disease. They consider the pathophysiology, as well as current and future treatment options.

The identification of modifiable risk factors that are associated with declining renal function is required to stem the increasing incidence of chronic kidney disease worldwide. In this Review, Howard Trachtman and colleagues discuss the impact of environmental chemicals on cardiorenal function. They highlight the ubiquity of exposure to environmental chemicals in the general public, the main sources of contamination, and the predominant adverse effects that might affect renal function.

Nephrogenic diabetes insipidus (NDI) is caused by inability of the kidneys to respond to arginine vasopressin and concentrate urine by reabsorption of water in the collecting duct. The disease can be congenital or acquired and has a substantial detrimental effect on the quality of life of affected patients. In this article, Bockenhauer and Bichet review the pathophysiology, diagnosis and current clinical management of NDI as well as potential future treatment strategies.

The high prevalence of chronic kidney disease (CKD) places considerable pressure on health-care systems worldwide. In this Review, Donal O'Donoghue and colleagues discuss the effectiveness of health-care interventions for early-stage CKD to limit progression to end-stage renal disease. They highlight the need to improve awareness of CKD and its risk factors, and discuss the optimum time to intervene and the most appropriate model of care to adopt.

Anaemia is a clinical hallmark of advanced kidney disease, characterized by insufficient erythropoiesis due to inadequate erythropoietin production in the kidney, inflammation and iron deficiency. Here, Mark Koury and Volker Haase discuss the hypoxic regulation of erythropoiesis and renal erythropoietin production, providing insight into the inter-relationships between erythropoietin synthesis, erythrocyte production, iron metabolism and inflammatory mediators. They also describe current clinical experience with pharmacologic activators of hypoxia-inducible factor signalling as an emerging approach to the treatment of renal anaemia.

Podocytes are susceptible to injury and undergo a series of adaptive, maladaptive or catastrophic responses depending on the severity and duration of the insult. Emerging evidence indicates a central role for Wnt/β-catenin signalling in mediating podocyte dysfunction and the development of proteinuria. Here, Lili Zhou and Youhua Liu describe advances in current understanding of the pathomechanisms of Wnt/β-catenin signalling in mediating podocyte injury and discuss the therapeutic potential of targeting this pathway for the treatment of proteinuric kidney disease.

Improved survival of patients with haematological malignancies owing to advancements in therapy emphasizes the need for heightened awareness of renal complications that can occur as a result of such malignancies or their treatment. Here, the authors examine the incidences, aetiologies, mechanisms and treatment options for a variety of renal disorders associated with haematological malignancies. As haematopoietic stem cell transplantation emerges as an important therapy for haematological malignancies, they also consider the renal complications of this procedure.

A new study reports abnormal peripheral lymphocyte counts and an increased incidence of hospital admission for infections among infants born to mothers with kidney transplants. Further studies are required to investigate the effects of in utero exposure to immunosuppressive agents on immune system development and long-term disease risk in this population.

Despite reductions in morbidity and mortality owing to widespread use of highly effective antiretroviral therapy (ART), HIV-positive patients remain at high risk of chronic kidney disease (CKD) and end-stage renal disease. A new report provides a HIV-specific CKD risk score to balance the potential benefits and harms of nephrotoxic ART.

Resident microorganisms in the human body vastly outnumber host cells and have an important role in human physiology. In this Review, Bromberg and colleagues discuss the basic principles that guide analyses of the microbiota, including the challenges of measuring and quantifying microbiota. They also discuss the influence of the microbiota on the immune system and the implications of these effects on organ failure and transplantation.

Abundant evidence suggests a physiological role of magnesium in cardiovascular function. As the kidney is a major regulator of magnesium homeostasis, serum magnesium levels and magnesium balance are often altered in patients with chronic kidney disease (CKD). In this article, Ziad Massy and Tilman Drüeke review the findings of experimental and clinical studies that provide evidence for a role of magnesium in the high frequency of cardiovascular disease in patients with CKD.